SURPASS-2
SURPASS-2 was the first head-to-head comparison of tirzepatide against a GLP-1 receptor agonist, using semaglutide 1 mg once weekly as the active comparator. Both agents were added to metformin background therapy. This is the key trial establishing tirzepatide’s superiority over the leading GLP-1 RA in terms of HbA1c reduction and weight loss at 40 weeks.
Ontology SURPASS-2 [part-of] SURPASS Clinical Trial Programme SURPASS-2 [studied_in] Tirzepatide SURPASS-2 [measured_by] HbA1c Reduction SURPASS-2 [compared_against] Semaglutide SURPASS-2 [relates] Type 2 Diabetes
Key Results
- HbA1c change from baseline: −2.01% (5mg), −2.24% (10mg), −2.30% (15mg) vs −1.86% (semaglutide 1mg)
- Treatment difference vs semaglutide: −0.15% (5mg, p=0.02), −0.39% (10mg, p<0.001), −0.45% (15mg, p<0.001) — all non-inferior and superior
- Body weight: Reductions greater than semaglutide by −1.9 kg (5mg), −3.6 kg (10mg), −5.5 kg (15mg); all p<0.001
- Hypoglycaemia (<54 mg/dL): 0.6% (5mg), 0.2% (10mg), 1.7% (15mg) vs 0.4% (semaglutide)
- Nausea: 17–22% tirzepatide vs 18% semaglutide
- Diarrhoea: 13–16% vs 12%
- Vomiting: 6–10% vs 8%
- Serious adverse events: 5–7% tirzepatide vs 3% semaglutide
Limitations
- Trial design: Open-label (neither patients nor investigators blinded); semaglutide dose 1mg (lower than the 2mg dose now more commonly used)
- Population: Metformin background only; relatively homogeneous; BMI 35.8 kg/m²; may not represent insulin-requiring or lean T2D
- Duration: 40 weeks — no long-term durability comparison
- Sponsorship: Funded by Eli Lilly — the manufacturer of tirzepatide and not semaglutide; semaglutide dose choice may not represent optimal semaglutide therapy
Connections
- Tirzepatide — studied_in, [2021], source: PMID 34170647
- HbA1c Reduction — measured_by, [2021], source: PMID 34170647
- Semaglutide — comparator_in, [2021], source: PMID 34170647
- SURPASS Clinical Trial Programme — part-of, [2021]