GLP-1 Clinical Trials Explained: STEP, SURMOUNT, SELECT, and What They Proved

By Editorial TeamUpdated May 28, 2026

Editorial content. This article reports public information and is not medical advice. Disclaimer.

Four clustered groups of abstract bars of varying heights arranged across a warm-sand field, most rendered in deep teal with one group accented in warm orange, suggesting distinct clinical trials reporting different outcome magnitudes — The major GLP-1 trials — STEP, SURMOUNT, SELECT, FLOW — each measured a different outcome.

Why the trial names matter

When you see a statistic like "semaglutide produced 15% weight loss" or "20% MACE reduction," these come from specific clinical trials. Understanding which trial produced which finding — and the study design behind it — helps evaluate how applicable the claim is to a specific patient.

This article covers the major GLP-1 trials in plain language: what they asked, who they enrolled, what they found, and what the limitations are.

The STEP trials (semaglutide for obesity)

Sponsor: Novo Nordisk
Drug: Semaglutide 2.4 mg weekly
Purpose: Establish semaglutide's weight loss efficacy and safety for the obesity indication (not T2D)

STEP 1 — The foundational obesity trial

Design: Randomised, double-blind, placebo-controlled
Population: 1,961 adults, BMI ≥30 or ≥27 with comorbidity, without T2D
Duration: 68 weeks
Key finding: 14.9% average weight loss vs 2.4% placebo

STEP 1 is the trial that established semaglutide as an effective obesity drug and led to the Wegovy FDA approval. The 15% average weight loss was, at the time, the largest pharmacological weight loss ever demonstrated in a Phase 3 trial.

STEP 2 — T2D population

Population: 1,210 adults with T2D and obesity
Finding: 9.6% average weight loss vs 3.4% placebo (lower than STEP 1 — T2D patients respond less well to semaglutide)

STEP 3 — Intensive lifestyle intervention added

Design: Semaglutide + intensive behavioural therapy vs placebo + intensive behavioural therapy
Finding: 16.0% average weight loss for semaglutide + therapy vs 5.7% for placebo + therapy

STEP 3 established that adding intensive behavioural support approximately 1 percentage point more to semaglutide's efficacy.

STEP 4 — What happens when you stop?

Design: All patients started semaglutide for 20 weeks, then randomised to continue or switch to placebo
Finding: Patients who continued semaglutide continued losing weight (additional 7.9%). Patients who switched to placebo regained most of their lost weight (average 6.9% regain)

STEP 4 established what has become a central clinical finding: GLP-1 therapy requires ongoing use. Weight regain after stopping is rapid and substantial.

STEP 5 — Two years of follow-up

Duration: 104 weeks
Finding: 15.2% average weight loss at 2 years; maintained from the 68-week plateau, but some lean mass continued to decline

STEP 5 provided the longest semaglutide weight loss data at the time and confirmed that benefit is maintained with continued use.

STEP TEENS — Adolescents

Population: 201 adolescents aged 12–17 with obesity
Finding: 16.1% average weight loss vs 0.6% placebo (68 weeks)

STEP TEENS provided the data for the adolescent Wegovy indication.

STEP HFpEF — Heart failure

Population: 529 adults with HFpEF (ejection fraction ≥45%) and obesity
Finding: 7.8-point KCCQ-CSS improvement vs placebo; 21.5m improvement in 6-minute walk test

STEP HFpEF led to the FDA approval of Wegovy specifically for HFpEF with obesity in 2024.

The SURMOUNT trials (tirzepatide for obesity)

Sponsor: Eli Lilly
Drug: Tirzepatide 5/10/15 mg weekly
Purpose: Establish tirzepatide for the obesity indication (Zepbound)

SURMOUNT-1 — The foundational tirzepatide obesity trial

Design: Randomised, double-blind, placebo-controlled
Population: 2,539 adults, BMI ≥30 or ≥27 with comorbidity, without T2D
Duration: 72 weeks
Key finding: 20.9% average weight loss at 15 mg vs 3.1% placebo

SURMOUNT-1 established tirzepatide's superiority over semaglutide's STEP 1 data (~21% vs ~15%), though cross-trial comparisons have limitations.

SURMOUNT-2 — T2D population

Population: 938 adults with T2D and obesity
Finding: 15.7% average weight loss at 15 mg vs 3.3% placebo

SURMOUNT-3 — Lifestyle intervention lead-in

Design: 12-week intensive lifestyle run-in, then randomised to tirzepatide vs placebo
Finding: 26.6% average weight loss at 15 mg from the start of the lead-in period

SURMOUNT-3 demonstrated the largest average pharmacological weight loss in a trial to date.

SURMOUNT-4 — Maintenance after weight loss

Design: All patients on tirzepatide for 36 weeks, then randomised to continue or switch to placebo
Finding: Continued tirzepatide produced additional 5.5% loss; placebo switch caused average 14% weight regain

Parallel finding to STEP 4: stopping tirzepatide results in rapid weight regain.

SURMOUNT-5 — Head-to-head vs semaglutide

Design: Tirzepatide (10/15 mg) vs semaglutide (2.4 mg), direct RCT
Population: 751 obese adults without T2D
Duration: 72 weeks
Finding: 20.2% vs 13.7% average weight loss (tirzepatide vs semaglutide)

SURMOUNT-5 is the most important data point for patients choosing between the two drugs — the only direct head-to-head RCT. For a full clinical breakdown of that comparison, see our tirzepatide vs semaglutide article.

SURMOUNT-OSA — Obstructive sleep apnoea

Finding: 55–63% reduction in apnoea-hypopnoea index vs placebo
Significance: Led to tirzepatide's pending OSA indication

The SELECT trial (cardiovascular outcomes)

Sponsor: Novo Nordisk
Drug: Semaglutide 2.4 mg weekly
Purpose: Establish cardiovascular outcomes in high-risk obese patients (without requiring T2D)

Design: Randomised, double-blind, placebo-controlled cardiovascular outcomes trial
Population: 17,604 adults with established CVD (prior MI, stroke, or PAD) and BMI ≥27 but WITHOUT T2D
Duration: Average 3.3 years (up to 5 years)
Primary endpoint: MACE (cardiovascular death, non-fatal MI, or non-fatal stroke)
Key finding: 20% reduction in MACE with semaglutide vs placebo (HR 0.80, 95% CI 0.72–0.90)

What made SELECT landmark: It was the first cardiovascular outcomes trial of an anti-obesity drug — and the first to show that pharmacological weight loss alone (the drug was prescribed for obesity, not T2D) reduces cardiovascular events. This led to the expanded Wegovy indication for ASCVD risk reduction.

The FLOW trial (kidney outcomes)

Sponsor: Novo Nordisk
Drug: Semaglutide 1 mg weekly (Ozempic dose)
Purpose: Establish kidney outcomes in T2D patients with CKD

Population: 3,533 adults with T2D and CKD (eGFR 50–75 and albuminuria)
Primary endpoint: Composite of sustained 40% eGFR decline, kidney failure, cardiovascular death, or kidney-cause death
Key finding: 24% relative risk reduction vs placebo

FLOW led to the expanded Ozempic indication for CKD protection in T2D patients.

Key things these trials did not prove

Understanding trial scope limitations:

STEP and SURMOUNT trials do not prove that GLP-1 drugs work long-term beyond 2–3 years without continued use (they mostly show what happens when you stop)
SELECT only enrolled patients with established CVD — the benefit for primary prevention (no prior CVD) is inferred, not directly demonstrated
STEP and SURMOUNT excluded patients under 18 (addressed by STEP TEENS and SURMOUNT TEEN separately)
The trials did not study pharmacogenomic predictors of non-response
Long-term safety beyond 5 years is not yet established from randomised data

Summary

The STEP trials established semaglutide for obesity (15% average weight loss). SURMOUNT trials established tirzepatide (21% average weight loss) and the SURMOUNT-5 head-to-head showed tirzepatide's superiority over semaglutide. SELECT established semaglutide's cardiovascular outcome benefit. FLOW established kidney protection. The most important single trial for a patient choosing between the two drugs is SURMOUNT-5. The most important trial for cardiovascular risk justification is SELECT. For a side-by-side drug comparison using this trial data, see Wegovy vs Mounjaro.