Browse the evidence

Obesity acts as an independent risk factor for chronic kidney disease progression through direct mechanisms (pro-inflammatory adipocytokines, renal hemodynamic alterations causing glomerular hyperfiltration) and indirect mechanisms (hypertension, type 2 diabetes).

Maintain a healthy weight to protect kidney function. Obesity directly stresses the kidneys through hormonal and blood flow changes, leading to protein leakage and reduced filtration. Weight loss interventions can slow this progression.

SGLT2 inhibitors reduce cardiovascular disease risk and mortality in Type 2 Diabetes patients, but are associated with increased risks of urogenital infections, dehydration, hypotension, osteoporotic fractures, and limb amputation.

SGLT2 inhibitors offer significant cardiovascular benefits but require caution in elderly patients and those with kidney disease due to risks of dehydration, hypotension, and infections. Monitor for signs of these side effects.

Acute exposure to moderate terrestrial altitude (2320 m) does not enhance metabolic stress or anabolic hormonal responses compared to normoxia during hypertrophy-oriented resistance training.

If you are training at moderate altitude (around 2300m), do not expect your muscles to grow faster or your hormones to spike more than they would at sea level, provided you are doing the same resistance training routine. The acute stress response is not enhanced by the altitude itself in this context.

Inhibition of HIF1α signaling allows regenerating skeletal muscle myofibers to bypass a neonatal maturation checkpoint, thereby accelerating muscle repair and growth following injury.

This research identifies a biological 'brake' on muscle repair: if HIF1α signaling stays high after an injury, the muscle gets stuck in an immature, small state. Pharmacologically lowering HIF1α (e.g., with PX-478 in mice) or genetically removing it allows the muscle to mature faster and grow larger. For humans, this suggests that strategies to modulate hypoxia signaling or mitochondrial fusion (Mfn2) might accelerate recovery from severe muscle trauma, though no such therapy is currently available for general use.

Short-chain fatty acids (SCFAs) such as acetate and propionate regulate glucose homeostasis primarily by activating the GPCR FFAR2 on enteroendocrine L-cells, stimulating the release of GLP-1, which in turn promotes insulin secretion and improves glucose tolerance.

To leverage the glucose-lowering benefits of short-chain fatty acids, focus on consuming fermentable dietary fibers (like those in oats, legumes, and resistant starches) to feed gut bacteria. These bacteria produce SCFAs (acetate, propionate, butyrate) which activate FFAR2 receptors in your gut. This triggers the release of GLP-1, a hormone that signals your pancreas to release insulin more effectively, thereby improving blood sugar control. This is particularly beneficial if you have insulin resistance or type 2 diabetes.

Resmetirom, a liver-targeted thyroid hormone receptor beta agonist, significantly improves both NASH resolution and fibrosis in patients with stage 2-3 fibrosis.

Resmetirom is a prescription medication for NASH with significant fibrosis that has shown the ability to improve both liver inflammation and scarring in clinical trials. It is not an over-the-counter supplement and requires medical supervision.

Obeticholic acid (OCA) reduces hepatic fibrosis without worsening NASH, but its efficacy is modest and it carries safety concerns leading to FDA rejection.

Obeticholic acid can reduce liver scarring in pre-cirrhotic NASH, but its modest benefits and side effects (itching, liver toxicity) led to FDA rejection, making it a less favorable option.

Pegozafermin, an FGF21 analogue, significantly improves fibrosis and NASH resolution in patients with stage 2-3 fibrosis.

Pegozafermin is an experimental FGF21 analogue that has shown significant improvements in liver scarring and NASH in clinical trials, offering hope for patients with stage 2-3 fibrosis.

GLP-1 receptor agonists (GLP-1 RAs) are dependent on residual beta-cell function and insulin availability, meaning that as Type 2 Diabetes progresses and beta-cell function declines, GLP-1 RAs lose efficacy and patients eventually require insulin therapy.

If you have Type 2 Diabetes, GLP-1 medications (like Ozempic or Trulicity) work by asking your pancreas to make more insulin. If your pancreas is still working well, these drugs are very effective. However, Type 2 Diabetes is progressive, and your pancreas naturally makes less insulin over time. Eventually, these drugs may stop working well enough on their own. At that point, adding insulin is not a failure; it is the necessary next step to keep your blood sugar safe and protect your body from complications.

GLP-1 agonists (e.g., semaglutide, tirzepatide) significantly delay gastric emptying and increase retained gastric contents, thereby increasing the risk of intraoperative pulmonary aspiration during general anesthesia even after standard preoperative fasting.

If you take GLP-1 agonists (like Ozempic or Wegovy) and are having surgery, tell your anesthesiologist. Standard fasting might not be enough to empty your stomach because these drugs slow digestion. Your doctor may use an ultrasound to check your stomach before surgery or adjust your anesthesia plan to prevent aspiration.

Central GIP receptor (GIPR) agonism decreases body weight and food intake in diet-induced obese mice by activating GABAergic neurons in the area postrema, a mechanism that is independent of hypothalamic GIPR signaling.

Newer weight-loss medications that combine GLP-1 and GIP (like tirzepatide) work partly by activating GIP receptors in your brain's satiety centers. This helps reduce food intake. While GIP was once thought to only help with insulin, its role in the brain is now recognized as beneficial for weight loss.

Multi-receptor incretin drugs are associated with an increased risk of adverse events (primarily gastrointestinal) compared to placebo, but do not significantly increase the risk of serious adverse events.

Be aware that multi-receptor incretin drugs commonly cause gastrointestinal side effects like nausea, which may lead to discontinuation for some. However, the risk of serious health events is not significantly higher than placebo. Discuss potential side effects with your doctor and report any severe or persistent symptoms.

Short-term selective dietary fat restriction (30% calorie reduction) decreases dopamine D2/3 receptor binding potential and neural activity in brain reward regions, leading to increased selection of high-fat, high-carbohydrate foods.

If you are on a low-fat diet, you may find yourself craving high-fat, high-carb foods more intensely. This is likely due to changes in your brain's dopamine system, not just hunger. Be aware that this biological shift can make sticking to a low-fat diet harder, even if you feel satiated by the food itself.

For polygenic obesity, precision medicine approaches targeting specific genetic variants or phenotypes have not yet translated into reliable clinical guidance for selecting obesity medications, making early weight loss response the only consistent predictor of long-term efficacy.

Do not rely on genetic testing or complex phenotyping to choose your obesity medication right now, as it does not reliably predict success for common obesity. Instead, use a 'trial and error' approach guided by side effect profiles, comorbidities, and patient preference. The most important indicator of whether a medication will work for you long-term is whether you lose at least 5% of your body weight within the first 12-16 weeks.

Epicardial adipose tissue (EAT) contributes to Heart Failure with Preserved Ejection Fraction (HFpEF) through two distinct mechanisms: mechanical pericardial restraint and local inflammatory/fibrotic secretion.

For patients with HFpEF, managing epicardial fat is crucial. While general weight loss helps, specific interventions like bariatric surgery or Mediterranean-style diets have been shown to reduce EAT volume and improve heart mechanics. Monitoring EAT via imaging can help assess risk and treatment efficacy.

Visceral fat accumulation activates the Renin-Angiotensin-Aldosterone System (RAAS) and Sympathetic Nervous System (SNS), leading to hypertension and sodium retention, independent of dietary salt intake.

High blood pressure in obesity is driven by hormones from belly fat, not just salt. Reducing visceral fat helps normalize these hormones and lower blood pressure.

Obesity increases the risk of various cancers, including breast, endometrial, ovarian, kidney, thyroid, and gastrointestinal cancers, through mechanisms involving chronic inflammation, adipokine secretion, and epigenetic dysregulation.

Obesity increases your risk of several types of cancer, including breast, endometrial, and gastrointestinal cancers. This risk is driven by chronic inflammation and hormones secreted by fat tissue.

Roux-en-Y Gastric Bypass (RYGB) and Laparoscopic Sleeve Gastrectomy (LSG) induce significantly greater cardiac reverse remodelling (reduction in left ventricular mass and concentric remodelling) than Laparoscopic Adjustable Gastric Band (LAGB) in obese patients.

If you are considering bariatric surgery for obesity, the type of surgery matters for your heart health. Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (LSG) are superior to Gastric Banding (LAGB) in reversing the structural changes in the heart caused by obesity. This benefit is driven by the greater reduction in visceral and epicardial fat, not just total weight loss. Discuss cardiac imaging and long-term heart health with your surgeon when choosing between these procedures.

Higher visceral adipose tissue (VAT) is independently associated with greater impairment in left ventricular peak circumferential strain (Ecc), indicating reduced myocardial contractility, regardless of cardiorespiratory fitness (CRF) or other regional fat depots.

Focus on reducing visceral fat (belly fat) rather than just total body weight. Even if you are not obese, high visceral fat is linked to early heart muscle dysfunction. Cardiovascular exercise and weight management are key to reducing this specific fat depot.

Endogenous gut-derived GLP-1, secreted in response to nutrients or non-caloric stimuli (like gastrointestinal distension), regulates feeding behavior and glucose metabolism via vagal sensory nerves without causing the adverse effects (nausea/vomiting) associated with GLP-1 receptor agonists.

You can influence your GLP-1 levels naturally. Eating GLP-1-stimulating foods (meat, fish, salad) first, followed by a wait before carbs, improves glycemic control and weight loss. Gastrointestinal distension from bulky, low-energy-density foods also triggers beneficial GLP-1 secretion via vagal nerves without causing nausea.

Weekly subcutaneous semaglutide (up to 2.4 mg) significantly reduces liver steatosis and liver enzymes in patients with NAFLD/NASH, but does not significantly improve liver fibrosis or achieve NASH resolution compared to placebo in patients with compensated cirrhosis.

For patients with advanced liver disease (cirrhosis), weekly semaglutide injections (2.4 mg) can significantly reduce liver fat and inflammation markers, but they should not expect it to reverse scarring (fibrosis) or cure NASH. The treatment is safe and effective for metabolic control and steatosis reduction, even if it doesn't change the fibrosis stage.

Resistance training in humans and mechanical overload in rodents does not elevate muscle protein lactylation, challenging the hypothesis that lactate promotes skeletal muscle hypertrophy.

You do not need to maximize lactate accumulation (the 'burn') to trigger muscle protein lactylation or hypertrophy. Resistance training increases blood lactate significantly, but this does not translate to increased muscle protein lactylation or drive hypertrophy via this specific mechanism. Focus on mechanical overload rather than chasing lactate as a signaling molecule for growth.

Pharmacological treatment of prediabetes with anti-hyperglycemic drugs (e.g., metformin, TZDs, insulin) fails to provide long-term protection against diabetes because it does not correct underlying insulin resistance or beta-cell dysfunction, and benefits disappear upon discontinuation.

Standard diabetes drugs (like metformin) do not cure prediabetes. They mask high blood sugar while you take them, but once you stop, your risk of developing diabetes is the same as if you never took the drug. Focus on fixing the root cause (insulin resistance) rather than just lowering the number.

Preoperative use of GLP-1 receptor agonists does not improve long-term weight loss, diabetes remission, or surgical safety outcomes in patients undergoing metabolic bariatric surgery compared to those who do not use GLP-1s.

If you are considering bariatric surgery, using GLP-1 drugs (like Ozempic or Wegovy) beforehand does not appear to make your surgery more successful or your weight loss better in the long run. In fact, it may just delay getting the more effective surgical treatment. If you are experiencing side effects from these drugs or they aren't working well enough, switching to surgery is a valid and effective path, but don't expect the drugs to give you a 'head start' on your results.