Peptide Graded

Semaglutide

Does Semaglutide work?

Yes, in large controlled trials. One trial followed 17,604 people.

AStrong human evidenceFDA approvedas of 2026-10-26

Semaglutide has one of the largest trial programs of any peptide: the STEP trials in obesity (STEP 1, 1,961 adults), the SUSTAIN trials in type 2 diabetes, SELECT (17,604 adults with cardiovascular disease and obesity, the largest), FLOW in kidney disease, and systematic reviews pooling tens of thousands of participants. Weight loss, glucose lowering and reductions in heart attack, stroke and kidney outcomes are all shown in randomized placebo-controlled trials. What remains open is what happens over decades and how to stop without regaining. 2356910

STEP 1 randomized 1,961 adults with obesity but no diabetes. They got weekly semaglutide or placebo for 68 weeks, alongside lifestyle counseling. Mean weight loss was 14.9 percent versus 2.4 percent. Half of semaglutide patients lost at least 15 percent. STEP 8 was a head-to-head trial in 338 adults. Semaglutide produced 15.8 percent weight loss versus 6.4 percent with daily liraglutide. STEP 4 showed what happens to people who stop. All took the drug for 20 weeks. Those then switched to placebo regained 6.9 percent over the next 48 weeks. Those who continued lost a further 7.9 percent. In the STEP 1 extension, participants who stopped treatment regained two-thirds of their lost weight within a year. 26812

SELECT enrolled 17,604 adults aged 45 and older. All had cardiovascular disease and overweight or obesity, but no diabetes. Over a mean of 40 months, cardiovascular death, heart attack or stroke occurred in 6.5 percent on semaglutide. On placebo it was 8.0 percent. That is a 20 percent relative reduction. The benefit held in the quarter of participants with heart failure. It held across all baseline weights. FLOW enrolled people with type 2 diabetes and chronic kidney disease. It showed a 24 percent reduction in kidney disease progression and cardiovascular death. 39101113

Evidence checklist

  • Randomised controlled trial STEP, SUSTAIN, SELECT, FLOW trials
  • Human study over 100 people SELECT, 17,604 adults; STEP 1, 1,961
  • More than one research group Many trial programmes plus pooled reviews
  • Clinical outcomes, not surrogate markers Heart attack, stroke, kidney outcomes reduced
  • Human safety data beyond case reports Large trials; GI effects, boxed thyroid warning

Read the full Semaglutide page

More on Semaglutide

Citations

  1. Ozempic (semaglutide) prescribing information, FDA, 2023 accessdata.fda.gov
  2. Wilding 2021, N Engl J Med: once-weekly semaglutide in adults with overweight or obesity (STEP 1) pubmed.ncbi.nlm.nih.gov
  3. Lincoff 2023, N Engl J Med: semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT) pubmed.ncbi.nlm.nih.gov
  4. Frías 2021, Lancet Diabetes Endocrinol: higher versus standard dose semaglutide in type 2 diabetes (SUSTAIN FORTE) pubmed.ncbi.nlm.nih.gov
  5. Diabetol Metab Syndr 2023: systematic review and meta-analysis of subcutaneous semaglutide in type 2 diabetes pubmed.ncbi.nlm.nih.gov
  6. Rubino 2022, JAMA: semaglutide versus liraglutide for weight loss (STEP 8) pubmed.ncbi.nlm.nih.gov
  7. Wegovy (semaglutide) prescribing information, DailyMed dailymed.nlm.nih.gov
  8. Rubino 2021, JAMA: continued semaglutide versus placebo for weight maintenance (STEP 4) pubmed.ncbi.nlm.nih.gov
  9. Deanfield 2024, Lancet: semaglutide in patients with obesity and heart failure, SELECT prespecified analysis pubmed.ncbi.nlm.nih.gov
  10. Lincoff 2023, N Engl J Med: SELECT trial (DOI record) doi.org
  11. Lancet 2025: semaglutide and cardiovascular outcomes by adiposity measures, SELECT prespecified analysis pubmed.ncbi.nlm.nih.gov
  12. Wilding 2022, Diabetes Obes Metab: weight regain after withdrawal of semaglutide, STEP 1 extension pubmed.ncbi.nlm.nih.gov
  13. Perkovic 2024, N Engl J Med: effects of semaglutide on chronic kidney disease in type 2 diabetes (FLOW) doi.org
  14. AJMC 2025: FDA approves semaglutide for MASH with fibrosis ajmc.com
  15. Healio 2026: FDA approves Wegovy pill, the first oral GLP-1 for obesity healio.com
  16. Jastreboff 2022, N Engl J Med: tirzepatide once weekly for obesity (SURMOUNT-1) pubmed.ncbi.nlm.nih.gov
  17. Karagiannis 2024, Diabetologia: tirzepatide versus semaglutide in type 2 diabetes, network meta-analysis pubmed.ncbi.nlm.nih.gov

Reference information only, not medical advice. Drawn from the Semaglutide article, fact-checked against the cited sources. No dosing anywhere on this site.