GLP-1 Trial Deep-Dives: Every Secondary Endpoint Decoded
Structured walkthroughs of pivotal GLP-1 trials. Each deep-dive decodes the primary endpoint, every secondary endpoint, AE rates, and pre-specified subgroup analyses with citations to the primary publication + ClinicalTrials.gov registry.
STEP-1 trial deep-dive: semaglutide 2.4 mg for obesity (Wilding 2021 NEJM)
STEP-1 · Phase 3 · N=1,961
STEP-1 is the pivotal NEJM trial that established once-weekly semaglutide 2.4 mg as a category-defining obesity drug. This deep-dive walks through every reported endpoint — body weight, waist, blood pressure, hs-CRP, HbA1c, IWQOL-Lite-CT, SF-36 — with the actual numbers from the Wilding 2021 publication and the ClinicalTrials.gov results posting, plus adverse-event incidence and FAQs about run-in, dose tolerance, and durability after treatment ends.
Last verified 2026-05-27
SURMOUNT-1 deep dive: tirzepatide 5/10/15 mg vs placebo at 72 weeks
SURMOUNT-1 · 3 · N=2,539
SURMOUNT-1 randomized 2,539 adults with obesity (without diabetes) to once-weekly tirzepatide 5 mg, 10 mg, 15 mg, or placebo for 72 weeks. The 15-mg arm lost a mean 20.9% of body weight on the treatment-regimen estimand (NEJM publication) vs 3.1% with placebo; 91% achieved at least 5% loss and 57% achieved at least 20% loss. Every prespecified cardiometabolic measure — waist, systolic blood pressure, fasting insulin, triglycerides, HbA1c — improved. GI adverse events were dose-dependent and discontinuations for AEs ran 4.3-7.1% on tirzepatide vs 2.6% on placebo.
Last verified 2026-05-27
SELECT trial deep-dive: semaglutide cuts MACE 20% in obesity without diabetes
SELECT · 3 · N=17,604
SELECT (Lincoff 2023, NEJM, PMID 37952131) was the first cardiovascular-outcomes trial of a GLP-1 receptor agonist run in adults with obesity but no diabetes. Across 17,604 participants followed a mean 39.8 months, weekly semaglutide 2.4 mg reduced the primary three-point MACE composite by 20% versus placebo. The result moved semaglutide from a weight-loss drug into the cardioprotection conversation and underpinned Wegovy's March 2024 FDA label expansion to reduce MACE risk in adults with obesity and established cardiovascular disease.
Last verified 2026-05-27
SURMOUNT-5 deep dive: tirzepatide vs semaglutide head-to-head at 72 weeks
SURMOUNT-5 · Phase 3b · N=751
SURMOUNT-5 is the first and only randomized head-to-head trial comparing tirzepatide (Zepbound) with semaglutide (Wegovy) in adults with obesity but without type 2 diabetes. Eli Lilly randomized 751 participants 1:1 to the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) for 72 weeks. The least-squares mean weight loss was −20.2% with tirzepatide vs −13.7% with semaglutide (P<0.001), a 6.5-percentage-point advantage. Tirzepatide also produced a larger waist-circumference reduction (−18.4 cm vs −13.0 cm) and roughly double the proportion of participants reaching ≥25% weight loss (36.5% vs 18.6%). Gastrointestinal adverse-event profiles were broadly similar, with vomiting and GERD numerically less common on tirzepatide and injection-site reactions more common.
Last verified 2026-05-27
SURPASS-2 deep-dive: tirzepatide vs semaglutide 1 mg head-to-head in T2D (Frias 2021)
SURPASS-2 · Phase 3 · N=1,879
SURPASS-2 (Frias 2021 NEJM, PMID 34170647) is the first registrational head-to-head comparison of two incretin agonists. 1,879 adults with type 2 diabetes inadequately controlled on metformin were randomized to once-weekly subcutaneous tirzepatide 5 mg, 10 mg, 15 mg, or semaglutide 1 mg for 40 weeks. Tirzepatide produced larger reductions in HbA1c (−2.01 to −2.30 percentage points vs −1.86 with semaglutide) and in body weight (−7.6 to −11.2 kg vs −5.7 kg) across every dose, with a similar GI-event profile and low hypoglycemia in both groups. The trial supplied the regulatory case that dual GIP/GLP-1 agonism delivers more glycemic and weight effect per dose than the leading GLP-1 monotherapy at its highest then-approved T2D dose.
Last verified 2026-05-27