Rare reports of pancreatitis inflammation of pancreas ; cannot be used if have history of medullary thyroid cancer. Cannot use if family history of medullary thyroid carcinoma MTC or if have multiple endocrine neoplasia syndrome type 2 MEN2.

stuffy or runny nose, sore throat, headache, upper respiratory infection, rare severe allergic reactions swelling of tongue, throat, face or body; severe rash. Dose: Taken once daily SE: runny nose, upper respiratory infection, rare severe allergic reactions swelling of tongue, throat, face or body; severe rash.

No weight gain; Lower doses used if kidney problems Saxagliptin. Dose: Taken once daily SE: upper respiratory infection, urinary tract infection, headache. No weight gain; Lower doses used if kidney problems Linagliptin. Dose: Taken once daily SE: runny nose, sore throat, rare reports of pancreatitis, rare severe allergic reactions, no weight gain; SGLT2 inhibitors: increase glucose excretion in the urine Canagliflozin.

Dose: Taken once daily Same as above with metformin and saxagliptin. Table is prepared with information from package inserts of the various medications and opinion of the UCSF Diabetes Teaching Center.

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Diagnosing Diabetes Treatment Goals What is Type 2 Diabetes? Home » Types Of Diabetes » Type 2 Diabetes » Treatment Of Type 2 Diabetes » Medications And Therapies » Type 2 Non Insulin Therapies » Table of Medications.

Use this table to look up the different medications that can be used to treat type 2 diabetes. Use the links below to find medications within the table quickly, or click the name of the drug to link to expanded information about the drug. Tolbutamide Orinase® various generics. SE: hypoglycemia, weight gain Preferred SFU for elderly Must be taken times daily.

Glimepiride Amaryl® various generics. Initial: mg daily Range: mg Dose: Taken once daily. SE: hypoglycemia, weight gain Need to take only once daily. Glipizide Glucotrol® Glucotrol XL® various generics. Initial: 5 mg daily Range: 2. Glyburide Micronase®, DiaBeta® various generics.

Initial: 2. Glyburide, micronized Glynase PresTab® various generics. Initial: 1. Initial: mg daily 0. SE: hypoglycemia Safe for elderly Duration of action is only 4 hours Take within minutes of meal. Initial: mg three times daily if A1C close to goal, use 60 mg Range: mg Dose: Taken three times daily.

SE: hypoglycemia Safe for elderly Duration of action is only 2 hours Take within 30 minutes of meal. Glucophage: mg, mg, mg tablets Glucophage XR: mg, mg tablets Fortamet: mg, mg tablets Glumetza: mg, mg tablets Generic metformin ER: mg, mg tablets. Initial: mg twice daily or mg once daily Range: mg Dose: Taken two or three times daily ER: Initial: mg once daily Range: mg Dosed once daily.

Acarbose Precose® various generics. SE: flatulence Take with first bite of meal Start with low dose and slowly ­ to minimize GI intolerance. Pioglitazone preferred over rosiglitazone Actos®. For secondary prevention, statins reduced all-cause mortality, cardiovascular mortality, coronary artery disease, myocardial infarction, and revascularization.

Intensive vs less intensive statin therapy reduced the risk of coronary artery disease and heart failure. In both of the systematic reviews, the quality of evidence, or certainty in the estimates, was high for most outcomes when evaluated in all older patients.

When the evaluation was restricted to those with diabetes, the estimates of beneficial effects were generally similar to those observed in all older patients, but the CIs were relatively wide, indicating imprecision.

Accordingly, the corresponding quality of evidence was considered to be moderate for older patients with diabetes. There was also no significant difference in estimates interaction between those with and without diabetes, suggesting that extrapolation of data from the older population at large to older individuals with diabetes is reasonable.

Given the heterogeneity of the population of older adults with diabetes, the role of the endocrinologist or the diabetes care specialist in the care of an individual patient may vary considerably during the course of the disease. Decision-making about this role requires active participation and good lines of communication among the endocrinologist or diabetes care specialist, the primary care physician, and the patient.

Because of the high burden of diabetes and its complications on overall health status 21 , 22 , many older patients benefit from care by an interdisciplinary team. The endocrinologist or diabetes care specialist functions as the leader of the diabetes care team, which includes a nurse educator, dietician, and others e.

The endocrinologist or diabetes care specialist may also serve the medical community by providing up-to-date training in the care of older patients with diabetes.

Possible roles of the endocrinologist or diabetes care specialist include the following. An endocrinologist or diabetes care specialist may not be needed for patients whose hyperglycemia and CVD prevention treatment goals are easily achieved with lifestyle alone or with simple oral agent therapy one or two medications.

Application of the Chronic Disease Model can facilitate diabetes quality care in the primary care setting Consultation may involve only a member not all of the diabetes care team e.

The endocrinologist or diabetes care specialist may be asked to initiate insulin therapy for a patient and then send the patient back to the primary care provider once stable, or they may consult to assist with glycemic management when a patient is hospitalized.

This situation may occur by default if the patient has no primary care provider or if the patient is already under the care of the endocrinologist or diabetes care specialist for long-standing T1D or other endocrine conditions.

Specific indications for the endocrinologist or diabetes care specialist to assume control of overall diabetes management for an older patient include complex hyperglycemia treatment use of three or more glucose-lowering agents; the addition of insulin, especially multiple types or injections , recurrent severe hypoglycemia, multiple diabetes complications, and a long history of diabetes.

The ADA defines diabetes and prediabetes based on glucose measures Importantly, individuals with prediabetes are at increased risk for progression to diabetes and development of CVDs; Table 1 24 lists the ADA criteria for prediabetes and diabetes. The fasting plasma glucose and HbA1c categories allow easy identification of both diabetes and prediabetes.

However, many people over the age of 60 years affected with diabetes and prediabetes are not diagnosed unless an oral glucose tolerance test is performed 2. Importantly, individuals with prediabetes are at increased risk for progression to diabetes and development of CVDs.

Population screening demonstrates a high rate of detection of newly diagnosed diabetes. Additionally, modeling such studies suggests that early detection and treatment of diabetes can reduce long-term complications Furthermore, diabetes and prediabetes criteria predict risk for subsequent diabetes and CVD similarly in both older and younger people.

The prevalence of disorders of sleep increases with age, and such disorders have been associated with the development or exacerbation of diabetes and risks of cardiovascular events. Therefore, assessment for sleep disorders and their treatment should be considered in older patients at risk for and with diabetes Classification and diagnosis of diabetes: standards of medical care in diabetes Diabetes Care.

Abbreviations: FPG, fasting PG; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; OGTT, oral glucose tolerance test; PG, plasma glucose. For all three tests, risk is continuous, extending below the lower limit of the range and becoming disproportionately greater at the higher end of the range.

In the absence of unequivocal hyperglycemia, diagnosis requires two abnormal test results from the same sample or in two separate test samples. The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of g anhydrous glucose dissolved in water.

The test should be performed in a laboratory using a method that is National Glycohemoglobin Standardization Program certified and standardized to the Diabetes Control and Complications Trial assay.

Progression from prediabetes to diabetes can be slowed substantially 27— Evidence supporting this observation includes recent meta-analyses involving nearly 50, subjects 31 , The reduced rate of progression to diabetes was maintained during 15 years of follow-up, although the lifestyle intervention was much less intense during the last 10 years 28 , Notably, the impact of this intervention is cost-effective Additionally, metformin was less effective in people over the age of 60 years estimated number needed to treat, The treatment strategies and goals developed for older adults depend on overall patient health, including medical complexity and functional status.

Table 2 33 , 34 provides a guide for the comprehensive assessment of the older adult, including the general medical assessment and diabetes-focused evaluations. Both aging and diabetes are independent risk factors for impaired functional status, and the interaction of these two factors is highly complex and unique for each patient.

For this reason, recent diabetes guidelines have generally concluded that care of the aging patient with diabetes requires an individualized, rather than purely algorithmic, approach 36— However, there is no standard tool recommended for the assessment and documentation of how effectively older adults function in their lives.

Functional status is most often documented using subsets of specific activities that are necessary for living independently. They include activities of daily living ADLs , that is, bathing, dressing, eating, toileting, and transferring, as well as instrumental ADLs IADLs , that is, preparing meals, shopping, managing money, using the telephone, and managing medications Table 2 In patients with diabetes, deficits in IADLs identified during routine evaluation should trigger a more in-depth evaluation of the patient, including a detailed assessment of hypoglycemia and hyperglycemia, microvascular and macrovascular complications, and cognition, as discussed in depth in this guideline.

Abbreviations: AAA, abdominal aortic aneurysm; ADL, activity of daily living; BMI, body mass index; IADL, instrumental activity of daily living. These are generally conducted by primary care providers. These are covered annually except for diabetes management visits, which are covered as recommended by the diabetes care team.

Functional status is based on assessment of independence or dependency having difficulty and receiving assistance of five ADLs bathing, dressing, eating, toileting, and transferring and five IADLs preparing meals, shopping, managing money, using the telephone, and managing medications Overall health in older adults has been described in terms of frameworks or categories that guide the clinician to consider multiple factors when assessing the health of an adult over the age of 65 years.

One such framework was developed by Blaum et al. The Blaum framework suggests considering chronic diseases fewer than three vs three or more , cognitive or visual impairment none, mild, moderate to severe , and IADL dependencies none vs two or more to define functional status.

This framework was used to identify three classes of patients corresponding to increasing levels of mortality risk and was thus validated as a tool for determining the likelihood of benefit of a treatment strategy based on life expectancy Conceptual Framework for Considering Overall Health and Patient Values in Determining Clinical Targets in Adults Aged 65 y and Older.

Frailty can be defined as a state of increased vulnerability to physical or psychological stressors because of decreased physiological reserves in multiple organ systems that cause a limited capacity to maintain homeostasis.

Moreover, it represents a predisability condition that can be responsive to intervention Screening for geriatric syndromes, including frailty, should be part of a stepped-care approach in older people with diabetes, particularly in primary and community care settings.

Where there is evidence of moderate to severe physical or cognitive impairment or functional loss, referral to geriatricians or other skilled clinicians for a comprehensive assessment is needed.

The importance of detecting frailty lies in the opportunity to consider targeted interventions that reduce functional decline and risk of disability.

An initial screen for physical impairment can be obtained by using the following commonly employed measures in geriatric practice 46 [ Table 5 47—51 ]. An international position statement on the management of frailty in diabetes mellitus: summary of recommendations J Frailty Aging ;— Sarcopenia is an age-related loss of muscle mass that has now been linked to progressive loss of muscle strength and reduced physical performance Sarcopenia is accelerated in the presence of diabetes.

Clinicians can refer patients with possible sarcopenia for a dual-energy X-ray absorptiometry scan, but this procedure is expensive and may not be convenient. Bioelectrical impedance analysis is an alternative method for the assessment of lean muscle mass and may be considered in place of dual-energy X-ray absorptiometry scanning.

Alternatively, a rapid screening test for sarcopenia in a clinical setting can be obtained using a simple five-question instrument called the Sarc-F, which looks at fall history, ability to lift objects, and difficulties with mobility.

This scale has been validated extensively and has been shown to be highly predictive of future disability and hospitalization The population burden of cognitive impairment in older individuals is even larger if predementia stages of cognitive dysfunction, such as mild cognitive impairment MCI , are also considered.

Epidemiological studies have found clear associations between diabetes and dementia risk A meta-analysis including over 1 million individuals presented a pooled overall relative risk RR for dementia in people with diabetes of 1.

Moreover, diabetes is associated with an increased risk of MCI RR, 1. Of note, these numbers primarily apply to patients with T2D because data on older individuals with T1D are still scarce.

With the aging of the population and trends in diabetes prevalence, the combination of cognitive impairment and diabetes is likely to become more common, having implications for diabetes care.

Clearly, cognitive impairment in patients with diabetes is associated with poorer diabetes self-management and glycemic control 60 , 61 , an increased frequency of hospital admissions and occurrence of severe hypoglycemic episodes 62 , 63 , and an increased occurrence of major cardiovascular events and death Early identification of individuals with cognitive impairment may avoid some of these poor outcomes 65— In the general population, screening for cognitive impairment and dementia is currently not recommended because of insufficient evidence on the balance of benefits and harms of screening This ratio may be different in people with diabetes because the harm of unrecognized cognitive impairment e.

The benefit of screening is that this harm might be at least partially avoided Therefore, an active approach to the detection of cognitive impairment i.

However, the evidence base upon which screening procedures can be operationalized i. With regard to the target group, the chance of encountering cognitive impairment should be sufficiently high to warrant screening. At this stage, we therefore suggest that screening should be limited to those over the age of 65 years; in younger patients, actively responding to cognitive complaints should be sufficient.

The purpose of screening is to identify marked clinically relevant stages of cognitive impairment i. A positive screening test should be complemented by an appropriate diagnostic evaluation, starting with history taking, to formally diagnose or rule out these conditions.

Notably, self-administered cognitive screening tools are becoming available and might offer an efficient alternative 72 , greatly facilitating widespread implementation.

With regard to the timing and frequency of screening, performing an initial assessment at the time of diabetes diagnosis or when a patient enters a care program would be appropriate. Screening could then be repeated annually, or even less frequently, depending on the perceived risk. In patients without cognitive complaints, screening should be repeated 2 to 3 years after an initial normal screening test result or 1 year after a borderline normal test result.

Cognitive complaints should always be evaluated. Thus far, no evidence supports a benefit of intensive glycemic treatment to preserve cognitive function in patients with diabetes However, further trials are underway, and cognition is increasingly considered an secondary outcome measure in drug trials in diabetes.

Technical remark: Medical and nonmedical treatment and care for cognitive symptoms in people with diabetes and cognitive impairment is no different from those in people without diabetes and cognitive impairment.

No randomized controlled trials RCTs have shown that simplified glucose-lowering treatment regimens improve adherence in patients with diabetes and cognitive impairment or that tailored glycemic targets reduce the risk of treatment-related adverse events, particularly hypoglycemic episodes.

However, patients with impaired cognition are known to have lower adherence and an increased risk of adverse events 60 , 61 , Therefore, the assumption that simplifying treatments and tailoring targets improve compliance and prevent treatment-related complications in patients with impaired cognition is reasonable.

Providing support for caregivers and involving them in all aspects of care are also important. Hypoglycemia has also been associated with morbidity and mortality in post hoc analyses of data from large clinical trials that included older adults. In one study that analyzed data from the Action in Diabetes and Vascular Disease: Preterax and Dimicron Modified Release Controlled Evaluation ADVANCE trial, patients had at least one severe hypoglycemic episode.

Severe hypoglycemia was also associated with other conditions such as respiratory and gastrointestinal conditions Although avoidance of hypoglycemia is a critical treatment strategy, overall glucose control remains an important goal.

Hyperglycemic crises, including diabetic ketoacidosis, hyperglycemic hyperosmolar syndrome, and the combination of the two hyperosmolar ketoacidosis , are severe complications of unrecognized or undertreated hyperglycemia in older adults.

Older adults with these conditions have higher mortality rates than do younger individuals Relaxing glycemic targets for older patients with a high burden of comorbidities and limited life expectancy may be appropriate, yet goals that minimize hyperglycemia are indicated for all patients.

As first noted in the Diabetes Control Complications Trial DCCT , achieving a lower mean glucose to reduce complications may come at the cost of increased hypoglycemia risk Because prevention of both microvascular and macrovascular disease via glycemic control may take years to realize, the health value of strict glycemic targets later in life has been controversial.

National and international guidelines that address glycemic targets generally agree on individualizing care based on overall health status and weighing the expected timing of benefits against life expectancy 37 , 79 , Several studies have illustrated the clinical challenge of selecting glycemic targets by associating HbA1c achieved with mortality.

The results showed a U-shaped association; the adjusted hazard ratios HRs of all-cause mortality were 1. A secondary analysis of the Action to Control Cardiovascular Risk in Diabetes ACCORD randomized trial further highlighted the complexity of targets by addressing setting vs achieving HbA1c targets.

Multiple treatment options were available to providers to achieve glucose goals. However, this finding was not reproduced in the recently published long-term results of the Veterans Affairs Diabetes Trial VADT Importantly, older individuals enrolled in diabetes clinical trials are more likely to have better overall health than are older individuals in the general population.

Numerous studies successfully achieved standard glycemic targets without increased hypoglycemia in older adults with good or intermediate health 85 , Because these trials exclude older adults with poor health, they support the concept that intensive strategies for selected individuals can be effective and safe.

The compendium of results from these and other published analyses suggests that although some patients may benefit from tighter targets, many are unable to reach these targets, and aggressive therapy may be harmful to some patients without the benefit of reducing complications.

Although measurement of HbA1c is a convenient and validated method for determining overall glycemic status, it does not assist in identifying hypoglycemia. Detailed assessment of glycemia in older adults may also indicate glycemic variability, which is directly calculated by CGM systems and predicts hypoglycemia in older adults with T1D Older adults with T2D also tend to display unique glucose patterns, with relatively more postprandial hyperglycemia than fasting hyperglycemia Knowledge of such patterns should lead to more tailored and potentially safer medication regimens, for example, adding premeal insulin to one large meal per day instead of progressive titration of long-acting basal insulin.

When available, CGM is an important tool for safely addressing high-risk glycemic patterns. CGM use in older adults is limited and is variable across populations, including patients with T1D, those with T2D, those using insulin pump therapy, and those using multiple daily injections of insulin.

For those older adults who have been enrolled in clinical trials, CGM used intermittently or continuously appears to be a useful tool for guiding therapy to allow improved glycemic control without increased hypoglycemia. In a clinical trial by Vigersky et al.

The population included individuals using various antihyperglycemic agents, including basal insulin but excluding prandial insulin. Interestingly, the results indicated that intermittent CGM can assist both patients and providers in adjusting diabetes regimens to achieve lower targets without increasing hypoglycemia risk In addition to its limitations in identifying glucose patterns, the HbA1c test must be interpreted with caution, which is particularly significant in older adults given the increased likelihood of relevant conditions that may alter red blood cell turnover e.

This topic has been explored in detail by others 92 , Nonetheless, older patients face a number of issues related to nutrition and exercise capacity. Weight loss should be approached with caution in older adults, as both intentional and unintentional weight loss may lead to severe nutritional deficiencies The recommendation of a combination of physical activity and nutritional therapy, including the recommended intake of calcium, vitamin D, and other nutrients, is an appropriate strategy for this population.

An increase in physical activity in older adults should reduce sedentary behavior, and moderate-intensity aerobic activity should be emphasized. Activities aimed at increasing flexibility, muscle strength, and balance are also recommended Intensive education regarding carbohydrate and calorie counting and meal planning can be useful for individuals with an active lifestyle to effectively modify insulin dosing and improve glycemic control 97 , A simpler diabetes meal planning approach emphasizing portion control and healthful food choices may be more suitable for older individuals with cognitive impairment or learning difficulties 99 , In the case of sarcopenia, nutritional therapy coupled with exercise training is thought to be beneficial.

Nutrition is an integral component of diabetes self-care for all people with diabetes regardless of age 79 , Notably, nutritional guidelines do not differ for older adults with or without diabetes.

However, older adults may experience unique challenges that impact their ability to follow a healthy diet i. Many studies support early screening for malnutrition in older patients, especially those at high risk for malnutrition acute care-admitted patients and home-care residents , Malnutrition is an important problem in the older adult population and has potentially serious consequences, such as prolonged hospitalization, increased costs, and a higher number of readmissions , Therefore, early detection and management of malnutrition are crucial for preventing future complications.

Moreover, a number of screening tools are already available to assess nutritional status, and certain assessments, such as the Mini Nutritional Assessment and Short Nutritional Assessment Questionnaire, can be easily administered to older individuals. Low-quality studies suggest that consuming energy-dense and protein-rich food could improve food consumption and prevent weight loss and malnutrition risk.

The PROT-AGE study group has recently recommended an average daily intake in the range of 1. Furthermore, experts have proposed a protein intake of at least 1. Studies on specific nutrients protein supplements, branched-chain amino acids, creatine have not shown consistent benefits , although the Society for Sarcopenia, Cachexia, and Wasting Diseases recommends measuring hydroxyvitamin D levels and replacing them if low in all sarcopenic patients Nutrition plans for patients with diabetes are generally individualized healthy diets based on preferences, abilities, and treatment goals.

We must emphasize healthful eating patterns consisting of nutrient-dense, high-quality foods rather than specific nutrients to improve overall health regarding body weight; glycemic, BP, and lipid targets; and reductions in the risk of diabetes complications The Mediterranean , Dietary Approaches to Stop Hypertension DASH , , and plant-based diets are all examples of healthful eating patterns.

Choosing vegetables, legumes, whole grains, and high-fiber breakfast cereals is the best way to increase fiber consumption, although increasing fiber should be avoided in cases of delayed gastric emptying gastroparesis. Additionally, meeting fluid intake recommendations is important for preventing constipation and fecal impaction in older adults Palatability, availability, affordability, and the difficulty of achieving low-sodium recommendations in a nutritionally adequate diet are all important considerations Additionally, older adults are much more likely to suffer the adverse effects of alcohol due to changes in their ability to metabolize alcohol, particularly those taking multiple medications and those who are at increased risk of adverse events , For nursing home residents, some studies — suggest that it is better to use regular diets for nursing home residents with diabetes.

As the most common fluid and electrolyte disturbance in older adults, dehydration needs to be prevented and managed in people living in long-term care facilities Many interventions can reduce its prevalence , in this population and, notably, diuretics and antihypertensives should be carefully managed after admission to avoid contributing to fluid and electrolyte depletion.

For community-dwelling older adults, maintaining a nutrient-dense diet is essential for promoting health and preventing nutrition-related complications Evidence indicates that restrictive diets impose significant risks of sarcopenia and malnutrition in community-dwelling older adults Glycemic management strategies must be adjusted to the individual needs of older patients.

Specific factors regarding certain drug classes are particularly important for older people with diabetes, especially those with CKD and heart disease. Metformin is highly effective, may reduce cardiovascular events and mortality, and does not cause hypoglycemia or weight gain 94 , 95 , , As clinical events that may precipitate acute kidney injury, such as radiocontrast dye, nephrotoxic drugs, hypotension, heart failure, and surgery, may cause metformin accumulation, with a potential risk for lactic acidosis, metformin use is often stopped when patients are hospitalized.

An additional concern is the development of vitamin B12 deficiency, and levels should be monitored yearly — Technical remark: To reduce the risk of hypoglycemia, avoid using sulfonylureas SUs and glinides, and use insulin sparingly.

SUs, repaglinide, and nateglinide can cause hypoglycemia and weight gain. Glyburide should be avoided in older individuals because of a substantially increased risk of hypoglycemia compared with that of glimepiride and glipizide , , , Furthermore, these medications are associated with increased fracture rates and bone loss in women , ; thus, use in older women with underlying bone disease, such as osteoporosis, could potentially be problematic.

α -Glucosidase inhibitors have only modest efficacy, and in older individuals, the gastrointestinal adverse effects of flatulence and diarrhea tend to cause a relatively high rate of nonadherence Dipeptidyl peptidase-4 DPP-4 inhibitors are generally well tolerated.

Recently, both empagliflozin and canagliflozin have been shown to decrease major adverse cardiovascular events MACE , heart failure, and the progression of CKD , These compounds cause an obligate increase in urine volume and an increase in urogenital candida infections.

Canagliflozin has also been shown to be associated with a decrease in bone mineral density at the hip, but not the femoral neck, lumbar spine, or distal radius , with a significant increase in fractures of arms and legs but not the spine Very rare cases of diabetic ketoacidosis have been reported in patients with T2D taking SGLT2 inhibitors, including patients over the age of 65 years , Glucagon-like peptide 1 GLP-1 receptor agonists increase insulin release, decrease glucagon secretion, delay gastric emptying, suppress appetite, and do not cause hypoglycemia; however, nausea is a common side effect Initial concern about an increased risk for pancreatitis has not been proven , In patients with T2D, insulin therapy is usually initiated when oral agents do not provide sufficient glycemic control Self-monitoring of blood glucose must be performed for insulin to be used safely and effectively.

Initially, a single long-acting insulin analog can be added as basal insulin therapy with dose adjustment to maintain fasting glucose in the desired range 79 , , Recently, insulin glargine U and insulin degludec, which are longer-acting basal insulins compared with insulin glargine U, showed overall similar levels of glycemic control but with less variability and hypoglycemia , If fasting glucose is near goal but the HbA1c remains above goal, rapid-acting insulin can be added first, prior to the largest meal and then prior to other meals, as necessary 79 , , Additionally, premixed insulins neutral protamine hagedorn with regular or analog insulin given twice daily may be a simpler approach , but the lack of flexibility, especially in patients who may skip or delay meals, may increase the risk of hypoglycemia Increasing from one to three or four injections per day means moving from a less complex to a more complex regimen, which may be limiting 79 , , The complexity of the treatment regimen must be balanced against the treatment goals and risks of hypoglycemia.

For patients with arthritis of their hands, the use of insulin pens, or other assistive appliances, can be helpful. Recently, fixed doses of GLP-1 receptor agonists and basal insulin, insulin degludec and liraglutide IDegLira and insulin glargine and lixisenatide LixiLan , have become available in a single syringe, and thus only one injection is needed.

A low dosage of the combination is started, and then the dosage is gradually titrated upward. Because T2D slowly worsens over time , increasing dosages and numbers of medications may be needed to control glucose levels. However, the sequence in which drugs should be added after metformin is not clear.

Recent recommendations indicate that GLP-1 receptor agonists and SGLT2 inhibitors be prescribed early, given their beneficial cardiovascular outcomes 24 , In general, the more drugs that are prescribed, the poorer is adherence to a particular regimen Of critical importance is the avoidance of hypoglycemia, which can have devastating outcomes in older patients.

Thus, SUs and insulin should be avoided if at all possible. Hypertension is a well-known risk factor for cardiovascular and kidney disease. The goals of treatment and the specific medications used for treatment may differ between patients with diabetes and those without diabetes, particularly older adults.

If lower BP targets are selected, careful monitoring of such patients is needed to avoid orthostatic hypotension. Choosing a BP target involves shared decision-making between the clinician and patient, with full discussion of the benefits and risks of each target. Thus, this level was recommended by the Eighth Joint National Committee evidence-based guideline for the management of high blood pressure in adults The mean age of subjects entering SPRINT was The way in which BP was measured in SPRINT unattended automated machine was subsequently noted to yield a SBP 16 mm Hg lower than a standard office BP measurement i.

This recommendation was based primarily on the SPRINT data; however, the guideline acknowledged the lack of randomized trial data supporting this target in patients with diabetes Four large prospective randomized studies have been performed in patients with diabetes and targeted two different BP goals: the United Kingdom Prospective Diabetes Study UKPDS , the ACCORD study , the ADVANCE trial , and the Hypertension Optimal Treatment HOT trial Thus, treatment approaches and goals are controversial.

Many clinicians may opt for this lower target in patients at high CVD risk after careful discussion of the pros and cons of such increased intensity of treatment with the patient. Importantly, consideration should also be given to a higher BP target if the patient develops symptomatic orthostatic hypotension, and medications that tend to cause orthostatic hypotension should be avoided Additionally, prescribing one or more hypertension medications to be taken at bedtime may have additional CVD benefits Several studies have demonstrated a reduction in the progression of diabetic CKD with the use of angiotensin-converting enzyme ACE inhibitors and angiotensin receptor blockers ARBs in patients with hypertension and advanced CKD — Subsequent head-to-head studies have shown that these two drug classes are essentially equivalent for diabetic CKD Moreover, ACE inhibitors have been shown to significantly reduce the risk of all-cause and CVD mortality, MACE, and heart failure, whereas ARBs significantly reduce only the risk of heart failure.

Neither drug class has been shown to significantly reduce the risk of stroke — Therefore, ACE inhibitors and ARBs should be the first-line therapy used for the treatment of hypertension in older patients with diabetes and should be included when more than one medication is needed, especially if albuminuria is present Nonetheless, these two drug classes should not be used together, especially in patients with CKD, due to increased risks of hyperkalemia and acute kidney injury The need for more than one drug to treat hypertension is common in patients with T2D The question of the third or fourth drugs to be added after renin-angiotensin system blockers and calcium blockers has not been addressed in either controlled clinical trials or meta-analyses.

If coronary artery disease is significant, a beta-blocker may be appropriate and can be added as a fourth drug to a prior three-drug regimen If a beta-blocker is used, carvedilol has been shown to have fewer metabolic effects than metoprolol Notably, when BP is not controlled with three or more medications, referral to a hypertension specialist is indicated Technical remark: The Writing Committee did not rigorously evaluate the evidence for specific LDL-C targets in this population, so we refrained from endorsing specific LDL-C targets in this guideline.

For patients aged 80 years old and older or with short life expectancy, we advocate that LDL-C goal levels should not be so strict. Epidemiological evidence documents that diabetes is an independent risk factor for CVD in both men and women.

Furthermore, in patients with diabetes, all major cardiovascular risk factors, including cigarette smoking, hypertension, and high serum cholesterol — , add to the degree of risk for CVD in older patients with diabetes.

Individuals with diabetes have more than twice the risk for CVD than do those who do not have diabetes. Cholesterol-lowering treatment with statins is equally efficacious in reducing RR and more effective in reducing absolute CVD events in older adults than in younger individuals because the older patients have a higher absolute risk for CVD.

Most studies indicate that diabetic dyslipidemia in older adults is undertreated Numerous studies have confirmed the relationship between hypercholesterolemia and CVD, including myocardial infarction and stroke. Similarly, in large RCTs and multiple meta-analyses, statin use has been found to be effective in primary and secondary prevention when using myocardial infarction, revascularization and stroke as endpoints , Most patients aged 65 years and older with diabetes do not have marked elevations of LDL-C, because the method of measuring LDL-C underestimates the LDL particle number.

However, these LDL-C levels are high enough to support the development of atherosclerosis Because LDL-C may be normal but LDL particles may be small , risk stratification should be used to determine the level of LDL-C that should be achieved in older patients with diabetes using statins.

Calculated non-HDL, which reflects all atherogenic particles, adds to the assessment of atherogenicity. Furthermore, risk stratification can be achieved by a number of CVD risk calculators, and, when indicated, coronary artery calcium may enhance risk stratification Apolipoprotein B measurement can be useful in some patients to help refine their LDL treatment goal.

A role for LDL-C in hyperglycemic patients became apparent in several early large clinical trials [ e. In contrast to statins, fibrates did not cause a significant reduction in stroke events compared with placebo in clinical trials.

The Prospective Study of Pravastatin in the Elderly at Risk PROSPER trial included men and women, and the average age was 75 years. In general, high-dose statin therapy is indicated for all patients with diabetes, irrespective of age, unless specifically contraindicated. Furthermore, although LDL-C levels are not necessarily elevated in patients with diabetes, statins still have a profound effect on the prevention of CVD, and thus all patients with T2D should be treated with statins.

Caveat: Most, but not all, studies support the value of statin use in the prevention of CVD in patients with diabetes. As described in the technical remark, the Writing Committee did not rigorously evaluate the evidence for specific LDL-C targets in older patients with diabetes.

Therefore, we refrained from proposing specific LDL-C targets. The reader is referred to numerous guidelines and consensus statements that address this important topic Table 6.

In statin-intolerant patients, ezetimibe may be administered to inhibit cholesterol absorption from the gastrointestinal tract The Improved Reduction of Outcomes: Vytorin Efficacy International Trial IMPROVE-IT demonstrated that the addition of ezetimibe to statin therapy positively affected CVD in patients with acute coronary syndrome.

In this trial, many of the patients were older than 65 years, and the CVD benefit was observed primarily in patients with diabetes , Additionally, PCSK9 inhibition has been shown to reduce LDL-C levels more than high-dose statins and to also reduce CVD outcomes.

PCSK9 inhibitors have been approved for patients who are unable to reach the LDL goal with the maximally tolerated statin dose, those with clinical CVD on high-dose statins who have not reduced their LDL-C levels to target , , and those with familial hypercholesterolemia.

The use of fibrates, as demonstrated in the Fenofibrate Intervention and Event Lowering in Diabetes FIELD study, resulted in no significant benefit regarding the primary endpoint or mortality, and it is therefore not recommended for CVD prevention in patients with diabetes.

There is also evidence that fenofibrate may be valuable in preventing the progression of retinopathy , Aging and diabetes have a profound effect on the cardiovascular system structure and function that increases the risk of CHF. Aging increases vascular stiffness and reduces elasticity, leading to increased SBP, myocyte hypertrophy, and impaired diastolic function Diabetes increases the risk of CHF due to associated comorbidities such as hypertension and complications such as macrovascular and microvascular disease and also directly affects the myocardium, causing cardiomyopathy — Therefore, the prevalence of CHF in older people with diabetes is high, reaching up to Patients with both diabetes and CHF are at particular risk of adverse events.

In the Reduction of Atherothrombosis for Continued Health REACH registry, which included 19, patients with diabetes and a mean age of CHF at baseline was independently associated with cardiovascular mortality HR, 2. CHF medications act in essentially the same way in those with and without diabetes.

Nevertheless, the cardiovascular safety of the various classes of hypoglycemic medications is less well understood. Hyperglycemia increases the risk of CHF and hence should be controlled, although no direct evidence supports a reduction in the risk of CHF by treating hyperglycemia.

Despite the common coexistence of diabetes and CHF in older people, optimal management is not fully evidence-based due to a lack of clinical trials in this age group. For this reason, treatment according to the recently published clinical practice guidelines is recommended Table 6. No associations of SUs, insulin, acarbose, or glinides with CHF or mortality were found — , but one study did suggest a possible link between glinides and heart failure Moreover, rosiglitazone increased the risk of all-cause mortality HR, 1.

A limited meta-analysis of seven RCTs reported that the risk for CHF was less with pioglitazone than with rosiglitazone 1. A more comprehensive meta-analysis of 94 RCTs demonstrated that pioglitazone was associated with reduced all-cause mortality OR, 0. Interestingly, the risk for hospitalization for CHF with DPP-4 inhibitors is inconsistent.

The HR was significant for saxagliptin HR, 1. Notably, the ability of these studies to detect CHF hospitalization risk with certainty may be limited, and further evidence is needed.

No increased risk of CHF hospitalization HR, 0. Furthermore, the SGLT2 inhibitor empagliflozin showed a decreased HR for hospitalization for heart failure 0.

Canagliflozin showed a similar benefit for heart failure in the CANVAS study In advanced CHF, palliative care with a focus on symptom control is effective in improving quality of life as well as reducing hypoglycemic medications in frail older people, as they are often unnecessarily overtreated , The cardiovascular safety profile of the SGLT2 inhibitor dapagliflozin has also recently been studied in a large randomized, placebo-controlled study median duration of 4.

A key result was a lower rate of cardiovascular death or hospitalization for heart failure 4. This appears to confirm a view held that these benefits are likely a class effect In contrast to the effects on the heart, an increase in lower extremity amputations was observed in patients taking canagliflozin in another long-term cardiovascular outcome study CANVAS , and the Food and Drug Administration FDA now requires a boxed warning regarding this effect of this medication Aging and diabetes have a synergistic effect on the structure and function of the vascular system that increases the risk of vascular disease.

Increased arterial wall thickening and stiffening and reduced compliance occur with aging With diabetes, endothelin vasoconstrictor and procoagulant production increases, and nitric oxide production vasodilator decreases, shifting the balance toward a vasoconstrictor, procoagulant, proliferative, and proinflammatory state that leads to the development of atherosclerosis Contributors to progressive atherosclerosis include hyperglycemia, dyslipidemia, obesity, and hypertension Moreover, diabetes increases the risk of ischemic stroke by twofold, independently of BP, as well as the RR of in-hospital or day stroke-related mortality.

Diabetes substantially increases the risk of peripheral arterial disease and its associated mortality by nearly twofold and increases peripheral arterial disease—related costs and length of hospital stay , According to one recent study, there is little or no increase in risk of mortality, myocardial infarction, or stroke if the following five risk factors are within normal ranges in patients with T2D: HbA1c, LDL, albuminuria, smoking status, and BP Although the available evidence suggests that large reductions in the classic complications of T2D, mainly myocardial infarction, stroke, amputations, and mortality, have occurred during the past 20 years , the burden of atherosclerosis in older patients with diabetes remains substantial, and multifactorial intervention in this age group is essential.

Moreover, the ADA also notes that addressing multiple cardiovascular risk factors at the same time can lead to greater benefits Lifestyle interventions including exercise and weight loss in obese older patients reduce intrahepatic fat content, increase insulin sensitivity, and improve overall metabolic risk factors for atherosclerosis 11 , Clinical trials have shown that in older patients with diabetes, tight glycemic control with HbA1c no lower than 7.

Furthermore, metformin treatment is associated with improved cardiovascular outcomes, regression of atherosclerosis, and low risk of lactic acidosis — In the EMPA-REG OUTCOME trial , the SGLT2 inhibitor empagliflozin showed lower rates of combined cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke HR, 0.

In a recently completed randomized trial of canagliflozin vs placebo in T2D mean age of Moreover, results from the LEADER trial demonstrated significant cardiovascular benefits from liraglutide in comparison with placebo The thiazolidinedione rosiglitazone was previously shown to increase the risk of myocardial infarction OR, 1.

The FDA has now entirely lifted the risk evaluation and mitigation strategy for rosiglitazone. Other hypoglycemic agents seem to have a neutral effect on cardiovascular outcome — , , although the addition of glinides or α -glucosidase inhibitors to metformin therapy showed a reduction in risk of acute myocardial infarction HR, 0.

A meta-analysis of clinical trials of hypertension treatment in T2D showed that cardiovascular outcomes reached a plateau after attaining an SBP of mm Hg. A more recent meta-analysis confirmed the cardiovascular benefits of lowering SBP to mm Hg but demonstrated that further reduction is associated with an increased risk of cardiovascular death, with no stroke reduction benefit All antihypertensive medications can be used in the treatment of hypertension in older people with diabetes, as no difference in mortality was observed with one drug class over the others, and the benefit may be due to the reduction in BP rather than a class effect The benefit of statins in reducing cardiovascular risk is established.

However, the evidence in older people is largely extrapolated from trials in younger populations. Interestingly, the addition of fibrate or niacin to statin therapy has shown no extra cardiovascular benefit , Older patients with diabetes have a high burden of atherosclerosis and are likely to benefit from aspirin therapy after assessment of their bleeding risk , Overall, frail older individuals with diabetes are unnecessarily overtreated, and reducing polypharmacy in this group may improve their quality of life.

The primary prevention of cardiovascular events in older patients with diabetes is challenging because of a general lack of evidence for safe and effective treatment in this age group. Older patients with diabetes have a higher baseline cardiovascular risk and therefore are likely to benefit more from risk reduction than are younger patients without diabetes.

However, this group of patients is largely heterogeneous with various levels of functional ability and life expectancy, which should be considered, as the current evidence is not generalizable to patients with poor functional status or multiple comorbidities or those with limited life expectancy.

Aspirin use in secondary prevention of CVD is now well established and has been shown to be effective in reducing cardiovascular morbidity and mortality in patients with a history of CVD The main adverse effect is an increased risk of gastrointestinal bleeding.

The excess risk may be as high as 5 per per year in real-world settings The evidence for use of aspirin in primary prevention, however, has been conflicting and unclear. Currently, the use of aspirin for primary prevention must remain a decision by the clinician on an individualized basis. Responses to standardized questionnaires suggest that vision loss due to diabetic retinopathy may significantly reduce quality of life and that treatment satisfaction may be significantly affected by the severity of macular edema — Retinopathy and neuropathy may affect the ability of a person to safely operate a motor vehicle The duration of diabetes predicts the presence of retinopathy, and control of hyperglycemia profoundly affects the onset and progression of diabetic retinopathy in both T1D and T2D 78 , , — The beneficial microvascular effects of intensive glycemic control persisted after closeout of the DCCT research group, UKPDS, and ACCORD trials , , In addition to poor glycemic control, the presence of albuminuria, hypertension, and dyslipidemia predict retinopathy — Furthermore, the observed present-day decline in the prevalence and incidence of retinopathy and vision impairment is thought to be the result of improved management of hyperglycemia, hypertension, and dyslipidemia , The benefit of strict BP control with respect to retinopathy, which was suggested in the UKPDS study but not confirmed in the ACCORD study , , has not been consistently demonstrated.

The use of ACE inhibitors or ARBs may have beneficial effects on retinopathy — Treatment with fenofibrate in trials intended for assessing cardiovascular protection has suggested that this drug may reduce the progression of diabetic retinopathy, but continued treatment beyond the closing of the clinical trials may be required to confer this benefit — , , , There is worldwide interest in developing evidence to support the use of fenofibrate for limiting the progression of diabetic retinopathy, but its safety and efficacy might best be justified by evidence from trials that are designed to examine visual and retinal findings as their primary outcome measures.

Periodic screening is justified for detecting vision-threatening retinopathy at an early stage and for offering measures to reduce its progression Panretinal photocoagulation is the mainstay of treatment of proliferative retinopathy but may produce an exacerbation of diabetic macular edema, a condition that affects a substantial number of older patients — Rather, the risk is associated with duration of diabetes and HbA1c Such data, together with the impact of retinal edema on vision, suggest that a large number of older patients might experience improvements in vision and quality of life from anti-VEGF therapy.

Intravitreal anti-VEGF therapy may be the most effective front-line modality for macular edema and may be an alternative to panretinal photocoagulation in the treatment of proliferative diabetic retinopathy , — Notably, Medicare claims data suggest that diabetic retinopathy may be associated with an increased risk of age-related macular degeneration Open-angle glaucoma and cataracts occur more commonly among persons with diabetes , Moreover, the risk for glaucoma increases with the duration of diabetes and fasting hyperglycemia.

Among older persons with T2D or T1D for 5 years, these additional risks lead us not only to endorse the recommendation of the ADA for an initial dilated and comprehensive eye examination by an ophthalmologist or optometrist but also to suggest screening thereafter at least annually , The prevalence of diabetic neuropathy appears to be increasing and is correlated with increased age, duration of diabetes, higher HbA1c, and lifelong glycemic control — Persons treated with metformin and having neuropathic manifestations should be evaluated because metformin may cause vitamin B12 deficiency.

The heterogeneity of peripheral and autonomic neuropathies in diabetes necessitates consideration of a differential diagnosis, especially if manifestations are lateralized or atypical — Persons with diabetes are at increased risk of falls and hip fracture — Thus, inquiry about falls should occur at least annually Evidence is inconclusive on whether specific glycemic targets or antihyperglycemic treatment regimens promote falls — Thiazolidinediones and SGLT-2 inhibitors might worsen fall-related outcomes by increasing fracture risk , , Furthermore, hypoglycemia may be a risk factor for adverse outcomes of falls 73— Pharmacologic therapy for painful diabetic neuropathy requires caution in older adults, with special concern for polypharmacy, oversedation, and orthostasis , — Neuropathy is associated with increased risk of falls in older individuals with diabetes , , — , and exploratory studies have found associations between diabetic neuropathy and abnormalities in gait, posture, and balance — Physical therapy interventions for those with functional deficits may reduce risk factors for falls and possibly the actual rate of falls and fractures — Referrals might specify imbalance, unsteadiness on feet, abnormality in gait, foot drop, history of falling, neuropathic foot ulcer, lack of coordination, or other functional deficits or consequences traceable to neuropathy.

Lower extremity amputation for nontraumatic indications is performed relatively infrequently but with higher incidence among individuals with diabetes, and individuals in some populations and geographic areas are at disproportionate risk for this situation — Evidence possibly linking amputation to canagliflozin therapy is preliminary Variably reported individual patient risk factors for lower extremity amputation may include peripheral sensory neuropathy, autonomic neuropathy, gait abnormalities, peripheral vascular disease, foot ulcer, history of previous amputation, certain foot deformities, greater body mass, chronic renal failure, poor vision, older age, and higher HbA1c — Foot ulcer increases amputation risk and utilization of medical care — However, further research is necessary to confirm trends in amputation rates and to establish whether a program of comprehensive foot care or specific management strategies for established foot complications may reduce the risk for amputation among older persons with diabetes , , — We endorse the standard of care concerning foot care as expressed by the ADA, which recommends patient self-care education, specifies the content and frequency of periodic comprehensive foot evaluations, recommends a multidisciplinary approach for foot ulcers and high-risk feet, and presents indications for referral for further vascular assessment, ongoing preventive care, and lifelong surveillance by foot care specialists Examiners should identify any history of foot ulcer, poorly fitted footwear, loss of protective sensation, vascular insufficiency, foot deformity, or preulcerative lesion.

For patients with altered gait due to neuropathy, local foot deformity, or unhealed ulcers, exercise programs may need to focus on non—weight-bearing activities Furthermore, specialty care may be required to determine the appropriateness of off-loading devices, monitoring of foot skin temperature, use of therapeutic footwear, and need for vascular or podiatric surgical interventions , , Lower extremity amputation is associated with reduced survival and a reduction in physical health-related quality of life, as well as delayed recovery and impaired return to baseline function among nursing home residents 1 , , The risk factor of vascular insufficiency must be considered among persons with diabetic foot ulcers , The goals of lower extremity revascularization in older patients include maintenance of functional capacity and independent living status.

Observational studies suggested similar limb salvage rates but less short-term mortality and morbidity after endovascular surgical revascularization , Notably, the decline in GFR reduces the clearance of insulin and many diabetes medications and increases the risk of hypoglycemia , The general recommendation for annual measurement of urinary albumin-to-creatinine ratio and eGFR should also be carried out in older adults However, progressive loss of GFR can occur in the absence of albuminuria In patients with an estimated limited lifespan who have normal urinary albumin excretion, the prognostic value of annual measurement of urinary albumin excretion over and above indicating an increased risk of CVD is likely minimal Table 7.

Medications Used to Treat Hyperglycemia and Special Concerns With Use in Older Patients With CKD and CVD. Reduced kidney function results in a prolongation of insulin half-life and a decrease in insulin requirements All insulin preparations can be used in patients with CKD, and no specific reductions in dosing are necessary for patients.

Postprandial rapid-acting insulin with a dose adjustment for the amount eaten may help patients with varying food intakes. SUs and their metabolites are renally cleared, leading to an increased risk of hypoglycemia as GFR declines.

Pioglitazone and rosiglitazone are hepatically metabolized and can be used in CKD without dosage adjustment , However, fluid retention limits their use in CKD, and they are associated with increased fracture rates and bone loss Thus, use in patients with underlying bone disease such as renal osteodystrophy or osteoporosis could potentially be problematic.

The DPP-4 inhibitors sitagliptin, saxagliptin, and alogliptin undergo some renal clearance and require dosage adjustment in patients with reduced eGFR see Table 7. Only a small amount of linagliptin is cleared renally, and no dosage adjustment is indicated with a reduced GFR In general, these drugs are very well tolerated.

SGLT2 inhibitors generally become less effective as GFR decreases Interestingly, empagliflozin and canagliflozin have been shown to delay the progression of CKD , The clearance of exenatide decreases as the GFR declines Nausea is a common side effect of these drugs and could potentially be problematic in older patients with compromised intake, especially those with progressing CKD.

Neither bromocriptine dopamine receptor agonist nor colesevelam bile acid sequestrant has been studied in patients with advanced CKD. Although it is clear that life expectancy for patients with T1D is improving , the number of people reaching 60 years and older is unknown.

There appears to be two reasons for the increasing number of older adults with T1D. First, those diagnosed with childhood T1D have taken advantage of the improved therapies for glycemic management and nonglycemic measures for the prevention and treatment of long-term complications.

Second, for reasons that are unclear, the number of cases of adult-onset T1D has increased. This phenomenon provides opportunities for the study of a population that numerically was not common in the past.

No RCTs have assessed outcomes for older individuals with T1D. In general, near normal glycemic targets are reserved for individuals with shorter durations of diabetes prior to the development of microvascular or macrovascular complications.

For questions, contact communications diabetes. Become a Member Order Resources Home About Contact DONATE. Next Previous. Key Messages Recommendations Figures Full Text References. Chapter Headings Introduction Diagnosis and Screening Reducing the Risk of Developing Diabetes Management Prevention and Treatment of Complications Diabetes in Long-Term Care Other Relevant Guidelines Relevant Appendix Author Disclosures.

Key Messages Diabetes in older people is distinct from diabetes in younger people and the approach to therapy should be different. This is especially true in those who have functional dependence, frailty, dementia or who are at end of life.

This chapter focuses on these individuals. Personalized strategies are needed to avoid overtreatment of the frail elderly. Sulphonylureas should be used with caution because the risk of hypoglycemia increases significantly with age.

DPP-4 inhibitors should be used over sulfonylureas because of a lower risk of hypoglycemia. Long-acting basal analogues are associated with a lower frequency of hypoglycemia than intermediate-acting or premixed insulin in this age group. Key Messages for Older People with Diabetes No two older people are alike and every older person with diabetes needs a customized diabetes care plan.

What works for 1 individual may not be the best course of treatment for another. Some older people are healthy and can manage their diabetes on their own, while others may have 1 or more diabetes complications.

Based on the factors mentioned above, your diabetes health-care team will work with you and your caregivers to select target blood glucose and glycated hemoglobin A1C levels, appropriate glucose-lowering medications, and a program for screening and management of diabetes-related complications.

Introduction This guideline refers primarily to type 2 diabetes in the older person. Diagnosis and Screening As noted in the Definition, Classification and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome chapter, p.

Reducing the Risk of Developing Diabetes Healthy behaviour interventions are effective in reducing the risk of developing diabetes in older people at high risk for the development of the disease 3.

Management Organization of care As interprofessional interventions specifically designed for older adults have been shown to improve glycemic control, referrals to diabetes health-care DHC teams should be facilitated 7—9.

Self-management education and support Self-management education and support programs are a vital aspect of diabetes care, particularly for older adults who may require additional education and support in light of other chronic conditions and polypharmacy Targets for glycemic control The same glycemic targets apply to otherwise healthy older adults as to younger people with diabetes see below , especially if these targets can be obtained using antihyperglycemic agents associated with low risk of hypoglycemia see Targets for Glycemic Control chapter, p.

Frailty Diabetes is a marker of reduced life expectancy and functional impairment in the older person. Monitoring glycemic control The same general principles pertain to self-monitoring of blood glucose SMBG in older people, as they do for any person with diabetes Monitoring Glycemic Control chapter, p.

Nutrition and physical activity Nutrition education can improve metabolic control in ambulatory older people with diabetes Figure 1 Clinical frailty scale. Noninsulin antihyperglycemic agents In lean older people with type 2 diabetes, the principal metabolic defect is impairment in glucose-induced insulin secretion Insulin therapy Insulin regimens in the older adult should be individualized and selected to promote patient safety.

Prevention and Treatment of Complications Hypertension Treatment of isolated systolic hypertension or combined systolic and diastolic hypertension in older people with diabetes is associated with a significant reduction in CV morbidity and mortality and microvascular events.

Dyslipidemia The treatment of dyslipidemia with statins for both primary and secondary prevention of CV events has been shown in most, although not all, studies to significantly reduce CV morbidity and mortality in older people with diabetes — Erectile dysfunction Type 5 phosphodiesterase PDE inhibitors appear to be effective for the treatment of erectile dysfunction in carefully selected older people with diabetes — Depression Depression is common in older people with diabetes, and a systematic approach to the treatment of this illness not only improves quality of life, but reduces mortality Osteoporosis Type 1 diabetes is associated with low bone density although the mechanism of bone loss is unknown.

Dementia Diabetes increases the risk of dementia in older people with diabetes, including both vascular dementia and Alzheimer's disease 62,, Polypharmacy Older people with diabetes are frequently on multiple medications, many of which may be inappropriate in the setting of complex comorbidity and limited life expectancy Diabetes in Long-Term Care The prevalence of diabetes is high in institutions and individuals frequently have established microvascular and CV complications, as well as substantial comorbidity — Recommendations Functionally independent older people with diabetes who have a life expectancy of greater than 10 years should be treated to achieve the same glycemic, BP and lipid targets as younger people with diabetes [Grade D, Consensus].

BP targets should be individualized for older adults who are functionally dependent, or who have orthostasis, or who have a limited life expectancy [Grade D, Consensus].

Antihyperglycemic agents that increase the risk of hypoglycemia or have other side effects should be discontinued in these people [Grade C, Level 3 , ].

A higher A1C target may be considered in older people with diabetes taking antihyperglycemic agent s with risk of hypoglycemia, with any of the following: [Grade D, Consensus for all] Functionally dependent: 7. Avoid symptomatic hyperglycemia and any hypoglycemia.

The clock drawing test may be used to predict which older individuals will have difficulty learning to inject insulin [Grade C, Level 3 ]. Older people who are able should receive diabetes education with an emphasis on tailored care and psychological support [Grade A, Level 1A 24 ].

In older people with type 2 diabetes, sulphonylureas should be used with caution because the risk of hypoglycemia increases substantially with age [Grade D, Level 4 ]. DPP-4 inhibitors should be used over sulfonylureas as second-line therapy to metformin because of a lower risk of hypoglycemia [Grade B, Level 2 ] In general, initial doses of sulphonylureas in the older person should be half of those used for younger people, and doses should be increased more slowly [Grade D, Consensus] Gliclazide and gliclazide MR [Grade B, Level 2 ,, ] and glimepiride [Grade C, Level 3 ] should be used instead of glyburide, as they are associated with a reduced frequency of hypoglycemic events Meglitinides may be used instead of glyburide to reduce the risk of hypoglycemia [Grade C, Level 2 for repaglinide; Grade C, Level 3 for nateglinide], particularly in individuals with irregular eating habits [Grade D, Consensus].

In older people, premixed insulins and prefilled insulin pens should be used to reduce dosing errors and to potentially improve glycemic control [Grade B, Level 2 , ]. Sliding scale reactive and correction supplemental insulin protocols should be avoided in elderly LTC residents with diabetes to prevent worsening glycemic control [Grade C, Level 3 , ].

Abbreviations: A1C, glycated hemoglobin; ACE, angiotensin-converting enzyme; ARC, angiotensin receptor blocker; BP, blood pressure; CBG, capillary blood glucose; CGM, continuous glucose monitoring; CHF, congestive heart failure; CSII; c ontinuous subcutaneous insulin infusion; CV, cardiovascular; CVD, cardiovascular disease; DHC, diabetes health care; DPP-4 , dipeptidyl peptidase-4; ESRD, end stage renal disease; GFR, glomerular filtration rate; GLP , glucagon-like peptide; HDL-C, high-density lipoprotein cholesterol; LTC , long-term care; MI , myocardial infarct; NPH , neutral protamine Hagedorn; SGLT , sodium glucose co-transporter; SMBG , self-monitoring of blood glucose; TZD , thiazolidinedione.

Other Relevant Guidelines Screening for Diabetes in Adults, p. S16 Reducing the Risk of Developing Diabetes, p. S20 Organization of Diabetes Care, p. S27 Self-Management Education and Support, p.

S36 Targets for Glycemic Control, p. S42 Glycemic Management in Adults With Type 1 Diabetes, p. S80 Pharmacologic Glycemic Management of Type 2 Diabetes in Adults, p.

S88 Hypoglycemia, p. S Screening for the Presence of Cardiovascular Disease, p. S Dyslipidemia, p. S Treatment of Hypertension, p. S Sexual Dysfunction and Hypogonadism in Men With Diabetes, p. Relevant Appendix Appendix 7. Therapeutic Considerations for Renal Impairment.

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Munshi MN, Slyne C, Segal AR, et al. Liberating A1C goals in older adults may not protect against the risk of hypoglycemia. J Diabetes Complications ;31 7 —9. Malabu UH, Vangaveti VN, Kennedy RL. Disease burden evaluation of fallrelated events in the elderly due to hypoglycemia and other diabetic complications: A clinical review.

Clin Epidemiol ;— Conway BN, Long DM, Figaro MK, et al. Glycemic control and fracture risk in elderly patients with diabetes. Diabetes Res Clin Pract ;— Whitmer RA, Karter AJ, Yaffe K, et al. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA ;— Meneilly GS, Tessier DM.

Diabetes, dementia and hypoglycemia. Can J Diabetes ;—6. de Galan BE, Zoungas S, Chalmers J, et al. Cognitive function and risks of cardiovascular disease and hypoglycaemia in patients with type 2 diabetes: The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation ADVANCE trial.

Bruce DG, DavisWA, Casey GP, et al. Severe hypoglycaemia and cognitive impairment in older patients with diabetes: The Fremantle Diabetes study. Miller CK, Edwards L, Kissling G, et al. Nutrition education improves metabolic outcomes among older adults with diabetes mellitus: Results from a randomized controlled trial.

Prev Med ;—9. Perotto M, Panero F, Gruden G, et al. Obesity is associated with lower mortality risk in elderly diabetic subjects: The Casale Monferrato study. Acta Diabetol ;—8.

Solerte SB, Fioravanti M, Locatelli E, et al. Improvement of blood glucose control and insulin sensitivity during a long-term 60 weeks randomized study with amino acid dietary supplements in elderly subjects with type 2 diabetes mellitus.

Am J Cardiol ;e—8e. Leenders M, Verdijk LB, van der Hoeven L, et al. Prolonged leucine supplementation does not augment muscle mass or affect glycemic control in elderly type 2 diabetic men.

J Nutr ; Lee CG, Schwartz AV, Yaffe K, et al. Changes in physical performance in older women according to presence and treatment of diabetes mellitus. J Am Geriatr Soc ;—8. Stessman J, Jacobs JM. Diabetes mellitus, physical activity, and longevity between the ages of 70 and Madden KM, Lockhart C, Cuff D, et al.

Short-term aerobic exercise reduces arterial stiffness in older adults with type 2 diabetes, hypertension, and hypercholesterolemia.

Diabetes Care ;—5. Madden KM, Lockhart C, Potter TF, et al. Aerobic training restores arterial baroreflex sensitivity in older adults with type 2 diabetes, hypertension, and hypercholesterolemia.

Clin J Sport Med ;— Tessier D, Menard J, Fulop T, et al. Effects of aerobic physical exercise in the elderly with type 2 diabetes mellitus. Arch Gerontol Geriatr ;— Ligtenberg PC, Godaert GL, Hillenaar EF, et al.

Influence of a physical training program on psychological well-being in elderly type 2 diabetes patients. Psychological well-being, physical training, and type 2 diabetes. Diabetes Care ;—7. Ligtenberg PC, Hoekstra JB, Bol E, et al. Effects of physical training on metabolic control in elderly type 2 diabetes mellitus patients.

Clin Sci ;— Dunstan DW, Daly RM, Owen N, et al. High-intensity resistance training improves glycemic control in older patients with type 2 diabetes. Castaneda C, Layne JE, Munoz-Orians L, et al.

A randomized controlled trial of resistance exercise training to improve glycemic control in older adults with type 2 diabetes. Brandon LJ, Gaasch DA, Boyette LW, et al. Effects of long-term resistive training on mobility and strength in older adults with diabetes.

J Gerontol A Biol Sci Med Sci ;—5. Cuff DJ, Meneilly GS, Martin A, et al. Effective exercise modality to reduce insulin resistance in women with type 2 diabetes. Ibanez J, Izquierdo M, Arguelles I, et al.

Twice-weekly progressive resistance training decreases abdominal fat and improves insulin sensitivity in older men with type 2 diabetes. Morrison S, Colberg SR, Mariano M, et al. Balance training reduces falls risk in older individuals with type 2 diabetes. Song CH, Petrofsky JS, Lee SW, et al. Effects of an exercise program on balance and trunk proprioception in older adults with diabetic neuropathies.

Diabetes Technol Ther ;— Home-based resistance training is not sufficient to maintain improved glycemic control following supervised training in older individuals with type 2 diabetes. Meneilly GS, Elahi D.

Metabolic alterations in middle-aged and elderly lean patients with type 2 diabetes. Meneilly GS, Elliott T. Metabolic alterations in middle-aged and elderly obese patients with type 2 diabetes. Meneilly GS, Elliott T, Tessier D, et al. NIDDM in the elderly. Arner P, Pollare T, Lithell H.

Different aetiologies of type 2 non-insulindependent diabetes mellitus in obese and non-obese subjects. Diabetologia ;—7. Libby G, Donnelly LA, Donnan PT, et al. New users of metformin are at low risk of incident cancer: A cohort study among people with type 2 diabetes.

Baur DM, Klotsche J, Hamnvik OP, et al. Type 2 diabetes mellitus and medications for type 2 diabetes mellitus are associated with risk for and mortality from cancer in a German primary care cohort.

Metabolism ;— Reinstatler L, Qi YP, Williamson RS, et al. Association of biochemical B 1 2 deficiency with metformin therapy and vitamin B 1 2 supplements: The National Health and Nutrition Examination survey, — Leung S, Mattman A, Snyder F, et al.

Metformin induces reductions in plasma cobalamin and haptocorrin bound cobalamin levels in elderly diabetic patients. Clin Biochem ;— Kancherla V, Elliott JL Jr, Patel BB, et al.

Long-term metformin therapy and monitoring for vitamin B12 deficiency among older veterans. Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of metformin oral solution, extended-release oral suspension, and tablets in children 10 to 16 years of age.

However, safety and efficacy of metformin extended-release tablets in the pediatric population have not been established. Although appropriate studies on the relationship of age to the effects of metformin have not been performed in the geriatric population, geriatric-specific problems are not expected to limit the usefulness of metformin in the elderly.

However, elderly patients are more likely to have age-related kidney problems, which may require caution in patients receiving metformin. This medicine is not recommended in patients 80 years of age and older who have kidney problems.

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur.

In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines. Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you.

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The presence of other medical problems may affect the use of this medicine.

Make sure you tell your doctor if you have any other medical problems, especially:. This medicine usually comes with a patient information insert.

Read the information carefully and make sure you understand it before taking this medicine. If you have any questions, ask your doctor. Carefully follow the special meal plan your doctor gave you. This is a very important part of controlling your condition, and is necessary if the medicine is to work properly.

Also, exercise regularly and test for sugar in your blood or urine as directed. Metformin should be taken with meals to help reduce stomach or bowel side effects that may occur during the first few weeks of treatment.

Swallow the tablet or extended-release tablet whole with a full glass of water. Do not crush, break, or chew it. While taking the extended-release tablet, part of the tablet may pass into your stool after your body has absorbed the medicine.

This is normal and nothing to worry about. Measure the oral liquid with a marked measuring spoon, oral syringe, or medicine cup. The average household teaspoon may not hold the right amount of liquid. Use the supplied dosing cup to measure the mixed extended-release oral suspension.

Ask your pharmacist for a dosing cup if you do not have one. Use only the brand of this medicine that your doctor prescribed. Different brands may not work the same way.

You may notice improvement in your blood glucose control in 1 to 2 weeks, but the full effect of blood glucose control may take up to 2 to 3 months. Ask your doctor if you have any questions about this. See "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Contraindications'.

This approach is reviewed in detail separately. See "Initial management of hyperglycemia in adults with type 2 diabetes mellitus", section on 'Contraindications to or intolerance of metformin' and "Initial management of hyperglycemia in adults with type 2 diabetes mellitus", section on 'Established cardiovascular or kidney disease' and "Management of hyperglycemia in patients with type 2 diabetes and advanced chronic kidney disease or end-stage kidney disease".

Evaluation — If glycemic goals are not met with a single agent, older patients should be evaluated for contributing causes similar to younger adults, such as difficulty adhering to the medication, side effects, or adherence to the nutrition plan [ 1,6 ].

If hyperglycemia above the individualized target persists, an additional agent is needed. In older patients who require more than one agent, pill-dosing dispensers may help improve adherence. As an alternative, family members or caregivers may be required to help administer medication. Additional nutritional counseling and diabetes self-management education and support programs, when available, should be offered to patients.

Choice of second drug — For older patients who have persistent hyperglycemia above their individualized glycemic target despite treatment with lifestyle intervention and metformin , a second agent should be selected.

The choice of a second agent should be individualized based upon efficacy, the patient's underlying comorbidities, risk of hypoglycemia, impact on body weight, side effects, and cost figure 1. See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Indications for a second agent' and "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Our approach'.

The individual agents are discussed in more detail in the individual topic reviews. See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus" and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus" and "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus" and "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus" and "Thiazolidinediones in the treatment of type 2 diabetes mellitus" and "Alpha-glucosidase inhibitors for treatment of diabetes mellitus".

Insulin is sometimes underutilized in older adults because of fear by the clinician, patient, or family that it is too complicated or dangerous. Addition of once-daily basal insulin to a non-insulin agent usually metformin is a low-complexity regimen with a relatively lower risk of hypoglycemia compared with regimens using multiple daily insulin doses [ 44 ].

Before beginning insulin therapy, it is important to evaluate whether the patient is physically and cognitively capable of using an insulin pen or drawing up and injecting the appropriate dose of insulin using syringes and vials , monitoring blood glucose, and recognizing and treating hypoglycemia.

For older patients taking a fixed daily dose of insulin who are capable of injecting insulin but not of drawing it into the syringe, a pharmacist or family member may prepare a week's supply of insulin in syringes and leave them in the refrigerator.

Such a plan may allow an older patient to remain living independently at home. Insulin pens, when available and affordable, are an alternative for patients who have difficulty administering insulin using vials and syringes due to vision or motor limitations.

Morning administration reduces the risk of nocturnal hypoglycemia, and fasting hyperglycemia is less of a concern in older patients [ 45 ]. See "Management of hyperglycemia in patients with type 2 diabetes and advanced chronic kidney disease or end-stage kidney disease", section on 'Treatment'.

Insulin therapy is discussed in detail elsewhere. See "General principles of insulin therapy in diabetes mellitus" and "Insulin therapy in type 2 diabetes mellitus". History of cardiovascular or kidney disease — Sodium-glucose co-transporter 2 SGLT2 inhibitors empagliflozin or canagliflozin or glucagon-like peptide 1 GLP-1 receptor agonists liraglutide or semaglutide are reasonable second agents for patients with established cardiovascular or kidney disease [ 46,47 ].

All of these drugs confer low risk of hypoglycemia on their own or in combination with other drugs that do not usually cause hypoglycemia.

GLP-1 receptor agonists should be titrated slowly, with monitoring for gastrointestinal GI side effects, which could precipitate dehydration and acute kidney injury AKI. We avoid use of SGLT2 inhibitors in patients with frequent bacterial urinary tract infections or genitourinary yeast infections, low bone density and high risk for falls and fractures, foot ulceration, and factors predisposing to diabetic ketoacidosis eg, pancreatic insufficiency, drug or alcohol abuse disorder because of increased risk while using these agents.

See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Cardiovascular effects'.

Avoidance of hypoglycemia — In older adults at increased risk of hypoglycemia, GLP-1 receptor agonists, SGLT2 inhibitors, and dipeptidyl peptidase 4 DPP-4 inhibitors are options as they are associated with a low hypoglycemia risk. DPP-4 inhibitors are useful only to improve mild hyperglycemia since they are relatively weak agents and usually lower A1C levels by only 0.

However, in frail older adults with late-onset diabetes, particularly patients at high risk of hypoglycemia and impaired awareness of hypoglycemia, a DPP-4 inhibitor can be a useful agent to lower glycemia to the individualized target. See "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Glycemic efficacy'.

Avoidance of weight gain — GLP-1 receptor agonists may be appropriate to use when avoidance of weight gain is a primary consideration and cost is not a major barrier. SGLT2 inhibitors are also associated with weight loss. However, in the absence of cardiovascular or kidney disease, the risks of SGLT2 inhibitors in older individuals eg, dehydration, falls, fractures may outweigh the benefits.

DPP-4 inhibitors, which are weight neutral, also may be a reasonable option. Cost concerns — If cost is a concern, adding a short- or intermediate-acting sulfonylurea with a relatively lower rate of hypoglycemia, such as glipizide , glimepiride , or gliclazide gliclazide not available in the United States , remains a reasonable alternative.

Choosing a sulfonylurea balances glucose-lowering efficacy, universal local availability, and low cost with risk of hypoglycemia and weight gain. Short- or intermediate-acting sulfonylureas can also be used cautiously in patients with impaired kidney function when other classes are contraindicated.

Generic pioglitazone is also inexpensive. However, we tend not to use pioglitazone in older adults due to risks of fluid retention, weight gain, heart failure, macular edema, and osteoporotic fracture.

See "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Hypoglycemia' and "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Safety'. A typical starting dose of a sulfonylurea is as follows see "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Dosing and monitoring' :.

In patients who are using sulfonylureas, the presence and frequency of hypoglycemia should be evaluated at each visit. All blood glucose monitoring BGM or continuous glucose monitoring CGM data that are available should be reviewed and the frequency and details of any recognized episodes of hypoglycemia determined.

See 'Monitoring of glycemia' below and "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Hypoglycemia'.

The reported frequency of sulfonylurea-related hypoglycemia in older adults is variable. In an analysis of adverse event data from a drug surveillance project, oral hypoglycemic agents accounted for 10 percent of hospitalizations for adverse drug events [ 49 ].

Long-acting sulfonylureas eg, glyburide should be avoided in older adults due to higher risk of hypoglycemia, especially in individuals with inconsistent timing or content of their meals or those with cognitive decline that prevents prompt recognition or treatment of hypoglycemic episodes [ 50 ].

Drug-induced hypoglycemia may be a limiting factor for sulfonylurea use in older adults and is most likely to occur in the following circumstances:. These issues may arise when there is a change in overall health status in older adults with diabetes.

Dual agent failure — For patients who do not achieve A1C goals with two agents eg, metformin plus sulfonylurea or another agent , we suggest starting or intensifying insulin therapy see "Insulin therapy in type 2 diabetes mellitus", section on 'Designing an insulin regimen'.

In patients on sulfonylureas and metformin who are starting insulin therapy, sulfonylureas are generally tapered and discontinued, while metformin is continued. Another option is two oral agents and a GLP-1 receptor agonist. It is reasonable to try a GLP-1 agonist before starting insulin in patients who are near glycemic goals, those who prefer to avoid insulin, and those in whom weight loss or avoidance of hypoglycemia is a primary consideration.

A once-weekly GLP-1 agonist formulation is particularly attractive for patients and caregivers. However, this option often increases costs and contributes to the problem of polypharmacy in older adults see 'Polypharmacy and deintensification' below.

The management of persistent hyperglycemia is reviewed in more detail separately. See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Dual agent failure'. Polypharmacy and deintensification — Use of multiple drugs is common in older adults.

Management of hyperglycemia and its associated risk factors often increases the number of medications even more in the older adult with diabetes. Side effects may exacerbate comorbidities and impede patients' ability to manage their diabetes. Therefore, the medication list should be kept current and reviewed at each visit [ 1,6 ].

Overtreatment and complicated regimens should be avoided. Complex regimens that may have been required in the past can often be simplified to be consistent with the modified glycemic targets of an older patient [ 53,54 ]. See 'Controlling hyperglycemia' above. It is important to look for any conditions that interfere with A1C measurement eg, anemia, recent infections, kidney failure, erythropoietin therapy, etc.

In these settings or when unexpected or discordant A1C values are encountered, medication adjustments should be based on glucose readings from a glucose meter or continuous glucose monitoring CGM rather than A1C.

See "Measurements of chronic glycemia in diabetes mellitus", section on 'Glycated hemoglobin A1C '. However, infrequent or no BGM may be adequate for older patients with type 2 diabetes who are diet treated or who are treated with oral agents not associated with hypoglycemia.

The effectiveness of BGM in terms of improving glycemic management in patients with type 2 diabetes is less clear than for type 1 diabetes. See "Glucose monitoring in the ambulatory management of nonpregnant adults with diabetes mellitus", section on 'Type 2 diabetes'. CGM use also should be considered for older patients with impaired awareness of hypoglycemia, those taking other medications that confer higher risk of hypoglycemia eg, sulfonylureas , and those who have difficulty performing BGM through fingerstick checks due to cognitive or physical limitations.

Advances in CGM have made it possible to use the technology in older and even frail patients. Professional CGM devices, applied like a patch on a patient's arm or abdomen depending on the CGM model , measure interstitial glucose levels every 5 to 15 minutes for 10 to 14 days.

These devices provide patterns of glucose excursions that can be the foundation for choosing or adjusting insulin doses in patients on multiple daily insulin regimens.

These CGM devices are covered by Medicare in qualifying patients. See "Glucose monitoring in the ambulatory management of nonpregnant adults with diabetes mellitus", section on 'CGM systems'.

Retinopathy, nephropathy, and foot problems are all important complications of diabetes mellitus in older patients. Monitoring recommendations for older patients with diabetes are similar to those in younger patients table 3.

In particular, complications that impair functional capacity eg, retinopathy, foot problems should be identified and treated promptly [ 12 ].

Retinopathy — The prevalence of retinopathy increases progressively with increasing duration of diabetes figure 2. See "Diabetic retinopathy: Classification and clinical features".

Regular eye examinations are extremely important for older patients with diabetes because poor vision can lead to social isolation, an increased risk of accidents, and impaired ability to measure blood glucose and draw up insulin doses.

A complete ophthalmologic examination should be performed by a qualified ophthalmologist or optometrist at the time of diagnosis and at least yearly thereafter. The purpose is to screen not only for diabetic retinopathy, but also for cataracts and glaucoma, which are approximately twice as common in older individuals with diabetes compared with those without diabetes [ 55,56 ].

See "Diabetic retinopathy: Screening". Nephropathy — The availability of effective therapy for diabetic nephropathy with angiotensin-converting enzyme ACE inhibitors, angiotensin receptor blockade agents ARBs , mineralocorticoid receptor antagonists, and sodium-glucose co-transport 2 SGLT2 inhibitors has led to the recommendation that all patients with diabetes be screened for increased urinary albumin excretion annually.

See "Moderately increased albuminuria microalbuminuria in type 1 diabetes mellitus" and "Moderately increased albuminuria microalbuminuria in type 2 diabetes mellitus".

However, the prevalence of increased urinary albumin excretion increases in the older population for reasons unrelated to diabetic nephropathy. For older patients who are already taking an ACE inhibitor or ARB and have progressive decline in glomerular filtration rate GFR or increase in albuminuria, referral to a nephrologist for further evaluation and treatment is warranted.

Foot problems — Foot problems are an important cause of morbidity in patients with diabetes, and risk is much higher in older patients.

Both vascular and neurologic disease contribute to foot lesions. See "Management of diabetic neuropathy". In addition to the increasing prevalence of neuropathy with age, more than 30 percent of older patients with diabetes cannot see or reach their feet, and they may therefore be unable to perform routine foot inspections.

We recommend that older patients with diabetes have their feet examined at every visit; this examination should include an assessment of the patient's ability to see and reach his or her feet and inquiry about other family members or friends who could be trained to do routine foot inspections.

Visits to a podiatrist on a regular basis should also be considered if feasible. A detailed neurologic examination and assessment for peripheral artery disease should be performed at least yearly. It is also important that prophylactic advice on foot care be given to any patient whose feet are at high risk.

See "Evaluation of the diabetic foot". In addition, they are at high risk for polypharmacy, functional disabilities, and other common geriatric syndromes that include cognitive impairment, depression, urinary incontinence, mobility impairment, falls, and persistent pain [ 1 ].

See "Comprehensive geriatric assessment". All older adults should undergo screening for mild cognitive impairment or dementia at initial evaluation and, thereafter, annually or as appropriate for the individual patient [ 12 ].

Despite limited treatment options, identification of underlying cognitive impairment is critical for assessing a patient's capacity to self-manage diabetes treatment and care. In particular, cognitive function and the possibility of depression should be assessed in older patients with diabetes when any of the following are present see "Evaluation of cognitive impairment and dementia" and "Screening for depression in adults" :.

Nursing home patients — Few studies have focused on management of older adults with diabetes residing in nursing homes [ 4 ]. Life expectancy, quality of life, severe functional disabilities, and other coexisting conditions affect goal setting and management plans.

See 'Controlling hyperglycemia' above and 'Avoiding hypoglycemia' above. Treatment regimens should be chosen with a focus on avoidance of hypoglycemia and control of hyperglycemic symptoms [ 17 ].

For patients requiring insulin, metformin combined with once-daily basal insulin is an effective, relatively simple regimen. If prandial insulin is necessary, it can be administered immediately after a meal to better match the meal size and minimize hypoglycemia.

Sliding scale insulin should not be used as a sole means of providing insulin. If a patient is temporarily managed with sliding scale insulin to determine the requisite dose s of insulin therapy, a more physiologic glucose control strategy should be implemented within a few days table 4.

End-of-life care — Management of patients with diabetes at the end of life must be tailored to individual needs and the severity of the illness. In general, the risks and consequences of hypoglycemia are greater than those of hyperglycemia in patients at the end of life. The goal is to avoid extreme hyperglycemia and dehydration as well as excessive treatment burdens such as multiple insulin injections or intensive monitoring.

For patients with type 2 diabetes who are no longer taking anything by mouth, discontinuation of diabetes medications is reasonable [ 59 ]. This is in contrast to patients with type 1 diabetes, in whom continuing a small amount of basal insulin is required to prevent iatrogenic acute hyperglycemia and ketoacidosis.

See "Palliative care: The last hours and days of life", section on 'Eliminating non-essential medications' and "Deprescribing", section on 'Glucose-lowering medications'.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. See "Society guideline links: Diabetes mellitus in adults".

Older adults with diabetes are a heterogeneous population that includes persons residing independently in communities, in assisted care facilities, or in nursing homes.

They can be fit and healthy, or frail with many comorbidities and functional disabilities. Therefore, older adults in particular require individualized goals for diabetes management, keeping in mind their limited life expectancy and comorbidities. See 'Goals' above. Thus, avoidance of hypoglycemia is an important consideration in establishing goals and choosing therapeutic agents in older adults.

See 'Avoiding hypoglycemia' above and "Hypoglycemia in adults with diabetes mellitus", section on 'Strategies to manage hypoglycemia'. See 'Cardiovascular risk reduction' above. The nutrition prescription is tailored for older people with diabetes based upon medical, lifestyle, and personal factors.

Exercise is beneficial to help maintain physical function, reduce cardiac risk, and improve body composition and insulin sensitivity in older patients with diabetes. See 'Lifestyle modification' above. Because of concern for hypoglycemia, some clinicians use insulin only for a short time to ameliorate glucose toxicity.

Once insulin secretion and sensitivity are improved, it may be possible to lower the dose or replace insulin with metformin or another oral hypoglycemic agent with lower risk of hypoglycemia. See 'Choice of initial drug' above. Metformin will likely reduce glycemia safely at any level of hyperglycemia and further may reduce progression of hyperglycemia or the risk of developing diabetes-related complications.

See 'Metformin' above. An alternative option for patients who present with A1C near their medication-treated target and who prefer to avoid medication is a three- to six-month trial of lifestyle modification before initiating metformin.

The approach to choosing alternative therapy in metformin-intolerant patients is similar in older and younger adults. See 'Contraindications to metformin' above and "Initial management of hyperglycemia in adults with type 2 diabetes mellitus", section on 'Contraindications to or intolerance of metformin'.

The therapeutic options for patients who do not reach glycemic goals with lifestyle intervention and metformin are similar in older and younger patients. All of the medications have advantages and disadvantages table 2. The choice of a second agent should be individualized based upon efficacy, risk of hypoglycemia, the patient's underlying comorbidities, the impact on weight, side effects, and cost figure 1.

See 'Persistent hyperglycemia' above and "Management of persistent hyperglycemia in type 2 diabetes mellitus". Another option is two oral agents and a glucagon-like peptide 1 GLP-1 receptor agonist.

See 'Dual agent failure' above. In particular, complications that impair functional capacity eg, retinopathy, foot problems should be identified and treated promptly. See 'Screening for microvascular complications' above.

of noninsulin glucose-lowering agents and insulin, respectively. It is important to match complexity of the treatment regimen to the self-management ability of older patients and their available social and medical support. Many older adults with diabetes struggle to maintain the frequent blood glucose testing and insulin injection regimens they previously followed, perhaps for many decades, as they develop medical conditions that may impair their ability to follow their regimen safely.

Individualized glycemic goals should be established Fig. Tight glycemic control in older adults with multiple medical conditions is considered overtreatment and is associated with an increased risk of hypoglycemia; unfortunately, overtreatment is common in clinical practice 50 — Deintensification of regimens in patients taking noninsulin glucose-lowering medications can be achieved by either lowering the dose or discontinuing some medications, so long as the individualized glycemic target is maintained.

When patients are found to have an insulin regimen with complexity beyond their self-management abilities, lowering the dose of insulin may not be adequate There are now multiple studies evaluating de-intensification protocols; in general, the studies demonstrate that de-intensification is safe and possibly beneficial for older adults Table Algorithm to simplify insulin regimen for older patients with type 2 diabetes.

eGFR, estimated glomerular filtration rate. Adapted with permission from Munshi and colleagues 56 , 82 , Treatment regimen simplification refers to changing strategy to decrease the complexity of a medication regimen, e.

ADL, activities of daily living. Metformin is the first-line agent for older adults with type 2 diabetes. However, it is contraindicated in patients with advanced renal insufficiency and should be used with caution in patients with impaired hepatic function or congestive heart failure because of the increased risk of lactic acidosis.

Metformin may be temporarily discontinued before procedures, during hospitalizations, and when acute illness may compromise renal or liver function.

Additionally, metformin can cause gastrointestinal side effects and a reduction in appetite that can be problematic for some older adults. Reduction or elimination of metformin may be necessary for patients experiencing gastrointestinal side effects.

Sulfonylureas and other insulin secretagogues are associated with hypoglycemia and should be used with caution. If used, sulfonylureas with a shorter duration of action, such as glipizide or glimepiride, are preferred.

Glyburide is a longer-acting sulfonylurea and should be avoided in older adults Oral dipeptidyl peptidase 4 DPP-4 inhibitors have few side effects and minimal risk of hypoglycemia, but their cost may be a barrier to some older patients.

DPP-4 inhibitors do not increase major adverse cardiovascular outcomes Glucagon-like peptide 1 GLP-1 receptor agonists have demonstrated cardiovascular benefits among patients with established atherosclerotic cardiovascular disease, and newer trials are expanding our understanding of their benefits in other populations While the benefits of this class are emerging, these drugs are injectable agents with the exception of oral semaglutide , which require visual, motor, and cognitive skills for appropriate administration.

They may also be associated with nausea, vomiting, and diarrhea. Given the gastrointestinal side effects of this class, GLP-1 receptor agonists may not be preferred in older patients who are experiencing unexplained weight loss.

Sodium—glucose cotransporter 2 inhibitors are administered orally, which may be convenient for older adults with diabetes. In patients with established atherosclerotic cardiovascular disease, these agents have shown cardiovascular benefits This class of agents has also been found to be beneficial for patients with heart failure and to slow the progression of chronic kidney disease.

While understanding of the clinical benefits of this class is evolving, side effects such as volume depletion may be more common among older patients. The use of insulin therapy requires that patients or their caregivers have good visual and motor skills and cognitive ability. Insulin therapy relies on the ability of the older patient to administer insulin on their own or with the assistance of a caregiver.

Insulin doses should be titrated to meet individualized glycemic targets and to avoid hypoglycemia. Once-daily basal insulin injection therapy is associated with minimal side effects and may be a reasonable option in many older patients. Multiple daily injections of insulin may be too complex for the older patient with advanced diabetes complications, life-limiting coexisting chronic illnesses, or limited functional status.

The needs of older adults with diabetes and their caregivers should be evaluated to construct a tailored care plan. Social and instrumental support networks e. Older adults in assisted living facilities may not have support to administer their own medications, whereas those living in a nursing home community living centers may rely completely on the care plan and nursing support.

Those receiving palliative care with or without hospice may require an approach that emphasizes comfort and symptom management, while de-emphasizing strict metabolic and blood pressure control.

Due in part to the success of modern diabetes management, patients with type 1 diabetes are living longer and the population of these patients over 65 years of age is growing 65 — Many of the recommendations in this section regarding a comprehensive geriatric assessment and personalization of goals and treatments are directly applicable to older adults with type 1 diabetes; however, this population has unique challenges and requires distinct treatment considerations Insulin is an essential life-preserving therapy for patients with type 1 diabetes, unlike for those with type 2 diabetes.

In order to avoid diabetic ketoacidosis, older adults with type 1 diabetes need some form of basal insulin even when they are unable to ingest meals. Insulin may be delivered through insulin pump or injections. In the older patient with type 1 diabetes, administration of insulin may become more difficult as complications, cognitive impairment, and functional impairment arise.

This increases the importance of caregivers in the lives of these patients. Many older patients with type 1 diabetes require placement in long-term care LTC settings i. Some providers may be unaware of the distinction between type 1 and type 2 diabetes.

Education of relevant support staff and providers in rehabilitation and LTC settings regarding insulin dosing and use of pumps and CGM is recommended as part of general diabetes education see recommendations Management of diabetes in the LTC setting is unique. Individualization of health care is important in all patients; however, practical guidance is needed for medical providers as well as the LTC staff and caregivers Training should include diabetes detection and institutional quality assessment.

LTC facilities should develop their own policies and procedures for prevention and management of hypoglycemia. Staff of LTC facilities should receive appropriate diabetes education to improve the management of older adults with diabetes.

Treatments for each patient should be individualized. Special management considerations include the need to avoid both hypoglycemia and the complications of hyperglycemia 2 , An older adult residing in an LTC facility may have irregular and unpredictable meal consumption, undernutrition, anorexia, and impaired swallowing.

Furthermore, therapeutic diets may inadvertently lead to decreased food intake and contribute to unintentional weight loss and undernutrition. It may be helpful to give insulin after meals to ensure that the dose is appropriate for the amount of carbohydrate the patient consumed in the meal.

Older adults with diabetes in LTC are especially vulnerable to hypoglycemia. They have a disproportionately high number of clinical complications and comorbidities that can increase hypoglycemia risk: impaired cognitive and renal function, slowed hormonal regulation and counterregulation, suboptimal hydration, variable appetite and nutritional intake, polypharmacy, and slowed intestinal absorption Oral agents may achieve similar glycemic outcomes in LTC populations as basal insulin 50 , Another consideration for the LTC setting is that, unlike in the hospital setting, medical providers are not required to evaluate the patients daily.

According to federal guidelines, assessments should be done at least every 30 days for the first 90 days after admission and then at least once every 60 days.

Although in practice the patients may actually be seen more frequently, the concern is that patients may have uncontrolled glucose levels or wide excursions without the practitioner being notified.

Providers may make adjustments to treatment regimens by telephone, fax, or in person directly at the LTC facilities provided they are given timely notification of blood glucose management issues from a standardized alert system. Strict glucose and blood pressure control may not be necessary E , and reduction of therapy may be appropriate.

Similarly, the intensity of lipid management can be relaxed, and withdrawal of lipid-lowering therapy may be appropriate. The management of the older adult at the end of life receiving palliative medicine or hospice care is a unique situation.

Overall, palliative medicine promotes comfort, symptom control and prevention pain, hypoglycemia, hyperglycemia, and dehydration , and preservation of dignity and quality of life in patients with limited life expectancy 71 , In the setting of palliative care, providers should initiate conversations regarding the goals and intensity of diabetes care; strict glucose and blood pressure control may not be consistent with achieving comfort and quality of life.

In a multicenter trial, withdrawal of statins among patients in palliative care has been found to improve quality of life, while similar evidence for glucose and blood pressure control are not yet available 76 — A patient has the right to refuse testing and treatment, whereas providers may consider withdrawing treatment and limiting diagnostic testing, including a reduction in the frequency of fingerstick testing 79 , Glucose targets should aim to prevent hypoglycemia and hyperglycemia.

Treatment interventions need to be mindful of quality of life. Careful monitoring of oral intake is warranted. The decision process may need to involve the patient, family, and caregivers, leading to a care plan that is both convenient and effective for the goals of care The pharmacologic therapy may include oral agents as first line, followed by a simplified insulin regimen.

If needed, basal insulin can be implemented, accompanied by oral agents and without rapid-acting insulin. Agents that can cause gastrointestinal symptoms such as nausea or excess weight loss may not be good choices in this setting.

As symptoms progress, some agents may be slowly tapered and discontinued. Different patient categories have been proposed for diabetes management in those with advanced disease There is very little role for A1C monitoring and lowering.

A patient with organ failure : Preventing hypoglycemia is of greater significance. Dehydration must be prevented and treated. In people with type 1 diabetes, insulin administration may be reduced as the oral intake of food decreases but should not be stopped.

For those with type 2 diabetes, agents that may cause hypoglycemia should be reduced in dose. The main goal is to avoid hypoglycemia, allowing for glucose values in the upper level of the desired target range. A dying patient : For patients with type 2 diabetes, the discontinuation of all medications may be a reasonable approach, as patients are unlikely to have any oral intake.

In patients with type 1 diabetes, there is no consensus, but a small amount of basal insulin may maintain glucose levels and prevent acute hyperglycemic complications.

Suggested citation: American Diabetes Association. Older adults: Standards of Medical Care in Diabetes— Diabetes Care ;43 Suppl. Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest.

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Fasting or preprandial glucose. Bedtime glucose. Blood pressure. View Large. Figure View large Download slide. When may regimen simplification be required?

The following alert strategy could be considered:. National Institute of Diabetes and Digestive and Kidney Diseases. Accessed 27 August Search ADS. Psychosocial care for people with diabetes: a position statement of the American Diabetes Association.

Institute of Medicine of the National Academies. Accessed 31 October Depression and all-cause mortality in persons with diabetes mellitus: are older adults at higher risk?

Results from the Translating Research Into Action for Diabetes Study. Empirical redefinition of comprehensive health and well-being in the older adults of the United States. Classification of older adults who have diabetes by comorbid conditions, United States, — Clinical complexity in middle-aged and older adults with diabetes: the Health and Retirement Study.

Cognitive decline and dementia in diabetes—systematic overview of prospective observational studies.

Association of type 2 diabetes with brain atrophy and cognitive impairment. Diabetes, glucose control, and 9-year cognitive decline among older adults without dementia. Effects of intensive glucose lowering on brain structure and function in people with type 2 diabetes ACCORD MIND : a randomised open-label substudy.

Action to Control Cardiovascular Risk in Diabetes Follow-On Memory in Diabetes ACCORDION MIND Investigators. ACCORDION MIND: results of the observational extension of the ACCORD MIND randomised trial. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial.

The influence of cognition on self-management of type 2 diabetes in older people. National Institute on Aging. Assessing cognitive impairment in older patients. Cognitive assessment Accessed 27 August The Mini-Cog as a screen for dementia: validation in a population-based sample. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment.

American Geriatrics Society Expert Panel on Care of Older Adults with Diabetes Mellitus. Guidelines abstracted from the American Geriatrics Society Guidelines for Improving the Care of Older Adults with Diabetes Mellitus: update.

American Psychological Association. Furthermore, the age-related variation of body composition leads to an increase in fat mass, especially visceral adiposity, and an equal decrease in lean and skeletal mass With aging, there is a decline in preadipocyte replication and an expansion of senescent cells in adipose tissue which enhance lipotoxicity and favor the generation of a pro-inflammatory status Moreover, some studies have showed that aging 1 impairs insulin secretion from β-cells in response to endogenous incretins GIP , 2 is associated with reduced insulin sensitivity, and 3 promotes β-cell death by inducing mitochondrial dysfunction In older subjects, abnormalities in both insulin sensitivity and insulin secretion lead gradually to impaired glucose tolerance and consequently to clinically manifest diabetes.

Postprandial hyperglycemia is a characteristic feature of type 2 diabetes in older patients. Therefore, an oral glucose tolerance test should be performed in older subjects with impaired fasting glucose to early detect diabetes, which otherwise could be undiagnosed using fasting plasma glucose alone 7.

Diabetes onset in elderly usually manifest with vague and not specific symptoms, such as dehydration, dry mouth, confusion, fatigue, lethargy, weight loss, and an increased tendency toward genitourinary infections Most common type 2 diabetes comorbidities, including cognitive impairment, disability, depression, apathy, urinary incontinence, polypharmacy, hearing, and visual impairment, falls and fractures, fall under geriatric syndromes 19 Figure 1.

With advanced age, malnutrition, physical inactivity, and unwanted weight loss become more frequent. Therefore, a comprehensive geriatric assessment including screening for microvascular complications, cardiovascular risk factors, and geriatric syndromes should be performed at initial diagnosis of diabetes in elderly patients There is evidence that type 2 diabetes is associated with cognitive dysfunctions.

Older diabetic patients have higher risk to develop mild cognitive impairment MCI , all-cause dementia and Alzheimer's disease Specific mechanisms underlying this association are still unclear; however, main factors involved are vascular dysfunction, high blood pressure, hyperglycemia, hypoglycemic events, insulin resistance, and neuroinflammation Furthermore, depressive and apathic symptoms frequently co-exist with diabetes 23 , and some studies have found that combination of diabetes and depression may express a toxic effect on the brain, increasing the risk for dementia In light of this, the American Diabetes Association ADA recommends for subjects over 65 years old with a level of evidence B a neuro-psychological screening at the initial visit and annually to early detect mild cognitive impairment and depression, by using some specific test Mini-Mental State Examination, Montreal Cognitive Assessment and Geriatric Depression Scale , and minimizing hypoglycemic events to reduce the risk of MCI Type 2 diabetes in elderly is a powerful risk factor for functional limitations, frailty, loss of independence, and disability Moreover, there is evidence that type 2 diabetes increases the risk of fracture risk and secondary hypogonadism, which also contribute to enhance risk of osteoporosis and muscle weakness in men 27 , With aging there is a progressive loss of strength and toughness of skeletal and muscle mass which leads to a status of osteo- and sarcopenia.

Changes in skeletal muscle protein turnover could accelerate these alterations in type 2 diabetic patients 29 , resulting in a greater risk of falling and bone fractures As testosterone decline with advancing age, the assessment of its concentrations may be useful in case of signs and symptoms of overt hypogonadism to better evaluate the risk of fracture in this selected population 31 , Indeed, there is evidence that older patients with type 2 diabetes have an increased risk of hip fractures, particularly in insulin-treated patients, and non-skeletal fall injuries A moderate but regular physical activity and a high adherence to Mediterranean dietary pattern showed some benefits in reducing the risk of falls and physical impairments in patients older than 75 years 34 , The American Geriatrics Society suggests to interrogate older patients about falls at least every 12 months, examine potentially reversible causes of falls medications, environmental factors, limiting factors and perform a complete basic evaluation when an injurious fall occurs level of evidence III, strength B Urinary incontinence is a frequent comorbidity of diabetes, although it is usually not-reported by patients Therefore, according to the American Geriatrics Society, physicians should always perform an annual screening for urinary incontinence which may be an important cause of social isolation, depression, falls, and fractures level of evidence III, strength A Both overtreatment and polypharmacy are very common among frail older diabetic subjects.

The prevalence of polypharmacy regimen, defined as the use of more than 5 medications, increases with age. Furthermore, one-quarter of US older diabetic adults are on potential overtreatment for tight glycemic control using glucose-lowering medications at high risk of hypoglycemia Polypharmacy in older diabetic patients may produce detrimental effects mainly due to increased risk of drug-drug interactions and adverse side effects However, a deintensification rather than intensification of pharmacological therapy should be advisable in diabetic patients in older age, in consideration of both benefits and risks associated with complex therapeutic regimens.

Moreover, older adults with diabetes should annually update the list of used medications for their own clinicians level of evidence II, strength A Older patients represent a very heterogeneous and challenging population concerning diabetes care and treatment. While treating diabetes in elderly, clinicians should be always aware of maintaining a good quality of life.

Patient-centered glycemic targets are needed in order to achieve the glycemic control avoiding dangerous or extreme glucose excursions. Elderly patients are highly vulnerable to hypoglycemic events, as a consequence of progressive age-related decrease in β-adrenergic receptor function.

Indeed, hypoglycemia in older age has been associated with an increased risk to develop cognitive impairment, dementia, all-cause hospitalization, and all cause mortality 42 — Use of insulin or insulin secretagogues, polypharmacy, coexisting comorbidities, renal insufficiency, dehydration, impairment of counter-regulatory responses represent the main predisposing risk factors for hypoglycemic episodes Assessment of potential risk factors for hypoglycemia is an important part of the clinical management of older diabetic subjects.

Moreover, both patients and caregivers have to be trained and well-educated on the prevention, detection, and treatment of hypoglycemic events On the other hand, both untreated or undertreated hyperglycemic events should be avoided in old people, given the higher risk of dehydration, dizziness, falls, and long-term mortality The paucity of randomized controlled trials RCTs for diabetes treatment in older adults does not allow to clearly establish the most appropriate therapeutic goals in the elderly.

standard therapy, vs. Actually, the best glycemic target to achieve for elderly diabetic patients is still a matter of debate Table 1 summarizes the glycemic goals for elderly affected by diabetes according different international guidelines.

These therapeutic objectives are in line with those for adults older than 65 years indicated by American Geriatrics Society HbA1c ranging between 7.

Beyond tailored glycemic goals, ADA highlights the importance of controlling any other cardiovascular risk factor with an appropriate lipid-lowering, anti-platelet, and anti-hypertensive therapy.

Table 1. Glycemic targets in elderly patients according to the current international guidelines. Differing from ADA, the American Association of Clinical Endocrinologists AACE advises an HbA1c goal of 6.

Studies comparing the effectiveness of anti-diabetes drugs in elderly are lacking, due to the exclusion of older diabetic adults from RCTs, given the high number of comorbidity and their enhanced cardiovascular risk. Every therapeutic strategy should be chosen considering age, health status, self-manageability, cognitive and nutritional status, and comorbidities Table 2.

Generally, in older adults at higher risk to experience hypoglycemic events, medications with low risk of hypoglycemia should be preferred. Furthermore, it is advisable to simplify poly-pharmacological regimens in order to reduce adverse effects and achieve most appropriate glycemic goals.

The latest consensus on the management of hyperglycemia in type 2 diabetes of the ADA and the European Association for the Study of Diabetes EASD 57 recommends to use drugs with proven cardiovascular benefit in patients with established clinical cardiovascular disease.

Anti-hyperglycemic agents considered safe and effective for type 2 diabetic older patients can be divided in oral and injectable drugs Table 3.

Table 2. Most frequent clinical phenotypes in elderly with suggested HbA1c target and glucose-lowering treatment. Table 3. Glucose-lowering medications available in Europe with specific characteristics to drive the treatment choice for old people with type 2 diabetes. Metformin is the first-line medication recommended in the management of type 2 diabetes.

It reduces both insulin-resistance and hepatic gluconeogenesis, lowering glucose concentrations without increasing hypoglycemic risk. Moreover, a once daily extended-release formulation of metformin is now available, which is associated with a better gastrointestinal tolerability profile and patients' compliance.

As it is excreted by the urine, a good glomerular filtration rate is needed The main adverse effects described are commonly gastrointestinal symptoms and very rarely lactic acidosis. It is a safe and effective anti-hyperglycemic drug, with low cost, and minimal risk of hypoglycemia.

Nevertheless, it should be carefully used under conditions of congestive heart failure and hepatic dysfunction, which could increase the risk of lactic acidosis Thiazolidinediones also act as insulin sensing agent influencing transcriptional processes by activation of peroxisome proliferator-activated receptor-γ PPAR-γ.

Pioglitazone is the only one remaining drug of this class, as it has proven to be safe in the presence of cardiovascular disease It is characterized by good efficacy, low cost, and no risk of hypoglycemia when used in monotherapy.

It can be used even in case of low GFR value 61 starting from the lowest dose of 15 mg to the maximum dose of 45 mg with meals. Pioglitazone is associated with weight gain and fluid retention, so that it is contraindicated in case of congestive heart failure NYHA class III, IV.

Furthermore, it is not advisable to use the drug in older person at risk for falls because it has proven to increase risk of non-osteoporotic bone fractures Finally, it is contraindicated in patients with or at high risk for bladder cancer Sulfonylureas are an insulin secretagogue class, which act by favoring β-cells membrane depolarization and consequently insulin secretion.

They are characterized by high glucose lowering efficacy and low cost, but they should be used with extreme caution because of the high risk of hypoglycemia and weigh gain. Short acting ones with lowest hypoglycemic risk, such as gliclazide, should be preferred in older diabetic patients, when initial therapy with metformin is contraindicated or not tolerated By contrast, long acting sulfonylureas, as glibenclamide, are considered inappropriate in elderly diabetes management.

Metiglinides are short-acting insulin secretagogue agents, that enhance early phase of insulin secretion at meals, lowering postprandial glucose levels. They present lower risk of hypoglycemia than sulfonylureas, since their activity is dependent on the presence of glucose Repaglinide is the most effective agent of this class, with a moderate effect on weight gain.

Use of repaglinide may be indicated for elderly patients with type 2 diabetes because of the low risk of hypoglycemia, high efficacy on postprandial hyperglycemia, and safe use in renal impairment Dipeptidyl peptidase 4 DPP-4 inhibitors belong to the class of incretin enhancer agents.

They inhibit the DPP-4 enzyme, thereby extending the life-time of GLP-1 and increasing insulin secretion in a glucose dependent manner. Drugs in this class are generally well-tolerated in older people, with neutral effect on body weight and very low risk of hypoglycemia 66 , DPP-4 inhibitors have proven to be effective in reducing baseline HbA1c levels and fasting plasma glucose Moreover, a study of 80 elderly diabetic patients treated with oral glucose-lowering drug DPP4-inhibitors or sulfonylureas for at least 24 months showed that patients using DPP-4 inhibitors had better sarcopenic parameters fat-free mass, skeletal muscle mass, and related indices, muscle strength, and gait speed as compared with those receiving sulfonylureas The cardiovascular safety of this class of agents has been confirmed by several randomized controlled trials 70 — Alogliptin, saxagliptin, sitagliptin, and linagliptin 70 — 74 have proven to neither increase nor decrease risk of the combined major adverse cardiovascular events MACE in type 2 diabetic patients with established cardiovascular disease.

In the EXAMINE trial, patients with type 2 diabetes and recent acute coronary syndromes assigned to alogliptin had an increased, although non-statistically significant, rate of HF hospitalization when compared to the placebo group Moreover, data from the TECOS trial report that sitagliptin is not associated with a higher fracture risk, major osteoporotic fractures, or hip fractures Therefore, DPP-4 inhibitors may be considered as an effective and safely treatment option for older patients with type 2 diabetes Sodium-glucose cotransporter 2 SGLT-2 inhibitors are the latest marketed oral anti-hyperglycemic agents in diabetes management.

Beyond glucose lowering efficacy, SGLT-2 inhibitors have also beneficial effects in reducing body weight and blood pressure. If SGLT-2 inhibitors are used in combination with diuretics, lowering the dose of diuretics is needed to minimize the risks of hypotension and dehydration SGLT2-inhibitors are generally well-tolerated in older adults, except for increased risk of mycotic genital infections in both sexes.

There is evidence from cardiovascular outcome trials 80 , 81 that this class has beneficial effects in reducing the composite endpoint of cardiovascular deaths, non-fatal myocardial infarction and non-fatal stroke as compared with placebo in patients with type 2 diabetes and high cardiovascular risk.

Similarly, in the multinational, observational CVD-REAL study, new users of empaglifozin, canaglifozin, and dapaglifozin reported lower risk of cardiovascular mortality, MACE and hospitalization for heart failure as compared with new users of other glucose-lowering drugs Moreover, a subgroup analysis of the EMPA-REG OUTCOME study showed a significant reduction in the risk of MACE especially in patients older than 65 years treated with empaglifozin Based on these results, ADA and EASD recommend their use in patients with established or at high risk of cardiovascular disease In the respective RCTs designed to test the efficacy and safety of SGLT-2 inhibitors on renal outcomes 83 , 84 , both empagliflozin and canagliflozin use was associated with reduced risk of sustained loss of kidney function, attenuated GFR decline, and a reduction in albuminuria, which supports a possible renoprotective effect of this drugs in people with type 2 diabetes.

Conversely, on May the Food and Drug Administration released a warning relative to an increased risk of diabetic ketoacidosis DKA associated with use of SGLT-2 inhibitors 86 , on the basis of a comparative evaluation with DPP-4 inhibitors on a cohort of more than , type 2 diabetic patients The increased incidence of DKA related to SGLT2-inhibitors may be probably related to the non-insulin-dependent glucose clearance, hyperglucagonemia, and volume depletion Therefore, although this class has many beneficial effects on cardiovascular and renal outcomes, caution is needed using SGLT2 inhibitors in elderly because of increased risk of genital infections, dehydration, orthostatic hypotension, lower extremities amputations, and bone fracture 89 , Glucagon-like peptide 1 receptor agonists GLP-1RAs are innovative and pleiotropic drugs that act by promoting insulin secretion and reducing glucagon secretion in a glucose dependent manner and favoring weight loss.

As they use the injectable way of administration, they require neuro-psychological and physical integrity. GLP-1RAs are highly effective in lowering glucose levels, with minimal risk of hypoglycemia 91 , The main adverse effects associated with GLP-1RAs use consist of nausea, vomiting, diarrhea, and an increase in heart rate Furthermore, there is strong evidence from RCTs 95 — 97 that these drugs can reduce the risk of MACE in type 2 diabetic patients with high cardiovascular risk.

Results from preclinical studies showed also favorable effects of GLP-1RAs on neuronal protection and cognitive performances 98 , Randomized controlled trials assessing effects of incretin therapy on cognitive function and Alzheimer's disease in humans are currently ongoing.

If these benefits will be confirmed, use of GLP-1RA may be a helpful option even in patients with mild cognitive impairment. Free and fixed-ratio combinations of GLP-1RAs and basal insulin formulations have been approved by regulatory agencies to potentiate antihyperglycemic effects and glycemic control in type 2 diabetic patients 57 , At the moment, two fixed-ratio combinations, insulin glargine plus lixisenatide IGlarLixi and insulin degludec plus liraglutide IDegLira , have been approved for treatment of type 2 diabetes A recent analysis compared effectiveness of fixed-ratio combination iGlarlixi vs.

IGlarLixi was associated with significantly higher HbA1c reductions, weight loss and number of patients reaching HbA1c target despite lower insulin doses, with similar rates oh hypoglycemic events and lower rates of gastrointestinal adverse events.

A meta-analysis of 26 RCTs have shown a mean reduction of 0. Moreover, when compared with intensive insulin therapy, either free or fixed combination of GLP-1RA and basal insulin led to a greater mean decrease of 0.

Based on this evidence, combination strategies, either free or fixed, represent a good option for intensifying basal insulin therapy in patients with type 2 diabetes who need amelioration of glycemic control, without increasing the risk of hypoglycemia and weight gain Insulin remains the most effective drug for type 2 diabetes The main limitations of insulin therapy are the risk of hypoglycemia and weight gain, although it can be administered at any GFR value.

Insulin therapy requires patients' autonomy, intact visual, motor, and cognitive ability in diabetes management Since its discovery in , several and innovative insulin formulations have been developed.

Insulin glargine U or U , degludec U or U , and detemir represent long acting insulin analogs which provide daily basal insulin profiles Compared with human insulin neutral protamine Hagedorn NPH , long-acting insulin analogs have a longer duration of action and a fatter pharmacokinetic profile, with a reduced risk of hypoglycemia Therefore, the newer basal insulins should be preferentially used in diabetic elderly, where they may be indicated as starting insulin therapy.

Prandial rapid aspart, lispro, glulisine and ultra-rapid acting faster aspart insulin analogs used at mealtime can be combined with basal insulin to sooner improve and intensify glycemic control However, both basal and prandial insulin require frequent titration to achieve the best anti-hyperglycemic effects.

Patients on enteral or parenteral nutrition may require frequent glucose monitoring intervals of 4—6 h to better titrate the insulin dose and to avoid hypo- and hyperglycemic events Caution is needed in insulin titration because a simple error can easily precipitate major hypoglycemic episodes, leading to falls, and bone fractures Alternatively, premixed insulin regimen, eliminating the challenge of mixing insulin, may have a role in elderly patients who have regular eating habits, with similar efficacy as compared with basal bolus therapy Therefore, use of insulin therapy in elderly patients often requires the assistance of a caregiver if patients' abilities are limited.

Older adults with type 2 diabetes represent a complex and heterogenous age group. Managing diabetes in older age remains an important clinical challenge for all physicians, either primary care providers or specialists. A comprehensive geriatric assessment should be performed at diagnosis of diabetes to better understand cognitive, visual and motor abilities, and coexisting comorbidities.

In the choice of anti-hyperglycemic strategies, drugs with proven tolerability, safety, and minimal hypoglycemic risk should be preferred.

Anti-diabetes treatment regimens in elderly must be simple, sustainable, and safe to best mirror patients' preferences, wishes, and needs. GB, MIM, KE, and DG conceived the manuscript. ML, GB, and MIM drafted the manuscript. JM, KE, and DG reviewed and edited the manuscript.

All authors gave the approval to the final version of the manuscript. MIM received a consultancy fee from MSD and has held lectures for Sanofi, Astrazeneca, and Novo Nordisk. JM has held lectures for Astra Zeneca, Boehringer-Ingelheim, Eli Lilly, MSD, Novo Nordisk, Sanofi, and Servier and received research support from Boehringer-Ingelheim, MSD, Novo Nordisk, Sanofi.

KE received a consultancy fee from Eli Lilly and has held lectures for Eli Lilly, Sanofi, and Novo Nordisk. DG received a consultancy fee from Eli Lilly and has held lectures for Eli Lilly and Sanofi.

The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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