Browse the evidence

Bariatric surgery (specifically Roux-en-Y gastric bypass) can establish a new, lower body weight set point by altering gastrointestinal signals to the brainstem, thereby suppressing the counterregulatory hunger and hypometabolism typically seen after diet-induced weight loss.

For morbid obesity, surgery may be necessary to reset the body's defended weight. Unlike dieting, which triggers hunger, surgery appears to suppress this hunger biologically. However, it is invasive and requires lifelong management.

Acute moderate altitude hypoxia (2320m) does not enhance the hormonal (GH, Cortisol, Testosterone) or inflammatory (IL-6, IL-10, TNF-alpha) response to a single hypertrophy-oriented resistance training session compared to normoxia.

If you are training at moderate altitude (approx 2300m), do not expect a single resistance training session to trigger a superior acute hormonal or inflammatory response compared to training at sea level. The anabolic signaling environment (GH, Testosterone) remains similar to normoxia. Focus on maintaining training volume and intensity rather than relying on altitude for acute hormonal amplification.

Obesity increases the risk of nephrolithiasis (kidney stones) through mechanisms including lower urine pH, increased urinary oxalate, uric acid, sodium, and phosphate excretion, and insulin resistance.

Obesity increases your risk of kidney stones by changing your urine chemistry, making it more acidic and increasing stone-forming minerals. Maintaining a healthy weight can help reduce this risk.

Metformin treatment alters gut microbiota composition (increasing Escherichia coli and decreasing Intestinibacter bartlettii) to enhance the production of short-chain fatty acids (propionate and butyrate) and modulate bile acid pools, which mediates glucose-lowering effects.

If you take metformin, your gut bacteria are actively helping lower your blood sugar by producing beneficial fatty acids. This is a key part of how the drug works, though it can cause temporary stomach upset for some people.

GLP-1 receptor agonists lower serum TSH levels in patients with Type 2 Diabetes, particularly those who experience weight loss, without necessarily changing free thyroxine (FT4) levels, suggesting a mechanism involving central nervous system GLP-1 receptors or improved thyroid hormone sensitivity.

If your TSH levels drop while on a GLP-1 medication, it is likely due to your weight loss or improved metabolic sensitivity, not necessarily a thyroid problem. Your doctor will likely check your Free T4 to ensure your thyroid function is normal. This change is generally considered a positive metabolic adaptation rather than a disease state.

The peptide drug GUB021794, a GLP-1 receptor agonist derived from a secretin backbone, promotes dose-dependent body weight loss in diet-induced obese mice comparable to the clinically approved drug semaglutide.

This research identifies a new peptide drug, GUB021794, which mimics the hormone GLP-1 to reduce appetite and body weight. In obese mice, it worked as well as the popular drug semaglutide but was designed to last longer in the body, allowing for once-weekly dosing instead of daily. This suggests a potential future treatment option for obesity that offers similar weight loss benefits with less frequent administration.

Adults with diabetes and overweight/obesity are significantly more likely to use weight-inducing (WI) medications than weight-reducing (WR) medications, with WI use being 4 to 20 times higher than WR use, despite clinical guidelines recommending preferential use of WR agents.

If you have diabetes and are overweight, your current medication might be working against your weight loss goals. Many common diabetes drugs cause weight gain. Ask your doctor about switching to weight-reducing options like GLP-1 agonists or SGLT2 inhibitors, which are now recommended for people with your profile. Be aware that these drugs can be expensive and may require injections, but they are designed to help you lose weight, unlike older medications.

High body mass index (BMI) is a strong independent risk factor for the development of chronic kidney disease (CKD) and end-stage renal disease (ESRD), primarily driven by compensatory glomerular hyperfiltration and increased intraglomerular pressure.

Maintaining a healthy weight is one of the most effective ways to prevent kidney disease. High body weight forces your kidneys to work harder (hyperfiltration), which damages them over time. Focus on sustainable lifestyle changes like proper nutrition and exercise to lower your BMI, especially if you have high blood pressure or diabetes.

High BMI acts as a direct risk factor for chronic kidney disease (CKD) through compensatory renal hyperfiltration and increased intraglomerular pressure, independent of diabetes or hypertension.

Maintaining a healthy weight is critical for kidney health. High body weight forces your kidneys to work harder (hyperfiltration), which damages them over time. This damage happens even if you don't have diabetes or high blood pressure. Weight management through lifestyle changes is the primary way to prevent this specific type of kidney injury.

Long-term use of GLP-1 receptor agonists (≥78 weeks) significantly increases the risk of deep vein thrombosis (DVT) compared to placebo or other anti-diabetic drugs.

If you are taking a GLP-1 medication (like Ozempic, Wegovy, or Victoza) for more than a year, be aware that your risk of deep vein thrombosis (DVT) is higher than if you were not taking it. This risk is most notable in people with existing cardiovascular disease. However, the absolute increase in risk is small. Discuss any history of blood clots with your doctor before starting or continuing long-term therapy.

Overall Venous Thromboembolism (VTE) risk is not significantly increased by GLP-1RA use, as the increase in DVT is offset by no change in Pulmonary Embolism (PE) risk.

Taking GLP-1 medications does not significantly increase your overall risk of blood clots (VTE) when looking at the big picture. While there is a small, non-significant upward trend, it is not statistically proven to be dangerous for the general population. The specific risk of DVT is only significant with very long-term use.

Among people with diabetes and high glycemic control (HbA1c ≥7.1%), overweight BMI (25-29.9 kg/m2) is associated with significantly lower mortality risk compared to normal weight BMI.

If you have diabetes and your blood sugar levels are consistently high (HbA1c ≥7.1%), being slightly overweight (BMI 25-29.9) might actually be associated with a lower risk of death compared to being normal weight. This does not mean you should gain weight, but it suggests that aggressive weight loss might not be the primary goal for everyone with poorly controlled diabetes. Focus on stabilizing your blood sugar and overall health.

SGLT2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors provide cardiovascular organ protection in type 2 diabetes through direct antioxidant and anti-inflammatory mechanisms, independent of glucose lowering.

If you have Type 2 Diabetes, ask your doctor about SGLT2 inhibitors or GLP-1 agonists. These drugs do more than just lower blood sugar; they actively protect your heart and kidneys by reducing inflammation and oxidative stress, which are major drivers of heart disease in diabetic patients.

GLP-1 receptor agonists reduce platelet aggregation and thrombus formation, thereby mitigating the risk of thrombotic cardiovascular events in diabetic patients.

GLP-1 agonists may help prevent blood clots by making platelets less sticky, which adds to their heart-protective benefits beyond just sugar control.

Intestinal deficiency of Acyl-CoA synthetase 5 (ACSL5) reduces food intake and protects against diet-induced obesity by increasing postprandial secretion of GLP-1 and PYY.

This research suggests that how your body processes dietary fat in the intestine—specifically through the enzyme ACSL5—can influence your hunger hormones (GLP-1 and PYY). When this process is altered, it can lead to increased feelings of fullness and reduced food intake, potentially protecting against weight gain on high-fat diets. While this is a genetic mechanism in mice, it highlights the importance of gut hormones in regulating appetite and energy balance.

Semaglutide (2.4 mg weekly) induces MASH resolution in patients with stage 2-3 fibrosis, though it does not significantly improve fibrosis itself.

Semaglutide 2.4 mg weekly is highly effective at resolving active liver inflammation (MASH) in patients with moderate fibrosis. However, it does not reverse the scarring (fibrosis) itself. Patients should expect significant weight loss and metabolic improvement, but should not assume their liver scarring will disappear with this drug alone.

Statins reduce the risk of developing MASLD and progression to liver fibrosis, and may reduce cardiovascular events in MASLD patients, despite not directly reducing liver fat.

If you have fatty liver and high cardiovascular risk, you should take statins. They do not remove liver fat, but they reduce inflammation and fibrosis, and significantly lower your risk of heart attacks and strokes. The benefits outweigh the theoretical risks.

Pioglitazone improves MASH resolution and may improve fibrosis, but is limited by side effects like weight gain and heart failure exacerbation.

Pioglitazone can resolve MASH and improve fibrosis, but it causes weight gain and fluid retention, which can worsen heart failure. It is not a first-line treatment but may be considered if other options fail and heart failure is not a concern.

Once-weekly semaglutide treatment is associated with a significant increase in pulse rate compared to once-daily sitagliptin.

If you take semaglutide, expect your resting heart rate to increase slightly (by about 3 beats per minute) compared to if you took sitagliptin. This is a known side effect. While usually not dangerous, it is worth monitoring, especially if you have underlying heart conditions.

Semaglutide treatment is associated with a higher risk of total adverse events and premature treatment discontinuation compared to sitagliptin, although the risk of serious adverse events is not significantly different.

Be prepared for a higher likelihood of side effects and stopping the medication early when starting semaglutide compared to sitagliptin. Most side effects are gastrointestinal. Slow dose escalation can help. However, serious adverse events are not significantly more common with semaglutide.

GLP-1 receptor agonists increase the risk of gallbladder disease, including cholelithiasis and cholecystitis, through mechanisms involving cholecystokinin (CCK) suppression, altered bile acid receptor signaling (FXR/TGR5), and disrupted gut-brain pathways, leading to bile stasis and gallstone formation.

If you are taking a GLP-1 agonist (like semaglutide or liraglutide), be aware that you have a higher risk of gallbladder problems, especially if you are taking higher doses or losing weight rapidly. Watch for symptoms like severe abdominal pain, nausea, or fever, and report them to your doctor immediately. Your doctor may monitor you more closely or adjust your treatment plan to mitigate this risk.

Activation of brown and beige adipose tissue through pharmacological means (e.g., β3-AR agonists, GLP-1RAs) or transplantation improves glucose metabolism, insulin sensitivity, and energy expenditure, offering a therapeutic strategy for obesity and type 2 diabetes.

Your body has a biological mechanism to burn extra energy as heat using brown and beige fat. While cold exposure and exercise can activate this, pharmaceutical approaches (like mirabegron or GLP-1 agonists) are being studied to enhance this process. This suggests that metabolic health is not just about calories in/out but also about the activity of specific fat tissues.

Biased agonism of GLP-1R and GIPR (favoring cAMP over beta-arrestin recruitment) yields superior glucose lowering, food intake suppression, and weight loss compared to unbiased agonism.

Current GLP-1/GIP drugs that favor cAMP signaling (biased) appear to offer better and longer-lasting glucose control and weight loss than those that do not. This is likely due to the drug staying on the receptor longer without being internalized. While this is proven in mice, it suggests that drug design matters for efficacy, not just receptor activation.

AgRP neuron inhibition is a necessary mechanism for the appetite-suppressing effects of incretin-based obesity therapies (GLP-1 and GIP analogs).

This research confirms that GLP-1 and GIP medications (like Ozempic or Wegovy) work by directly inhibiting the brain's hunger-promoting neurons (AgRP). This neural inhibition is a key reason these drugs successfully suppress appetite.