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 11 citations Evidence strength 5/5

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STEP 4 [7]Continued vs withdrawn after 20 weeks48 further weeksContinued: further lossWithdrawn: regain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.

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. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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