Browse the evidence

Targeting the Ghrelin Receptor (GHSR1a) with inverse agonists or antagonists like LEAP2 reduces food intake and postprandial glucose, offering a potential treatment for type-2 diabetes and obesity.

A new approach to blocking hunger involves a natural peptide called LEAP2. In a small study, giving LEAP2 intravenously reduced how much people ate and lowered their blood sugar after meals. This suggests it might help people with type-2 diabetes or obesity, but more research is needed to see if these benefits last long-term.

Consuming mycoprotein provides a sustained release of essential amino acids (EAAs) and branched-chain amino acids (BCAAs) compared to milk protein, supporting muscle protein synthesis without rapid spikes.

To support muscle growth, include mycoprotein (like Quorn) in your diet. It digests slower than milk or meat, providing a steady stream of amino acids over several hours, which is beneficial for muscle protein synthesis. Aim for 60-80g servings to maximize this effect.

Mycoprotein consumption reduces postprandial insulin response and energy intake at high doses (132g) compared to chicken, without altering glycemic response.

If you are overweight or obese, incorporating mycoprotein into your meals, particularly in larger portions (around 132g of protein), may help reduce your insulin response and naturally lower your calorie intake at the next meal compared to chicken.

A delayed-morning, earlier-evening time-restricted feeding (TRF) protocol (10:00–18:00 h) improves nocturnal glycemic control in men with overweight/obesity compared to extended feeding (07:00–22:00 h), while maintaining positive subjective adherence.

For men with overweight or obesity, shifting your eating window to start at 10:00 AM and end by 6:00 PM can significantly improve blood sugar levels during sleep compared to eating from 7:00 AM to 10:00 PM. This approach is metabolically effective and more socially sustainable than extreme early-fasting protocols, provided you maintain your total calorie and macronutrient intake.

Low carbohydrate diets induce rapid short-term weight loss partly through ketosis (suppressing appetite via ketone bodies) and diuresis (water loss from glycogen depletion), but may increase LDL cholesterol and reduce diet quality due to low fiber intake.

Low carbohydrate diets can lead to rapid initial weight loss due to water loss and appetite suppression from ketones, but long-term adherence is hard and may raise LDL cholesterol. Ensure you get enough fiber from non-starchy vegetables to protect gut health.

Weekly subcutaneous administration of IBI362, a GLP-1 and glucagon receptor dual agonist, produces significant body weight loss and improves metabolic parameters in Chinese adults with overweight or obesity.

IBI362 is a once-weekly injection that helps overweight and obese Chinese adults lose weight and improve metabolic health. It works by targeting two hormones (GLP-1 and glucagon) to reduce appetite and increase energy expenditure. In this study, participants lost between 4.8% and 6.4% of their body weight over 12 weeks, with side effects like nausea being mostly mild. This suggests it is a viable option for those seeking pharmacological weight loss support.

Time-restricted eating (TRE), specifically early TRE, can improve cardiometabolic markers such as blood pressure and glucose control even in the absence of weight loss (eucaloric conditions).

If you have prediabetes, try eating within an early window (e.g., 8 am to 4 pm) without changing your total calories. You might see improvements in blood pressure and blood sugar control even if your weight stays the same.

Performing low-load resistance exercise (30% 1RM) to volitional fatigue during periods of physical inactivity preserves type II muscle fiber cross-sectional area and satellite cell content in older adults.

If you are older and forced to be inactive (e.g., due to injury or illness), do not stop exercising. Perform resistance exercises with light weights (about 30% of your max) until you are completely exhausted. Do this three times a week. This will help you keep your muscle size and health, especially in your fast-twitch muscle fibers, which are most likely to shrink when you stop moving.

Tirzepatide significantly reduces HbA1c and body weight in adults with Type 1 Diabetes (T1D) without increasing the risk of diabetic ketoacidosis (DKA) or time below range.

If you have Type 1 Diabetes and struggle with weight or high blood sugar despite insulin, ask your doctor about tirzepatide. This study shows it can lower your A1c and help you lose significant weight (over 10% in some cases) without increasing the risk of dangerous ketones or low blood sugar, provided it is managed carefully by a specialist.

Newer emerging anti-obesity medications, specifically GLP-1/GIP/Glucagon receptor agonists (e.g., tirzepatide, retatrutide), demonstrate superior weight loss efficacy compared to older single-mechanism drugs.

Newer drugs like tirzepatide (Mounjaro/Mounjaro) can lead to nearly 21% weight loss in some patients, significantly higher than older drugs. These require weekly injections and are more expensive. Discuss with your doctor if the higher efficacy justifies the cost and injection burden for your specific health goals.

Sarcopenic obesity in elderly women is associated with significantly lower muscle strength and lean body mass, along with elevated pro-inflammatory markers (specifically IL-6) and glucose levels compared to nonsarcopenic obesity.

For elderly women, carrying excess fat combined with low muscle mass is worse for inflammation and strength than carrying excess fat alone. Screening for 'sarcopenic obesity' using appendicular lean mass relative to BMI can identify those at highest risk for disability, allowing for earlier, targeted strength and nutrition interventions.

A ketogenic diet (KD) improves insulin sensitivity and reduces insulin requirements in patients with type 2 diabetes and obesity by lowering glycemic response and reducing pancreatic insulin secretion.

To improve insulin sensitivity, restrict carbohydrates to under 50g per day while maintaining high fat intake (approx 75% of calories) and moderate protein (1-1.4g/kg). Expect initial side effects like fatigue or 'keto flu' due to electrolyte shifts, which typically resolve as your body adapts.

GLP-1 receptor agonists (semaglutide, tirzepatide) and bariatric surgery (RYGB) extend the duration of weight loss prior to plateau by weakening the physiological appetite feedback control circuit, whereas diet restriction fails to weaken this circuit and thus plateaus within ~12 months.

If you are using GLP-1s or had surgery, your prolonged weight loss is due to a physiological change in how your body regulates appetite, not just willpower. Dieting alone triggers a strong appetite feedback loop that causes early plateaus; these interventions bypass that loop.

Dual (GLP-1/GIP) and Triple (GLP-1/GIP/Glucagon) receptor agonists offer superior weight loss and metabolic benefits compared to GLP-1 mono-agonism by leveraging complementary mechanisms.

Newer multi-agonists (dual/triple) like retatrutide show much higher weight loss (up to 24%) than older GLP-1 drugs. They work by hitting multiple metabolic targets at once, which may be necessary for patients who don't respond sufficiently to GLP-1 alone.

Triple agonists targeting GLP-1, GIP, and Glucagon receptors (GCGR) offer additional metabolic benefits, including increased energy expenditure and weight loss, by combining the insulinotropic effects of incretins with the lipolytic and anorectic effects of glucagon.

For patients with Type 2 Diabetes and obesity who need more than standard treatment, triple-agonist medications (targeting GLP-1, GIP, and Glucagon) are in early development. These drugs aim to boost weight loss and energy expenditure by leveraging the body's natural hormonal responses to food. Because they are still in early trials, their long-term safety and optimal dosing are not yet fully established, but they represent a promising next step for complex metabolic cases.

Tirzepatide demonstrates potential for cardiovascular protection, including reduced risk of major adverse cardiovascular events (MACE-4) and improved lipid profiles, in patients with Type 2 Diabetes.

Beyond lowering blood sugar, Tirzepatide may improve heart health by lowering bad cholesterol and triglycerides and reducing the risk of heart attacks and strokes. This is particularly important for diabetic patients with existing heart risks.

Tirzepatide shows promise for treating Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH) by reducing liver fat content and improving liver enzymes, likely through indirect weight loss and metabolic effects.

For diabetics with fatty liver, Tirzepatide may help reduce liver fat and improve liver enzymes, likely by aiding weight loss and metabolic health. However, more specific clinical trials are needed to confirm its efficacy as a primary treatment for NASH.

Diets high in rapidly digestible carbohydrates increase the insulin-to-glucagon ratio, shifting energy partitioning toward adipose storage and away from metabolically active tissues, which triggers compensatory hunger and reduced metabolic rate.

To manage weight, focus on reducing rapidly digestible carbohydrates (refined grains, added sugars) to lower insulin levels. This prevents the hormonal trapping of energy in fat cells and reduces the biological drive to overeat and slow metabolism.

Lifestyle interventions (diet and exercise) combined with GLP-1 receptor agonists (GLP-1RAs) may mitigate gastrointestinal side effects and enhance weight loss, though their efficacy requires confirmation via randomized controlled trials.

If you are taking a GLP-1RA, do not abandon lifestyle changes. Focus on dietary strategies like smaller, lower-fat meals to manage nausea and other side effects. This may help you stay on the medication longer and potentially achieve greater weight loss, although more research is needed to confirm these benefits.

In obese patients with preexisting hip or knee osteoarthritis, GLP-1 receptor agonist use is associated with a significantly reduced odds of conversion to total joint arthroplasty (THA and TKA) within one year, independent of weight loss.

If you are obese and have existing hip or knee osteoarthritis, using a GLP-1 receptor agonist (like semaglutide or liraglutide) is associated with a lower risk of needing joint replacement surgery within a year, even if your weight doesn't change significantly. This suggests the drug may have direct protective effects on your joints, not just benefits from weight loss. Discuss this potential benefit with your doctor, especially if you are considering these medications for weight management or diabetes.

GLP-1 receptor agonists (GLP-1RAs) promote significant weight loss and BMI reduction in people with HIV (PWH), with tirzepatide and longer treatment duration (>6 months) being the strongest predictors of achieving >5% weight loss.

If you have HIV and are struggling with weight gain, GLP-1 receptor agonists (like semaglutide or tirzepatide) are a proven, effective treatment option. The study shows that sticking with the medication for more than 6 months and reaching the maximum dose significantly increases your chances of losing more than 5% of your body weight. Tirzepatide, in particular, showed the strongest association with significant weight loss in this population.

Supplementing meals with 3-4 grams of leucine can improve or normalize muscle protein synthesis in aging muscle, acting as a trigger for the mTOR pathway.

If you are older, adding 3-4 grams of leucine to your meals (or eating leucine-rich foods like beef or whey) can help trigger muscle growth. However, if you already eat enough protein, you might not need extra leucine supplements.

Eloralintide (LY3841136), a selective amylin receptor agonist, promotes significant body weight loss primarily through fat mass reduction with favorable gastrointestinal tolerability compared to non-selective amylin agonists.

Eloralintide is a once-weekly injection that targets specific receptors to reduce appetite and food intake. In early trials, it led to modest but significant weight loss (up to 4.4% in 4 weeks) primarily by burning fat, with fewer stomach side effects than some competitors. It is currently in early clinical stages and not yet widely available.

Daily administration of 100 mg mirabegron (a selective β3-AR agonist) increases energy expenditure and skin temperature in humans without cardiovascular side effects, offering a pharmacological alternative to cold exposure for activating brown adipose tissue.

If you are looking to boost metabolic rate through medication, 100 mg of mirabegron daily has been shown in studies to increase energy expenditure and skin temperature without causing heart issues. This is a repurposed drug originally for bladder issues, but it targets fat-burning pathways. Note that higher doses (150-200mg) may cause heart rate and blood pressure increases, so 100mg is the identified safe effective dose in the cited research.