Browse the evidence

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.

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.

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.

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.

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.

GIP accounts for 60% to 80% of the postprandial insulin response.

Understanding GIP's role can help in managing postprandial insulin levels.

GIP is overexpressed in obese individuals, which may exacerbate insulin resistance.

Addressing GIP levels may be important in treating obesity-related insulin resistance.

Novel GLP-1-based therapeutics are rapidly advancing and may reshape the future landscape of obesity and type 2 diabetes treatment.

Practitioners should consider the potential of these novel agents in treating obesity and type 2 diabetes.

Triple agonists such as retatrutide target GIP, GLP-1, and glucagon receptors to amplify metabolic effects.

Consider the potential of triple agonists in enhancing metabolic outcomes for patients.

NN1706 lowers body weight & improves glycemic control in obese rodents and monkeys.

NN1706 may also be beneficial for weight management and glycemic control in animal models of obesity.

Increased heart rate was observed across NN1706 treatment cohorts.

Clinicians should monitor heart rate in patients receiving NN1706 treatment.

Challenges with GLP-1s include side effects, nutritional deficiencies, and low long-term adherence.

Clinicians should be aware of and manage these challenges when prescribing GLP-1s.

Gastrointestinal tract adverse events were reported by 63.4% of participants on semaglutide.

Practitioners should monitor for gastrointestinal side effects in patients taking semaglutide.

GLP-1RA prescriptions significantly increased across all BMI categories among youth and adults with type 1 diabetes over the last 15 years.

Clinicians should consider the increasing use of GLP-1RAs in managing obesity in T1D patients.

GLP-1RAs may have little or no effect on breast cancer risk.

Practitioners should consider that GLP-1RAs may not significantly increase breast cancer risk based on current evidence.

The review focuses on glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in the context of anti-obesity drug discovery.

Practitioners should consider the role of GLP-1 RAs in developing new anti-obesity therapies.

Postoperative weight regain (WR) affects 20-30% of patients after bariatric surgery.

Clinicians should be aware that a significant portion of bariatric surgery patients may experience weight regain.