GLP-1 Evidence

Drug

Semaglutide: what the trials show

Semaglutide at 2.4 mg weekly produced about 15% mean body-weight loss over 68 weeks. That number is real, replicated, and frequently misread.

Updated 3 min read 32 citations Evidence strength 5/5

Loose round tablets stamped with an identifying code, seen from above
Larry D. Moore · CC BY 4.0 · Wikimedia Commons

The headline trial

STEP 1 randomised adults with overweight or obesity and without diabetes to weekly semaglutide 2.4 mg or placebo, both with lifestyle intervention, for 68 weeks [9]. Mean weight change was about −14.9% on drug versus −2.4% on placebo. Roughly a third of participants on drug lost 20% or more of body weight — an outcome that had previously been the province of bariatric surgery.

Two things are worth holding onto. First, that is a mean: the distribution is wide, and a substantial minority lose very little. Second, the placebo arm also received lifestyle counselling, so the 2.4% is not "doing nothing" — the drug effect is measured on top of advice that itself does something.

The number is smaller if you have diabetes

STEP 2 ran the same design in adults with type 2 diabetes and found roughly 9.6% weight loss at the same dose [8]. That gap between about 15% and about 10% shows up repeatedly across the class and is not specific to semaglutide. Comparative meta-analysis across GLP-1 agonists shows the same pattern on both weight and glycaemic endpoints [3].

Semaglutide 2.4 mg weekly — mean weight change by population
TrialPopulationDurationMean weight changePlacebo
STEP 1 [9]Obesity, no diabetes68 weeks≈ −14.9%≈ −2.4%
STEP 2 [8]Obesity + type 2 diabetes68 weeks≈ −9.6%≈ −3.4%
STEP 4 [7]Continued vs withdrawn after 20 weeks48 further weeksContinued: further lossWithdrawn: regain
SELECT [5]Obesity + cardiovascular disease~4 yearsSustained ≈ −10%≈ −1.5%

How long does it keep working?

Longer than the 68-week trials suggested. A meta-analysis of the longer-term data found the effect sustained well beyond a year [1], and the SELECT cardiovascular trial — which ran about four years and was not designed as a weight trial — showed weight loss plateauing at roughly 10% and then holding, rather than eroding [5]. The plateau is real; the reversal that critics predicted is not, provided treatment continues.

Sustained weight loss on continued treatment

Semaglutide versus tirzepatide

For type 2 diabetes, SURPASS-2 compared tirzepatide against semaglutide 1 mg and favoured tirzepatide. For obesity specifically, the direct comparison at obesity doses came later and was decisive: tirzepatide produced substantially greater mean weight loss than semaglutide [10], consistent with the earlier real-world and indirect comparisons [11].

That does not automatically make tirzepatide the right choice for an individual — tolerability, cost, supply and comorbidities all bear on it — but on weight loss alone the ordering is not in dispute. See tirzepatide.

Where semaglutide has a guideline behind it

Beyond weight, semaglutide has moved into formal guidance for metabolic dysfunction-associated steatotic liver disease, where the joint European guidelines address its role [2]. It is also the only agent in the class with a completed cardiovascular outcome trial in a non-diabetic obese population [5], which is covered on the cardiovascular page.

Common questions

Is Wegovy different from Ozempic?
Same molecule, different licensed dose and indication. The obesity trials used 2.4 mg weekly; the diabetes dosing is lower. Effect sizes quoted for weight loss come from the higher dose.
Why did I lose less than 15%?
Because 15% is a mean. Response varies widely between individuals in every trial, and people with type 2 diabetes lose roughly a third less on average [8].
Does it stop working after a few months?
No. Weight loss slows and plateaus, typically over the second year, but the longer-term data show the loss is maintained on continued treatment [1][5].
Can I take it just to lose a few kilograms and then stop?
You can, but expect most of the loss to return. That is the consistent finding of the withdrawal data [6][7] and is discussed in full on the stopping page.
Chemistry laboratory bench with glassware and reagent bottles in place
Cjp24 · CC BY-SA 3.0 · Wikimedia Commons
The evidence behind this page A stacked bar showing the composition of the 32 publications cited on this page by study type. 922meta-analysis (9)randomised trial (22)other (1)
32 publications, 2017–2025. That is a mix with both trials and syntheses in it, which is the position from which a claim about cause is reasonable. Source: this page’s own citation list, below.

References

Every citation below links to the original peer-reviewed record on PubMed or via DOI. Nothing here is a substitute for medical advice.

  1. Effect of glucagon-like peptide-1 receptor agonists and co-agonists on body composition: Systematic review and network meta-analysis Karakasis P, Patoulias D, Fragakis N, et al. · Metabolism: clinical and experimental · 2025 · Meta-analysis DOIPubMed 39719170
  2. Subcutaneously administered tirzepatide vs semaglutide for adults with type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials Karagiannis T, Malandris K, Avgerinos I, et al. · Diabetologia · 2024 · Meta-analysis DOIPubMed 38613667Full text
  3. Long-Term Efficacy and Safety of Once-Weekly Semaglutide for Weight Loss in Patients Without Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Moiz A, Levett JY, Filion KB, et al. · The American journal of cardiology · 2024 · Meta-analysis DOIPubMed 38679221
  4. EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD) Journal of hepatology · 2024 · Clinical guideline DOIPubMed 38851997
  5. A systematic review of the effect of semaglutide on lean mass: insights from clinical trials Bikou A, Dermiki-Gkana F, Penteris M, et al. · Expert opinion on pharmacotherapy · 2024 · Systematic review DOIPubMed 38629387
  6. Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis Yao H, Zhang A, Li D, et al. · BMJ (Clinical research ed.) · 2024 · Meta-analysis DOIPubMed 38286487Full text
  7. Assessment of Thyroid Carcinogenic Risk and Safety Profile of GLP1-RA Semaglutide (Ozempic) Therapy for Diabetes Mellitus and Obesity: A Systematic Literature Review Feier CVI, Vonica RC, Faur AM, et al. · International journal of molecular sciences · 2024 · Systematic review DOIPubMed 38673931Full text
  8. Once-weekly  semaglutide  for obesity  or overweight: A systematic review and meta-analysis He K, Guo Q, Zhang H, et al. · Diabetes, obesity & metabolism · 2022 · Meta-analysis DOIPubMed 34866313
  9. Efficacy and Safety of Semaglutide for Weight Loss in Obesity Without Diabetes: A Systematic Review and Meta-Analysis Tan HC, Dampil OA, Marquez MM · Journal of the ASEAN Federation of Endocrine Societies · 2022 · Meta-analysis DOIPubMed 36578889Full text
  10. Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial Wharton S, Freitas P, Hjelmesæth J, et al. · The lancet. Diabetes & endocrinology · 2025 · Randomised controlled trial DOIPubMed 40961952
  11. Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity Wharton S, Lingvay I, Bogdanski P, et al. · The New England journal of medicine · 2025 · Randomised controlled trial DOIPubMed 40934115
  12. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity Garvey WT, Blüher M, Osorto Contreras CK, et al. · The New England journal of medicine · 2025 · Randomised controlled trial DOIPubMed 40544433
  13. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes Davies MJ, Bajaj HS, Broholm C, et al. · The New England journal of medicine · 2025 · Randomised controlled trial DOIPubMed 40544432
  14. evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer's disease Cummings JL, Atri A, Feldman HH, et al. · Alzheimer's research & therapy · 2025 · Randomised controlled trial DOIPubMed 39780249Full text
  15. Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials Butler J, Shah SJ, Petrie MC, et al. · Lancet (London, England) · 2024 · Randomised controlled trial DOIPubMed 38599221Full text
  16. Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial Deanfield J, Verma S, Scirica BM, et al. · Lancet (London, England) · 2024 · Randomised controlled trial DOIPubMed 39181597
  17. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial Ryan DH, Lingvay I, Deanfield J, et al. · Nature medicine · 2024 · Randomised controlled trial DOIPubMed 38740993Full text
  18. Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial Colhoun HM, Lingvay I, Brown PM, et al. · Nature medicine · 2024 · Randomised controlled trial DOIPubMed 38796653Full text
  19. Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis Bliddal H, Bays H, Czernichow S, et al. · The New England journal of medicine · 2024 · Randomised controlled trial DOIPubMed 39476339
  20. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. · The New England journal of medicine · 2023 · Randomised controlled trial DOIPubMed 37952131
  21. Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population (STEP 6): a randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial Kadowaki T, Isendahl J, Khalid U, et al. · The lancet. Diabetes & endocrinology · 2022 · Randomised controlled trial DOIPubMed 35131037
  22. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial Garvey WT, Batterham RL, Bhatta M, et al. · Nature medicine · 2022 · Randomised controlled trial DOIPubMed 36216945Full text
  23. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension Wilding JPH, Batterham RL, Davies M, et al. · Diabetes, obesity & metabolism · 2022 · Randomised controlled trial DOIPubMed 35441470Full text
  24. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial Wadden TA, Bailey TS, Billings LK, et al. · JAMA · 2021 · Randomised controlled trial DOIPubMed 33625476Full text
  25. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial Rubino D, Abrahamsson N, Davies M, et al. · JAMA · 2021 · Randomised controlled trial DOIPubMed 33755728Full text
  26. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial Davies M, Færch L, Jeppesen OK, et al. · Lancet (London, England) · 2021 · Randomised controlled trial DOIPubMed 33667417
  27. Once-Weekly Semaglutide in Adults with Overweight or Obesity Wilding JPH, Batterham RL, Calanna S, et al. · The New England journal of medicine · 2021 · Randomised controlled trial DOIPubMed 33567185
  28. The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity Friedrichsen M, Breitschaft A, Tadayon S, et al. · Diabetes, obesity & metabolism · 2021 · Randomised controlled trial DOIPubMed 33269530Full text
  29. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial Pratley RE, Aroda VR, Lingvay I, et al. · The lancet. Diabetes & endocrinology · 2018 · Randomised controlled trial DOIPubMed 29397376
  30. Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity Blundell J, Finlayson G, Axelsen M, et al. · Diabetes, obesity & metabolism · 2017 · Randomised controlled trial DOIPubMed 28266779Full text
  31. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity Aronne LJ, Horn DB, le Roux CW, et al. · The New England journal of medicine · 2025 · Clinical trial DOIPubMed 40353578
  32. Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity Rodriguez PJ, Goodwin Cartwright BM, Gratzl S, et al. · JAMA internal medicine · 2024 · Journal article DOIPubMed 38976257Full text