Browse the evidence

Tirzepatide, a dual GLP-1/GIP receptor agonist, demonstrates superior kidney and cardiovascular benefits compared to GLP-1 RAs alone, including significant reductions in albuminuria and eGFR decline.

Tirzepatide (Mounjaro/Zepbound) is a newer option that targets both GLP-1 and GIP hormones. It may offer better kidney and heart protection than older GLP-1 drugs. Discuss with your doctor if you have kidney disease, as it can slow kidney function decline significantly. It is also highly effective for weight loss.

Oral ingestion of 15g essential amino acids (EAA) stimulates a greater insulin response compared to intravenous infusion of an equivalent dose, primarily mediated by the incretin hormone GIP, and this mechanism remains intact in older adults.

Consuming 15g of essential amino acids orally triggers a stronger insulin response than injecting the same amount, driven by gut hormones (specifically GIP). This 'incretin effect' helps manage blood sugar and remains effective in older adults, suggesting EAA supplementation can support metabolic health across the lifespan.

GLP-1 receptor agonists (GLP-1RAs) induce significant weight loss, leading to improved physical functioning, daily living capacity, and mental well-being, despite common gastrointestinal side effects.

GLP-1RAs are effective for weight loss and improving daily functioning. Expect gastrointestinal side effects like nausea, which often subside after a few weeks. The benefits of weight loss and improved mobility often motivate patients to persist despite these side effects.

Female patients report greater benefits from GLP-1RA treatment compared to male patients, particularly in mental well-being and physical functioning.

Be aware that female patients may report greater improvements in quality of life and mental well-being from GLP-1RAs than male patients. This is a documented trend in patient experiences.

GLP-1RAs improve the management of sweet cravings and reduce emotional eating.

GLP-1RAs can help reduce sweet cravings and emotional eating, making it easier to maintain weight loss. This is a reported benefit by patients.

Acute exercise triggers the release of 'exerkines' (such as IL-6, BNP, and FGF21) from various tissues, which act as systemic signals to coordinate energy mobilization, metabolic adaptation, and cross-tissue communication.

Understand that your muscles and organs 'talk' to each other during exercise through chemical signals called exerkines. This is why exercise benefits not just the muscles working, but also your heart, brain, and metabolism. Consistent exercise ensures these beneficial signals are regularly released.

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.

Lorcaserin extended release (XR) 20 mg once daily is bioequivalent to lorcaserin immediate release (IR) 10 mg twice daily in terms of total exposure (AUC), offering a convenience advantage with potentially lower peak concentrations (Cmax).

If you are prescribed lorcaserin XR, take 20 mg once a day, with or without food. This formulation is designed to provide the same total amount of medication as the older twice-daily version but with a lower peak concentration, which may reduce side effects like headaches. Consistency is key; take it at the same time each day.

Lorcaserin IR and XR promote weight loss and improve glycemic control in overweight or obese patients with type 2 diabetes when used as an adjunct to lifestyle modifications.

If you have type 2 diabetes and are overweight, lorcaserin (10 mg once or twice daily) can help you lose weight and lower your HbA1c. It works best when combined with diet and exercise. Common side effects like headaches are usually mild.

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.

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.

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.

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.