Browse the evidence

Obesity pharmacotherapy (GLP-1/GIP agonists) reduces body weight with minimal loss of lean mass and improves cardiovascular outcomes, potentially mitigating the adverse effects of intermittent fasting.

If you are considering obesity pharmacotherapy (like GLP-1 agonists), know that it can lead to significant weight loss (up to 21% in some trials) with minimal loss of muscle mass, which is a key advantage over intermittent fasting. It also reduces cardiovascular risk. However, long-term safety is still being studied, and combining it with lifestyle changes (diet and exercise) is recommended for the best outcomes.

GLP-1 receptor agonists (e.g., Liraglutide, Semaglutide) and dual/triple agonists are highly effective for weight loss and diabetes remission, acting on both homeostatic and hedonic appetite pathways, but require continuous use to maintain effects.

GLP-1 medications (like Semaglutide or Liraglutide) are highly effective for significant weight loss and diabetes remission, often working better than diet alone. They work by reducing both physical hunger and the 'craving' for food. However, they must be taken continuously; stopping them usually leads to weight regain. Discuss with your doctor if you are a candidate, considering the cost and injection requirement.

Dual GLP-1/GIP receptor agonists (e.g., tirzepatide) achieve weight loss magnitudes (15-20%) comparable to bariatric surgery, significantly outperforming older pharmacotherapies and single-agonist GLP-1s.

If you have obesity, newer dual-agonist medications (like tirzepatide) are currently the most effective non-surgical treatment available, offering weight loss results similar to bariatric surgery. They work by targeting multiple hormonal pathways to reduce appetite and improve metabolism. Consult a doctor to see if you qualify based on your BMI and comorbidities.

Retatrutide, a triple agonist of GLP-1, GIP, and glucagon receptors, produces significant, dose-dependent reductions in body weight, BMI, and metabolic markers in obese adults with or without type 2 diabetes.

Retatrutide is a weekly injection that significantly reduces body weight (average ~14%) and improves metabolic health in obese adults, including those with type 2 diabetes. It works by targeting three hormone receptors (GLP-1, GIP, glucagon) to reduce appetite and improve insulin sensitivity. Higher doses (8-12 mg) generally produce greater weight loss. Common side effects include nausea and vomiting, which are often manageable. It is a prescription medication requiring medical supervision.

In real-world clinical practice, tirzepatide produces significantly greater weight loss and higher rates of achieving 5%, 10%, and 15% weight reduction thresholds compared to semaglutide in adults with overweight or obesity.

If you are choosing between semaglutide and tirzepatide for weight loss, real-world data suggests tirzepatide is likely to produce roughly double the weight loss at one year compared to semaglutide. You are also significantly more likely to hit major weight loss milestones (5%, 10%, 15%) with tirzepatide. However, this comes with the caveat that these specific findings are based on formulations labeled for Type 2 Diabetes, and insurance coverage may be more difficult to obtain for tirzepatide than semaglutide.

Weekly subcutaneous VK2735, a GIP/GLP-1 receptor dual agonist, produces significant, dose-dependent weight loss in adults with obesity or overweight (≥1 comorbidity) over 13 weeks, with the 15 mg dose achieving a mean 14.7% reduction.

Take VK2735 once weekly as prescribed. Start with the lowest dose (2.5 mg) and follow the titration schedule to minimize side effects. Combine with a 500 kcal daily caloric deficit and 150 minutes of exercise per week for best results. Expect significant weight loss (up to 14.7% at 15 mg) within 13 weeks, with side effects like nausea typically subsiding after the titration phase.

Newer obesity management medications (OMMs), specifically semaglutide (2.4 mg) and tirzepatide (10-15 mg), demonstrate high efficacy comparable to metabolic bariatric surgery (MBS) in the short term (26-52 weeks), with tirzepatide achieving >15% TBWL.

For those seeking non-surgical weight loss, newer medications like semaglutide (2.4 mg) and tirzepatide (10-15 mg) are the most effective options available, with tirzepatide showing short-term weight loss (15.2%) comparable to surgical procedures. These require weekly administration and are generally more effective than older medications like orlistat. They are best used in conjunction with lifestyle interventions.

Higher dietary fiber intake is inversely associated with body weight gain, fasting insulin, and cardiovascular disease risk factors in young adults, independent of fat and carbohydrate intake.

To support healthy weight and metabolic function, prioritize high-fiber foods. This study suggests that higher fiber intake is linked to lower body weight, lower insulin levels, and better cardiovascular markers, independent of how much fat or carbohydrate you eat. Focus on getting enough fiber rather than strictly limiting fat or carbs.

Regular physical activity improves whole-body insulin sensitivity (SI) through both acute mechanisms (AMPK/TBC1D1-mediated GLUT4 translocation during exercise) and chronic adaptations (increased capillarization and beta-cell function), with high-intensity interval training (HIIT) and sprint interval training (SIT) offering superior or time-efficient benefits compared to moderate continuous exercise.

To improve insulin sensitivity, aim for regular physical activity. While moderate continuous exercise is effective, incorporating High-Intensity Interval Training (HIIT) or Sprint Interval Training (SIT) may offer time-efficient benefits, especially for those with prediabetes or obesity. Consistency is key, as acute improvements in insulin sensitivity can last up to 72 hours but are lost if exercise stops for 5 days. Focus on both aerobic and resistance exercises for comprehensive glycaemic regulation.

Increasing dietary fibre intake significantly improves glycaemic control, reducing HbA1c by a mean difference of -2.00 mmol/mol and fasting plasma glucose by -0.56 mmol/L in adults with diabetes.

If you have diabetes, increasing your fibre intake can help lower your HbA1c and fasting blood sugar. You do not need to cut out carbohydrates; instead, choose carbohydrate sources that are high in fibre, such as whole grains and vegetables.

Replacing processed carbohydrates (high GI/GL grains, potatoes, added sugars) with unprocessed carbohydrates (whole grains, legumes, whole fruits) or healthy fats reduces the risk of obesity, type 2 diabetes, and cardiovascular disease.

Focus on the quality of your carbohydrates rather than just cutting them out. Swap refined grains, potatoes, and sugary drinks for whole grains, legumes, and whole fruits. This shift is strongly linked to better metabolic health and lower disease risk.

Tirzepatide demonstrates greater comparative weight loss and metabolic benefits than semaglutide in real-world observational studies, particularly in patients without pre-existing diabetes.

If you are using Semaglutide and not achieving your weight loss goals, switching to Tirzepatide may result in greater weight loss and better metabolic outcomes, especially if you do not have Type 2 Diabetes. Real-world data suggests Tirzepatide is more potent than Semaglutide in routine practice.

Sleep restriction (4 hours time-in-bed for five nights) significantly reduces myofibrillar protein synthesis (MyoPS) rates in healthy young men, but performing high-intensity interval exercise (HIIE) during this period maintains MyoPS at control levels.

If you are experiencing sleep restriction (e.g., 4 hours of sleep for several nights), your body's ability to build muscle protein drops significantly. However, doing High-Intensity Interval Exercise (HIIE) during this period can keep your muscle protein synthesis rates normal. Do not skip exercise when you are sleep-deprived; instead, consider HIIE as a tool to protect your muscle mass.

Low carbohydrate dietary approaches (LCDs) are as effective as or superior to other dietary approaches for managing Type 2 diabetes, particularly by reducing the requirement for glucose-lowering medications.

Adopt a low carbohydrate diet (under 130g carbs/day) to manage Type 2 diabetes. This approach is supported by evidence as being as effective or superior to standard low-fat diets, with the added benefit of significantly reducing the need for diabetes medications. Work with your doctor to reduce medications, especially insulin, as your blood glucose improves to avoid hypoglycemia.

ADORA2A C allele carriers (CT/CC genotype) experience significant ergogenic improvements in resistance exercise power, velocity, and endurance following acute caffeine supplementation, refuting prior claims that they are non-responders.

If you have the ADORA2A C allele (CT or CC genotype), you can still use caffeine to boost your workout performance. Take 3 mg per kg of body weight about an hour before training. You will likely see improvements in strength, power, and endurance similar to those without this genetic variant. Do not avoid caffeine based on the myth that you are a non-responder.

GLP-1/GIP co-agonists (e.g., tirzepatide) induce greater weight loss and have a more favorable gastrointestinal tolerability profile compared to GLP-1 monotherapy (e.g., semaglutide or liraglutide).

If you are considering GLP-1 therapy for obesity, discuss the potential benefits of dual agonists like tirzepatide with your provider. They may offer greater weight loss and potentially fewer gastrointestinal side effects compared to GLP-1 monotherapy, although individual responses vary.

Resistance exercise sensitizes skeletal muscle to amino acids for 24-48 hours, allowing a moderate protein dose (~20g) to maximally stimulate muscle protein synthesis (MPS) without requiring higher doses.

After your resistance training session, consume ~20 grams of high-quality protein (like whey, eggs, or meat). This amount is sufficient to maximally trigger muscle growth. You do not need to force-feed yourself 40-50g post-workout for better results; save those extra calories for your total daily intake.

Regular physical exercise reduces liver fat and improves insulin sensitivity in NAFLD/MAFLD patients, independent of weight loss, by enhancing skeletal muscle metabolic flexibility and glucose disposal.

Engage in regular physical activity, such as aerobic or resistance exercise, to reduce liver fat and improve insulin sensitivity. You do not need to lose weight for this benefit to occur, although weight loss can help. Consistency is key, as benefits are lost quickly if you stop exercising. If structured gym time is hard to maintain, increasing everyday movement (like walking) can also provide metabolic benefits.

Semaglutide 2.4 mg/week induces significant weight loss in patients with severe obesity, including those with a history of bariatric surgery, achieving outcomes comparable to or exceeding those of non-surgical patients.

If you have severe obesity, even if you have had weight loss surgery before, a weekly injection of 2.4 mg semaglutide can still help you lose weight. It is not a wasted effort due to your surgical history.

Long-term use of GLP-1 receptor agonists (semaglutide 2.4mg or tirzepatide 15mg) produces significant weight loss (4-21%) and improved cardiometabolic markers, but discontinuation leads to rapid weight regain and increased cardiac risk.

GLP-1 agonists like Wegovy and Mounjaro are highly effective for significant weight loss (up to 20%) when taken long-term. However, they are not a 'cure'; stopping the medication typically results in weight regain and increased heart disease risk. If you use these, view them as a long-term tool alongside lifestyle changes, not a quick fix.

Semaglutide (GLP-1 receptor agonist) produces significant weight loss (15.5% in adolescents, 12.5% in adults) and cardiovascular benefits, making it a prioritized treatment for those with metabolic risk factors.

Semaglutide is a highly effective weekly injection that can lead to significant weight loss (12-15%) and cardiovascular benefits. It is particularly recommended for those with metabolic risks or low satiety.

A ketogenic diet (carbohydrate restriction <50g/day) promotes weight loss and visceral adiposity reduction by inducing nutritional ketosis, which suppresses appetite via beta-hydroxybutyrate (BHB) signaling and increases energy expenditure through fat oxidation.

To use this diet, restrict carbohydrates to under 50 grams per day (under 20g for therapeutic effects). Focus on healthy fats and moderate protein. Expect initial weight loss and reduced hunger due to ketone production. Monitor your progress with blood ketone levels (0.5-3.0 mmol/L) to ensure you are in ketosis.

Ketogenic diets improve glycemic control in Type 2 Diabetes patients by reducing carbohydrate intake, thereby lowering insulin levels and HbA1c, and reducing the need for insulin medication.

If you have Type 2 Diabetes, restricting carbs to under 30g/day can significantly lower your HbA1c and reduce your need for insulin. Work with your doctor to adjust medications as your blood sugar improves.

Tirzepatide, a dual GIP/GLP-1 receptor agonist, significantly reduces body weight (exceeding 20% in some contexts) and improves glycemic control (HbA1c) in patients with Type 2 Diabetes and Obesity when administered via subcutaneous injection once weekly.

Tirzepatide is a once-weekly subcutaneous injection approved for Type 2 Diabetes and Obesity. It works by mimicking two gut hormones (GLP-1 and GIP) to improve insulin sensitivity and reduce appetite. Clinical trials show it leads to significant weight loss (often >20%) and better blood sugar control than some existing drugs like semaglutide. Common side effects like nausea are usually temporary and managed by starting with a low dose and increasing slowly. It is not a standalone cure but works best with lifestyle changes.