Browse the evidence

Metformin reduces the risk of progression from prediabetes to type 2 diabetes by 31% and is recommended for specific high-risk subgroups (age 25-59, BMI ≥35, FPG ≥6.1 mmol/L, or history of gestational diabetes).

If lifestyle changes alone are not enough, your doctor may prescribe metformin. It is typically started at a low dose (500 mg) and increased to 1,500 mg daily to minimize stomach issues. Use the extended-release version if possible. Monitor your blood sugar every 6 months. This is particularly recommended if you are younger, have a higher BMI, or have a history of gestational diabetes.

Second-generation obesity management medications (semaglutide and tirzepatide) produce 15-20% body weight loss, significantly exceeding the 5-10% typically achieved by lifestyle interventions alone.

Second-generation obesity medications like semaglutide and tirzepatide are significantly more effective for weight loss than lifestyle changes alone, achieving 15-20% body weight reduction. They work by targeting hormonal pathways that regulate appetite and metabolism, addressing the biological drivers of obesity rather than relying solely on willpower.

Discontinuation of second-generation OMMs leads to significant weight regain, highlighting the chronic nature of obesity and the need for long-term management or intensive lifestyle support upon discontinuation.

Stopping OMMs typically leads to significant weight regain. If you choose to discontinue, work with your healthcare provider to intensify lifestyle interventions, including dietary strategies and physical activity, to help maintain your weight loss.

Once-weekly subcutaneous semaglutide 2.4 mg produces significant weight loss in adults with overweight or obesity, with efficacy largely independent of baseline characteristics such as age, race, BMI, and glycemic status, though females and those with lower baseline body weight experience greater magnitude of loss.

If you have obesity or overweight, once-weekly semaglutide (2.4 mg) is a highly effective treatment for weight loss, regardless of your age, race, or starting weight. However, be aware that women and those with a lower starting body weight tend to lose more weight than men or those with a higher starting body weight. This treatment is used alongside lifestyle changes.

Tirzepatide (5-15 mg weekly) produces superior weight loss (10.7-20.9%) compared to placebo in adults with obesity (BMI ≥30 or ≥27 with comorbidities) via dual GIP/GLP-1 receptor agonism.

Tirzepatide is a once-weekly injection that significantly reduces body weight (up to 20%+) in obese adults. It works by mimicking gut hormones to suppress appetite and slow digestion. Start with the lowest dose and increase gradually to minimize stomach upset. Combine with a 500-calorie daily deficit and 150 minutes of weekly exercise for best results.

Once-weekly subcutaneous semaglutide (up to 2.4 mg) significantly reduces body weight, BMI, and waist circumference in adults with obesity or overweight compared to placebo, with effects demonstrating a dose-response relationship.

For adults with obesity or overweight, once-weekly semaglutide (titrated up to 2.4 mg) combined with lifestyle changes is a highly effective medical intervention for significant weight loss, outperforming lifestyle changes alone. While gastrointestinal side effects like nausea are common, they are usually manageable and do not typically lead to stopping treatment.

Once-weekly semaglutide improves cardiometabolic markers including HbA1c, fasting plasma glucose, blood pressure, and lipid profiles in overweight/obese patients, independent of or alongside weight loss.

Beyond weight loss, semaglutide helps improve blood sugar control (HbA1c), blood pressure, and lipid profiles in overweight/obese individuals, offering broader cardiovascular protection.

Tirzepatide (5, 10, and 15 mg once-weekly) provides superior glycemic control (HbA1c reduction) and greater body weight loss compared to placebo, GLP-1 receptor agonists, and basal insulin in adults with type 2 diabetes.

Tirzepatide is a once-weekly injection that lowers blood sugar and helps with weight loss more effectively than existing GLP-1 drugs (like semaglutide) and basal insulin. It works by mimicking two gut hormones (GIP and GLP-1). While it is very effective, it can cause stomach issues like nausea and diarrhea, which might lead some people to stop taking it, especially at higher doses. It does not increase the risk of low blood sugar (hypoglycemia) on its own.

Semaglutide 2.4 mg once weekly improves symptoms, exercise capacity, and reduces inflammation in patients with obesity-phenotype heart failure with preserved ejection fraction (HFpEF) across all obesity classes (BMI 30-34.9, 35-39.9, and ≥40 kg/m²), with clinical benefits directly proportional to the magnitude of weight loss.

If you have heart failure with preserved ejection fraction and obesity, semaglutide (2.4 mg weekly) is a proven treatment that improves your heart symptoms, exercise ability, and inflammation. The more weight you lose, the more you benefit, regardless of whether your obesity is Class I, II, or III. This treatment works best when combined with a moderate caloric deficit (500 kcal/day) and regular physical activity.

Pharmacotherapy is recommended for postmenopausal females and males aged 50+ who have had a previous hip or vertebral fracture, or have a 10-year major osteoporotic fracture risk of 20% or more.

If you are over 50 and have had a hip or vertebral fracture, or have a high 10-year fracture risk (20% or more), you should strongly consider pharmacotherapy. This is a strong recommendation based on high-certainty evidence. Your doctor will help you choose the right medication based on your specific risks and preferences.

Liraglutide (3.0 mg daily) is effective for weight loss but significantly less so than Semaglutide, with a mean weight loss of 6.4% compared to 15.8%.

Liraglutide (3.0 mg daily) is an FDA-approved option for weight loss, but it produces roughly half the weight loss of Semaglutide (6.4% vs 15.8%). It requires daily injections, which may be burdensome, and you must reach the 3.0 mg dose to see full effects. If you cannot tolerate Semaglutide, this is a viable alternative, but expect less dramatic results.

Certain anti-diabetic medications, specifically insulin, can increase body weight, creating a conflict in treating obesity and T2DM simultaneously.

If you are prescribed insulin for diabetes, be aware it can cause weight gain. Discuss weight-neutral or weight-loss promoting alternatives (like GLP-1 agonists or SGLT2 inhibitors, though not explicitly named here, implied by 'anti-obesity drugs') with your doctor if weight management is a priority.

Once-weekly semaglutide (2.4 mg) significantly improves heart failure symptoms, physical limitations, and exercise capacity in patients with obesity-related heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes, independent of the magnitude of weight loss.

If you have heart failure with preserved ejection fraction, are obese, and have type 2 diabetes, once-weekly semaglutide (2.4 mg) can significantly reduce your heart failure symptoms and help you lose weight. This treatment works even if your weight loss isn't as dramatic as in people without diabetes, suggesting it helps your heart directly. It is administered as a weekly injection, starting at a low dose to minimize side effects, and titrated up over 16 weeks.

GLP-1 receptor agonists delay gastric emptying, which reduces postprandial lipid and carbohydrate surges and contributes to satiety.

GLP-1 medications slow down how fast food leaves your stomach. This helps you feel full longer and prevents sharp spikes in blood sugar after meals.

GLP-1 receptor agonists reduce the risk of major adverse cardiovascular events (MACE), death, and stroke in patients with type 2 diabetes.

If you have type 2 diabetes, GLP-1 receptor agonists can significantly lower your risk of heart attacks, strokes, and death. This benefit is independent of weight loss and is supported by large-scale data involving over 60,000 patients.

Once-weekly subcutaneous semaglutide (2.4 mg) significantly alters the circulating proteome in individuals with obesity, downregulating proteins associated with cardiovascular disease risk and inflammatory pathways beyond what is explained by weight loss and glycemic control alone.

If you have obesity and are considering semaglutide, know that it does more than just help you lose weight. It actively changes your blood proteins to lower your risk of heart disease and inflammation, even independent of the weight you lose. This makes it a valuable tool for cardiovascular protection in high-risk individuals, not just a weight-loss aid. The benefits are supported by large, rigorous clinical trials.

Tirzepatide 15mg is associated with a higher rate of adverse events compared to other GLP-1RAs, although not significantly different from placebo in some metrics, it ranks highest in SUCRA for adverse events.

Tirzepatide 15mg is highly effective but comes with a higher risk of side effects like nausea and diarrhea compared to other GLP-1s. Patients should be prepared for this and work with their doctor on dose titration to manage it.

GLP-1 receptor agonists reduce the risk of Major Adverse Cardiovascular Events (MACE) by 13-26% in patients with type 2 diabetes and high cardiovascular risk.

If you have type 2 diabetes and heart disease or high heart risk, GLP-1 medications like semaglutide or liraglutide are recommended not just for blood sugar, but to protect your heart. Studies show they can lower the risk of heart attacks and strokes by 13-26% compared to placebo.

GLP-1 receptor agonists improve cardiovascular outcomes by reducing major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, in patients with type 2 diabetes and established cardiovascular disease.

If you have type 2 diabetes and existing heart disease, certain GLP-1 medications (like liraglutide, semaglutide, or dulaglutide) can significantly lower your risk of heart attack, stroke, or cardiovascular death. This benefit is independent of weight loss and is a key reason these drugs are recommended for high-risk patients.

Discontinuation of semaglutide treatment leads to significant weight regain, resulting in net weight loss that is substantially lower than the peak loss achieved during treatment.

If you stop taking semaglutide, you will likely regain most of the weight you lost. The net weight loss after stopping is much smaller than the peak loss. Long-term maintenance may require continued treatment.

GLP-1 receptor agonists (Liraglutide, Semaglutide) and Tirzepatide reduce food intake primarily by increasing satiety and reducing neural activation in brain areas associated with appetite and reward, rather than just delaying gastric emptying.

Semaglutide (2.4 mg weekly) works by acting on your brain to make you feel full sooner and reducing the desire for high-calorie foods. It is not just about stomach emptying. Start with a low dose to minimize side effects, titrating up to 2.4 mg over several months.

Incretin-based therapies improve cardiovascular risk factors (lipids, blood pressure) and reduce the risk of major cardiovascular events and heart failure in individuals with obesity.

For those with obesity, incretin therapies like semaglutide offer cardiovascular protection, lowering risks of heart events and heart failure, independent of just weight loss.

Subcutaneous semaglutide increases the risk of gastrointestinal adverse events (nausea, diarrhea, vomiting) compared to placebo and other antidiabetic agents, but does not increase the risk of serious adverse events, hypoglycemia, acute pancreatitis, or diabetic retinopathy.

While semaglutide is effective, be aware that it commonly causes nausea, diarrhea, or vomiting, especially when starting or increasing the dose. These side effects are usually mild and temporary. Importantly, it does not appear to increase the risk of serious conditions like pancreatitis, hypoglycemia, or eye problems compared to other treatments.

Antihyperglycemic therapies reduce the risk of Major Adverse Cardiovascular Events (MACE) in a glycemic-dependent manner, where every 1% reduction in HbA1c is associated with a 14% relative reduction in MACE risk.

If you have type 2 diabetes, achieving a 1% reduction in your HbA1c through medication or lifestyle is associated with a 14% lower risk of major cardiovascular events like heart attack or stroke. This benefit is consistent across various drug classes, suggesting that effective glycemic control is a primary strategy for cardiovascular protection.