Browse the evidence

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.

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.

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.

Changes in soluble LDL receptor (sLDLR) levels are strongly associated with changes in atherogenic lipoprotein phenotype (ALP) markers, including triglycerides, VLDL, and small LDL particles, independent of diet type (low-carbohydrate vs. low-fat) and BMI change.

This research highlights that soluble LDL receptor (sLDLR) levels track closely with atherogenic lipid profiles (high triglycerides, small LDL) during weight loss, regardless of whether you choose a low-carb or low-fat diet. While sLDLR itself is not a standard clinical target, its association with these markers suggests that individuals with high sLDLR may have a specific metabolic phenotype (atherogenic dyslipidemia) that requires careful monitoring of lipid health during weight loss interventions.

Tirzepatide treatment significantly reduces food cravings and preferences for energy-dense foods (high fat, high sugar, fast food fats) in people with obesity, independent of caloric restriction.

If you struggle with intense cravings for high-fat or high-sugar foods, tirzepatide can help reduce these urges. This isn't just about willpower; the medication physiologically lowers the 'pull' of these foods, making it easier to stick to a healthy diet.

Tirzepatide specifically reduces cravings for fast-food fats (e.g., pizza, hamburgers) more than other high-fat foods (e.g., sausage, fried fish).

Tirzepatide may be particularly effective at reducing cravings for specific fast-food items like pizza and burgers compared to other high-fat foods.