{"id":"semaglutide","name":"Semaglutide","aliases":["Ozempic","Wegovy","Rybelsus","GLP-1 receptor agonist"],"url":"https://lyoresearch.com/compounds/semaglutide","summary":"Semaglutide is a once-weekly GLP-1 receptor agonist approved for type 2 diabetes and, at a higher dose, for weight management. In large randomised trials it produces roughly 15% average weight loss over 68 weeks and reduces major cardiovascular events in people with existing heart disease. Gastrointestinal side effects are common and are the main reason people stop. It is a prescription medicine; products sold outside that channel are unlicensed copies.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"30+ RCTs","regulatory_status":"Approved (Rx)","outcomes":[{"outcome":"Body weight","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"15+ RCTs","evidence":"STEP programme. Roughly 15% mean loss at 68 weeks versus placebo; consistent across trials.","references":[{"citation":"Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1).","where":"N Engl J Med, 2021;384:989–1002","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Wilding+STEP+1+semaglutide+2021+NEJM"}]},{"outcome":"Blood glucose (HbA1c)","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"10+ RCTs","evidence":"SUSTAIN programme; the original approval basis in type 2 diabetes.","references":[{"citation":"Sorli C, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in type 2 diabetes (SUSTAIN 1).","where":"Lancet Diabetes Endocrinol, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Sorli+SUSTAIN+1+semaglutide+2017"}]},{"outcome":"Major cardiovascular events","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"1 large RCT","evidence":"SELECT trial, 17,604 participants: a 20% relative reduction in people with established cardiovascular disease and no diabetes.","references":[{"citation":"Lincoff AM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT).","where":"N Engl J Med, 2023;389:2221–2232","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Lincoff+SELECT+semaglutide+cardiovascular+2023"}]},{"outcome":"GI side effects","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":true,"human_studies":"All trials","evidence":"Nausea, vomiting and constipation are the most common reasons people stop. Well quantified.","references":[{"citation":"Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1).","where":"N Engl J Med, 2021;384:989–1002","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Wilding+STEP+1+semaglutide+2021+NEJM"},{"citation":"Lincoff AM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT).","where":"N Engl J Med, 2023;389:2221–2232","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Lincoff+SELECT+semaglutide+cardiovascular+2023"}]},{"outcome":"Lean mass loss","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":true,"human_studies":"Sub-studies","evidence":"A share of weight lost is lean tissue; magnitude and clinical importance still debated.","references":[{"citation":"Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1).","where":"N Engl J Med, 2021;384:989–1002","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Wilding+STEP+1+semaglutide+2021+NEJM"},{"citation":"Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension.","where":"Diabetes Obes Metab, 2022","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Wilding+STEP+1+extension+withdrawal+semaglutide+2022"}]}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Authorised by the EMA. Grey-market versions are unlicensed medicines."},{"region":"United States","status":"Approved, prescription-only","note":"FDA-approved. Compounded versions were permitted during shortage and are now restricted."},{"region":"United Kingdom","status":"Approved, prescription-only","note":"MHRA has issued warnings about counterfeit pens."},{"region":"Sweden","status":"Approved, prescription-only","note":"Subsidy rules for weight management differ from diabetes."}],"faq":[{"q":"How much weight do people lose on semaglutide?","a":"In the STEP 1 trial, adults without diabetes lost about 15% of body weight on average over 68 weeks, compared with about 2.4% on placebo. Individual results vary widely."},{"q":"Does the weight come back after stopping?","a":"Largely, yes. In the trial that withdrew treatment after a year, participants regained about two-thirds of the lost weight within the following year."},{"q":"Is semaglutide a peptide?","a":"Yes — it is a 31-amino-acid peptide, a modified form of the natural hormone GLP-1."},{"q":"Why are there so many fake versions?","a":"Demand outstripped supply for several years, and the molecule is relatively simple to synthesise. Products sold outside the prescription channel are unlicensed and, in enforcement seizures, frequently underdosed or misidentified."}],"references":[{"cite":"Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1).","where":"N Engl J Med, 2021;384:989–1002","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Wilding+STEP+1+semaglutide+2021+NEJM","note":"1,961 adults; −14.9% vs −2.4% at 68 weeks."},{"cite":"Sorli C, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in type 2 diabetes (SUSTAIN 1).","where":"Lancet Diabetes Endocrinol, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Sorli+SUSTAIN+1+semaglutide+2017","note":"First of the SUSTAIN programme."},{"cite":"Lincoff AM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT).","where":"N Engl J Med, 2023;389:2221–2232","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Lincoff+SELECT+semaglutide+cardiovascular+2023","note":"17,604 participants; hazard ratio 0.80 for MACE."},{"cite":"Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension.","where":"Diabetes Obes Metab, 2022","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Wilding+STEP+1+extension+withdrawal+semaglutide+2022","note":"Two-thirds of lost weight regained within a year of stopping."}],"last_reviewed":"2026-09-01","literature_searched_to":"2026-09-01","changelog":[{"date":"2026-09-01","note":"Initial publication."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}