Ozempic, Wegovy, Rybelsus
Evidence Grade A — Regulatory approved. 4412 published studies. 583 registered clinical trials.
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Semaglutide is a once-weekly injection (sold as Ozempic for diabetes and Wegovy for weight management) or daily tablet (Rybelsus for diabetes) that mimics GLP-1, a natural gut hormone that controls blood sugar and appetite. It has become one of the most widely discussed medications in the world, with clinical trial data spanning over 50,000 patients showing significant benefits for diabetes, weight loss, heart disease, and kidney protection.
4,412 published studies: 2543 human, 206 animal, 98 in-vitro, 1247 reviews
Semaglutide is one of the most extensively studied peptide medications available today, with clinical trial data spanning over 50,000 patients. It is sold as Ozempic for type 2 diabetes (approved 2017), Rybelsus as an oral tablet for diabetes (approved 2019), and Wegovy for weight management (approved 2021). Wegovy has since received additional approvals for reducing heart attack and stroke risk, for use in adolescents aged 12 and older, and for liver disease related to obesity.
In clinical trials, patients taking Wegovy lost an average of 14.9% of their body weight over 68 weeks, and the SELECT trial demonstrated a 20% reduction in major cardiovascular events such as heart attack and stroke. Research is now exploring its potential in early Alzheimer's disease. The main side effects are gastrointestinal, particularly nausea, and a key limitation is that most weight tends to return after stopping treatment.
When you eat, your gut releases a hormone called GLP-1 that tells your pancreas to produce insulin, signals your brain that you are full, and slows the rate food leaves your stomach. Semaglutide is an engineered version of this hormone, modified to last about a week in the body instead of minutes. It works through the same natural pathways but with a much stronger and longer-lasting effect, reducing calorie intake by roughly 35% and producing significant weight loss alongside improved blood sugar control.
Semaglutide's evidence is among the most extensive for any medication. In weight management trials, patients lost an average of 14.9% of body weight over 68 weeks. The SELECT trial showed a 20% reduction in heart attacks and strokes in people with obesity, making Wegovy the first obesity treatment proven to reduce cardiovascular events. The FLOW trial demonstrated kidney protection in people with diabetes. An FDA review in January 2024 found no evidence linking semaglutide to suicidal thoughts. Key limitations include gastrointestinal side effects (particularly nausea, which tends to improve over time), a boxed warning about thyroid tumours observed in rodents (not confirmed in humans), and the problem of weight regain — approximately two-thirds of lost weight returns within a year of stopping treatment. Research is now exploring its potential in early Alzheimer's disease, with results expected in 2025–2026. Semaglutide has been substantially surpassed in weight loss by tirzepatide.
PEG-rhGH and Semaglutide Combination Therapy in Non-Diabetic Obese Adults
GLP-1 RA for Stage 1 Type 1 Diabetes
Promoting Healthy Children and Youth
Semaglutide PrIor to CathEeter Ablation in Patients With Atrial Fibrillation
SHAPE-ENDO: Multimodal Pre-Surgical Optimization in Patients With Obesity and Early-Stage Endometrial Cancer
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Liraglutide is marketed as Victoza for type 2 diabetes (approved 2010) and Saxenda for weight management (approved 2014). The LEADER trial, involving over 9,300 patients followed for nearly four years, established that liraglutide reduced the risk of major cardiovascular events by 13% — a landmark finding that helped establish GLP-1 treatments as a class with heart benefits. Saxenda is also approved for adolescents aged 12 and older. While historically significant, liraglutide has been substantially surpassed by newer agents. In a direct comparison, semaglutide achieved 15.8% weight loss compared to liraglutide's 6.4%. Liraglutide remains relevant as a lower-intensity option and as a benchmark against which newer treatments are measured. It has over a decade of real-world safety data, making it one of the best-understood medications in this class.
Setmelanotide is marketed as Imcivree (Rhythm Pharmaceuticals; approved November 2020 for POMC, PCSK1, or LEPR deficiency; June 2022 for Bardet-Biedl syndrome; December 2024 expanded to patients aged 2 years and older). Genetic testing confirming an eligible mutation is required before treatment. In patients with POMC or PCSK1 deficiency, approximately 80% achieved at least 10% weight loss in clinical trials. In Bardet-Biedl syndrome, 32.3% achieved the same threshold. The most common side effects are injection-site reactions and skin darkening (due to the melanocortin pathway's connection to pigmentation). Setmelanotide exemplifies precision medicine — it is highly effective in the specific genetic populations it targets but is not indicated for common obesity.
HGH Fragment 176-191 has no marketing authorisation. A Phase IIa trial in obesity (approximately 300 patients) failed to demonstrate statistically significant weight loss at any dose tested. The clinical development programme was discontinued. The disconnect between animal data (which showed significant fat reduction in obese mice) and the failed human trial is the defining feature of this compound's development history. Products available through unregulated channels lack pharmaceutical quality assurance. The failed Phase II trial represents the highest level of clinical evidence available.
