Semaglutide

AApproved (Rx)OzempicWegovyRybelsus
In one paragraphSemaglutide 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 gradeA Established
Human trials30+ RCTs
Outcomes graded5
Last reviewed1 September 2026
EvidenceWhat it isHow it worksUnknownsRegulationQuestionsReferences

What the human research shows

One of the best-evidenced molecules of the decade, with large, consistent effects on weight and blood sugar and a documented cost in side effects. The grades are A because tens of thousands of people have been through controlled trials — not because it is without trade-offs.

OutcomeGradeEffect sizeHuman studiesWhere the evidence comes from
Body weightAEstablishedLarge15+ RCTsSTEP programme. Roughly 15% mean loss at 68 weeks versus placebo; consistent across trials.1
Blood glucose (HbA1c)AEstablishedLarge10+ RCTsSUSTAIN programme; the original approval basis in type 2 diabetes.2
Major cardiovascular eventsAEstablishedModerate1 large RCTSELECT trial, 17,604 participants: a 20% relative reduction in people with established cardiovascular disease and no diabetes.3
GI side effectsadverseAEstablishedLargeAll trialsNausea, vomiting and constipation are the most common reasons people stop. Well quantified.13
Lean mass lossadverseBProbableModerateSub-studiesA share of weight lost is lean tissue; magnitude and clinical importance still debated.14
AMultiple good human trials, consistentBSome human trials, mostly consistentCFew or weak human studiesDAnimal or anecdotal onlyeffect size · red = adverse

Literature searched to 1 September 2026. Human studies only; animal and cell work informs the mechanism section and nothing else.

What it is

Semaglutide is a modified version of GLP-1, a hormone the gut releases after eating. The modifications extend its half-life from minutes to about a week, which is what makes once-weekly injection possible.

It was approved for type 2 diabetes in 2017 and for chronic weight management in 2021. It is one of the most prescribed medicines in the world and the reason the word “peptide” entered ordinary conversation.

How it is thought to work

It activates GLP-1 receptors in the pancreas, gut and brain: more insulin when glucose is high, slower stomach emptying, and reduced appetite through central signalling. The weight-loss effect is mostly the last of these.

What is still unknown

  • What happens to weight and cardiometabolic risk after stopping; regain is substantial in the trials that have looked.
  • The long-term significance of lean-mass loss, and whether it matters more in older adults.
  • Rare adverse events at population scale, which trials are not powered to detect.

Regulatory status

European Union
Approved, prescription-only

Authorised by the EMA. Grey-market versions are unlicensed medicines.

United States
Approved, prescription-only

FDA-approved. Compounded versions were permitted during shortage and are now restricted.

United Kingdom
Approved, prescription-only

MHRA has issued warnings about counterfeit pens.

Sweden
Approved, prescription-only

Subsidy rules for weight management differ from diabetes.

Questions people actually ask

How much weight do people lose on semaglutide?
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.
Does the weight come back after stopping?
Largely, yes. In the trial that withdrew treatment after a year, participants regained about two-thirds of the lost weight within the following year.
Is semaglutide a peptide?
Yes — it is a 31-amino-acid peptide, a modified form of the natural hormone GLP-1.
Why are there so many fake versions?
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

  1. 1
    Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1).N Engl J Med, 2021;384:989–10021,961 adults; −14.9% vs −2.4% at 68 weeks.
  2. 2
  3. 3
    Lincoff AM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT).N Engl J Med, 2023;389:2221–223217,604 participants; hazard ratio 0.80 for MACE.
  4. 4
    Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension.Diabetes Obes Metab, 2022Two-thirds of lost weight regained within a year of stopping.

Change log

  • 2026-09-01Initial publication.