SURPASS-2: what the trial showed
In 1,879 patients with type 2 diabetes on metformin, tirzepatide at 5, 10, and 15 mg weekly lowered HbA1c by 2.01 to 2.30 percentage points over 40 weeks versus 1.86 with semaglutide 1 mg, and produced 1.9 to 5.5 kg more weight loss, with similar gastrointestinal side effects.
Main cited publication: Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. New England Journal of Medicine, 2021. PMID 34170647. Results are summarized from the cited trial report and any companion publications listed below.
At a glance
| Design | Phase 3, randomised, open-label, active comparator, 1:1:1:1 allocation, 40 weeks |
|---|---|
| Population | 1,879 adults with type 2 diabetes on metformin; mean baseline HbA1c 8.28%, mean age 56.6 years, mean weight 93.7 kg |
| Intervention | Tirzepatide 5 mg, 10 mg, or 15 mg once weekly |
| Comparator | Semaglutide 1 mg once weekly |
| Follow-up | 40 weeks |
| Registration | NCT03987919 |
| Funding | Eli Lilly |
Primary outcome
Change in HbA1c from baseline to 40 weeks.
| Tirzepatide 5 mg, 10 mg, or 15 mg once weekly | Semaglutide 1 mg once weekly | Effect |
|---|---|---|
| -2.01, -2.24, and -2.30 percentage points (5, 10, 15 mg) | -1.86 percentage points (semaglutide 1 mg) | Differences -0.15 (95% CI -0.28 to -0.03), -0.39 (-0.51 to -0.26), and -0.45 (-0.57 to -0.32) percentage points; noninferior and superior at all doses |
Key findings
- Weight loss was greater with tirzepatide at every dose: least-squares mean differences of -1.9 kg, -3.6 kg, and -5.5 kg versus semaglutide (P<0.001 for all).
- The comparator was semaglutide 1 mg, the diabetes dose available at the time, not the 2 mg diabetes dose or the 2.4 mg obesity dose.
- Hypoglycaemia (glucose below 54 mg/dl) was reported in 0.6%, 0.2%, and 1.7% of tirzepatide patients by dose and 0.4% with semaglutide.
Harms and safety
- Gastrointestinal events were the most common adverse events in all groups: nausea 17 to 22% with tirzepatide versus 18% with semaglutide, diarrhoea 13 to 16% versus 12%, vomiting 6 to 10% versus 8%.
- Serious adverse events were reported in 5 to 7% of tirzepatide patients and 3% of semaglutide patients.
Limitations
- Open-label design, which matters for patient-reported and weight outcomes.
- The semaglutide dose was 1 mg; higher-dose comparisons come from later trials in obesity rather than this one.
- 40 weeks of follow-up and no cardiovascular outcome data; industry funded.
Where it sits in guidelines
Tirzepatide (Mounjaro) received EU marketing authorisation for type 2 diabetes in September 2022, with a later extension to weight management. European diabetes guidance positions GLP-1 based agents according to cardiovascular and weight goals rather than HbA1c alone.
CliniAtlas answers that use this trial
Written for healthcare professionals as an orientation to the primary publication, not as a substitute for reading it. For literature search, education, and professional evidence review only. Not for diagnosis, treatment selection, triage, monitoring, prognosis, or patient-specific clinical decision-making.