Evidence Grade A — Regulatory approved. 4762 published studies. 559 registered clinical trials.
Medically reviewed by a licensed medical professional
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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.
Semaglutide is also known by these brand and alternate names:
4,762 published studies: 2708 human, 221 animal, 111 in-vitro, 1341 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.
PeptideTrace tracks 559 registered clinical trials for Semaglutide sourced from ClinicalTrials.gov.
Personalized Pharmaco-Lifestyle Interventions for Severe Mental Illnesses (LIFETRAIN)
GLP-1 RA for Stage 1 Type 1 Diabetes
SHIELD-T1D: Shingrix and GLP-1 Agonist for Beta-Cell Preservation in Recent-Onset Type 1 Diabetes.
Promoting Healthy Children and Youth
Semaglutide PrIor to CathEeter Ablation in Patients With Atrial Fibrillation
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Semaglutide is a 31-amino-acid modified GLP-1 analogue with 94% homology to native human GLP-1. It features a C18 fatty diacid chain attached at lysine-26 enabling non-covalent albumin binding, an Aib substitution at position 8 for DPP-4 resistance, and an Arg34Lys swap. These modifications give it a half-life of approximately 155–184 hours (~7 days), enabling once-weekly subcutaneous dosing. An oral formulation uses SNAC co-formulation for transcellular gastric absorption.
Semaglutide binds the GLP-1 receptor (class B GPCR), activating the Gs/adenylyl cyclase/cAMP/PKA signaling cascade. This produces glucose-dependent insulin secretion from pancreatic β-cells, glucagon suppression from α-cells, delayed gastric emptying, and centrally mediated appetite suppression via hypothalamic and brainstem GLP-1R populations. Ad libitum caloric intake is reduced by approximately 35%. The oral formulation (Rybelsus) uses sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) to raise local gastric pH, enhancing semaglutide solubility and enabling passive transcellular absorption.
Semaglutide is marketed as Ozempic (SC injection for type 2 diabetes, approved December 5, 2017), Rybelsus (oral tablets for type 2 diabetes, approved September 20, 2019), and Wegovy (SC injection for chronic weight management, approved June 4, 2021). Wegovy has since been approved for cardiovascular risk reduction in overweight/obese adults with established CVD (March 2024), adolescents aged 12+ (December 2022), and noncirrhotic MASH with F2-F3 fibrosis (August 2025, accelerated approval). Oral Wegovy 25 mg was approved December 2025. In the STEP 1 trial (N=1,961), semaglutide 2.4 mg achieved 14.9% mean body weight loss versus 2.4% with placebo over 68 weeks. In SELECT (N=17,604), it reduced 3-point MACE by 20% (HR 0.80; 95% CI 0.72–0.90). The SUSTAIN program showed HbA1c reductions of 1.5–1.8%, and SUSTAIN 6 demonstrated cardiovascular superiority (HR 0.74 for MACE). The FLOW trial showed a 24% reduction in kidney disease progression in patients with T2DM and CKD.
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Bimagrumab is in Phase II/III development (not yet approved). A Phase II trial (75 patients with type 2 diabetes and obesity) showed 20.5% fat mass reduction with 3.6% lean mass increase — essentially reshaping body composition without net appetite suppression. The BELIEVE Phase IIb trial (507 patients) showed that bimagrumab plus semaglutide achieved 22% weight loss with the weight lost being 88% fat — significantly better body composition than semaglutide alone. Bimagrumab is not a peptide. Its strategic significance is as a combination partner to address the muscle loss problem inherent in weight loss with current obesity drugs. Eli Lilly's acquisition positions it alongside tirzepatide.
Pemvidutide is in Phase II/III development (not yet approved). In the MOMENTUM Phase II trial (391 patients, 48 weeks), the 2.4 mg dose achieved 15.6% weight loss. Body composition analysis showed 78% of weight lost was fat mass, with only 22% lean mass — a favourable ratio. A Phase IIb MASH trial (212 patients) showed MASH resolution in up to 75% of patients at the highest dose. Pemvidutide's balanced receptor profile and no-titration dosing regimen represent potential practical advantages. The high rate of MASH resolution in Phase II positions it as a candidate for liver disease indications alongside obesity.
MariTide is in Phase II/III development (not yet approved). Phase II results (592 patients, 52 weeks) showed 16–20% weight loss across doses. Body composition analysis showed 26–37% fat mass reduction with 8–13% lean mass reduction. Notably, weight loss appeared to continue beyond the 52-week treatment period without plateau. MariTide's monthly dosing would be a significant convenience advantage if efficacy is confirmed in Phase III. The ongoing weight loss trajectory without plateau is particularly interesting and distinguishes it from some GLP-1 agonists where weight loss plateaus. Amgen is conducting Phase III trials.
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