Browse the evidence

GLP-1 receptor agonist therapy is associated with significant gastrointestinal adverse events and weight regain upon discontinuation, limiting its long-term durability compared to surgery.

GLP-1 medications like semaglutide or liraglutide can help you lose 15-25% of your body weight, but you may experience nausea, vomiting, or digestive issues. Crucially, if you stop taking the medication, you are likely to regain the weight. Surgery offers more sustained weight loss and cardiovascular protection, though it involves surgical risks.

Resmetirom (THR-β agonist) improves biopsy-confirmed MASH resolution and fibrosis without causing significant weight loss, acting through a lipid-centric mechanism.

If you have MASH, resmetirom is a daily pill that targets liver fat and inflammation directly. It works even if you don't lose weight, making it a distinct option from weight-loss drugs.

Using GLP-1 receptor agonists for weight loss results in higher social stigma and lower willingness to affiliate compared to losing weight through diet and exercise, and is stigmatized even more than remaining at a higher weight without attempting weight loss.

If you use GLP-1s for weight loss, be aware that you may face significant social judgment, potentially more than if you stayed at your current weight. This stigma stems from perceptions that medication is an 'easy shortcut' compared to diet and exercise. This social penalty can undermine the psychological benefits of weight loss and may discourage continued treatment. It is important to seek support and understand that this stigma is a social bias, not a reflection of your health efforts.

Regaining weight after discontinuing GLP-1 receptor agonists is stigmatized to a similar degree as regaining weight after discontinuing diet and exercise, and both are stigmatized more than maintaining weight loss.

If you regain weight after stopping GLP-1s, you may face social judgment similar to that faced by those who regain weight after dieting. This stigma is not unique to medication users. Recognize that weight regain is a common outcome and does not reflect a lack of character. Focus on sustainable health practices rather than avoiding social judgment.

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.

Bariatric surgery (specifically Roux-en-Y Gastric Bypass and Sleeve Gastrectomy) is the most effective intervention for sustained weight loss and metabolic improvement, significantly altering gut microbiota diversity and reducing systemic inflammation.

Bariatric surgery, such as Roux-en-Y Gastric Bypass or Sleeve Gastrectomy, offers the most significant and durable weight loss for severe obesity. It works by restricting stomach size and altering gut hormones and microbiota. Patients must commit to lifelong vitamin supplementation to prevent deficiencies.

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.

Fasting serum beta-hydroxybutyrate levels increased from a median of 95 μmoL/l to 185 μmoL/l over eight weeks.

Increased ketone levels can be expected with low-energy meal replacement diets.

Tirzepatide may result in an increase in non-serious adverse events (risk ratio 1.33, 95% CI 1.03 to 1.71) compared to placebo.

Clinicians should monitor for non-serious adverse events when prescribing tirzepatide.

Long term dietary intake of gluten was not associated with risk of coronary heart disease.

Practitioners should be cautious in promoting gluten-free diets for individuals without celiac disease, as it may not reduce coronary heart disease risk.

Participants in the highest fifth of estimated gluten intake had a multivariable hazard ratio for coronary heart disease of 0.95.

The data suggests that higher gluten intake does not significantly increase coronary heart disease risk, but caution is warranted due to the lack of statistical significance.

A BMI of 25.0 to 29.9 kg/m2 at age 18 years is associated with a hazard ratio of 1.66 for premature death.

BMI categories should be monitored in adolescents for long-term health implications.

Among participants who never smoked, a BMI of 22.0 to 24.9 kg/m2 at age 18 years was associated with increased premature death (hazard ratio, 1.50).

Non-smokers with a BMI in this range should be counseled on potential health risks.

Overall low-carbohydrate-diet and low-fat-diet scores were not associated with total mortality.

Practitioners should consider that overall low-carb and low-fat diets may not impact mortality rates.

The rates of CVD and death are higher in men compared to women and in rural compared to urban areas.

Public health interventions should target men and rural populations to reduce CVD incidence.

Participants with the lowest carbohydrate intake (quartile 4 of LCD) had a 32% higher risk of overall mortality compared to the highest quartile (Q1).

Practitioners should be cautious in recommending low-carbohydrate diets due to potential increased mortality risk.

Low-carbohydrate diets are associated with a 50% higher risk of cardiovascular disease mortality.

Health professionals should consider the cardiovascular risks associated with low-carbohydrate diets.

Pooled data from nine prospective cohort studies indicated a positive association between low-carbohydrate diets and cancer mortality (RR 1.08, 95% CI 1.01-1.14).

Further research is needed to understand the implications of low-carbohydrate diets on cancer risk.

The simultaneous target of low sodium intake (<2 g/day) with high potassium intake (>3.5 g/day) is extremely uncommon.

Practitioners should note the difficulty in achieving both low sodium and high potassium intakes in dietary practices.

Participants with diabetes were at higher risk of all-cause and CVD mortality and CVD incidence.

Healthcare providers should monitor diabetes patients closely for CVD and mortality risks.

Low grip strength may be useful to identify a higher-risk subgroup of patients with diabetes.

Clinicians should consider grip strength assessments in diabetes management.

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.

Cardiovascular disease (CVD) was the most common cause of death in South Asia, accounting for 35.5% of deaths.

Health policies should prioritize CVD prevention strategies in South Asia.