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Hyperglycemia and weight management

Hyperglycemia and weight management

See "Metformin in Control alcohol consumption treatment Hyperrglycemia adults with type 2 Energize your workouts mellitus", section anf 'Contraindications'. This happens weightt of a problem with the Hyperglycemia and weight management called insulin. Many Hyperglycemia and weight management find that writing down everything they eat helps keep them on target. Weigyt the problem, research also has shown that fat cells of people who are obese and who have more abdominal fat actually release molecules that can be harmful to the pancreas. Resources ADA Professional Membership ADA Member Directory Diabetes. If you are new to exercise and looking to take the first step toward balancing your blood sugar, walking for 30 minutes daily is a great place to start. Similarly, patients without severely increased albuminuria have some benefit, but the absolute benefits are greater among those with severely increased albuminuria.

Hyperglycemia and weight management -

The reason why type 2 diabetes develops is not completely clear. But being overweight plays a role. In people who are overweight, the body sometimes needs as much as two to three times more insulin than it would if it was at a healthy weight. In those who develop diabetes, that is more insulin than the pancreas is able to produce.

When the pancreas tries to make that much insulin, it is pushed beyond its capacity and insulin-producing cells start to die. That makes the situation worse because the pancreas then has even fewer cells with which to make insulin. Compounding the problem, research also has shown that fat cells of people who are obese and who have more abdominal fat actually release molecules that can be harmful to the pancreas.

So the more abdominal fat you have, the higher the risk of damage to your pancreas. Getting to a lower weight reduces many of these problems. When you weigh less, your pancreas is better able to keep up with your body's need for insulin. In some cases, weight loss is enough to restore blood sugar to a normal level, which eliminates diabetes.

Even if it doesn't get your blood sugar completely back to normal, it may lower your need for insulin therapy or other medications to control diabetes. It also lessens your risk for other serious complications of diabetes, including heart problems, kidney disease and nerve damage.

The benefits of healthy weight as it relates to diabetes continue over time, too. Many people mistakenly believe that a person's risk for diabetes automatically goes up with age.

In fact, your diabetes risk rises over time only if you gain weight and are less active as you age. Lifestyle change includes diet and physical activity, as well as behaviors that facilitate these changes, and is an essential component of any weight management plan.

We emphasize lifestyle change as our initial approach to body weight reduction and reserve pharmacotherapy and metabolic surgery for patients who do not achieve targeted weight loss with lifestyle change alone. We tailor our specific recommendations to patients' goals and preferences and encourage "intensive" lifestyle modification, where available, for highly motivated patients.

Diet — Diagnosis of type 2 diabetes is often a powerful motivator for lifestyle change. Dietary modification is a highly effective strategy for weight loss and for management of glycemia and hypertension in patients who are willing to commit to it, with metabolic benefit likely outlasting the effect of weight loss per se.

The improvement in glycemia is related both to the degree of caloric restriction and weight reduction [ 12,14,15 ]. Body weight loss of 5 to 10 percent may also improve nonalcoholic steatohepatitis, sleep apnea, and other comorbidities of type 2 diabetes [ 16 ].

Consumption of sugar-sweetened beverages, including natural fruit juice, should be specifically queried and strongly discouraged in order to manage glycemia, weight, and reduce risk for CVD and fatty liver [ 17 ]. See "Medical nutrition therapy for type 2 diabetes mellitus", section on 'Designing a nutrition care plan' and "Management of nonalcoholic fatty liver disease in adults", section on 'Initial lifestyle interventions'.

In a two-year analysis of the DiRECT trial, only 11 percent of intervention participants had weight loss of 15 kg or more compared with 24 percent in the one-year analysis [ 18 ].

However, 36 percent of participants maintained diabetes remission, compared with 3 percent of control patients. Several studies have evaluated the long-term efficacy of diet alone or with exercise in patients with newly diagnosed type 2 diabetes see "Medical nutrition therapy for type 2 diabetes mellitus".

In the United Kingdom Prospective Diabetes Study UKPDS , for example, all patients were given a low-calorie, low-fat, high complex carbohydrate diet [ 21 ]. Furthermore, the mean glucose value was substantially higher with diet alone than with diet plus an oral hypoglycemic drug or insulin. The likelihood of a successful glycemic response to diet is determined in large part by the initial fasting blood glucose.

Pharmacologic therapy — Pharmacotherapy targeted solely for weight management is effective in patients with type 2 diabetes. Although metformin is usually started for the management of hyperglycemia, it is also frequently an effective medication to promote modest weight loss.

When additional body weight reduction is a primary goal of therapy, we choose medications that promote weight loss and lower glucose. Glucagon-like peptide 1 GLP-1 receptor and dual GLP-1 and glucose-dependent insulinotropic polypeptide GIP agonist therapies promote weight loss and help prevent weight gain due to other glucose-lowering pharmacotherapies.

We add these medications sequentially to metformin if additional glucose lowering or weight loss is a treatment goal. See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus" and "Obesity in adults: Drug therapy".

Surgical therapy — Weight loss surgery in patients with obesity and type 2 diabetes results in the largest degree of sustained weight loss and, in parallel, improvements in blood glucose management and the most frequent sustained remissions of diabetes.

Weight loss surgery is an option to treat poorly managed type 2 diabetes when other modalities have failed. This topic is reviewed in detail separately.

See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Bariatric metabolic surgery'. Exercise — Regular exercise is beneficial in type 2 diabetes, independent of weight loss.

It leads to improved glycemic management due to increased responsiveness to insulin; it can also delay the progression of impaired glucose tolerance to overt diabetes [ 22,23 ]. These beneficial effects are directly due to exercise, but concurrent weight reduction plays a contributory role.

In one study, however, only 50 percent of patients with type 2 diabetes were able to maintain a regular exercise regimen [ 24 ].

See "Exercise guidance in adults with diabetes mellitus". Shorter-duration, intensive exercise may be appropriate for physically fit individuals [ 25 ].

Resistance training may be particularly important for individuals with type 2 diabetes who do not have overweight or obesity, in whom relative sarcopenia may contribute to diabetes pathophysiology [ 26 ].

Intensive lifestyle modification — In patients with established type 2 diabetes, intensive behavioral modification interventions focusing on weight reduction and increasing activity levels are successful in reducing weight and improving glycemic management while, at the same time, reducing the need for glucose-lowering and other medications [ 15,18, ].

The intensive intervention included caloric restriction maximum 30 percent calories from fat, minimum 15 percent protein, and the remainder from carbohydrates, in the form of liquid meal replacements, frozen food entrees, or structured meal plans , moderate-intensity physical activity goal minutes weekly , and weekly group or individual sessions with registered dietitians, behavioral psychologists, and exercise specialists.

The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for angina. Although the anticipated follow-up period was After a median follow-up of 9.

The improvement in weight and glycemia did not reduce the occurrence of cardiovascular events. Possible reasons for this finding include the lower-than-expected rates of cardiovascular events in both groups, improved overall cardiovascular risk factor treatment with medical therapy antihypertensives, statins in the standard diabetes education arm, enrollment of a relatively healthy patient population, gradual weight loss in the control group such that the differential weight loss between the two groups was only 2.

A sustained weight loss of greater than that achieved in the trial may be required to reduce the risk of CVD. In an observational post hoc analysis of the Look AHEAD trial, weight loss of 10 percent or greater in the first year was associated with a reduction in the primary outcome 1. However, this post hoc analysis is problematic.

Moreover, the degree of weight loss is difficult to achieve and maintain through lifestyle intervention alone. Weight loss, weight loss maintenance, and exercise remain important components of diabetes management due to overall health benefits.

The following summarizes several other major observations from the Look AHEAD trial [ 27,31, ]:. The difference was attenuated but remained significant throughout the trial 6 versus 3. Changes in waist circumference and physical fitness were also significantly better in the intervention group throughout the study.

By study end, mean A1C was significantly lower in the intervention group 7. Psychological interventions — Patients with type 2 diabetes often experience significant stress, a condition often called diabetes distress, related to the many self-care responsibilities required for glycemic management lifestyle modifications, medication, and blood glucose monitoring [BGM] [ 42 ].

Concurrent depression similarly may interfere with self-care. See "Overview of general medical care in nonpregnant adults with diabetes mellitus", section on 'Comorbid conditions'. Psychotherapy reduces psychological distress and improves glycemic management in some [ 43,44 ], but not all [ 45 ], studies.

In a meta-analysis of 12 trials of patients with type 2 diabetes randomly assigned to psychological intervention or usual care, mean A1C was lower in the intervention group pooled mean difference Measures of psychological distress were also significantly lower in the intervention group, but there were no differences in weight management.

Pregnancy planning — All women of childbearing age with diabetes should be counseled about the potential effects of diabetes and commonly used medications on maternal and fetal outcomes and the potential impact of pregnancy on their diabetes management and any existing complications.

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. 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.

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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.

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toolbar search search input Search input auto suggest. Table 1 Antidiabetes therapies associated with weight gain. Drug class. Mechanism of action. How mechanism of action leads to weight gain. View Large. Baseline patient characteristic predictive of weight gain. Table 3 Antidiabetes therapies that are weight neutral or have weight-loss potential.

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Accessed 2 Jan The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. Management of hyperglycemia in type 2 diabetes, a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes.

Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial.

Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes.

Impact of intensive lifestyle intervention on depression and health-related quality of life in type 2 diabetes: the Look AHEAD Trial. A randomized study on the effect of weight loss on obstructive sleep apnea among obese patients with type 2 diabetes: the Sleep AHEAD study.

Look AHEAD Research Group. Eight-year weight losses with an intensive lifestyle intervention: the Look AHEAD study. UK Prospective Diabetes Study UKPDS Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes UKPDS Determinants of weight gain in the action to control cardiovascular risk in diabetes trial.

Characterizing and understanding body weight patterns in patients treated with pregabalin. Diet and exercise intervention in a general population—mediators of participation and adherence: the Inter99 study. The DCCT Research Group.

Weight gain associated with intensive therapy in the Diabetes Control and Complications Trial. de Luis. Decreased basal levels of glucagon-like peptide-1 after weight loss in obese subjects. Leptin reverses weight loss-induced changes in regional neural activity responses to visual food stimuli.

Hyperglycemix Van GaalAndré Scheen; Weight Hypergglycemia in Type 2 Heart health Current and Emerging Approaches to Treatment. Hyperglycemia and weight management Care 1 June ; 38 6 : — Diabetes is a growing global health Hyperglycwmia, as is obesity. Diabetes and obesity are intrinsically linked: obesity increases the risk of diabetes and also contributes to disease progression and cardiovascular disease. Although the benefits of weight loss in the prevention of diabetes and as a critical component of managing the condition are well established, weight reduction remains challenging for individuals with type 2 diabetes due to a host of metabolic and psychological factors. Mayo Clinic offers appointments in Arizona, Florida and Minnesota and Hyperglyceemia Mayo Clinic Health Thermogenic pills for enhanced performance locations. Insulin and weight Hyperglycemia and weight management often Control alcohol consumption hand in hand, but weight Hyperglycfmia is Hyperglycemia and weight management. If managdment 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. Hyperglycemia and weight management

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