Primary literature for the major GLP-1 receptor agonist trials. Each entry sourced with DOI.
STEP-1
Wilding JPH et al.. Once-Weekly Semaglutide in Adults with Overweight or Obesity. NEJM 2021. DOI: 10.1056/NEJMoa2032183
Foundational sema weight trial. 14.9% mean loss vs 2.4% placebo at 68 weeks.
STEP-4
Rubino D et al.. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo. JAMA 2021. DOI: 10.1001/jama.2021.3224
Discontinuation produces regain. Established obesity as chronic disease.
SURMOUNT-1
Jastreboff AM et al.. Tirzepatide Once Weekly for the Treatment of Obesity. NEJM 2022. DOI: 10.1056/NEJMoa2206038
Foundational tirz weight trial. Mean weight loss 15.0% (5 mg), 19.5% (10 mg) and 20.9% (15 mg) vs 3.1% placebo at 72 weeks (treatment-regimen estimand; 22.5% at 15 mg under the efficacy estimand).
SELECT
Lincoff AM et al.. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. NEJM 2023. DOI: 10.1056/NEJMoa2307563
20% MACE reduction in 17,604 adults BMI ≥27 + CVD. Basis for Wegovy CV indication.
SURMOUNT-OSA
Malhotra A et al.. Tirzepatide for OSA and Obesity. NEJM 2024. DOI: 10.1056/NEJMoa2404881
AHI reduction ~30 events/hr. ~50% disease remission. Basis for December 2024 Zepbound OSA approval.
FLOW
Perkovic V et al.. Effects of Semaglutide on Chronic Kidney Disease in T2D. NEJM 2024. DOI: 10.1056/NEJMoa2403347
24% reduction major kidney events. Stopped early.
STEP-HFpEF
Kosiborod MN et al.. Semaglutide in HFpEF and Obesity. NEJM 2023. DOI: 10.1056/NEJMoa2306963
KCCQ-CSS improvement. Direct cardiac effects beyond weight.
SURPASS-3
Heise T et al.. Tirzepatide vs Insulin Degludec as Add-on to Metformin. Lancet 2021. DOI: 10.1016/S0140-6736(21)01443-4
Tirz superior to titrated insulin degludec in T2D.
SYNERGY-NASH
Loomba R et al.. Tirzepatide for MASH with Fibrosis. NEJM 2024. DOI: 10.1056/NEJMoa2401943
44-62% MASH resolution by dose at 52 weeks.
ESSENCE
Sanyal AJ, Newsome PN et al.. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. NEJM 2025. DOI: 10.1056/NEJMoa2413258
Part 1 (planned 72-week analysis of the first 800 patients with F2 to F3 fibrosis): steatohepatitis resolved without worsening fibrosis in 62.9% on semaglutide 2.4 mg vs 34.3% on placebo; fibrosis improved in 36.8% vs 22.4%. Basis for the August 2025 accelerated approval of Wegovy for MASH.
SUSTAIN-6
Marso SP et al.. Semaglutide and CV Outcomes in T2D. NEJM 2016. DOI: 10.1056/NEJMoa1607141
26% MACE reduction. Basis for 2020 Ozempic CV indication.
REWIND
Gerstein HC et al.. Dulaglutide and CV Outcomes in T2D. Lancet 2019. DOI: 10.1016/S0140-6736(19)31149-3
MACE reduction. Basis for 2020 Trulicity CV indication.
LEADER
Marso SP et al.. Liraglutide and CV Outcomes in T2D. NEJM 2016. DOI: 10.1056/NEJMoa1603827
MACE reduction. Basis for 2017 Victoza CV indication.