Browse the evidence

Lifestyle modifications, specifically calorie restriction of 500-750 kcal/day and ≥ 150 minutes of exercise per week, are the first-line treatment for obesity, though long-term maintenance is challenging without pharmacological or surgical support.

Start with a daily calorie deficit of 500-750 kcal and aim for at least 150 minutes of exercise per week. This is the first step in managing obesity. Remember, long-term success is often about finding a sustainable lifestyle you can stick to, rather than a specific 'magic' diet.

Orforglipron, an oral non-peptide GLP-1 receptor agonist, produces clinically significant, dose-dependent reductions in body weight, HbA1c, systolic blood pressure, and atherogenic lipids (LDL, VLDL, triglycerides) with high consistency across trials.

Orforglipron is an oral medication that helps reduce weight, blood sugar, blood pressure, and bad cholesterol. It works by mimicking a gut hormone (GLP-1). You take one pill a day. It can cause stomach issues like nausea, but doctors can help manage this by starting with a low dose and increasing it slowly. It is designed for people with obesity or type 2 diabetes who want to avoid injections.

Triple receptor agonists (retatrutide) produce the highest magnitude of weight loss reported to date in pharmacotherapy for obesity, surpassing dual and single GLP-1 agonists.

Retatrutide is currently the most effective drug for weight loss in this class, working by targeting three hormonal pathways (GLP-1, GIP, and glucagon). It is administered once weekly. Expect significant weight loss, but also expect gastrointestinal side effects like nausea during the initial weeks, which typically subside.

Intragastric balloons (Obalon, Orbera, ReShape Duo) provide temporary weight loss (12-25% EWL) when combined with lifestyle modifications.

Intragastric balloons are temporary devices placed in the stomach to help with weight loss. They work by taking up space, making you feel full sooner. Clinical trials show they can lead to 12-25% excess weight loss when combined with lifestyle changes, significantly outperforming lifestyle changes alone. They require an endoscopic procedure and are typically removed after 6 months.

Tirzepatide (10 mg and 15 mg) provides statistically superior weight reduction and waist circumference reduction compared to semaglutide (2.4 mg) and liraglutide (3 mg) in patients with obesity or overweight without type 2 diabetes.

For patients with obesity or overweight without type 2 diabetes, Tirzepatide (10mg and 15mg doses) administered once weekly, alongside lifestyle changes, achieves significantly greater weight loss and waist circumference reduction than Semaglutide (2.4mg) or Liraglutide (3mg). The safety profile is generally comparable across all three treatments.

Incretin polyagonists (dual and triple agonists) produce weight loss and metabolic improvements comparable to, or approaching, those of bariatric surgery, serving as a potent non-surgical alternative.

If you have obesity and want significant weight loss without surgery, incretin polyagonists (like tirzepatide or retatrutide) are now a viable, highly effective medical option. They work by mimicking gut hormones to reduce appetite and improve metabolism. While they require weekly injections (or soon, oral pills), they can achieve weight loss results similar to bariatric surgery. Expect some initial stomach upset, which usually fades as your body adjusts. Consult a doctor to see if you are a candidate.

Preservation of lean mass during GLP-1/GIP-induced weight loss requires high-quality protein distribution (1.2–1.5 g/kg/day) and resistance exercise to mitigate sarcopenia and maintain oncologic treatment tolerance.

To prevent muscle loss while on GLP-1/GIP drugs, eat 1.2–1.5 grams of protein per kilogram of body weight daily, spread across meals, and engage in regular resistance exercise.

Lifestyle interventions involving ≥150 minutes of exercise per week combined with caloric restriction are associated with the highest odds of long-term weight loss maintenance (5-10%).

To keep weight off long-term, aim for at least 150 minutes of exercise per week, ideally closer to 275 minutes, while maintaining a healthy diet. This combination offers the best chance of keeping 5-10% of your weight off permanently.

GLP-1 receptor agonists (semaglutide, tirzepatide) induce significant weight loss and reduce systemic inflammation through both weight-dependent mechanisms and direct anti-inflammatory effects on cytokines (TNF-α, IL-6, CRP) and gut microbiota composition.

GLP-1 agonists like semaglutide and tirzepatide are highly effective for weight loss and reducing inflammation. They work by mimicking a gut hormone to increase satiety and slow digestion, while also directly lowering inflammatory markers. These are prescription medications requiring weekly injections, typically starting at a lower dose and titrating up to minimize side effects.

GLP-1 receptor agonists (liraglutide, semaglutide, tirzepatide) significantly reduce the progression to type 2 diabetes and improve normoglycemia in prediabetic individuals, with effects partially sustained after withdrawal.

For individuals with prediabetes, GLP-1 receptor agonists like liraglutide, semaglutide, and tirzepatide are effective in preventing type 2 diabetes and restoring normal blood sugar levels. While some benefits may diminish after stopping the medication, the initial reduction in diabetes risk is significant.

Incretin-based pharmacotherapy (specifically GLP-1 and GLP-1/GIP agonists like semaglutide and tirzepatide) is effective for significant weight loss and cardiovascular risk reduction in obesity, but discontinuation leads to rapid weight regain and loss of cardiometabolic benefits, necessitating long-term or lifelong therapy.

Incretin drugs like semaglutide and tirzepatide are highly effective for weight loss and heart health, but they are not a cure. If you stop taking them, you will likely regain the weight and lose the heart benefits. Therefore, these medications should be viewed as a long-term or lifelong treatment for obesity, combined with lifestyle changes, rather than a short-term fix.

The median total weight loss percentage after eight weeks was 10.2%.

Practitioners can expect an average weight loss of around 10% in similar programs.

Tirzepatide at maximum tolerated dose (MTD) is more cost-effective and clinically superior to semaglutide at MTD for weight management in US adults with obesity or overweight, resulting in lower total healthcare costs, higher quality-adjusted life years (QALYs), and reduced incidence of type 2 diabetes and cardiovascular disease.

For US adults with obesity or overweight, tirzepatide at its maximum tolerated dose is a more effective and cost-saving option than semaglutide. It leads to greater weight loss, fewer cases of diabetes and heart disease, and significant long-term healthcare cost savings, making it a superior clinical and economic choice when combined with diet and exercise.

Intake of one serving per day of combined plant protein sources (nuts, legumes, and soy) is associated with a lower risk of CHD compared to red meat.

Incorporating plant proteins may be beneficial for heart health.

GLP-1 receptor agonists (semaglutide) and dual agonists (tirzepatide) are clinically effective for glycemic control and significant weight loss, with tirzepatide demonstrating superior magnitude of weight loss compared to semaglutide in head-to-head trials.

GLP-1 and dual agonists are highly effective for weight loss and blood sugar control. Tirzepatide generally produces greater weight loss than semaglutide. However, high costs and insurance restrictions (often requiring prior failure of other drugs like metformin) limit access. Discuss cardiovascular benefits if you have existing heart disease.

Tirzepatide treatment (10-15 mg once weekly) significantly improves waist-to-height ratio (WHtR) categories compared to placebo, with 54.7% of participants improving their WHtR category at 72 weeks versus 9.6% on placebo.

If you have obesity or overweight with related health complications, treatment with tirzepatide (10-15 mg weekly) combined with lifestyle changes significantly improves your waist-to-height ratio, a key marker for cardiometabolic risk, far more effectively than placebo. This suggests a substantial reduction in central adiposity.

Resistance exercise appears effective in reducing Glycated Haemoglobin (HbA1c) in people with type 2 diabetes.

Incorporating resistance exercise may help lower HbA1c levels in diabetic patients.

Current cardiovascular guidelines emphasize lifestyle modifications for weight loss.

Clinicians should incorporate lifestyle changes as a primary strategy for weight loss.

Increased physical activity in the ICU shows a positive effect on muscle mass and function.

Encouraging physical activity in ICU patients may help improve muscle mass and function.

A plant-based diet providing 1.6 g/kg/day of protein induces muscle hypertrophy and strength gains comparable to a mixed diet containing ~80% animal protein when total protein intake is matched.

If you are vegan or prefer plant-based eating, you can build muscle and strength just as effectively as omnivores. The key is to ensure you are consuming enough total protein—specifically around 1.6 grams per kilogram of body weight per day. You can achieve this through whole foods and supplements like soy protein isolate. Do not worry about the 'quality' or 'bioavailability' of plant protein as much as you worry about hitting your daily total protein target.

Muscle strength is a stronger determinant of quality of life and functional decline in older adults than muscle mass, making strength assessment superior to mass assessment for sarcopenia diagnosis.

Focus on maintaining or improving your leg strength (e.g., through resistance training) rather than just worrying about muscle size. Strength is the key metric for staying independent and healthy as you age.

Regular physical exercise is associated with better sarcopenia-related quality of life in PLWH, reducing the odds of poor quality of life.

Engage in regular physical activity to improve your quality of life and functional status, even if it doesn't immediately increase muscle mass. Consistency is key.

Tirzepatide produced a mean weight loss of −7.14 kg in individuals without diabetes and −5.87 kg in individuals with type 2 diabetes (T2D).

Tirzepatide may be an effective option for weight management in both diabetic and non-diabetic obese adults.

Post-menopausal females should ingest at least the RDA of 0.8 g·kg−1·d−1 of protein.

Practitioners should recommend a minimum protein intake of 0.8 g·kg−1·d−1 for post-menopausal women.