Browse the evidence

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.

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.

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.

GLP-1 receptor agonist (GLP-1RA) treatment in obese individuals causes a modest absolute decrease in skeletal muscle mass, but preserves or improves relative muscle mass and strength, resulting in maintained or enhanced physical performance.

If you are taking GLP-1 medications for weight loss, expect a small, normal amount of muscle loss alongside your fat loss. This is not pathological wasting; your muscles are actually working better relative to your new body weight. Focus on maintaining strength through activity, as your mobility and endurance may actually improve.

Fixed-ratio combinations (FRCs) of basal insulin and GLP-1 receptor agonists are indicated for patients with type 2 diabetes who are inadequately controlled on oral antihyperglycemic drugs (OADs) with an HbA1c less than 10% and within 2% of their glycemic goal, or for those already on basal insulin who remain above goal.

If you are taking oral diabetes medications but your blood sugar is still too high (HbA1c less than 10% and within 2% of your target), or if you are already on basal insulin but your levels are still above goal, ask your doctor about a fixed-ratio combination (FRC). These are single injections that combine a long-acting insulin with a GLP-1 medication. They are designed to lower blood sugar effectively, minimize weight gain, and reduce the number of injections you need to manage compared to traditional basal-bolus therapy.

For patients with Type 2 Diabetes requiring basal insulin, a glycated hemoglobin (HbA1c) goal of less than 7% is appropriate, whereas a goal of less than 6.5% is less likely to be appropriate due to increased risks of hypoglycemia and weight gain.

If you are on basal insulin, aim for an HbA1c of less than 7%. Trying to get it below 6.5% when you are on insulin can increase your risk of dangerous low blood sugar and weight gain without providing significant additional long-term benefits. Your doctor should adjust your goal based on your specific health situation, but <7% is generally the safe target for insulin users.

Orforglipron significantly improves lipid profiles, including reductions in total cholesterol, LDL cholesterol, and triglycerides, along with increases in HDL cholesterol, independent of weight loss magnitude.

Orforglipron not only helps with weight loss but also significantly improves heart health markers. It lowers bad cholesterol (LDL) and triglycerides while raising good cholesterol (HDL). These improvements occur alongside weight loss and contribute to a lower risk of cardiovascular disease, making it a comprehensive treatment for obesity-related metabolic risks.

Delaying the onset of type 2 diabetes by two years in individuals with obesity is associated with a 3.7-year increase in median life expectancy and reduced long-term mortality, primarily driven by lower cardiovascular mortality.

For individuals with obesity, preventing or delaying the onset of type 2 diabetes is a critical lever for extending life expectancy. This study suggests that even a modest two-year delay in developing diabetes can add nearly four years to your life, largely by protecting your heart. Focus on metabolic health markers (like blood sugar and insulin sensitivity) as aggressively as you focus on weight, as the timing of diabetes onset directly impacts how long you live.

Treatment with extended-release naltrexone/bupropion (NB) produces weight loss that is disproportionately derived from fat mass rather than lean mass compared to placebo, resulting in a favorable shift in the lean-to-fat mass ratio.

If you are using naltrexone/bupropion for weight loss, the medication helps you lose more fat and preserve more muscle than dieting alone. This is beneficial for long-term metabolic health. Ensure you are following a caloric deficit and staying active as instructed.

Consuming 50g of isomaltulose (ISO) as a preload before a mixed meal significantly enhances the secretion of gut hormones GLP-1, GIP, and PYY compared to sucrose (SAC), with a particularly pronounced effect on PYY levels in both healthy individuals and those with Type 2 Diabetes.

If you want to boost your gut hormones (GLP-1, PYY) which help regulate appetite and insulin, try eating 50g of isomaltulose (often found in products like Palatinose) about one hour before your main meal. This specific timing and dose triggers a much stronger hormonal response than regular table sugar (sucrose), especially regarding PYY, which is linked to satiety. Note that this did not significantly lower blood glucose in the subsequent meal in this study, so it is a tool for hormonal modulation, not necessarily glycemic control.

Dual and tri-agonists targeting GLP-1, GIP, and Glucagon receptors provide superior metabolic homeostasis and cardiovascular benefits compared to mono-agonists by leveraging cooperative hormonal signaling.

Current GLP-1 treatments are effective, but newer dual and triple hormone therapies (targeting GLP-1, GIP, and Glucagon receptors) offer broader metabolic and cardiovascular benefits. These are available as weekly or daily injections, and in some cases, oral formulations, addressing the burden of daily dosing.

GLP-1 receptor agonists (specifically liraglutide and semaglutide) reduce major adverse cardiovascular events (MACE), with benefits potentially driven by anti-atherogenic or plaque-stabilization properties, particularly in secondary prevention.

If you have Type 2 Diabetes and heart disease, injectable GLP-1 medications like liraglutide or semaglutide have been shown to reduce the risk of heart attack, stroke, and cardiovascular death. These benefits appear to come from protecting blood vessels (anti-atherogenic effects). Oral alternatives like DPP-4 inhibitors do not offer this specific heart protection.

Monogenic obesity caused by leptin deficiency can be effectively treated with recombinant leptin therapy, restoring normal appetite regulation.

This intervention is not for the general population. It applies only to a tiny fraction of individuals with confirmed monogenic leptin deficiency. Standard weight loss strategies remain the primary approach for >99% of cases.

Effective obesity medications (e.g., GLP-1/GIP agonists) work by lowering the adipose mass set point through counteracting adaptive hormonal responses, allowing homeostasis at a lower weight, but require lifelong use to maintain this new set point.

Obesity medications are not a temporary fix but a long-term management tool for a chronic disease. They work by resetting your body's biological 'thermostat' to a lower weight. If you stop taking them, your biology will fight to regain the weight. Therefore, these medications should be viewed as lifelong treatments, similar to blood pressure medication, to maintain your health.