SURPASS-2 is a diabetes trial, which means its primary endpoint is blood sugar. It is included here because it is the earliest head-to-head between tirzepatide and semaglutide, and because its weight numbers are quoted more often than its HbA1c numbers.
What the trial asked
Whether tirzepatide at 5, 10 or 15 mg is noninferior, and then superior, to semaglutide 1 mg for lowering HbA1c in people with type 2 diabetes.
Design
Phase 3, open-label, randomised 1:1:1:1, 40 weeks. Note the comparator: semaglutide 1 mg, the diabetes dose at the time, not the 2.4 mg weight-management dose used in STEP 1 or the 1.7 to 2.4 mg used in SURMOUNT-5.
Who was enrolled
1879 patients with type 2 diabetes. Baseline mean HbA1c was 8.28 percent, mean age 56.6 years, mean weight 93.7 kg.
Primary endpoint and result
Primary endpoint: change in HbA1c from baseline to week 40.
| Arm | HbA1c change | Difference vs semaglutide 1 mg (95% CI) |
|---|---|---|
| Tirzepatide 5 mg | -2.01 points | -0.15 (-0.28 to -0.03); P=0.02 |
| Tirzepatide 10 mg | -2.24 points | -0.39 (-0.51 to -0.26); P less than 0.001 |
| Tirzepatide 15 mg | -2.30 points | -0.45 (-0.57 to -0.32); P less than 0.001 |
| Semaglutide 1 mg | -1.86 points |
Tirzepatide was noninferior and superior to semaglutide at every dose.
Key secondary results
Body weight fell more with tirzepatide than with semaglutide: least-squares mean differences of -1.9 kg (5 mg), -3.6 kg (10 mg) and -5.5 kg (15 mg), all P less than 0.001. The abstract gives only the differences, not the absolute change in each arm, so the explorer lists these arms without a bar.
Adverse events and discontinuation
Gastrointestinal events were most common and mainly mild to moderate. Nausea: 17 to 22 percent across tirzepatide doses and 18 percent with semaglutide. Diarrhoea: 13 to 16 percent and 12 percent. Vomiting: 6 to 10 percent and 8 percent. Hypoglycaemia (glucose under 54 mg/dL): 0.6, 0.2 and 1.7 percent on 5, 10 and 15 mg versus 0.4 percent on semaglutide. Serious adverse events: 5 to 7 percent with tirzepatide, 3 percent with semaglutide. The abstract does not give discontinuation percentages.
Funding and registration
Eli Lilly. ClinicalTrials.gov NCT03987919.
What this trial does not show
- It is not a weight-loss trial. Participants were selected for diabetes, not obesity, and weight was secondary.
- The semaglutide arm was 1 mg. Any inference about 2.4 mg semaglutide from this trial is an extrapolation.
- Open-label, 40 weeks, no placebo arm. It cannot say how either drug compares with no treatment.
- No cardiovascular outcomes. For semaglutide's cardiovascular trial in diabetes, see SUSTAIN-6.
Where the numbers come from
PubMed abstract of the primary paper (PubMed 34170647), fetched 4 September 2026. The weight-management versus diabetes trials guide explains why this trial's design differs from SURMOUNT.
Sources
- Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2). N Engl J Med 2021;385(6):503-515. PubMed 34170647 Accessed September 4, 2026.
- ClinicalTrials.gov NCT03987919 Accessed September 4, 2026.
Canonical URL: https://formblendsresearch.com/trials/surpass-2. Written by the FormBlends editorial team. This page is educational and is not medical advice; see the medical disclaimer.