Evidence Grade A — Regulatory approved. 4702 published studies. 588 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:
4,702 published studies: 2693 human, 220 animal, 110 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 588 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
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 (Phase 1)
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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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Danuglipron's original twice-daily formulation achieved 8–13% weight loss in Phase IIb but with treatment discontinuation rates exceeding 50%, with nausea affecting up to 73% of patients. Pfizer discontinued the twice-daily formulation and is developing a once-daily modified-release version. Danuglipron is not a peptide. Its development trajectory illustrates that even effective weight loss compounds can fail commercially if tolerability is inadequate. The reformulation effort aims to reduce peak drug concentrations that likely drive the gastrointestinal side effects.
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.
CT-388 is in Phase II/III development (not yet approved). Phase II results (469 patients, 48 weeks) showed 22.5% placebo-adjusted weight loss at the highest dose, with low discontinuation rates due to adverse events (5.9%). Phase III trials are underway. The combination of high efficacy and low discontinuation rates in Phase II is notable — many obesity drugs achieve high weight loss but suffer from tolerability-driven dropouts. Roche's $2.7 billion acquisition of the developer signals significant confidence in the programme.
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