Amylase Lipase Pancreatic Chronic hyperglycemia and medication side effects. Later signs and symptoms If hyperglycemia sixe treated, medicaation can cause toxic Gluten-free paleo, called ketones, to build up in the blood and urine. Pioglitazone use and risk of bladder cancer: Population based cohort study. It is an integral component of diabetes management and diabetes self-management education.

Chronic hyperglycemia and medication side effects -

Acute hyperglycemia can be treated by direct administration of insulin in most cases. Severe hyperglycemia can be treated with oral hypoglycemic therapy and lifestyle modification. In diabetes mellitus by far the most common cause of chronic hyperglycemia , treatment aims at maintaining blood glucose at a level as close to normal as possible, in order to avoid serious long-term complications.

This is done by a combination of proper diet, regular exercise, and insulin or other medication such as metformin , etc. Those with hyperglycaemia can be treated using sulphonylureas or metformin or both. These drugs help by improving glycaemic control. Hyperglycemia can also be improved through minor lifestyle changes.

Increasing aerobic exercise to at least 30 minutes a day causes the body to make better use of accumulated glucose since the glucose is being converted to energy by the muscles. Diets higher in healthy unsaturated fats and whole wheat carbohydrates such as the Mediterranean diet can help reduce carbohydrate intake to better control hyperglycemia.

Carbohydrates are the main cause for hyperglycemia—non-whole-wheat items should be substituted for whole-wheat items. Although fruits are a part of a complete nutritious diet, fruit intake should be limited due to high sugar content.

Hyperglycemia is lower in higher income groups since there is access to better education, healthcare and resources. Low-middle income groups are more likely to develop hyperglycemia, due in part to a limited access to education and a reduced availability of healthy food options.

Hyperglycemia is one of the main symptoms of diabetes and it has substantially affected the population making it an epidemic due to the population's increased calorie consumption.

The origin of the term is Greek : prefix ὑπέρ- hyper- "over-", γλυκός glycos "sweet wine, must ", αἷμα haima "blood", -ία, -εια -ia suffix for abstract nouns of feminine gender.

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In other projects. Wikimedia Commons. Too much blood sugar, usually because of diabetes. Not to be confused with the opposite disorder involving low blood sugar , hypoglycemia. Medical condition. Diabetes Care. doi : PMID Retrieved 24 December Annals of Movement Disorders.

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View Topic. Font Size Small Normal Large. Management of persistent hyperglycemia in type 2 diabetes mellitus. Formulary drug information for this topic.

No drug references linked in this topic. Find in topic Formulary Print Share. View in. Language Chinese English. Author: Deborah J Wexler, MD, MSc Section Editor: David M Nathan, MD Deputy Editor: Katya Rubinow, MD Contributor Disclosures.

All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jan This topic last updated: Jan 11, Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes Diabetes Care ; S Davies MJ, Aroda VR, Collins BS, et al.

Management of hyperglycaemia in type 2 diabetes, A consensus report by the American Diabetes Association ADA and the European Association for the Study of Diabetes EASD. Diabetologia ; Kirkman MS, Briscoe VJ, Clark N, et al. Diabetes in older adults. Diabetes Care ; Wei N, Zheng H, Nathan DM.

Empirically establishing blood glucose targets to achieve HbA1c goals. American Diabetes Association Professional Practice Committee. Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes UKPDS UK Prospective Diabetes Study UKPDS Group.

Lancet ; United Kingdom Prospective Diabetes Study UKPDS. BMJ ; prospective diabetes study Overview of 6 years' therapy of type II diabetes: a progressive disease. Prospective Diabetes Study Group. Diabetes ; Turner RC, Cull CA, Frighi V, Holman RR.

Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies UKPDS JAMA ; GRADE Study Research Group, Nathan DM, Lachin JM, et al.

Glycemia Reduction in Type 2 Diabetes - Glycemic Outcomes. N Engl J Med ; Bressler P, DeFronzo RA. Drugs and diabetes. Diabetes Reviews ; Brown JB, Nichols GA, Perry A. The burden of treatment failure in type 2 diabetes. Shah BR, Hux JE, Laupacis A, et al. Clinical inertia in response to inadequate glycemic control: do specialists differ from primary care physicians?

Ziemer DC, Doyle JP, Barnes CS, et al. An intervention to overcome clinical inertia and improve diabetes mellitus control in a primary care setting: Improving Primary Care of African Americans with Diabetes IPCAAD 8. Arch Intern Med ; Grant RW, Buse JB, Meigs JB, University HealthSystem Consortium UHC Diabetes Benchmarking Project Team.

Quality of diabetes care in U. academic medical centers: low rates of medical regimen change. Fanning EL, Selwyn BJ, Larme AC, DeFronzo RA. Improving efficacy of diabetes management using treatment algorithms in a mainly Hispanic population. Grant RW, Cagliero E, Sullivan CM, et al.

A controlled trial of population management: diabetes mellitus: putting evidence into practice DM-PEP. Das SR, Everett BM, Birtcher KK, et al. J Am Coll Cardiol ; Tsapas A, Avgerinos I, Karagiannis T, et al. Comparative Effectiveness of Glucose-Lowering Drugs for Type 2 Diabetes: A Systematic Review and Network Meta-analysis.

Ann Intern Med ; Maruthur NM, Tseng E, Hutfless S, et al. Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis. Palmer SC, Mavridis D, Nicolucci A, et al.

Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes: A Meta-analysis. Rodbard HW, Rosenstock J, Canani LH, et al. Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial.

Lingvay I, Catarig AM, Frias JP, et al. Efficacy and safety of once-weekly semaglutide versus daily canagliflozin as add-on to metformin in patients with type 2 diabetes SUSTAIN 8 : a double-blind, phase 3b, randomised controlled trial. Lancet Diabetes Endocrinol ; Henry RR, Gumbiner B, Ditzler T, et al.

Intensive conventional insulin therapy for type II diabetes. Metabolic effects during a 6-mo outpatient trial. Hemmingsen B, Christensen LL, Wetterslev J, et al. Comparison of metformin and insulin versus insulin alone for type 2 diabetes: systematic review of randomised clinical trials with meta-analyses and trial sequential analyses.

BMJ ; e Yki-Järvinen H, Ryysy L, Nikkilä K, et al. Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus.

A randomized, controlled trial. Wulffelé MG, Kooy A, Lehert P, et al. Combination of insulin and metformin in the treatment of type 2 diabetes. Kooy A, de Jager J, Lehert P, et al. Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus.

Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes UKPDS Russell-Jones D, Vaag A, Schmitz O, et al. Diamant M, Van Gaal L, Stranks S, et al. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes DURATION-3 : an open-label randomised trial.

Shyangdan DS, Royle P, Clar C, et al. Glucagon-like peptide analogues for type 2 diabetes mellitus. Cochrane Database Syst Rev ; :CD Singh S, Wright EE Jr, Kwan AY, et al. Glucagon-like peptide-1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus: a systematic review and meta-analysis.

Diabetes Obes Metab ; Frías JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. Curovic VR, Jongs N, Kroonen MYAM, et al. Optimization of Albuminuria-Lowering Treatment in Diabetes by Crossover Rotation to Four Different Drug Classes: A Randomized Crossover Trial.

Shields BM, Dennis JM, Angwin CD, et al. Patient stratification for determining optimal second-line and third-line therapy for type 2 diabetes: the TriMaster study.

Nat Med ; Zheng SL, Roddick AJ, Aghar-Jaffar R, et al. Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes: A Systematic Review and Meta-analysis.

Shi Q, Nong K, Vandvik PO, et al. Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials. Marso SP, Bain SC, Consoli A, et al.

Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. Marso SP, Daniels GH, Brown-Frandsen K, et al.

Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. Mann JFE, Ørsted DD, Brown-Frandsen K, et al. Liraglutide and Renal Outcomes in Type 2 Diabetes. Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes REWIND : a double-blind, randomised placebo-controlled trial.

Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. Palmer SC, Tendal B, Mustafa RA, et al.

Sodium-glucose cotransporter protein-2 SGLT-2 inhibitors and glucagon-like peptide-1 GLP-1 receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials.

BMJ ; m Kanie T, Mizuno A, Takaoka Y, et al. Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis.

Cochrane Database Syst Rev ; CD Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy.

Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in Patients with Chronic Kidney Disease. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes.

Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.

Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. Patorno E, Htoo PT, Glynn RJ, et al. Sodium-Glucose Cotransporter-2 Inhibitors Versus Glucagon-like Peptide-1 Receptor Agonists and the Risk for Cardiovascular Outcomes in Routine Care Patients With Diabetes Across Categories of Cardiovascular Disease.

Colling C, Atlas SJ, Wexler DJ. Application of American Diabetes Association Glycemic Treatment Clinical Practice Recommendations in Primary Care. Glycemia Reduction in Type 2 Diabetes - Microvascular and Cardiovascular Outcomes.

Wexler DJ, de Boer IH, Ghosh A, et al. Comparative Effects of Glucose-Lowering Medications on Kidney Outcomes in Type 2 Diabetes: The GRADE Randomized Clinical Trial.

JAMA Intern Med ; Hirst JA, Farmer AJ, Dyar A, et al. Estimating the effect of sulfonylurea on HbA1c in diabetes: a systematic review and meta-analysis. Nauck MA, Kahle M, Baranov O, et al. Addition of a dipeptidyl peptidase-4 inhibitor, sitagliptin, to ongoing therapy with the glucagon-like peptide-1 receptor agonist liraglutide: A randomized controlled trial in patients with type 2 diabetes.

Zaccardi F, Dhalwani NN, Dales J, et al. Comparison of glucose-lowering agents after dual therapy failure in type 2 diabetes: A systematic review and network meta-analysis of randomized controlled trials. Davies MJ, D'Alessio DA, Fradkin J, et al.

Management of Hyperglycemia in Type 2 Diabetes, A Consensus Report by the American Diabetes Association ADA and the European Association for the Study of Diabetes EASD. Nathan DM, Buse JB, Davidson MB, et al.

Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Chiasson JL, Josse RG, Hunt JA, et al.

The efficacy of acarbose in the treatment of patients with non-insulin-dependent diabetes mellitus. Hyperglycaemia has been associated with oral contraceptives containing high doses of oestrogen.

Growth hormone therapy and somatostatin analogues may also induce hyperglycaemia. Clinicians should be aware of medications that may alter glycaemia. Efforts should be made to identify and closely monitor patients receiving drugs that are known to induce hyperglycaemia.

Abstract Drug-induced hyperglycaemia and diabetes is a global issue. Publication types Review. Substances Insulin Pharmaceutical Preparations.

Your health care Cbronic sets your target Huperglycemia sugar range. For many Gluten-free paleo who have hyperglycwmia, Mayo Clinic generally hyperglydemia the following target blood sugar levels before meals:. For many people who have diabetes, the American Diabetes Association generally recommends the following target blood sugar levels:. Your target blood sugar range may differ, especially if you're pregnant or you have other health problems that are caused by diabetes. Your target blood sugar range may change as you get older. Contributor Disclosures. Please read the Effetcs Chronic hyperglycemia and medication side effects the end of hypefglycemia page. All efvects these treatments and Common DKA symptoms need to be tempered ecfects on individual Gluten-free paleo, such as age, life expectancy, and comorbidities. Although studies of anc surgery, aggressive insulin therapy, Effdcts behavioral interventions to achieve weight loss have noted remissions of type 2 diabetes mellitus that may last several years, the majority of patients with type 2 diabetes require continuous treatment in order to maintain target glycemia. Treatments to improve glycemic management work by increasing insulin availability either through direct insulin administration or through agents that promote insulin secretionimproving sensitivity to insulin, delaying the delivery and absorption of carbohydrate from the gastrointestinal tract, increasing urinary glucose excretion, or a combination of these approaches.

Chronic hyperglycemia and medication side effects -

Pharmacists hold a vital role in identifying and managing drug-induced hyperglycemia or diabetes. Across all patient care settings, pharmacists can identify agents that can cause drug-induced diabetes during medication reconciliations and comprehensive medication reviews.

Once identified, pharmacists can suggest alternative agents, clarify duration of treatment, or suggest guideline-directed treatment when needed and as appropriate.

For those without diabetes, counseling on lifestyle modifications to help prevent progression to diabetes is beneficial. Regular monitoring of blood glucose and hemoglobin A1C is also important to ensure the patient has not progressed to a diabetes diagnosis.

A patient with prediabetes may benefit from initiating metformin, which is a commonly used medication in the prediabetic population. In patients with established diabetes, pharmacists can recommend guideline-directed medical therapy for diabetes management after assessing appropriateness of treatment, including contraindications or drug interactions.

Diabetes control is crucial for prevention of microvascular and macrovascular diabetes complications. Pharmacists are one of the most accessible healthcare professionals, allowing for consistent follow-up with patients between physician appointments.

Pharmacists are also able to report medication adverse effects and events through the FDA MedWatch. This can ultimately improve health outcomes and reduce further comorbidities and healthcare costs.

Drug-induced diabetes is one of the many potential causes of a diabetes diagnosis. It is imperative that pharmacists and other healthcare providers have an understanding of medications with a higher risk for hyperglycemia and diabetes.

Shared decision-making should take place between the prescribing physician and patient when considering drug therapy to treat a condition.

Patients should be counseled and given information on risk versus benefit of these medications as well as potential adverse events. With this knowledge, patients are more likely to seek medical attention if issues occur, such as symptoms of hypoglycemia or hyperglycemia, medication access, or adverse events.

Pharmacists can also assist with close monitoring of relevant laboratory values as well as lifestyle and medication management. The content contained in this article is for informational purposes only.

The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk. Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future.

National diabetes statistics report, Accessed August 25, Luna B, Feinglos MN. Drug-induced hyperglycemia. Anyanwagu U, Idris I, Donnelly R. Drug-induced diabetes mellitus: evidence for statins and other drugs affecting glucose metabolism.

Clin Pharmacol Ther. Chen J, Huang XF, Shao R, et al. Molecular mechanisms of antipsychotic drug—induced diabetes. Front Neurosci.

Jain V, Patel RK, Kapadia Z, et al. Drugs and hyperglycemia: a practical guide. Zhang R, Cai XL, Liu L, et al. Type 1 diabetes induced by immune checkpoint inhibitors. Chin Med J Engl.

Piqray alpelisib package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation. Revised July André F, Ciruelos E, Rubovszky G, et al. Alpelisib for PIK3CA -mutated, hormone receptor—positive advanced breast cancer.

N Engl J Med. Carrillo M, Rodriguez RM, Walsh CL, Mcgarvey M. Alpelisib-induced diabetic ketoacidosis: a case report and review of literature.

AACE Clin Case Rep. Nguyen P, Musa A, Samantray J. Alpelisib-induced diabetic ketoacidosis. Huang X, Liu G, Guo J, Su Z. Int J Biol Sci. Rugo HS, André F, Yamashita T, et al. Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer.

Ann Oncol. Dayabandara M, Hanwella R, Ratnatunga S, et al. Antipsychotic-associated weight gain: management strategies and impact on treatment adherence. Neuropsychiatr Dis Treat.

Cernea S, Dima L, Correll CU, Manu P. Pharmacological management of glucose dysregulation in patients treated with second-generation antipsychotics. Molecular mechanisms of antipsychotic drug-induced diabetes. Citrome L, Collins JM, Nordstrom BL, et al.

Incidence of cardiovascular outcomes and diabetes mellitus among users of second-generation antipsychotics. J Clin Psychiatry. Ulcickas Yood M, DeLorenze GN, Quesenberry CP Jr, et al. Association between second-generation antipsychotics and newly diagnosed treated diabetes mellitus: does the effect differ by dose?

BMC Psychiatry. Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV. Guidelines for the use of antiretroviral agents in pediatric HIV infection: insulin resistance, asymptomatic hyperglycemia, diabetes mellitus [Table 15f].

Updated April 7, Spach DH. Antiretroviral medications and initial therapy. National HIV Curriculum. Updated June 4, Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV: limitations to treatment safety and efficacy.

Updated June 3, One possibility is that bile acid sequestrants act in the GI tract to reduce glucose absorption. In a meta-analysis of five short-term trials 16 to 26 weeks in patients with type 2 diabetes inadequately treated with oral agents or insulin, the addition of colesevelam compared with placebo modestly reduced A1C levels mean difference 0.

The meta-analysis was limited by the high or unclear risk of bias in the individual trials. Side effects can include constipation, nausea, and dyspepsia. In contrast to its effects on LDL cholesterol, colesevelam increases triglyceride concentrations by approximately 20 percent [ 66,67 ].

The clinical implications of this increase are unknown. See "Lipoprotein classification, metabolism, and role in atherosclerosis", section on 'Apolipoprotein C-III'.

Given the modest glucose-lowering effectiveness, expense, and limited clinical experience, we typically do not recommend colesevelam to improve glycemic management in patients with type 2 diabetes.

See "Management of hyperprolactinemia", section on 'Overview of dopamine agonists'. A quick-release formulation of bromocriptine has been approved by the FDA for the treatment of type 2 diabetes mellitus [ 68 ]. In short-term clinical trials in patients with type 2 diabetes mellitus, bromocriptine up to 4.

Common side effects include nausea, vomiting, dizziness, and headache [ 70 ]. The mechanism of action in reducing blood sugar is unknown. Given its modest glucose-lowering effect, very frequent GI side effects, and the availability of more effective drugs, we do not recommend bromocriptine for the treatment of type 2 diabetes.

BARIATRIC METABOLIC SURGERY — In patients with type 2 diabetes and obesity, bariatric and metabolic surgical procedures that result in sustained, major weight loss have been shown to lead to at least temporary remission of diabetes in a substantial fraction of patients.

Bariatric surgical procedures are targeted at weight loss in the setting of obesity; the term "metabolic surgery" is used when a major goal of surgery is to improve diabetes or other metabolic diseases eg, nonalcoholic fatty liver disease.

Patient selection — Surgical treatment of obesity is an option to treat type 2 diabetes in appropriate surgical candidates with [ 71 ]:. Surgical treatment has also been endorsed in patients with type 2 diabetes with BMI 30 to Given the increasing availability of potent GLPbased therapies and lack of comparative effectiveness data for bariatric surgery and these potent agents, we review these options with our patients and engage in shared decision-making.

See "Initial management of hyperglycemia in adults with type 2 diabetes mellitus", section on 'Diabetes education' and "Bariatric surgery for management of obesity: Indications and preoperative preparation", section on 'Indications'.

Outcomes — Unblinded trials have compared bariatric surgery with medical therapy for the treatment of type 2 diabetes see "Outcomes of bariatric surgery", section on 'Diabetes mellitus'.

However, relapse of diabetes usually occurs over time, with 35 to 50 percent of patients who initially achieved diabetes remission after surgery experiencing a recurrence [ 72,75 ].

Nevertheless, bariatric surgery improves glycemia substantially and significantly more than medication therapy, and most patients have marked improvement in glycemic management for at least 5 to 15 years after surgery.

The effects of bariatric surgery on diabetes-related complications are reviewed in detail elsewhere. See "Outcomes of bariatric surgery", section on 'Diabetic complications'. Risks and concerns — Despite these impressive metabolic results, concerns remain about acute postoperative complications including the need for reoperations and rehospitalizations and rare, but potentially severe, adverse events; the long-term success rates in maintaining weight loss [ 71,80,81 ]; and the reproducibility of the results in patients with an extensive history of diabetes or with different surgical teams [ 82 ].

Some weight regain is typical within two to three years of bariatric procedures, and different procedures result in different levels of weight loss and corresponding reductions in glycemia.

Bariatric surgical procedures are reviewed in detail elsewhere. See "Bariatric procedures for the management of severe obesity: Descriptions" and "Bariatric surgery for management of obesity: Indications and preoperative preparation" and "Bariatric operations: Early fewer than 30 days morbidity and mortality".

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" and "Society guideline links: Diabetes mellitus in children" and "Society guideline links: Diabetic kidney disease".

These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10 th to 12 th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword s of interest. This decision is based on glycated hemoglobin A1C assay results calculator 1 typically performed every three to six months after initial therapy.

After a successful initial response to lifestyle intervention and oral therapy, the majority of patients do not maintain target A1C levels during the subsequent three to five years. See 'Indications for a second agent' above. Options include glucagon-like peptide 1 GLP-1 receptor agonists, a dual-acting GLP-1 and glucose-dependent insulinotropic polypeptide GIP receptor agonist tirzepatide , sodium-glucose co-transporter 2 SGLT2 inhibitors, short-acting sulfonylureas eg, glipizide , glimepiride , repaglinide if sulfonylurea not chosen as initial therapy , insulin, dipeptidyl peptidase 4 DPP-4 inhibitors, and pioglitazone figure 1 and table 2.

For patients with persistent hyperglycemia while taking a maximally tolerated dose of metformin, the choice of a second medication should be individualized based on efficacy, risk for hypoglycemia, the patient's comorbid conditions, impact on weight, side effects, and cost. These agents have been shown to have the best glycemic efficacy algorithm 1.

Gastrointestinal GI side effects, contraindications, and cost may limit their use. To select a medication, we use shared decision-making with a focus on beneficial and adverse effects within the context of the degree of hyperglycemia as well as a patient's comorbidities and preferences algorithm 2.

See 'Established cardiovascular or kidney disease' above. The majority of patients in the cardiovascular and renal outcomes trials had established cardiovascular disease CVD or diabetic kidney disease DKD with severely increased albuminuria, and therefore, these are the primary indications for one of these drugs.

Patients at high CVD risk but without a prior event might benefit, but the data are less supportive. Similarly, patients without severely increased albuminuria have some benefit, but the absolute benefits are greater among those with severely increased albuminuria.

The choice of an alternative glucose-lowering medication is guided by efficacy, patient comorbidities, preferences, side effects, and cost. algorithm 2. See 'Dual agent failure' above. For most patients who do not achieve target A1C with initial dual therapy, we suggest starting insulin or a GLP-1 receptor agonist Grade 2B if neither already chosen as a second agent.

In patients on sulfonylureas and metformin who are starting insulin therapy, sulfonylureas are generally tapered and discontinued, while metformin is continued. In patients on DPP-4 inhibitors who are starting a GLP-1 receptor agonist or dual-acting GLP-1 and GIP receptor agonist, the DPP-4 inhibitor is discontinued, while metformin is continued.

See 'Dual agent failure' above and 'Insulin initiation and intensification' above. Related Pathway s : Diabetes: Initial therapy for non-pregnant adults with type 2 DM. An alternative is two oral agents and a GLP-1 receptor agonist or dual-acting GLP-1 and GIP receptor agonist, particularly for patients in whom weight loss or avoidance of hypoglycemia is a primary consideration.

These GLPbased therapies should not be combined with DPP-4 inhibitors. Another option for patients close to glycemic goals is three oral agents eg, metformin , sulfonylurea plus: DPP-4 inhibitor, SGLT2 inhibitor, or pioglitazone.

Although guidelines suggest combining SGLT2 inhibitors and GLP-1 receptor agonists, we do not usually add an SGLT2 inhibitor to GLP-1 receptor agonist therapy for management of hyperglycemia alone, given the absence of data showing additive cardiovascular and kidney benefit and increased patient burden cost, polypharmacy, adverse effects.

Bariatric surgery may also be an option in patients with lower BMI 30 to Patients seeking bariatric surgery should be counseled to develop coping skills, eliminate maladaptive behavior, and understand the risks and benefits of the surgery.

See 'Bariatric metabolic surgery' above and "Bariatric surgery for management of obesity: Indications and preoperative preparation", section on 'Preoperative counseling'. Why UpToDate? Product Editorial Subscription Options Subscribe Sign in. Learn how UpToDate can help you.

Select the option that best describes you. View Topic. Font Size Small Normal Large. Management of persistent hyperglycemia in type 2 diabetes mellitus. Formulary drug information for this topic.

No drug references linked in this topic. Find in topic Formulary Print Share. View in. Language Chinese English. Author: Deborah J Wexler, MD, MSc Section Editor: David M Nathan, MD Deputy Editor: Katya Rubinow, MD Contributor Disclosures.

All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jan This topic last updated: Jan 11, Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes Diabetes Care ; S Davies MJ, Aroda VR, Collins BS, et al.

Management of hyperglycaemia in type 2 diabetes, A consensus report by the American Diabetes Association ADA and the European Association for the Study of Diabetes EASD. Diabetologia ; Kirkman MS, Briscoe VJ, Clark N, et al. Diabetes in older adults.

Diabetes Care ; Wei N, Zheng H, Nathan DM. Empirically establishing blood glucose targets to achieve HbA1c goals. American Diabetes Association Professional Practice Committee. Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes UKPDS UK Prospective Diabetes Study UKPDS Group.

Lancet ; United Kingdom Prospective Diabetes Study UKPDS. BMJ ; prospective diabetes study Overview of 6 years' therapy of type II diabetes: a progressive disease. Prospective Diabetes Study Group. Diabetes ; Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies UKPDS JAMA ; GRADE Study Research Group, Nathan DM, Lachin JM, et al.

Glycemia Reduction in Type 2 Diabetes - Glycemic Outcomes. N Engl J Med ; Bressler P, DeFronzo RA. Drugs and diabetes. Diabetes Reviews ; Brown JB, Nichols GA, Perry A. The burden of treatment failure in type 2 diabetes. Shah BR, Hux JE, Laupacis A, et al.

Clinical inertia in response to inadequate glycemic control: do specialists differ from primary care physicians? Ziemer DC, Doyle JP, Barnes CS, et al. An intervention to overcome clinical inertia and improve diabetes mellitus control in a primary care setting: Improving Primary Care of African Americans with Diabetes IPCAAD 8.

Arch Intern Med ; Grant RW, Buse JB, Meigs JB, University HealthSystem Consortium UHC Diabetes Benchmarking Project Team. Quality of diabetes care in U. academic medical centers: low rates of medical regimen change.

Fanning EL, Selwyn BJ, Larme AC, DeFronzo RA. Improving efficacy of diabetes management using treatment algorithms in a mainly Hispanic population. Grant RW, Cagliero E, Sullivan CM, et al. A controlled trial of population management: diabetes mellitus: putting evidence into practice DM-PEP.

Das SR, Everett BM, Birtcher KK, et al. J Am Coll Cardiol ; Tsapas A, Avgerinos I, Karagiannis T, et al. Comparative Effectiveness of Glucose-Lowering Drugs for Type 2 Diabetes: A Systematic Review and Network Meta-analysis. Ann Intern Med ; Maruthur NM, Tseng E, Hutfless S, et al.

Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis. Palmer SC, Mavridis D, Nicolucci A, et al.

Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes: A Meta-analysis. Rodbard HW, Rosenstock J, Canani LH, et al. Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial.

Lingvay I, Catarig AM, Frias JP, et al. Efficacy and safety of once-weekly semaglutide versus daily canagliflozin as add-on to metformin in patients with type 2 diabetes SUSTAIN 8 : a double-blind, phase 3b, randomised controlled trial.

Lancet Diabetes Endocrinol ; Henry RR, Gumbiner B, Ditzler T, et al. Intensive conventional insulin therapy for type II diabetes. Metabolic effects during a 6-mo outpatient trial.

Hemmingsen B, Christensen LL, Wetterslev J, et al. Comparison of metformin and insulin versus insulin alone for type 2 diabetes: systematic review of randomised clinical trials with meta-analyses and trial sequential analyses. BMJ ; e Yki-Järvinen H, Ryysy L, Nikkilä K, et al.

Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus. A randomized, controlled trial. Wulffelé MG, Kooy A, Lehert P, et al.

Combination of insulin and metformin in the treatment of type 2 diabetes. Kooy A, de Jager J, Lehert P, et al. Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus.

Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes UKPDS Russell-Jones D, Vaag A, Schmitz O, et al.

Diamant M, Van Gaal L, Stranks S, et al. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes DURATION-3 : an open-label randomised trial. Shyangdan DS, Royle P, Clar C, et al.

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