Browse the evidence

Metformin augmentation for non-responders to initial behavioral interventions provides a potential rescue effect but is associated with gastrointestinal side effects that challenge adherence.

If behavioral changes alone don't improve your insulin sensitivity, adding metformin might help, but be prepared for potential stomach issues. Starting with a low dose and using extended-release versions can help manage side effects.

Maintaining weight loss induced by anti-obesity drugs may require lifelong use unless effective adjunct strategies for weight maintenance are available.

If you use medication for weight loss, understand that it may need to be long-term. This is similar to managing other chronic conditions. The goal of research like POWERS is to find adjunct strategies that might reduce this dependency.

Semaglutide treatment in patients with chronic ankle instability (CAI) significantly improves patient-reported functional outcomes (FAAM, FAOS, CAIT) and reduces the incidence of recurrent ankle sprains and surgery, with approximately one-third of the benefit mediated by weight loss.

For patients with chronic ankle instability, especially those who are overweight or have type 2 diabetes, semaglutide may offer benefits beyond metabolic control. It is associated with improved ankle function, fewer sprains, and lower surgery rates. While weight loss contributes to this, it is not the only factor. Patients should discuss this potential orthopedic benefit with their prescribing physician, particularly if they are considering surgical intervention for ankle instability.

Semaglutide use for rapid weight loss causes 'semaglutide face,' characterized by facial hollowing, skin sagging, and premature aging due to subcutaneous fat loss, collagen depletion, and muscle mass reduction.

If you are using semaglutide for weight loss, be aware that rapid fat and muscle loss can cause your face to look hollow or sagged. This is a known side effect called 'semaglutide face.' You can discuss preventative or corrective measures like dermal fillers, PRP, or radiofrequency microneedling with your provider to maintain your appearance while losing weight.

GLP-1 receptor agonists (GLP-1RAs) are perceived by primary care providers as effective and promising tools for managing recurrent weight gain after metabolic bariatric surgery (MBS), offering renewed optimism and life-changing results for patients.

If you have had bariatric surgery and are regaining weight, GLP-1 medications like semaglutide are a viable and effective option to help you lose weight again. However, they are not a magic bullet; you must continue to focus on diet and exercise. The main barrier is cost, so work with your provider to navigate insurance coverage or assistance programs.

GLP-1 receptor agonists (e.g., semaglutide, tirzepatide) significantly suppress hunger, reduce 'food noise' (intrusive thoughts about food), and increase early satiety during the dynamic weight loss phase, leading to reduced portion sizes and cravings.

When starting GLP-1 medications, expect a significant reduction in hunger and intrusive thoughts about food ('food noise'). This is a biological effect, not just willpower. You may feel full faster and eat smaller portions. This effect is strongest in the first few months (dynamic phase). If you stop the medication, hunger and food noise typically return, so long-term adherence is often necessary for sustained benefits.

Bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB), significantly improves psoriasis symptoms and quality of life, with effects potentially linked to increased GLP-1 levels post-surgery.

If you have severe obesity and psoriasis, and lifestyle changes plus medications haven't worked, bariatric surgery (especially gastric bypass) can be a powerful option. It not only helps with weight but can significantly improve your psoriasis symptoms, likely by boosting your body's natural GLP-1 levels. This is a major step, so it's reserved for those with higher BMI or uncontrolled comorbidities.

Testosterone Replacement Therapy (TRT) increases lean body mass and improves body composition in men with documented low testosterone, but no trials have evaluated its combined use with GLP-1 RAs.

If you are a man with low testosterone, TRT can help preserve muscle. However, doctors should check your levels before starting, and there is no proof yet that taking TRT alongside GLP-1s prevents muscle loss better than TRT alone.

The Russian semaglutide-based drug Velgia® (WRYC12301) demonstrates bioequivalence, high safety, and lack of immunogenicity compared to the reference drug Wegovy® at doses of 0.25 mg and 2.4 mg.

This study confirms that the Russian semaglutide product Velgia® is bioequivalent to the brand-name Wegovy® at both 0.25 mg and 2.4 mg doses. It has a comparable safety profile with mild side effects and no detected immunogenicity (antibody formation). For patients seeking this treatment, this generic option offers the same pharmacokinetic exposure as the reference drug.

A history of metabolic surgery (specifically sleeve gastrectomy) significantly attenuates the weight-loss efficacy of liraglutide in patients with mild obesity, resulting in substantially lower total weight loss compared to non-surgical patients.

If you have had weight-loss surgery (especially sleeve gastrectomy), standard doses of liraglutide may not work as well as they do for others. Your doctor might need to increase your dose to 3.0 mg (if approved/available) or switch you to a different medication like tirzepatide to achieve similar weight loss results. Do not assume the standard dose will be sufficient.

Tirzepatide maintenance therapy (either at maximum tolerated dose or reduced to 5 mg) is designed to prevent the weight regain seen with placebo, with rescue protocols available for significant regain.

This paper outlines a trial testing if you can stay on a lower dose of tirzepatide (5mg) or stay on your highest effective dose to keep weight off, compared to stopping it. It also includes a safety net: if you regain more than half your lost weight, you get 'rescue' treatment.

Tirzepatide use is associated with a significantly lower risk of suicidal ideation or suicide attempts compared to other anti-obesity medications in a real-world cohort.

Current real-world evidence suggests that tirzepatide is not associated with an increased risk of suicide and may be associated with a lower risk compared to other anti-obesity medications. However, because this is an observational study, it does not prove causation. Patients with a history of suicidality were excluded, so this data does not apply to high-risk individuals. Consult your provider for personalized psychiatric risk assessment.

GLP-1 receptor agonist therapy for obesity effectively supports weight loss and improves quality of life, but long-term sustainability is undermined by high medication costs, inadequate multidisciplinary support, and significant side effects leading to discontinuation.

GLP-1 medications like Tirzepatide and Semaglutide are effective for weight loss and improving quality of life for many users. However, long-term success is not guaranteed. High costs and side effects are the main reasons people stop treatment. If you are considering or using these medications, be aware that discontinuation often leads to weight regain. Ensure you have a plan for managing costs and side effects, and consider seeking multidisciplinary support (dietary, psychological) to improve adherence and sustainability.

Tirzepatide, a dual GIP/GLP-1 receptor agonist, achieves superior weight loss and hepatic steatosis reduction compared to semaglutide, with preliminary cardiovascular non-inferiority data.

If you have Type 2 Diabetes and fatty liver disease, ask your doctor about Tirzepatide. It is a newer medication that has shown superior weight loss and liver fat reduction compared to other GLP-1 drugs. While cardiovascular outcome data is still being finalized, it is a powerful option for managing both conditions.

The menopausal transition is associated with a reduction in lean or muscle mass, with postmenopausal women showing approximately 5.7% lower muscle mass compared to premenopausal women, although this correlation may be confounded by aging and measurement limitations of DXA.

If you are going through menopause, expect a potential decline in muscle mass, particularly during the perimenopausal transition. This is not necessarily inevitable or irreversible. Focus on resistance training and adequate protein intake during this window, as it is a critical period where interventions may be most effective in preventing sarcopenia.

Older women may exhibit elevated fasted muscle protein synthesis (MPS) rates compared to younger women or age-matched men, but their MPS response to anabolic stimuli like resistance exercise or protein ingestion may be blunted.

As you age, your muscles may not respond as strongly to exercise and protein as they did when you were younger. This doesn't mean exercise is useless, but it does mean you may need to be more consistent and potentially adjust your protein intake to maximize muscle protein synthesis.

Garcinia cambogia (Hydroxycitric acid/HCA) supplementation reduces visceral fat and improves fasting blood glucose and insulin sensitivity in overweight/obese individuals.

Garcinia cambogia (HCA) at 1,000 mg/day may help reduce visceral fat and improve blood sugar in overweight people, but it is not a magic bullet. It works by blocking fat synthesis and suppressing appetite.

Coleus forskohlii (Forskolin) supplementation reduces body fat, increases lean mass, and improves insulin sensitivity in overweight/obese men.

Coleus forskohlii (Forskolin) taken daily for 12 weeks may help reduce body fat and increase lean mass in overweight men, improving insulin sensitivity. It works by increasing cAMP, which stimulates fat breakdown.

Banaba leaf extract (Corosolic acid) and Resistant Maltodextrin (RMD) improve blood glucose control and insulin sensitivity through distinct mechanisms.

Banaba leaf extract and Resistant Maltodextrin (RMD) can improve blood glucose control and insulin sensitivity. Banaba works by promoting glucose uptake, while RMD delays carbohydrate absorption and increases SCFA production.

Carriers of the TCF7L2 rs7903146 T allele exhibit significantly attenuated weight loss and metabolic improvements compared to non-T allele (CC) carriers when following a partial meal replacement (pMR) hypocaloric diet.

If you have the TCF7L2 rs7903146 T allele, expect your weight loss to be roughly half as fast as someone with the CC genotype on a similar meal-replacement diet. Focus on metabolic health markers (blood sugar, insulin) as early wins, as these improve significantly even if the scale moves slower.

Animal-based proteins provide a modest but statistically significant advantage in stimulating muscle protein synthesis (MPS) compared to plant-based proteins, primarily driven by higher leucine content and bioavailability.

If you are over 65, prioritize animal proteins (whey, milk, eggs) or ensure your plant protein is high-leucine (soy, pea blends) to maximize muscle growth. For younger adults, plant and animal proteins appear functionally equivalent for MPS when doses are matched.

The MPS advantage of animal proteins over plant proteins is significantly more pronounced in older adults (65+) than in younger adults, likely due to the 'leucine threshold'.

If you are over 65, ensure your plant proteins are high-leucine (e.g., soy, pea) or consider animal proteins to overcome age-related anabolic resistance. Younger adults can likely use either source effectively.

GLP-1 receptor agonist therapy initiated at least one year after bariatric surgery produces additional significant weight loss with a favorable safety profile.

If you had bariatric surgery and are struggling with weight regain, GLP-1 medications (like semaglutide or dulaglutide) can help you lose more weight safely. Start with a low dose and work up slowly to minimize stomach issues. Combining the medication with a structured lifestyle program (like the VA's MOVE!) yields the best results.

GLP-1 receptor agonists (GLP-1RAs) improve reproductive outcomes in obese women with PCOS or unexplained infertility by reducing body weight, improving insulin sensitivity, and modulating endometrial immune balance (increasing Treg cells, decreasing pro-inflammatory cytokines, and restoring Th17/Treg balance).

For women with obesity and fertility issues (like PCOS), GLP-1 medications can help restore ovulation and improve the uterine environment by lowering inflammation. However, these drugs must be stopped before you conceive because they can harm the developing embryo. The goal is to use them during the preconception phase to fix metabolic and immune imbalances, then switch to pregnancy-safe management once pregnant.