It is indicated for the management of type 2 diabetes in the U. but is not available in Europe. A meta-analysis showed that in patients with type 2 diabetes, pramlintide is associated with a small but significant reduction in HbA 1c —0.

Pramlintide was associated with a significant reduction in weight from baseline compared with control —2. Pramlintide was associated with a higher incidence of mild-to-moderate, mainly transient, nausea than control.

Some studies have reported the incidence of hypoglycemia mild to moderate to be higher with pramlintide versus placebo, whereas others have reported the converse Although several antiobesity agents have been withdrawn from the market because of safety concerns, five are now available in the U.

These pharmacotherapies have been demonstrated to help people with type 2 diabetes achieve their weight-loss goals and provide them with an HbA 1c -reducing benefit 70 — Orlistat is indicated for obesity management, including weight loss and weight maintenance, when used in conjunction with a reduced-calorie diet, and reduction of the risk of weight regain after prior weight loss Orlistat functions as an antiobesity agent by inhibiting gastrointestinal lipases, thereby reducing absorption of dietary fat In a 4-year study of obese patients without diabetes, orlistat mg t.

plus lifestyle changes produced moderate weight loss —5. Orlistat also provided weight-loss benefits for patients with diabetes. After 52 weeks of orlistat treatment mg t.

combined with a reduced-calorie diet and a weight-management program, obese patients with type 2 diabetes achieved —5. Retrospective analysis of seven studies of orlistat mg t. confirmed that orlistat-treated patients had significantly greater decreases in body weight than the placebo group —3.

Orlistat was generally well tolerated, and gastrointestinal effects were the most commonly reported AEs, but all events were considered mild or moderate 75 , Lorcaserin is a selective small-molecule agonist of the 5-hydroxytryptamine 2C serotonin receptor 5HT2C , which regulates mechanisms related to satiety, ingestive behavior, glucose tolerance, and hepatic insulin sensitivity Unlike previously available antiobesity agents, lorcaserin has a low affinity for the 5HT2B receptor subtype, whose activation has been linked to the development of valvular heart disease It is interesting to note that the reductions in HbA 1c observed with lorcaserin are equal to or higher than those observed with other antiobesity agents, such as phentermine plus topiramate and NB, despite a smaller amount of weight loss 71 , 73 , This suggests that the antihyperglycemic effect of lorcaserin may be due to more than weight loss alone.

Although hypoglycemia was slightly more frequent in the lorcaserin treatment groups than in the placebo group, no severe hypoglycemia was reported No evidence of increased depression, suicidal thoughts, or echocardiogram-detected valvular regurgitations were found in the lorcaserin treatment arms.

Overall, the most common AEs with lorcaserin were headache, back pain, nasopharyngitis, and nausea. Phentermine is a norepinephrine- and dopamine-releasing agent with a lower effect with dopamine vs. norepinephrine approved for the short-term treatment of obesity Topiramate has several pharmacological mechanisms of action and has been assessed as a single agent for weight reduction in obese patients with and without type 2 diabetes and hypertension 81 — A phase 3 study examined the efficacy of the combination of phentermine 7.

For patients with diabetes, significantly greater reductions in HbA 1c —0. PHEN 7. Phentermine plus topiramate was well tolerated; constipation, paresthesia, and dry mouth were the most commonly reported treatment-emergent AEs However, the FDA has required a Risk Evaluation and Mitigation Strategy for phentermine plus topiramate to educate prescribers and patients on the increased risk of orofacial clefts in infants exposed to phentermine plus topiramate during the first trimester of pregnancy Naltrexone is an opioid receptor antagonist, whereas bupropion is a norepinephrine and dopamine reuptake inhibitor The combination increases pro-opiomelanocortin POMC neuronal firing, which may have anorectic effects.

In patients with type 2 diabetes, NB therapy significantly decreased HbA 1c from baseline —0. NB-treated patients experienced significantly greater weight reduction from baseline than patients in the placebo group —5.

Compared with placebo, treatment with NB was associated with a higher incidence of nausea, constipation, and vomiting but was not associated with increased depression, suicidal thoughts, or hypoglycemia. NB may represent a novel pharmacological approach for the treatment of obesity, but further studies are required to assess its effects on cardiovascular outcomes, because systolic blood pressure and pulse rate have been found to be higher with NB than with placebo Liraglutide 3.

has been shown to provide weight-reduction benefits for obese patients; after 20 weeks, the placebo-subtracted reduction in weight from baseline with liraglutide 3. A further study showed that after 1 year, subjects who received liraglutide 3.

The weight reductions observed with liraglutide 3. primarily result from reductions in fat mass and body fat percentage including visceral fat rather than in lean tissue mass 88 , Similar to liraglutide 1. Recent safety concerns about an increased risk of major cardiac AEs have led to market withdrawal of existing antiobesity medications or a lack of new treatments being approved Assessment of cardiovascular safety has now emerged as a major consideration for all new antiobesity and glucose-lowering agents under current review by the FDA Given the significant need for effective and safe weight-loss medication, it is perhaps not surprising that many more antiobesity therapies are in development, as detailed in the the recent article by Rodgers et al.

The potential of these therapies in patients with type 2 diabetes, as well as their cardiovascular safety, will need to be established. As our knowledge of the physiology of appetite and energy homeostasis improves, so too will our ability to understand how therapies might be combined to provide effective weight management in patients with type 2 diabetes, while also minimizing AEs.

Therapies that are currently under clinical investigation are included in Table 5. Similar to liraglutide 3. has been shown to provide weight-reduction benefits in obese people with or without prediabetes After 24 weeks, the placebo-subtracted difference in percentage weight reduction was —3.

GLP-1R agonists for oral delivery are also currently under investigation in preclinical and clinical studies Because GLP-1R agonists and basal insulins offer complementary pharmacologic effects on prandial and fasting glycemia 94 , there is growing clinical interest in combinations of these two agents.

The combination of exenatide 10 µg b. with insulin glargine approved in the U. and Europe led to greater reductions in HbA 1c levels, compared with insulin glargine alone —1.

Treatment with exenatide and insulin glargine led to a weight decrease of —1. The number of hypoglycemic events between groups did not differ significantly.

Liraglutide with insulin degludec IDegLira —now approved in Europe—is another combination currently being investigated for the treatment of type 2 diabetes.

Initial clinical data show that IDegLira led to greater reductions in HbA 1c —1. IDegLira also provided a modest weight loss of —0. IDegLira also resulted in significantly fewer hypoglycemic episodes than insulin degludec. A combination of insulin glargine with lixisenatide has also been investigated The addition of lixisenatide to insulin glargine produced greater reductions in HbA 1c —0.

placebo, —3. The addition of lixisenatide also had a favorable effect on body weight difference vs. placebo —0. Nausea, vomiting, and symptomatic hypoglycemia were more commonly reported with lixisenatide than with insulin glargine alone.

Given the role of leptin and amylin in controlling food intake and energy expenditure and the role of incretins GLP-1 in glucose and weight control 97 , 98 , that many of the therapies in preclinical development involve these different hormones is no surprise.

Therapies that are currently being studied are included in Table 5. Because results with recombinant human leptin or metreleptin human leptin analog have been disappointing in reducing HbA 1c levels and weight for obese patients with type 2 diabetes 97 , approaches are now focused on leptin-related synthetic peptides, such as leptin receptor antagonists or leptin-related synthetic peptide analogs or mimetics, and leptin combination therapies Initial preclinical and clinical data suggest that leptin and amylin—two hormones involved in the control of satiety—have additive effects However, a subsequent trial was recently halted due to safety concerns Responsiveness to leptin is associated with decreased food intake, improved glucose tolerance and insulin sensitivity, and with decreased triglycerides and lower plasma cholesterol concentrations.

These results suggest that the pharmacology of leptin in combination with other agents, such as GLP-1R agonists and amylin analogs, warrants additional study as a potential antihyperglycemic therapy that is associated with weight loss. Another potential therapy is the combination of amylin analogs and GLP-1R agonists.

Because both agents can slow gastric emptying, it is possible that these two agents combined may have synergistic effects, but the gastrointestinal tolerance should be evaluated. Another incretin pathway compound in early-stage development is a peptide that acts as an agonist at both the GLP-1 and GIP receptors A preclinical study indicates that this dual agonist has the potential to enhance the antihyperglycemic and antiobesity effects observed with monoagonism because it affects adiposity-induced insulin resistance and pancreatic insulin deficiency.

A recent study in rodents found that a new monomeric peptide triagonist, simultaneously acting at three key metabolically related peptide hormone receptors GLP-1, GIP, glucagon , provided additional glucose control and weight-reducing benefits over dual coagonism Extensive clinical investigation into the efficacy and safety of coagonist therapy for the treatment of patients with obesity and type 2 diabetes is now required.

Owing to the complex pathophysiology of diabetes, additional therapeutic targets are under investigation as potential agents for glycemic control, many in combination with GLP-1R agonists PYY is an incretin hormone that also has a role in satiety The associated hypothesis is that PYY may further enhance the glucose-lowering and weight-reducing effects of GLP-1R agonists.

Fibroblast growth factor 21 has broad metabolic effects, including enhancing insulin sensitivity, decreasing triglyceride concentrations, and inducing weight loss, and this activity acts additively with GLP-1 , Another agent under clinical investigation as an antiobesity agent is beloranib, a fumagillin-class methionine aminopeptidase-2 inhibitor that has recently completed phase 2 trials Further research with all of these targets is required to determine their suitability as antihyperglycemic agents.

Although lifestyle interventions aimed at prompting weight loss are important in the management of type 2 diabetes and the benefits of weight reduction are irrefutable, most patients remain overweight or obese.

A shift in the approach to weight management in people with type 2 diabetes is clearly needed. Recent approvals of therapies that provide both glycemic control and weight reduction, and the healthy pipeline of antiobesity medications, bode well for a wider choice in the future, with some agents targeting the central nervous system to reduce food intake and others targeting the hormonal pathways involved in weight regulation and glucose homeostasis.

The emergence of a range of pharmacotherapies with varying modes of action, coupled with ongoing improvements in our knowledge of the physiology of appetite and energy homeostasis, provides the prospect of a rational combination therapy that is both effective and tolerable.

The authors are grateful to Dr. Jennifer Chang of AXON Communications for writing assistance in the development of the manuscript. received grant support from National Research Funds, Belgium, and also received grant support for hepatic research from the European Union consortium Hepadip and Resolve consortia.

Duality of Interest. Writing assistance for the manuscript was funded by Novo Nordisk. Novo Nordisk was also provided with the opportunity to perform a medical accuracy review.

also received an unrestricted research grant from Novo Nordisk and Novartis. No other potential conflicts of interest relevant to this article were reported.

Author Contributions. and A. conceived and designed the manuscript, analyzed and interpreted the data, drafted and revised the paper, and approved the final version for publication. Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest.

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Volume 38, Issue 6. Previous Article Next Article. Weight Gain With Conventional Therapies. Antidiabetes Therapies With Weight-Loss Potential.

Antiobesity Pharmacotherapies. Future Prospects in Clinical Development. Future Prospects in Preclinical Development. Potential Therapeutic Targets. Article Information. Article Navigation. Review May 12 Weight Management in Type 2 Diabetes: Current and Emerging Approaches to Treatment Luc Van Gaal ; Luc Van Gaal.

Corresponding author: Luc Van Gaal, luc. gaal uza. This Site. Google Scholar. André Scheen André Scheen. Diabetes Care ;38 6 — Article history Received:.

Connected Content. See "Pregestational preexisting diabetes: Preconception counseling, evaluation, and management". When to start — Early institution of treatment for diabetes, at a time when the A1C is not substantially elevated, is associated with improved glycemic management over time and decreased long-term complications [ 46 ].

Pharmacologic therapy should be initiated along with consultation for lifestyle modification focusing on dietary and other lifestyle contributors to hyperglycemia. Weight loss and weight loss maintenance underpins all effective type 2 diabetes therapy, and lifestyle change reduces the risk of weight gain associated with sulfonylureas and insulin.

However, for those patients who have clear and modifiable contributors to hyperglycemia and who are motivated to change them eg, commitment to reduce consumption of sugar-sweetened beverages , a three-month trial of lifestyle modification prior to initiation of pharmacologic therapy is warranted.

Choice of initial therapy — Our suggestions are based upon clinical trial evidence and clinical experience in achieving glycemic targets and minimizing adverse effects table 1 , with the recognition that there is a paucity of high-quality, head-to-head drug comparison trials and long-duration trials or ones with important clinical endpoints, such as effects on complications.

The long-term benefits and risks of using one approach over another are unknown. In selecting initial therapy, we consider patient presentation eg, presence or absence of symptoms of hyperglycemia, comorbidities, baseline A1C level , individualized treatment goals and preferences, the glucose-lowering efficacy of individual drugs, and their adverse effect profile, tolerability, and cost [ 47 ].

We prefer initiating a single agent typically metformin and then sequentially adding additional glucose-lowering agents as needed, rather than starting with combination therapy [ 48 ]. Related Pathway s : Diabetes: Initial therapy for non-pregnant adults with type 2 DM.

Asymptomatic, not catabolic — The majority of patients with newly diagnosed type 2 diabetes are asymptomatic, without symptoms of catabolism eg, without polyuria, polydipsia, or unintentional weight loss. Hyperglycemia may be noted on routine laboratory examination or detected by screening. Metformin — In the absence of specific contraindications, we suggest metformin as initial therapy for patients with newly diagnosed type 2 diabetes who are asymptomatic.

We begin with mg once daily with the evening meal and, if tolerated, add a second mg dose with breakfast. The dose can be increased slowly one tablet every one to two weeks as tolerated to reach a total dose of mg per day. See 'When to start' above and "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Dosing'.

Metformin is the preferred initial therapy because of glycemic efficacy see 'Glycemic efficacy' below , promotion of modest weight loss, very low incidence of hypoglycemia, general tolerability, and favorable cost [ 47 ]. Metformin does not have adverse cardiovascular effects, and it appears to decrease cardiovascular events [ ].

See "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Cardiovascular effects'. Metformin is far less expensive and has more clinical practice experience than glucagon-like peptide 1 GLP-1 receptor agonists and sodium-glucose cotransporter 2 SGLT2 inhibitors.

Although some guidelines and experts endorse the initial use of these alternative agents as monotherapy or in combination with metformin [ 48,52 ], we prefer initiating a single agent typically metformin and then sequentially adding additional glucose-lowering agents as needed, rather than starting with combination therapy.

In the clinical trials that demonstrated the protective effects of GLP-1 receptor agonists and SGLT2 inhibitors, these agents were added to background metformin therapy in most participants.

Further, the cardiorenal benefits of GLP-1 receptor agonists and SGLT2 inhibitors have not been demonstrated in drug-naïve patients without established CVD or at low cardiovascular risk or without severely increased albuminuria.

Although each diabetes medication is associated with adverse events, metformin is associated with less weight gain and fewer episodes of hypoglycemia compared with sulfonylureas, and with less edema, heart failure HF , and weight gain compared with thiazolidinediones. See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects'.

Although virtually all recommendations for initial pharmacologic therapy outside of China, where alpha-glucosidase inhibitors are recommended as an alternate first-line monotherapy [ 53 ] endorse use of metformin , there are, in fact, relatively few relevant direct comparative effectiveness data available.

Contraindications to or intolerance of metformin — For patients who have gastrointestinal intolerance of metformin , slower titration, ensuring that the patient is taking the medication with food, or switching to an extended-release formulation may improve tolerability.

For patients who still cannot tolerate metformin or have contraindications to it, we choose an alternative glucose-lowering medication guided initially by patient comorbidities, and in particular, the presence of atherosclerotic CVD ASCVD or albuminuric chronic kidney disease.

See "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Contraindications'. When compared with placebo, the GLP-1 receptor agonists liraglutide , semaglutide , and dulaglutide demonstrated favorable atherosclerotic cardiovascular and kidney outcomes [ ].

The SGLT2 inhibitors empagliflozin , canagliflozin , and dapagliflozin have also demonstrated benefit, especially for HF hospitalization, risk of kidney disease progression, and mortality [ ]. 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. 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.

As examples:. SGLT2 inhibitors with cardiovascular benefit empagliflozin or canagliflozin are good alternatives, especially in the presence of HF. Given the high cost of these classes of medications, formulary coverage often determines the choice of the first medication within the class.

See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Microvascular outcomes'.

Choice of agent is primarily dictated by provider preference, insurance formulary restrictions, eGFR, and cost. In the setting of declining eGFR, the main reason to prescribe SGLT2 inhibitors is to reduce progression of DKD. However, kidney and cardiac benefits have been shown in patients with eGFR below this threshold.

Dosing in the setting of DKD is reviewed in detail elsewhere. See "Treatment of diabetic kidney disease", section on 'Type 2 diabetes: Treat with additional kidney-protective therapy'. An alternative or an additional agent may be necessary to achieve glycemic goals.

GLP-1 receptor agonists are an alternative in patients with DKD as their glycemic effect is not related to eGFR. In addition, GLP-1 receptor agonists have been shown to slow the rate of decline in eGFR and prevent worsening of albuminuria.

See 'Microvascular outcomes' below and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus" and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus".

Of note, 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.

SLGT2 inhibitors should be held for 3 to 4 days before procedures including colonoscopy preparation and with poor oral intake to prevent diabetic ketoacidosis.

See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Contraindications and precautions'. Repaglinide acts at the sulfonylurea receptor to increase insulin secretion but is much shorter acting than sulfonylureas and is principally metabolized by the liver, with less than 10 percent renally excreted.

Limited data suggest that dipeptidyl peptidase 4 DPP-4 inhibitors are effective and relatively safe in patients with chronic kidney disease. However, linagliptin is the only DPP-4 inhibitor that does not require a dose adjustment in the setting of kidney failure.

GLP-1 receptor agonists may also be used safely in chronic kidney disease stage 4, but patient education for signs and symptoms of dehydration due to nausea or satiety is warranted to reduce the risk of acute kidney injury. Insulin may also be used, with a greater portion of the total daily dose administered during the day due to the risk of hypoglycemia, especially overnight, in chronic kidney disease and end-stage kidney disease ESKD.

See "Management of hyperglycemia in patients with type 2 diabetes and advanced chronic kidney disease or end-stage kidney disease", section on 'Patients not on dialysis'.

Without established cardiovascular or kidney disease — For patients without established CVD or kidney disease who cannot take metformin , many other options for initial therapy are available table 1.

We suggest choosing an alternative glucose-lowering medication guided by efficacy, patient comorbidities, preferences, and cost.

Although historically insulin has been used for type 2 diabetes only when inadequate glycemic management persists despite oral agents and lifestyle intervention, there are increasing data to support using insulin earlier and more aggressively in type 2 diabetes.

By inducing near normoglycemia with intensive insulin therapy, both endogenous insulin secretion and insulin sensitivity improve; this results in better glycemic management, which can then be maintained with diet, exercise, and oral hypoglycemics for many months thereafter. Insulin may cause weight gain and hypoglycemia.

See "Insulin therapy in type 2 diabetes mellitus", section on 'Indications for insulin'. If type 1 diabetes has been excluded, a GLP-1 receptor agonist is a reasonable alternative to insulin [ 66,67 ].

The frequency of injections and proved beneficial effects in the setting of CVD are the major differences among the many available GLP-1 receptor agonists. In practice, given the high cost of this class of medications, formulary coverage often determines the choice of the first medication within the class.

Cost and insurance coverage may limit accessibility and adherence. See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Patient selection'. Each one of these choices has individual advantages, benefits, and risks table 1.

See "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus" and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Patient selection' and "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Patient selection' and "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Potential indications'.

See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Weight loss' and "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Patient selection' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Weight loss'.

The choice of sulfonylurea balances glucose-lowering efficacy, universal availability, and low cost with risk of hypoglycemia and weight gain.

Pioglitazone , which is generic and another relatively low-cost oral agent, may also be considered in patients with specific contraindications to metformin and sulfonylureas. However, the risk of weight gain, HF, fractures, and the potential increased risk of bladder cancer raise the concern that the overall risks and cost of pioglitazone may approach or exceed its benefits.

See "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus" and "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Potential indications'. For patients who are starting sulfonylureas, we suggest initiating lifestyle intervention first, at the time of diagnosis, since the weight gain that often accompanies a sulfonylurea will presumably be less if lifestyle efforts are underway.

However, if lifestyle intervention has not produced a significant reduction in symptoms of hyperglycemia or in glucose values after one or two weeks, then the sulfonylurea should be added.

Side effects may be minimized with diabetes self-management education focusing on medication reduction or omission with changes in diet, food accessibility, or activity that may increase the risk of hypoglycemia.

See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Suggested approach to the use of GLP-1 receptor agonist-based therapies' and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Mechanism of action' and "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Mechanism of action' and "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Hypoglycemia'.

Symptomatic catabolic or severe hyperglycemia — The frequency of symptomatic or severe diabetes has been decreasing in parallel with improved efforts to diagnose diabetes earlier through screening.

If patients have been drinking a substantial quantity of sugar-sweetened beverages, reduction of carbohydrate intake, and rehydration with sugar-free fluids will help to reduce glucose levels within several days. See "Insulin therapy in type 2 diabetes mellitus", section on 'Initial treatment'.

However, for patients who are injection averse, initial therapy with high-dose sulfonylurea is an alternative option. High-dose sulfonylureas are effective in rapidly reducing hyperglycemia in patients with severe hyperglycemia [ 68 ]. Metformin monotherapy is not helpful in improving symptoms in this setting, because the initial dose is low and increased over several weeks.

However, metformin can be started at the same time as the sulfonylurea, slowly titrating the dose upward. Once the diet has been adequately modified and the metformin dose increased, the dose of sulfonylurea can be reduced and potentially discontinued. Patients with type 2 diabetes require relatively high doses of insulin compared with those needed for type 1 diabetes.

Insulin preparations, insulin regimens, and timing of dosing are discussed in detail elsewhere. See "Insulin therapy in type 2 diabetes mellitus". See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Administration'.

We typically use glimepiride 4 or 8 mg once daily. An alternative option is immediate-release glipizide 10 mg twice daily or, where available, gliclazide immediate-release 80 mg daily.

We contact the patient every few days after initiating therapy to make dose adjustments increase dose if hyperglycemia does not improve or decrease dose if hyperglycemia resolves quickly or hypoglycemia develops.

See "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Sulfonylureas'. Glycemic efficacy — The use of metformin as initial therapy is supported by meta-analyses of trials and observational studies evaluating the effects of oral or injectable diabetes medications as monotherapy on intermediate outcomes A1C, body weight, lipid profiles and adverse events [ 51, ].

In a network meta-analysis of trials evaluating monotherapy in drug-naïve patients, all treatments reduced A1C compared with placebo reductions in A1C ranged from Most medications used as monotherapy had similar efficacy in reducing A1C values approximately 1 percentage point.

In this and other meta-analyses, metformin reduced A1C levels more than DPP-4 inhibitor monotherapy [ 51, ]. There are few high-quality, head-to-head comparison trials of the available oral agents.

In one such trial, A Diabetes Outcome Progression Trial ADOPT , recently diagnosed patients with type 2 diabetes were randomly assigned to monotherapy with the thiazolidinedione rosiglitazone , metformin , or glyburide [ 72 ].

At the four-year evaluation, 40 percent of the subjects in the rosiglitazone group had an A1C value less than 7 percent, as compared with 36 percent in the metformin group and 26 percent in the glyburide group. Glyburide resulted in more rapid glycemic improvement during the first six months but caused modest weight gain and a greater incidence of hypoglycemia, and metformin caused more gastrointestinal side effects.

Rosiglitazone caused greater increases in weight, peripheral edema, and concentrations of low-density lipoprotein LDL cholesterol. There was also an unexpected increase in fractures in women taking rosiglitazone. The study was limited by a high rate of withdrawal of study participants.

Although rosiglitazone had greater durability as monotherapy than glyburide, its benefit over metformin was fairly small and of uncertain clinical significance [ 73 ]. See "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Safety'.

Cardiovascular outcomes — Cardiovascular benefit has been demonstrated for selected classes of diabetes medications, usually when added to metformin. See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Monotherapy failure'.

The cardiovascular effects of diabetes drugs are reviewed in the individual topics. 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' and "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Insulin therapy in type 2 diabetes mellitus".

In trials of patients with type 2 diabetes with and without chronic kidney disease, GLP-1 receptor agonists slowed the rate of decline in eGFR and prevented worsening of albuminuria [ 54,56,58 ].

These trials and other trials evaluating microvascular outcomes are reviewed in the individual topics. Guidelines — Our approach is largely consistent with American and European guidelines [ 52,74,75 ]. A consensus statement regarding the management of hyperglycemia in type 2 diabetes by the American Diabetes Association ADA and the European Association for the Study of Diabetes EASD was developed in and has been updated regularly, with the most recent revision published in [ 75 ].

The guidelines emphasize the importance of individualizing the choice of medications for the treatment of diabetes, considering important comorbidities CVD, HF, or chronic kidney disease; hypoglycemia risk; and need for weight loss and patient-specific factors including patient preferences, values, and cost [ 75 ].

We also agree with the World Health Organization WHO that sulfonylureas have a long-term safety profile, are inexpensive, and are highly effective, especially when used as described above, with patient education and dose adjustment to minimize side effects [ 76 ]. Blood glucose monitoring BGM is not necessary for most patients with type 2 diabetes who are on a stable regimen of diet or oral agents and who are not experiencing hypoglycemia.

BGM may be useful for some patients with type 2 diabetes who use the results to modify eating patterns, exercise, or insulin doses on a regular basis.

See "Glucose monitoring in the ambulatory management of nonpregnant adults with diabetes mellitus", section on 'Type 2 diabetes'. The balance among efficacy in lowering A1C, side effects, and costs must be carefully weighed in considering which drugs or combinations to choose.

Avoiding insulin, the most potent of all hypoglycemic medications, at the expense of poorer glucose management and greater side effects and cost, is not likely to benefit the patient in the long term.

See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Our approach'. 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: 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.

Weight reduction through diet, exercise, and behavioral modification can all be used to improve glycemic management, although the majority of patients with type 2 diabetes will require medication. See 'Diabetes education' above. Glycemic targets are generally set somewhat higher for older adults and for those with comorbidities or a limited life expectancy and little likelihood of benefit from intensive therapy.

See 'Glycemic management' above and "Glycemic control and vascular complications in type 2 diabetes mellitus", section on 'Choosing a glycemic target'. In the absence of specific contraindications, we suggest metformin as initial therapy for most patients Grade 2B.

Although some guidelines and experts endorse the initial use of alternative agents as monotherapy or in combination with metformin, we prefer initiating a single agent typically metformin and then sequentially adding additional glucose-lowering agents as needed.

See 'Metformin' above and 'Glycemic efficacy' above. We suggest initiating metformin at the time of diabetes diagnosis Grade 2C , along with consultation for lifestyle intervention.

See 'When to start' above. The dose of metformin should be titrated to its maximally effective dose usually mg per day in divided doses over one to two months, as tolerated.

See 'Contraindications to or intolerance of metformin' above. 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.

See 'Without established cardiovascular or kidney disease' above. Each one of these choices has individual advantages and risks table 1.

Choice of medication is guided by efficacy, patient comorbidities, preferences, and cost. However, the improvement in glycemic control for a given weight loss was greater initially than at one year, suggesting that energy restriction, in addition to weight loss, may contribute to initial improvement.

Neither percent overweight nor diabetes treatment affected weight loss. Wing RR , Koeske R , Epstein LH , Nowalk MP , Gooding W , Becker D. Long-term Effects of Modest Weight Loss in Type II Diabetic Patients.

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Mayo Clinic offers appointments in Arizona, Florida and Minnesota and at Mayo Clinic Health System locations. Insulin and weight gain often go hand in hand, but weight control is possible. If you need insulin therapy, here's how to minimize — or avoid — weight gain.

People who take insulin often gain weight. Insulin is a hormone that regulates how the body absorbs sugar, also known as glucose. The weight gain can be frustrating because keeping a healthy weight is important to manage your diabetes.

The good news is that you can maintain your weight while taking insulin. When you take insulin, sugar can enter your cells. This makes the sugar levels in your blood go down. This is the goal of treatment. But if you take in more calories than you need to keep a healthy weight, your cells will get more sugar than they need.

This happens in people who don't have diabetes, too. How many calories you need depends on how active you are. Sugar that your cells don't need to use becomes fat. Eating healthy foods and being physically active most days of the week can help you not gain weight. The following tips can help you keep the pounds off:.

Count calories. Eating and drinking fewer calories helps you prevent weight gain. Keep fruits, vegetables and whole grains in your refrigerator and pantry. Plan for every meal to have the right mix of starches, fruits and vegetables, proteins, and fats.

Generally, recommended meals would consist of half nonstarchy vegetable, one-quarter protein and one-quarter a starch, such as rice, or a starchy vegetable, such as corn or peas. Shrink the sizes of your portions, don't take second helpings and drink water instead of high-calorie drinks.

Talk to your health care provider, nurse or a dietitian about how to plan meals and where to find resources. Be physically active. Physical activity burns calories. A recommended goal for most adults is at least minutes a week or 30 minutes five days a week of moderately intense aerobic activity plus muscle-strengthening exercises at least two times a week.

Aerobic activities can include walking, bicycling, water aerobics, dancing or gardening. Talk with your provider about activities and exercises that are right for you. Also, ask your provider how to handle exercise. Physical activity helps your body use insulin more efficiently.

Depending on how much exercise you're planning on doing, you may need to cut back on your insulin dosage or have a snack. It's possible for your blood sugar to drop even hours after exercise.

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All authors had full access to all data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. Editorial and writing support in the preparation of this manuscript was provided by Yasmin Issop, PhD, and Luke Shelton, PhD, of Excerpta Medica, funded by Sanofi US, Inc.

All named authors meet the International Committee of Medical Journal Editors ICMJE criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published.

Caroline M. Apovian has received research funding from Aspire Bariatrics, GI Dynamics, Orexigen, Takeda, the Vela Foundation, Gelesis, Energesis, and Coherence Lab; has participated on the Advisory Boards for Nutrisystem, Zafgen, Sanofi, Orexigen, EnteroMedics, GI Dynamics, Scientific Intake, Gelesis, Novo Nordisk, SetPoint Health, Xeno Biosciences, Rhythm Pharmaceuticals, Eisai, and Takeda.

Takeda Speakers Bureau for the medication Contrave. Ownership interest in Science Smart LLC. Patrick M. Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Section of Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston Medical Center, Harrison Avenue, Suite , Boston, MA, , USA.

Western Washington Medical Group, Diabetes and Nutrition Education, Bothell, WA, USA. Department of Psychiatry and Behavioral Sciences, Weight Management Center, Medical University of South Carolina, Charleston, SC, USA.

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Reprints and permissions. Apovian, C. Body Weight Considerations in the Management of Type 2 Diabetes. Adv Ther 36 , 44—58 Download citation. Received : 25 June Published : 21 November Issue Date : January Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Download PDF. Abstract Obesity is one of the main risk factors for type 2 diabetes T2D , representing a major worldwide health crisis.

Funding : Sanofi US, Inc. 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 Article 24 September The management of type 1 diabetes in adults.

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Introduction The increasing prevalence of both obesity and type 2 diabetes T2D represents major public health crises worldwide. Relationship Between Obesity and T2D While the underlying cause of T2D is multifactorial, the cardinal features are a decline in insulin production by pancreatic β-cells and peripheral insulin resistance [ 8 ].

Full size image. Strategies Used for Weight-Loss in T2D The primary clinical goals of weight-loss in patients with T2D are achievement of glycemic targets, improvement of lipid profile, and normalization of blood pressure [ 13 ].

Effects of Antihyperglycemia Drugs on Body Weight The effects of antihyperglycemia therapy on clinical outcomes including body weight vary both between and within the drug classes Fig.

Table 1 Mechanisms of action, effects on body weight, side effects, and dosing schedule of antidiabetes drug classes Full size table. Conclusions Current major guidelines recommend that when choosing antihyperglycemic treatments for patients who are overweight or have obesity, wherever possible, consideration should be given to medications that promote weight-loss or that are weight-neutral [ 8 ].

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Obesity is also becoming more prevalent in people with type 1 diabetes; one study reported a sevenfold increase in the last 20 years. In addition, intensive insulin therapy and some antihyperglycemic medications are associated with weight gain which, in turn, leads to obesity-related comorbid conditions.

The relationship between increasing body fat accumulation and adverse health outcomes exists throughout the range of overweight and obesity in men and women of all age groups. Weight loss has been shown to improve glycemic control by increasing insulin sensitivity and glucose uptake and diminishing hepatic glucose output.

For most adults aged 18 to 65, a BMI of 25 to Waist Circumference WC is the measurement around the waist. Previous Article Next Article.

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Read about the link between the two. The three P's of diabetes refer to the most common symptoms of the condition. Those are polydipsia, polyuria, and polyphagia. High blood glucose can…. Singer Nick Jonas, who has type 1 diabetes, debuted a new blood glucose monitoring device during a Super Bowl television commercial.

A Quiz for Teens Are You a Workaholic? How Well Do You Sleep? Health Conditions Discover Plan Connect. What to Know About Diabetes and Weight Loss. Medically reviewed by Michelle L. Griffith, MD — By Jacquelyn Cafasso on May 19, Unexpected weight loss Benefits of weight loss for diabetes Diabetes medication Tips for weight loss When to talk with a pro Takeaway Your weight can affect diabetes, but diabetes can also affect your weight.

How can diabetes cause weight loss? The benefits of weight loss for diabetes. Diabetes medications and weight loss. Adjusting medications for weight loss As you lose weight, your may need less medication to keep your blood sugar in target range.

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