Browse the evidence

Morbid obesity (BMI ≥40 kg/m2) in young adults (16-49 years) is associated with a massive loss of future life years (8.3 years) and high mortality risk, with 72% of deaths in this demographic linked to obesity.

For young adults with morbid obesity (BMI ≥40), the health risks are severe and immediate in terms of life expectancy. This group loses an average of 8.3 years of life, with 72% of deaths linked to obesity. Early intervention is critical to prevent premature mortality.

GLP-1 agonists (e.g., semaglutide, liraglutide) and metformin can aid in weight management, but GLP-1 agonists do not reset the weight set point, leading to significant weight regain upon discontinuation.

GLP-1 agonists and metformin can help with weight loss, but they do not cure the underlying biological tendency to regain weight. If you use them, expect to use them long-term to maintain results. They are tools to manage weight, not a one-time fix.

BCAA supplementation significantly increases strength gains (specifically bench press and squat 1RM) in men undergoing resistance training, with greater magnitude than in women.

If you are a male recreational weightlifter, adding a BCAA supplement (2.5g Leucine, 1.25g Isoleucine, 1.25g Valine daily) to your 4-day/week resistance training program may help you lift more weight, particularly in the bench press and squat, compared to training without it. This benefit appears stronger in men than in women.

In healthy young humans, changes in skeletal muscle mass in response to resistance exercise, disuse, and aging are primarily driven by alterations in muscle protein synthesis (MPS), while muscle protein breakdown (MPB) remains largely unchanged or plays a negligible role.

To maintain or build muscle, prioritize resistance exercise and protein intake to stimulate muscle protein synthesis. You do not need to worry about 'blocking' muscle breakdown as a primary strategy, as your body naturally regulates this, and forcing suppression may be counterproductive. Consistent loading is the key lever.

Deuterated water (D2O) ingestion is a valid and increasingly used method for measuring long-term muscle protein synthesis in humans, providing insights that complement acute tracer infusion methods.

For researchers, D2O is a reliable tool for measuring long-term muscle protein synthesis. For practitioners, this validates that consistent, long-term training and nutrition strategies are what drive muscle changes, rather than just acute post-workout spikes.

In aging skeletal muscle, the progressive loss of mass (sarcopenia) is largely driven by anabolic resistance—a desensitized muscle protein synthesis response to stimuli like loading and protein ingestion—rather than increased protein breakdown.

Older adults should prioritize resistance training and adequate protein intake to overcome anabolic resistance. While muscle loss is slower with age, maintaining activity levels can prevent many age-related muscle deficits.

Patients with specific comorbidities, specifically dyslipidaemia and obstructive sleep apnoea (OSA), have significantly higher odds of receiving both anti-obesity medication (AOM) prescriptions and metabolic and bariatric surgery (MBS).

Having comorbidities like high cholesterol or sleep apnea can increase your chances of being prescribed obesity treatments. If you don't have these, you may face more hurdles. Discuss your overall metabolic health with your provider, as obesity itself is a valid reason for treatment.

GLP-1 receptor agonists significantly reduce binge eating behaviors and alcohol consumption, offering therapeutic potential for substance use disorders and eating disorders independent of weight loss.

If you struggle with binge eating or alcohol use, GLP-1 medications might help reduce these cravings directly, not just by making you lose weight. Clinical trials show significant improvements in binge eating scores and reduced alcohol intake. This suggests the drug affects the brain's reward system, offering a new tool for managing these specific behaviors.

In drug-naive patients with prediabetes, initiating GLP-1 RA as first-line therapy significantly reduces the 1-year risk of requiring additional glucose-lowering medication compared to metformin, but is associated with a significantly higher risk of treatment nonadherence.

For patients with prediabetes, GLP-1 RA is more effective than metformin at preventing the need for extra diabetes medications over one year. However, patients are more likely to stop taking GLP-1 RA than metformin. Clinicians should proactively manage expectations regarding side effects and adherence to maximize the benefit.

In drug-naive patients with diabetes, initiating GLP-1 RA as first-line therapy reduces the 1-year risk of requiring additional glucose-lowering medication compared to metformin, with no significant difference in adherence rates.

For patients with diabetes, GLP-1 RA is more effective than metformin at preventing the need for extra diabetes medications over one year, with similar adherence rates. This makes GLP-1 RA a strong first-line option for diabetes management.

Self-reported dietary intake methods (Remote Food Photography Method) significantly underestimate energy intake compared to doubly labelled water (DLW) derived estimates, leading to an overestimation of the prevalence of Low Energy Availability (LEA) in female soccer players.

If you are a female soccer player or coach using food photography or logs to track energy availability, be aware that you are likely under-reporting intake by about 22%. This means you might think you have Low Energy Availability (a risk factor for injury and hormonal issues) when you actually don't. Do not make drastic dietary changes based solely on self-reported data without considering this potential under-reporting bias.

Increasing cardiorespiratory fitness and losing body mass index (BMI) independently and synergistically slow the progression of deficit accumulation frailty (a marker of biological aging) in adults with type 2 diabetes and overweight/obesity.

If you have type 2 diabetes and are overweight, focusing on improving your aerobic fitness (like brisk walking for >175 minutes a week) and losing weight (targeting >7% loss) can significantly slow biological aging. These two actions work independently: improving fitness helps even if you don't lose much weight, and losing weight helps even if your fitness doesn't change much. Doing both provides the greatest benefit. This applies even if you are over 65.

Long-term pharmacotherapy for obesity requires medications with proven efficacy and safety, as lifestyle modification alone is often insufficient for sustained weight loss.

If lifestyle changes alone aren't enough, consult a doctor about long-term obesity medications. These drugs are designed for sustained use and can help manage weight effectively, but they come with side effects and costs that need to be managed.

Older anti-obesity medications (Orlistat, Naltrexone/Bupropion, Phentermine/Topiramate, Liraglutide) have limited efficacy compared to newer GLP-1/GIP agonists.

Older obesity medications provide moderate weight loss (8-10%). They are established options but are less effective than the newest injectable treatments.

Tirzepatide treatment (5-15 mg weekly for 72 weeks) significantly improves both insulin sensitivity and beta-cell function in adults with obesity or overweight (BMI ≥27 kg/m2) with prediabetes or normoglycemia, independent of type 2 diabetes.

If you have obesity or are overweight and have prediabetes or normal blood sugar, tirzepatide (a once-weekly injection) can significantly improve how your body handles insulin and how well your pancreas functions. This happens partly because you lose weight, but also directly from the medication itself, potentially lowering your risk of developing type 2 diabetes.

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.

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.