Browse the evidence

GIP secretion is robustly stimulated by dietary lipids (fats) via GPR40, GPR120, and GPR119 receptors, with fat inducing a threefold higher GIP response compared to an oral glucose tolerance test.

Fats are the most potent natural trigger for GIP secretion, causing levels to rise three times higher than glucose. This secretion depends on specific receptors (GPR40/120/119) and bile acids.

Very Low-Calorie Diets (VLCDs) produce rapid weight loss (15-25% in 3-6 months) but are associated with high attrition and significant weight regain (>50%) at 1-2 year follow-ups.

VLCDs can help you lose weight quickly (15-25% in a few months), but they are hard to sustain. Most people regain more than half the weight within 1-2 years if they don't have a structured plan to transition to normal food and maintain lifestyle changes. Use VLCDs only under medical supervision and as part of a broader program.

A 1-week diet break (increasing carbohydrate intake to energy balance) following intermittent energy restriction improves leg muscle endurance in adult athletes without compromising fat loss goals.

If you are an athlete cutting weight, schedule a 1-week 'diet break' where you eat at maintenance calories (focusing on carbs) every 3-4 weeks. This will not add fat, but it will significantly improve your leg endurance and mental alertness, making your training sessions more effective. Time this break before a key training block or competition.

Time-restricted eating (TRE) improves glucose homeostasis, lipid metabolism, and blood pressure in individuals with metabolic conditions, independent of weight loss.

If you have metabolic risks like prediabetes or high blood pressure, try limiting your daily eating window to 8-10 hours, preferably starting earlier in the day (e.g., 8am-4pm). This timing aligns with your body's natural rhythms and can improve insulin sensitivity and blood pressure, even if your weight doesn't change. Ensure you are eating enough protein within that window to protect muscle mass, especially if you are older.

GLP-1 receptor agonists suppress appetite through a non-aversive neural pathway (NTS GLP1R neurons projecting to PVH) that is distinct from the nausea-inducing pathway (Area Postrema GLP1R neurons projecting to PBN/CeA), allowing for weight loss without nausea.

GLP-1 medications like semaglutide work through two separate brain pathways: one that makes you feel full without feeling sick, and another that causes nausea. You can achieve significant weight loss through the 'fullness' pathway even if you experience some nausea, but the nausea itself isn't required for the fat loss. If nausea is severe, it may indicate you are activating the nausea pathway more than the satiety pathway, and dose adjustments might help optimize the benefit-to-side-effect ratio.

Endoscopic sleeve gastroplasty (ESG) using full-thickness suturing produces significant, durable weight loss (approx. 13-15% total body weight loss at 12 months) and improves metabolic markers, serving as a safer, reversible alternative to bariatric surgery.

If you are looking for a weight loss solution that is less invasive than surgery but more effective than dieting alone, ESG is a viable option. It involves an endoscopic procedure to suture the stomach, creating a sleeve that slows digestion and increases fullness. Expect about 13-15% weight loss over a year, combined with lifestyle changes. It is safer than traditional surgery and reversible.

Older anti-obesity medications (orlistat, naltrexone/bupropion, phentermine/topiramate) produce modest weight loss (5-11%) and are less effective than newer GLP-1/GIP agonists.

Older weight-loss drugs like Orlistat produce modest weight loss (around 7%) and have significant gastrointestinal side effects. They are less effective than newer GLP-1 medications.

Tirzepatide improves islet cell function and insulin sensitivity more effectively than placebo and GLP-1 receptor agonists, evidenced by greater reductions in fasting insulin, C-peptide, glucagon, and HOMA2-IR.

Tirzepatide helps your body use insulin more efficiently than older GLP-1 drugs. This is shown by larger drops in your fasting insulin and blood sugar resistance markers. This improvement in metabolic health is a key benefit of the medication, alongside weight loss.

Metformin is an effective and well-tolerated adjunctive pharmacological intervention for treating and preventing antipsychotic-induced weight gain in patients with severe mental illness.

If you are taking antipsychotics like Clozapine or Olanzapine and gaining weight, ask your doctor about adding Metformin. It is the most studied off-label option for this specific problem. Studies show it helps reduce weight and prevents further gain, though you may experience some stomach issues initially. It is generally well-tolerated compared to other alternatives.

Topiramate is effective for reducing antipsychotic-induced weight gain but is limited by poor tolerability, specifically cognitive difficulties and paresthesia.

Topiramate can help reduce weight gain from antipsychotics, but it is not usually the first choice because it often causes side effects like tingling sensations (paresthesia) and trouble concentrating. It is typically reserved for patients who cannot take Metformin.

Real-world use of tirzepatide for obesity management without type 2 diabetes involves significantly slower dose escalation and lower adherence compared to clinical trial protocols, with most patients remaining on doses ≤10 mg and roughly half discontinuing treatment within six months.

In real-world practice, tirzepatide is often used at lower doses (≤10 mg) than in clinical trials, and about half of patients stop treatment within six months. If you are using it, expect that dose escalation may be slower than recommended, and persistence is a challenge. If you discontinue, switching to another GLP-1 agonist like semaglutide is a common next step.

Plasma Branched-Chain Amino Acid (BCAA) levels are significantly associated with lower body fat percentage and higher lean mass percentage in sedentary adults undergoing protein supplementation and exercise.

Higher levels of BCAA in your blood are linked to less body fat and more lean muscle in people who supplement protein and exercise. This suggests that ensuring adequate BCAA intake (via protein) is important for optimizing body composition.

The unregulated online sale of sports supplements poses a significant public health risk due to the prevalence of adulterated products containing undeclared prohibited substances.

Be extremely cautious when buying supplements online. The market is poorly regulated, and products may contain undeclared drugs. Look for third-party testing seals or buy from reputable physical stores with known supply chains to avoid contamination.

Anti-obesity medications (AOMs) are significantly underutilized in clinical practice, with only 1.4% of eligible patients receiving prescriptions despite nearly half of the adult population meeting eligibility criteria.

If you are eligible for anti-obesity medications based on your BMI and health conditions, you are not currently receiving them in most cases. This is not necessarily a reflection of your health status but a systemic gap in care. Discussing these options with your provider and understanding insurance coverage is essential, as prescription rates remain extremely low despite high eligibility.

High-dose chronic NSAID (ibuprofen) administration blunts muscle hypertrophy and strength gains in young adults undergoing resistance training, likely by inhibiting the COX pathway and prostanoid synthesis required for satellite cell activity and myonuclear accretion.

If your goal is maximum muscle growth, avoid taking high-dose NSAIDs like ibuprofen (1200mg/day) daily during your training blocks. While they reduce pain, they likely blunt your muscle gains by interfering with the biological signals needed for repair. Save them for occasional use if necessary, but do not rely on them as a daily recovery tool.

Carrying the TCF7L2 rs7903146 T risk allele confers a modestly greater benefit for diet/lifestyle interventions in improving fasting glucose control in overweight or obese adults compared to non-carriers.

If you have a family history of type 2 diabetes, you likely carry the TCF7L2 risk variant. This paper suggests that standard diet and lifestyle changes (like those used in the included trials) may be particularly effective for you in lowering fasting glucose levels compared to those without the variant. Focus on consistent dietary quality and physical activity, as your body may be primed to benefit significantly from these changes in terms of blood sugar regulation.

Nine weeks of set-volume equated hip thrust training produces gluteus maximus hypertrophy equivalent to back squat training, despite higher acute gluteal muscle activation during hip thrusts.

If your goal is glute growth, you can use either hip thrusts or back squats. They produce similar muscle growth when you do the same number of sets and reps. Don't feel pressured to only do hip thrusts just because they 'feel' like more glute work; squats are equally effective for building the glutes over time.

Hip thrust training transfers to deadlift strength gains similarly to back squat training.

If you are trying to get stronger at the deadlift, doing hip thrusts will help just as much as doing squats. You don't need to do deadlifts exclusively to improve your deadlift.

In patients with type 2 diabetes, initiating GLP-1 receptor agonists (GLP-1RA) is associated with a significantly higher risk of gastroparesis compared to initiating SGLT2 inhibitors or insulin glargine, while insulin glargine is associated with a higher risk of all-cause mortality compared to GLP-1RA.

If you have type 2 diabetes and are considering a GLP-1RA (like semaglutide or dulaglutide), be aware that these drugs can slow down your stomach emptying, increasing the risk of gastroparesis. This risk is higher with GLP-1RA than with SGLT2 inhibitors (like empagliflozin) or insulin glargine. However, GLP-1RA is associated with a lower risk of death compared to insulin. If you are already at risk for gastroparesis, talk to your doctor about SGLT2 inhibitors as a first-line alternative to GLP-1RA.

Emerging pharmacotherapies, specifically GLP-1 receptor agonists and multi-agonists, induce 15-25% weight loss, challenging the necessity of bariatric surgery for patients with BMI 30-40 kg/m2.

If you have obesity (BMI 30-40) and are considering surgery, discuss GLP-1 based medications (like semaglutide or tirzepatide) with your doctor. These drugs can produce 15-25% weight loss, which is comparable to surgery, offering a non-surgical option with significant metabolic benefits.

Current bariatric surgery guidelines (BMI >= 35, or 30-34.9 with comorbidities) may need re-evaluation due to the efficacy of pharmacotherapy.

If your BMI is between 30 and 40, you may not need surgery. Ask your doctor about GLP-1 medications, which are now effective enough to potentially replace surgery for many patients.

Women experience a significantly lower efficacy-to-tolerability ratio than men when treated with GLP-1 receptor agonists, characterized by disproportionately higher rates of persistent nausea and vomiting relative to weight loss.

If you are a woman taking a GLP-1 medication like semaglutide or tirzepatide, you are statistically more likely to experience nausea and vomiting than a man taking the same drug, even if you lose more weight. This is not a failure of willpower but a biological difference in how your body processes the drug, likely driven by estrogen levels. Discussing this with your provider may lead to strategies like slower dose escalation or phase-specific dosing to manage side effects.

Once-weekly insulin icodec provides glycemic control similar to once-daily insulin glargine with comparable hypoglycemia rates, potentially improving patient acceptability through reduced injection frequency.

If daily injections are burdensome, ask your doctor about once-weekly insulin icodec. It works as well as daily insulin for blood sugar control and has similar side effects, but offers the convenience of fewer injections.

Parents with children under 18 lose significantly less weight than nonparents in intensive behavioral lifestyle interventions, with the disparity being most pronounced in African American females.

If you are a parent participating in a weight loss program, expect that you may lose less weight than peers without children, even if you try just as hard. This is not a failure of your willpower but a result of logistical barriers and home food environment challenges. To improve outcomes, seek programs that offer flexible scheduling, childcare support, or strategies specifically designed to manage the conflict between children's food preferences and your dietary goals.