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Phase 3 RCT (open-label, head-to-head comparison) · PMID 35143054

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

Tirzepatide 15mg achieved HbA1c reduction of -2.46% vs -1.86% for semaglutide 1mg

Last updated · 2021 · Frías JP, Davies MJ, Rosenstock J, et al. · New England Journal of Medicine
Key findings
  • Tirzepatide 15mg achieved HbA1c reduction of -2.46% vs -1.86% for semaglutide 1mg
  • Tirzepatide 15mg weight loss: -12.4 kg vs -6.2 kg for semaglutide 1mg
  • All tirzepatide doses (5, 10, 15mg) were noninferior to semaglutide 1mg for HbA1c
  • 10mg and 15mg tirzepatide were superior to semaglutide for both HbA1c and weight
  • 1,879 patients with T2D enrolled

Summary

SURPASS-2 was the critical head-to-head comparison of tirzepatide vs semaglutide in type 2 diabetes. The open-label Phase 3 trial randomized 1,879 patients with T2D (inadequately controlled on metformin alone) to tirzepatide 5mg, 10mg, or 15mg weekly, or semaglutide 1mg weekly, for 40 weeks. Note: semaglutide 1mg (Ozempic dose) was used, not the higher 2.4mg (Wegovy dose).

Key Findings

  • HbA1c reduction at 40 weeks:
    • Tirzepatide 5mg: -2.01%
    • Tirzepatide 10mg: -2.24%
    • Tirzepatide 15mg: -2.46%
    • Semaglutide 1mg: -1.86%
  • Body weight change:
    • Tirzepatide 5mg: -7.6 kg
    • Tirzepatide 10mg: -9.3 kg
    • Tirzepatide 15mg: -12.4 kg
    • Semaglutide 1mg: -6.2 kg
  • Proportion reaching HbA1c <5.7% (normoglycemia): 29-46% with tirzepatide vs 20% with semaglutide
  • GI adverse events broadly similar between groups
  • Non-inferiority and superiority confirmed for tirzepatide 10mg and 15mg vs semaglutide 1mg for both HbA1c and weight

Relevance to Tirzepatide

SURPASS-2 provided the head-to-head evidence that tirzepatide is superior to Semaglutide for both glycemic control and weight loss in T2D. The 2x greater weight loss (12.4 kg vs 6.2 kg) demonstrated the added value of dual GIP/GLP-1 agonism over GLP-1 agonism alone. An important caveat: the comparator was semaglutide 1mg (T2D dose), not 2.4mg (obesity dose). Nevertheless, the magnitude of difference strongly suggests tirzepatide’s dual mechanism provides a meaningful efficacy advantage. This trial was central to Mounjaro’s FDA approval.

Citation

Frías JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021;385(6):503-515. doi:10.1056/NEJMoa2107519.

See Also

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