Browse the evidence

GCGR-based multi-agonists (mazdutide, pemvidutide, survodutide, retatrutide) produce significantly greater weight loss than existing GLP-1 or GLP-1/GIP therapies by synergistically combining appetite suppression with increased energy expenditure.

If you have obesity and struggle with weight loss despite lifestyle changes, GCGR-based multi-agonists (like mazdutide, retatrutide, etc.) are emerging as highly effective treatments. They work by targeting multiple hormonal pathways to suppress appetite and increase energy expenditure, often resulting in greater weight loss than current GLP-1 drugs. While they are injectable and can cause GI side effects, starting with lower doses and titrating up can help manage these effects. Consult a healthcare provider to see if you are a candidate, especially if you have comorbidities like T2DM or CV disease.

Combining a Very Low-Calorie Ketogenic Diet (VLCKD) with liraglutide produces significantly greater weight loss and metabolic improvements compared to VLCKD alone, primarily through synergistic appetite suppression.

If you are struggling to lose weight with a very low-calorie ketogenic diet alone, adding liraglutide can significantly boost your results. In this study, adding the drug led to nearly 6kg more weight loss over 4 months. Be aware that you are much more likely to experience nausea or constipation, but for most participants, this did not stop them from completing the program. Consult a doctor to see if this combination is safe and appropriate for you, especially given the cost and side effect profile.

Regular aerobic exercise significantly improves cardiac function and reduces blood pressure in patients with cardiovascular disease and hypertension.

If you have high blood pressure or heart issues, start with moderate aerobic exercise like brisk walking or cycling. Aim for 3-5 days a week, doing 20-60 minutes at a time. Keep the intensity at 50-80% of what you can tolerate. This routine can lower your blood pressure by 5-17 mmHg, which is comparable to some medications. Always consult your doctor before starting.

Tirzepatide induces rapid, clinically significant weight loss and fat mass reduction within 30 days while preserving fat-free mass in adults with overweight or obesity.

If you are starting tirzepatide for obesity, expect to lose about 4 kg in the first month, mostly from fat stores rather than muscle. This happens even if you are still in the early dose-escalation phase. Adhering to the prescribed lifestyle changes (Mediterranean diet and walking) is part of the protocol, but the drug itself drives significant early fat loss. This rapid initial response can help maintain motivation for long-term treatment.

Treating 50% of moderate- to high-risk obesity patients (Class II and III, excluding diabetes) with 2.4 mg weekly semaglutide plus lifestyle intervention for 68 weeks reduces population prevalence of these obesity classes and yields significant annual societal cost savings.

For healthcare policymakers and insurers, implementing widespread access to 2.4 mg weekly semaglutide for moderate-to-high risk obesity (excluding diabetics) alongside lifestyle programs can significantly reduce the prevalence of severe obesity and save billions in societal costs over time. This requires ensuring affordability and addressing long-term adherence.

GLP-1 agonists (e.g., semaglutide) and abstinence-based dietary interventions (Bright Line Eating) are the most effective non-surgical weight loss methods because they directly target the neurological addiction to ultra-processed foods.

If you struggle with food addiction, standard dieting will likely fail. Consider treatments that address the biological addiction, such as GLP-1 agonists or strict abstinence-based programs like Bright Line Eating, which have shown higher sustained success rates by targeting the root neurological drivers.

For patients with Type 2 Diabetes and BMI ≥35 kg/m², referral to multidisciplinary obesity services or bariatric surgery is clinically indicated and superior to standard specialist diabetes clinic management for achieving glycaemic targets and remission.

If you have Type 2 Diabetes and a BMI over 35, standard medication adjustments are often not enough to reach healthy blood sugar levels. You meet the criteria for bariatric surgery or specialized obesity programs, which are proven to help achieve remission. You should actively ask your specialist for a referral to these services, as they are often under-utilized due to systemic barriers.

Low-load resistance training (40% 1RM) performed to failure produces significant muscle hypertrophy and strength gains regardless of whether rest intervals are short (30s) or long (150s).

You do not need to rush your rest periods when using lighter weights (40% of your max). Whether you rest 30 seconds or 2.5 minutes between sets, as long as you take the set to failure, your muscle growth and strength gains will be the same. Use the rest time that allows you to maintain good form and feel less fatigued.

Retatrutide, a triple hormone agonist (GLP-1, GIP, glucagon), administered subcutaneously once weekly, produces substantial, progressive weight loss (up to 24.2%) and HbA1c reduction in adults with obesity and type 2 diabetes, significantly outperforming placebo and, in some metrics, the dual agonist tirzepatide.

Retatrutide is a once-weekly injection that combines three hormones to help you lose significant weight and lower blood sugar. It works best if you start with a low dose and increase it slowly to manage stomach side effects. While it causes more nausea than other drugs, it leads to greater weight loss, potentially helping you reach a level of weight loss that can put type 2 diabetes into remission. You should expect regular check-ins and lifestyle counseling alongside the medication.

GLP-1 receptor agonists and co-agonists induce significant weight loss (10–25%) in adults without diabetes, with newer multi-agonists (e.g., tirzepatide, retatrutide) demonstrating superior efficacy compared to earlier single-agonists.

If you have obesity or overweight with related health issues, GLP-1 medications (like semaglutide or tirzepatide) are now a standard, effective treatment option that can produce significant weight loss (10-25%), comparable to surgery. Newer oral options exist, and these drugs work independently of diabetes status. Consult a doctor to see if you qualify, as they are typically reserved for those who haven't succeeded with lifestyle changes alone.

Retatrutide (LY3437943) administered subcutaneously once weekly produces significant, dose-dependent weight loss and improved glycaemic control in adults with obesity or type 2 diabetes, outperforming placebo and dulaglutide at higher doses (8-12 mg).

Retatrutide is a once-weekly injection that significantly reduces body weight (up to 26 kg in trials) and improves blood sugar control in people with obesity or type 2 diabetes. It works by targeting three hormone receptors (GIP, GLP-1, Glucagon). Higher doses (8-12 mg) are more effective but may cause mild gastrointestinal side effects that usually improve over time. It appears more effective than some existing treatments like dulaglutide for weight loss.

Tirzepatide treatment in patients with obesity and type 1 diabetes results in significant weight loss (median 8.5-12.2%) and reduced insulin requirements without increasing hypoglycemia or serious adverse events.

If you have Type 1 Diabetes and obesity, Tirzepatide is a viable option for weight loss and reducing insulin needs. Start with a low dose (2.5mg) and increase slowly to minimize nausea. You must work with your doctor to adjust your insulin doses to prevent hypoglycemia. Combine the medication with a modest calorie deficit and regular exercise for best results.

Phenotype-guided prescribing of anti-obesity medications (matching drug to underlying pathophysiology like 'hungry brain' or 'hungry gut') results in significantly greater weight loss compared to standard non-phenotype-guided care.

If standard weight loss medications aren't working well, ask your doctor about 'phenotype-guided' prescribing. This involves identifying whether your obesity is driven by 'hungry brain' (satiety issues), 'hungry gut' (satiety signals), 'emotional hunger', or 'slow burn' (metabolism). Matching the right drug (like Phentermine/Topiramate for hungry brain or Liraglutide for hungry gut) to your specific type can nearly double your chances of losing more than 10% of your body weight compared to standard care.

Pharmacologic weight loss medications, particularly FDA-approved anti-obesity agents (GLP-1 agonists, phentermine, lorcaserin), are safe and effective for inducing weight loss in patients with cirrhosis without worsening liver disease severity (MELD score).

For patients with cirrhosis and obesity, current guidelines limit treatment to lifestyle changes due to safety concerns. However, this study indicates that FDA-approved weight-loss medications (like GLP-1 agonists) and other weight-loss associated drugs (like metformin) can be used safely in patients with advanced liver disease. These medications resulted in significant weight loss (average 7.22 kg for FDA-approved drugs) without worsening liver disease markers (MELD score) or increasing hospitalizations. Patients should discuss these options with their hepatologist, as individual safety profiles vary, and some medications may require dose adjustments or avoidance in severe hepatic impairment.

Tirzepatide, a dual GIP and GLP-1 receptor agonist, produces substantial, clinically meaningful, and sustained weight reduction in adults with obesity (BMI ≥30 or ≥27 with comorbidities) when used as an adjunct to lifestyle intervention, demonstrating superior efficacy compared to selective GLP-1 receptor agonists.

If you have obesity (BMI ≥30, or ≥27 with health issues like high blood pressure or sleep apnea), tirzepatide is a once-weekly injection that works by mimicking gut hormones (GIP and GLP-1) to help you lose weight. It is used alongside a reduced-calorie diet and exercise. The dose starts low (2.5 mg) and increases every 4 weeks to minimize stomach issues, reaching up to 15 mg. Clinical trials are designed to show it causes more weight loss than older drugs like semaglutide.

Combination anti-obesity medications (AOMs) are more effective than monotherapy for treating weight regain after bariatric surgery, with patients prescribed three or more AOMs losing significantly more weight than those on one.

If you have regained weight after bariatric surgery, taking just one weight-loss medication may not be enough. This study suggests that using a combination of anti-obesity medications, along with lifestyle changes, leads to significantly greater weight loss than using a single medication. Talk to your doctor about whether a combination approach is right for you, keeping in mind that access and cost can be barriers.

Long-term treatment with semaglutide 2.4 mg (up to 68 weeks) produces significant weight loss (mean 14.5-14.8%) and improves cardiometabolic biomarkers (blood pressure, HbA1c, LDL, triglycerides) in real-world patients with obesity or overweight.

If you have obesity or overweight with a related health condition, semaglutide 2.4 mg taken once weekly can lead to significant weight loss (around 15% of body weight) and improvements in blood pressure, blood sugar, and cholesterol over a year. This is based on real-world data from thousands of patients, suggesting it works effectively outside of strict clinical trial settings. You must be willing to stay on the medication for at least a year to see these full benefits.

In overweight or obese adults, tirzepatide produces significantly greater weight loss than semaglutide over a 6-month period, particularly in patients without diabetes.

If you are overweight or obese and considering medication, tirzepatide appears to offer greater weight loss benefits than semaglutide over a 6-month period, especially if you do not have diabetes. However, real-world effectiveness can vary based on adherence and cost, so discuss these factors with your provider.

Adhering to a low carbohydrate diet (LCD) for six months significantly increases the rate of type 2 diabetes remission compared to control diets, with moderate certainty evidence.

If you have type 2 diabetes, switching to a low carbohydrate diet (less than 130g carbs per day) for six months can significantly increase your chances of reversing the condition. This benefit is most pronounced if you are not currently using insulin, though improvements are still seen in insulin users. Work with your doctor to monitor your progress and adjust medications as needed.

Low-carbohydrate and ketogenic diets improve glycemic control and reduce body weight in patients with type 2 diabetes, with ketogenic diets showing stronger effects than low-carb diets.

If you have Type 2 Diabetes, reducing carbohydrates (especially to <50g/day for a ketogenic diet) can significantly improve blood sugar control and help with weight loss. This often allows for a reduction in diabetes medication. However, you must be monitored by a healthcare provider, especially if you take SGLT-2 inhibitors, due to the risk of ketoacidosis. Focus on long-term sustainability and individual tolerance.

Adopting a low-carbohydrate or ketogenic diet improves glycemic control, promotes weight loss, and reduces medication requirements in patients with type 2 diabetes and obesity.

If you have type 2 diabetes or obesity, reducing carbohydrates (especially to <130g/day, or <50g/day for ketosis) is a valid medical strategy. You must work with your doctor to reduce diabetes medications (especially insulin and sulphonylureas) immediately to avoid low blood sugar. Focus on eating until you are full rather than counting calories, as this diet naturally reduces hunger.

Initiating time-restricted eating (≤10h daily window) and high-intensity interval training (HIT) during the preconception period improves maternal insulin sensitivity and glycaemic control, thereby reducing the risk of gestational diabetes and adverse offspring metabolic outcomes.

Start optimizing your metabolic health before you conceive. Adopt a daily eating window of 10 hours or less to improve insulin sensitivity. Incorporate 2-3 short sessions of high-intensity interval training per week (e.g., 4-10 bursts of effort separated by rest). If pregnant, shorten the work bouts to under 60 seconds to ensure fetal safety. Focus on improving insulin sensitivity rather than rapid weight loss.

Regular physical activity, including both aerobic and resistance training, improves metabolic and reproductive features in PCOS independent of significant weight loss.

Aim for 150 minutes of moderate activity (like brisk walking) or 75 minutes of vigorous activity per week, plus two days of muscle-strengthening exercises. You don't need to lose weight to see metabolic benefits from exercise. Start with 10-minute bouts and gradually increase duration by 5% each week.

High-dose mazdutide (9-10 mg once-weekly) produces robust, statistically significant body weight loss (approx. 10-12%) in Chinese adults with overweight or obesity, with a favorable safety profile despite transient gastrointestinal side effects.

If you are an adult with overweight or obesity, once-weekly injections of mazdutide (9-10 mg) can lead to significant weight loss (around 10%) over 3-4 months. While you may experience temporary stomach issues like nausea or diarrhea, these usually improve over time. This treatment is most effective when combined with maintaining your current diet and exercise habits.