PeptideTreatments
Reviewed by Peptide Treatments Medical Advisory Board

Semaglutide: Research & Evidence

Established Evidence

Published research, clinical trial data, and evidence grading for Semaglutide across studied indications.

Back to Semaglutide overview

Research Summary

Semaglutide is supported by one of the largest clinical trial programs in metabolic medicine. The SUSTAIN program (trials 1-10) established its efficacy in type 2 diabetes, with SUSTAIN-6 (n=3,297) confirming cardiovascular safety and a 26% reduction in MACE over 2.1 years. The STEP program (trials 1-5) demonstrated weight loss efficacy, with STEP 1 (n=1,961) showing 14.9% mean weight loss at 68 weeks. The SELECT trial (n=17,604) was practice-changing, showing a 20% MACE reduction in patients with obesity and established CVD but without diabetes. The FLOW trial (n=3,533) demonstrated a 24% reduction in major kidney disease events in type 2 diabetes with CKD, leading to early termination for efficacy. The ESSENCE phase 3 trial (n=800 interim) showed 62.9% MASH resolution at 72 weeks. The EVOKE trials (n=3,808) investigated Alzheimer's disease but did not meet primary endpoints, though biomarker improvements were observed. Over 60,000 patients have been studied across programs, with a systematic review of 56 trials confirming semaglutide among the most effective treatments for obesity and cardiometabolic disease.

Evidence by Indication (4 indications)

Indication Tier Trials Summary
Weight loss Tier A 8 STEP trials — robust Phase III RCT data, FDA-approved
Type 2 diabetes Tier A 12 SUSTAIN trials — FDA-approved for T2D
Cardiovascular risk reduction Tier A 4 SELECT trial — significant MACE reduction
NASH/liver fibrosis Tier B 3 Phase II data showing liver fat reduction

Graded using our evidence tier methodology.

Research Gap Score /10

Higher score = larger gap between therapeutic potential and available clinical evidence.

Citations (9 sources)

  1. 1. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1) Clinical Trial

    Wilding JPH, Batterham RL, Calanna S, et al. (2021), New England Journal of Medicine

  2. 2. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT) Clinical Trial

    Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. (2023), New England Journal of Medicine

  3. 3. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes (FLOW) Clinical Trial

    Perkovic V, Tuttle KR, Rossing P, et al. (2024), New England Journal of Medicine

  4. 4. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6) Clinical Trial

    Marso SP, Bain SC, Consoli A, et al. (2016), New England Journal of Medicine

  5. 5. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis Clinical Trial

    Newsome PN, Buchholtz K, Cusi K, et al. (2021), New England Journal of Medicine

  6. 6. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis (ESSENCE) Clinical Trial

    Sanyal AJ, et al. (2025), New England Journal of Medicine

  7. 7. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults with Overweight or Obesity Clinical Trial

    Rubino DM, Greenway FL, Khalid U, et al. (2022), JAMA

  8. 8. Associations of semaglutide with first-time diagnosis of Alzheimer's disease in patients with type 2 diabetes Study

    Wang W, et al. (2024), Alzheimer's & Dementia

  9. 9. A systematic review and meta-analysis of the efficacy and safety of pharmacological treatments for obesity in adults Meta-Analysis

    Multiple authors (2025), Nature Medicine