Browse the evidence

GLP-1 receptor agonists provide significant cardiovascular risk reduction in both diabetic and non-diabetic patients with established cardiovascular disease, a benefit that is significantly under-recognized by physicians, particularly for non-diabetic patients.

For patients with obesity and established cardiovascular disease, GLP-1 agonists offer significant cardiovascular risk reduction (20% reduction in MACE in non-diabetics). Prescribers should be aware of these benefits to ensure appropriate patient selection and counseling, regardless of diabetic status.

The gut pathobiont Bilophila wadsworthia acts as a glycine sink by metabolizing glycine via the glycine reductase pathway, thereby lowering circulating glycine levels and negatively impacting metabolic markers.

The presence of the gut bacteria Bilophila wadsworthia consumes glycine, reducing its beneficial effects. Vegan diets tend to reduce this bacteria, thereby increasing glycine. While probiotics targeting this specific bacteria are not yet standard, understanding this link highlights why microbiome composition matters for metabolic health.

Imaging-based body composition assessment (DXA, CT, or MRI) is required to demonstrate that weight loss from anti-obesity drugs is attributable to fat mass reduction rather than lean mass loss, as mandated by updated US FDA and Korean MFDS guidelines.

If you are taking anti-obesity medication, ask your provider about body composition analysis (DXA or CT) rather than relying solely on weight. This ensures your weight loss is coming from fat stores and not muscle tissue, which is critical for long-term metabolic health and is now a regulatory standard for drug approval.

DXA is the preferred imaging modality for anti-obesity drug trials due to its balance of low radiation, cost-effectiveness, and accessibility, although CT and MRI offer superior precision for visceral fat and muscle quality assessment.

For most obesity drug trials, DXA is the standard imaging tool because it is cheap, safe, and widely available. However, if detailed analysis of visceral fat or muscle quality (myosteatosis) is needed, CT or MRI may be used despite higher costs.

MASLD is an independent risk factor for cardiovascular disease, including heart failure (particularly HFpEF), atrial fibrillation, and atherosclerosis, driven by shared mechanisms like insulin resistance and inflammation.

If you have fatty liver disease (MASLD), you are at a significantly higher risk for heart problems, including heart failure and atrial fibrillation, even if your liver enzymes are normal. This risk is driven by the same metabolic issues that cause fatty liver. You need regular cardiovascular screening and aggressive management of blood pressure, cholesterol, and blood sugar to protect your heart.

GLP-1 receptor agonists are associated with gastrointestinal side effects (nausea, vomiting, diarrhea) and potentially increased risks of pancreatitis and thyroid cancer.

GLP-1 agonists commonly cause GI issues like nausea and diarrhea, especially when starting or increasing the dose. Serious but rare risks include pancreatitis and thyroid cancer. Monitor your health and report severe symptoms to your doctor.

GLP-1 based therapies carry class-wide safety warnings including gastrointestinal effects, gallbladder events, pancreatitis risk, and a boxed warning for medullary thyroid carcinoma based on rodent data.

These medications work well but can cause nausea, vomiting, or other GI issues. Your doctor will start you on a low dose and slowly increase it to help your body adjust. If you have a family history of specific thyroid cancers, you cannot take these drugs.

Creatine supplementation does not significantly affect fat mass (FM), BMI, or body fat percentage (BFP) in the general population, although specific loading protocols with maintenance phases may lead to modest BFP reductions.

Do not take creatine expecting it to burn fat or change your body fat percentage. It will not significantly affect your fat mass or BMI. Its primary benefit is adding lean muscle mass when combined with resistance training.

GLP-1 receptor agonists provide renoprotective effects by slowing eGFR decline and reducing albuminuria in patients with type 2 diabetes and chronic kidney disease.

If you have diabetes and kidney issues, GLP-1 medications can help protect your kidneys and heart, not just your blood sugar. This protection happens through multiple mechanisms, including reducing inflammation and improving blood flow to the kidneys. However, gastrointestinal side effects are common and may require dose adjustments or management strategies.

Tirzepatide sensitizes leptin signaling in hypothalamic POMC and GLP-1R neurons, increasing POMC neuronal firing by decreasing inhibitory postsynaptic input.

Tirzepatide works in part by making your brain's natural weight-regulating hormones more effective. This leads to reduced hunger and increased energy expenditure, contributing to weight loss.

Discontinuation of incretin-based pharmacotherapy (GLP-1 or dual GLP-1/GIP agonists) leads to partial or complete weight regain due to the reactivation of homeostatic neurohormonal systems (increased ghrelin, decreased leptin and peptide YY), confirming obesity as a chronic condition requiring long-term management.

If you stop taking your incretin medication (like semaglutide or tirzepatide), your body's natural hunger signals will likely return, causing you to regain the weight you lost. This is a biological response, not a lack of willpower. To keep the weight off, you must treat obesity as a chronic condition and continue your medication and lifestyle habits long-term, just as you would for high blood pressure.

GLP-1 receptor agonists improve cardiovascular outcomes in patients with atherosclerotic cardiovascular disease (ASCVD) and heart failure with preserved ejection fraction (HFpEF), but may increase heart failure hospitalization risk in patients with heart failure with reduced ejection fraction (HFrEF).

If you have heart disease or heart failure, GLP-1 RAs can significantly reduce your risk of major cardiovascular events like heart attack or stroke, especially if you have HFpEF. However, if you have HFrEF (reduced ejection fraction), these drugs may increase your risk of hospitalization, so your doctor will need to carefully weigh the risks and benefits.

Retatrutide has the highest adverse event risk among the treatments studied.

Clinicians should be aware of the higher risk of adverse events when prescribing retatrutide.

Gastrointestinal adverse events were reported in 79.6% of the cagrilintide-semaglutide group and 39.9% in the placebo group.

Clinicians should monitor for gastrointestinal side effects in patients receiving cagrilintide-semaglutide.

Gastrointestinal adverse events were more common with oral semaglutide than with placebo (74.0% vs. 42.2%).

Clinicians should monitor for gastrointestinal side effects in patients taking oral semaglutide.

Treatment persistence was high, with 80% of patients completing 6 months of therapy.

High treatment persistence suggests that patients are likely to continue tirzepatide therapy.

Gastrointestinal adverse events were the most frequently reported but rarely led to treatment discontinuation.

Practitioners should monitor for gastrointestinal side effects but can expect them to be manageable.

Gastrointestinal adverse effects were the most commonly reported side effects of retatrutide.

Clinicians should monitor for gastrointestinal side effects in patients treated with retatrutide.

One-year discontinuation was significantly higher for patients without type 2 diabetes (64.8%) compared with those with type 2 diabetes (46.5%).

Practitioners should be aware that patients without type 2 diabetes may struggle more with adherence to GLP-1 RA therapy.

69,213,936 prescriptions for obesity medications (OMDs) were dispensed in the US from July 2017 to February 2024, with a mean annual growth rate of 5.3%.

Healthcare providers should be aware of the increasing trend in OMD prescriptions.

Gastrointestinal adverse events were common with maridebart cafraglutide, although less frequent with dose escalation and a lower starting dose.

Clinicians should monitor for gastrointestinal side effects when prescribing maridebart cafraglutide.

The restore diet reduced gut microbiome diversity but enhanced the persistence of L. reuteri strain.

Practitioners should note that while diversity may decrease, specific beneficial strains can be enhanced through targeted dietary interventions.

Prolonged, intense weight-bearing exercise can increase intestinal permeability but effects are transient.

While intense exercise can temporarily affect gut health, these effects are not long-lasting.

In patients with cardiometabolic HFpEF, tirzepatide showed a 58% lower risk of hospitalization for heart failure or all-cause mortality compared with sitagliptin.

Tirzepatide may also be a beneficial treatment option for patients with HFpEF and cardiometabolic conditions.