Browse the evidence

A unimolecular antibody-peptide conjugate combining GIP receptor antagonism and GLP-1 receptor agonism (AMG 133) produces significant, sustained body weight loss in obese non-human primates when administered via once-weekly subcutaneous injection.

This research identifies AMG 133 as a potent obesity treatment in primates, achieving nearly 17% body weight loss with once-weekly injections. For humans, this suggests a future therapy that is more convenient than daily injections and potentially better tolerated than current single-target GLP-1 drugs, though it is not yet available for clinical use.

Retatrutide, a triple incretin agonist, alleviates adipose tissue fibrosis and dysfunction by reprogramming lipid metabolism and suppressing inflammatory pathways, rather than solely reducing fat mass.

Retatrutide is a potent injectable medication for obesity that works by fundamentally changing how fat tissue functions—reducing inflammation and fibrosis and improving metabolic health—rather than just suppressing appetite. It requires regular injections (every 3 days) and is most effective for individuals with significant diet-induced metabolic dysfunction.

In Heart Failure with Reduced Ejection Fraction (HFrEF), NuSH therapies show promise in reducing cardiovascular mortality and MACE, but require cautious patient selection and monitoring due to potential chronotropic effects (increased heart rate) and arrhythmia risks observed with earlier generation agents.

For heart failure with reduced ejection fraction (HFrEF), NuSH therapies are not yet a standard first-line treatment due to safety concerns like increased heart rate. However, recent real-world data suggests they may significantly reduce mortality in stable patients. If your doctor considers this, ensure you are clinically stable, have a normal resting heart rate, and are monitored closely. It is crucial to combine this therapy with resistance training and high protein intake to prevent muscle loss, which can be a side effect of rapid weight loss.

Specific gut microbial metabolites (SCFAs, Bile Acids, Tryptophan derivatives) stimulate GLP-1 secretion from intestinal L cells via specific receptors (FFAR2/3, TGR5, GPR142).

Consuming fiber (for SCFAs), specific fermented foods (for BAs), and tryptophan-rich foods can naturally boost GLP-1 by activating specific gut receptors. This supports metabolic and musculoskeletal health.

GLP-1 receptor agonists exert tissue-protective effects across multiple organs (pancreas, heart, liver, adipose, muscle, kidney, brain) primarily by driving mitochondrial remodeling, including improved biogenesis, quality control, and reduced oxidative stress.

GLP-1 medications (like semaglutide or liraglutide) do more than just help you lose weight; they actively improve the energy-producing centers (mitochondria) in your heart, liver, and other organs. This cellular repair helps protect these organs from damage, offering benefits that go beyond simple calorie reduction.

In pancreatic beta cells, GLP-1 receptor agonists directly protect against apoptosis and improve insulin secretion by enhancing mitochondrial ATP production, reducing oxidative stress, and promoting autophagy.

For people with Type 2 Diabetes, GLP-1 drugs help preserve the insulin-producing cells in the pancreas by keeping their energy factories (mitochondria) healthy and reducing cellular stress. This helps maintain the body's natural ability to produce insulin.

GLP-1 receptor agonists exert direct antihypertensive effects independent of weight loss by modulating the sympathetic nervous system, improving endothelial function, enhancing renal sodium excretion, and suppressing the renin-angiotensin-aldosterone system.

Even without losing weight, GLP-1 medications help lower blood pressure by directly relaxing blood vessels, helping your kidneys excrete more sodium, and calming the nervous system signals that raise blood pressure. They also reduce the activity of hormones that constrict blood vessels.

Semaglutide likely results in little to no difference in quality of life with a mean difference of 2.12 (95% CI 0.95 to 3.28) in SF-36 physical functioning score at medium-term follow-up.

While semaglutide aids in weight loss, its impact on quality of life may be minimal.

Adverse events (AEs) were more common in the T2D group (78.3% vs. 50.0%).

Healthcare providers should monitor for gastrointestinal symptoms in T2D patients using tirzepatide.

Among adults aged 50 and older with newly diagnosed type 2 diabetes, the prevalence of undiagnosed (silent) hypertension reaches 50%, significantly higher than in younger diabetic cohorts.

If you are over 50 and have just been diagnosed with type 2 diabetes, you have a 1 in 2 chance of having high blood pressure that you don't know about. Because you likely have no symptoms, you must get your blood pressure checked immediately at diagnosis to prevent long-term heart and kidney damage.

In older adults (≥50 years) with newly diagnosed type 2 diabetes, mean systolic blood pressure often remains below the clinical hypertension threshold (140 mmHg) despite a high prevalence of silent hypertension, indicating subclinical vascular changes.

If you are over 50 with type 2 diabetes, do not assume your blood pressure is safe just because it is under 140 mmHg. Your blood vessels may already be stiffening, and your risk for heart disease is high even without a formal hypertension diagnosis. Monitor your BP closely and manage other risk factors like cholesterol and weight.

Age, BMI, HbA1c, family history of hypertension, and waist circumference are independent predictors of silent hypertension in newly diagnosed type 2 diabetes patients.

Your risk of having undiagnosed high blood pressure when you get diabetes depends on your age, weight, blood sugar control, family history, and waist size. If you have these risk factors, you are more likely to have silent hypertension and should be screened aggressively.

SGLT2 inhibitors provide significant cardiovascular and renal protection in type 2 diabetes patients through mechanisms independent of glycemic control, including metabolic reprogramming and fuel switching.

If you have type 2 diabetes, ask your doctor about SGLT2 inhibitors. They protect your heart and kidneys through mechanisms beyond just lowering blood sugar, such as helping your body use different fuels. This can significantly reduce your risk of serious complications.

In patients with type 2 diabetes, the magnitude of weight loss achieved through semaglutide treatment (ranging from no loss to >10% loss) does not correlate with the risk of major adverse cardiovascular events (MACE), indicating that the drug's cardioprotective effects are independent of weight reduction.

If you are taking semaglutide for type 2 diabetes and cardiovascular risk, do not stop the medication if you are not losing as much weight as expected. The drug provides cardiovascular protection through direct effects on your blood vessels and heart, independent of how much weight you lose. Focus on the long-term heart health benefits rather than the number on the scale.

Classifying individuals by a 'leptin phenotype' (relatively high or low leptin for a given body fat percentage) does not predict differential energy expenditure, metabolic adaptation, or susceptibility to weight change in response to caloric restriction or overfeeding.

Do not rely on fasting leptin levels to predict your weight loss success or failure. Whether your leptin is 'high' or 'low' for your body fat percentage does not appear to change how your body responds to dieting or overeating in terms of energy expenditure or weight change. Focus on sustainable caloric deficits and activity rather than hormonal profiling for prediction.

A 2-week exposure to either a low-carbohydrate (LC) or low-fat (LF) diet does not significantly alter sweet or salty taste detection thresholds or preferences compared to each other.

Switching to a low-carb or low-fat diet for just two weeks will not change your taste buds or your cravings for sweet and salty foods. If you are expecting your food preferences to shift quickly as a result of the diet itself, this short timeframe is likely too short to observe such changes.

In elderly patients with type 2 diabetes, maintaining the Triglyceride-Glucose index combined with a Body Shape Index (TyG-ABSI) within an optimal range (specifically avoiding both extremely low and extremely high values) is associated with the lowest all-cause mortality risk.

If you have Type 2 Diabetes, standard weight metrics like BMI might not fully capture your mortality risk. Research suggests that a combination of insulin resistance markers (Triglyceride-Glucose index) and body shape (ABSI) provides a more accurate prediction of health outcomes. Crucially, this risk follows a 'U-shape': both extremely high and extremely low values of this combined index are associated with higher mortality. Therefore, the goal is not simply to minimize these numbers, but to maintain them within an optimal, balanced range, while closely monitoring kidney function (eGFR) as it mediates this risk.

Elevated Remnant Cholesterol Inflammatory Index (RCII) is independently associated with a significantly higher risk of incident cardiovascular disease (CVD), including heart disease and stroke.

If you are over 45, ask your doctor about your Remnant Cholesterol Inflammatory Index (RCII). It combines your cholesterol levels with inflammation markers to better predict heart disease risk than weight or BMI alone. High RCII indicates a need for targeted lifestyle interventions focusing on both lipid management and inflammation reduction.

RCII partially mediates the association between ABSI and incident CVD, with the mediation proportion increasing across higher ABSI quartiles.

Understanding that inflammation and lipid metabolism (RCII) play a role in how abdominal fat (ABSI) affects heart health can guide more targeted treatments. For those with high ABSI, addressing inflammation may provide additional cardiovascular protection beyond just weight management.

Adipose tissue (AT) dysfunction, rather than fat mass alone, is the primary mechanistic link between obesity and adverse health outcomes, explaining why some individuals with obesity remain metabolically healthy while others with normal weight develop obesity-related diseases.

Your health risk from obesity is not just about how much you weigh, but how your fat tissue is functioning. Factors like visceral fat, inflammation, and insulin sensitivity matter more than BMI alone. Focus on metabolic health markers rather than just the scale.

Obesity accelerates biological cardiovascular ageing by inducing structural and functional cardiac and vascular changes that mimic those of chronological ageing, independent of traditional risk factors.

Your heart ages based on how you treat it, not just your birth year. Obesity forces your heart to work harder and remodels it to look and function like an older, non-obese heart. Losing weight can reverse these changes, effectively turning back the biological clock of your cardiovascular system.

Leptin therapy is effective for weight loss only in patients with leptin deficiency (low circulating levels), not in those with leptin resistance (high levels).

Leptin injections are only effective for people with a specific genetic deficiency causing low leptin levels. For most people with obesity, leptin levels are high, and leptin injections do not work.

Bariatric surgery is a highly effective therapeutic option for individuals with severe obesity (BMI ≥40 or ≥35 with comorbidities) that induces T2DM remission through metabolic changes beyond simple restriction.

If you have a BMI of 40 or higher (or 35+ with diabetes/liver disease), consult a specialist about bariatric surgery. It is a proven, durable treatment that can reverse diabetes through hormonal changes, not just weight loss, but requires lifelong medical monitoring.

Resmetirom, a selective thyroid hormone receptor beta (THR-β) agonist, significantly reduces hepatic fat content and improves fibrosis markers in patients with non-cirrhotic MASH.

If you have MASH (formerly NASH) with significant liver fat, ask your doctor about resmetirom. It is an FDA-approved medication that targets the liver specifically to reduce fat and improve fibrosis. The standard dose is 80mg or 100mg taken once daily. It is not a supplement but a prescription drug with specific eligibility criteria (non-cirrhotic MASH).