# SURPASS-2: what the trial showed

Canonical page: https://cliniatlas.com/trials/surpass-2/

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. https://pubmed.ncbi.nlm.nih.gov/34170647/

## 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: -2.01, -2.24, and -2.30 percentage points (5, 10, 15 mg)
- Semaglutide 1 mg once weekly: -1.86 percentage points (semaglutide 1 mg)
- Effect: 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

- https://cliniatlas.com/evidence/tirzepatide-versus-semaglutide-type-2-diabetes/

Ask about this trial against live sources (free, no sign-in): https://cliniatlas.com/?q=What%20did%20the%20SURPASS-2%20trial%20show%20and%20how%20should%20it%20be%20interpreted%3F

---

CliniAtlas is an EU-hosted clinical evidence search platform for verified
healthcare professionals, built in Split, Croatia, with the University of
Split School of Medicine. Free for verified clinicians and students:
https://cliniatlas.com/

For literature search, education, and professional evidence review only.
Not for diagnosis, treatment selection, triage, monitoring, prognosis, or
patient-specific clinical decision-making.