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RCT · PMID 34170647

Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2) — VialBase Research

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Last updated · 2021 · Frias, J.P., Davies, M.J., Rosenstock, J., Perez Manghi, F.C., Fernandez Lando, L., Bergman, B.K., Liu, B., Cui, X., Brown, K. · New England Journal of Medicine
Key findings
  • All tirzepatide doses superior to semaglutide 1mg for HbA1c reduction
  • Tirzepatide 15mg produced 12.4 kg weight loss vs 6.2 kg with semaglutide
  • First head-to-head trial showing superiority over a GLP-1 RA

Summary

SURPASS-2 was the pivotal head-to-head comparison of tirzepatide versus semaglutide 1 mg in patients with type 2 diabetes on metformin. All three tirzepatide doses demonstrated superiority over semaglutide for both HbA1c reduction and weight loss at 40 weeks, establishing tirzepatide as a best-in-class incretin therapy.

Key Findings

  • HbA1c reduction: -2.01% (5mg), -2.24% (10mg), -2.30% (15mg) vs -1.86% (semaglutide 1mg)
  • All tirzepatide doses met superiority for HbA1c vs semaglutide
  • Weight loss: -7.6 kg (5mg), -9.3 kg (10mg), -11.2 kg (15mg) vs -5.7 kg (semaglutide 1mg)
  • Tirzepatide 10mg and 15mg were superior for weight loss vs semaglutide
  • Up to 51% of tirzepatide 15mg patients achieved HbA1c <5.7% (normoglycemia)
  • Comparable GI adverse event profiles between treatments

Methodology

Open-label, active-comparator, phase 3 RCT. 1,879 patients with T2DM on metformin randomized 1:1:1:1 to tirzepatide 5mg, 10mg, or 15mg vs semaglutide 1mg, all once weekly for 40 weeks. Co-primary endpoints: HbA1c change and proportion achieving HbA1c <7%.

Limitations

  • Comparator was semaglutide 1mg, not the 2.4mg weight management dose
  • Open-label design introduces potential bias
  • T2DM population — cannot directly apply to obesity without diabetes
  • 40-week duration — longer-term comparative data needed
  • Semaglutide 2mg (Ozempic maximum) not tested as comparator

Relevance to Content

The key comparative trial for tirzepatide vs semaglutide content. The caveat about semaglutide dose (1mg, not 2.4mg) must be noted in any honest comparison. Still demonstrates the added value of dual GIP/GLP-1 agonism. Essential for “semaglutide vs tirzepatide” comparison articles.

See Also

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