Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes

The SURPASS-2 trial, published in the New England Journal of Medicine, was a phase 3, randomized, open-label, assessor-blinded study that directly compared tirzepatide — the first dual GIP/GLP-1 agonist — with semaglutide 1 mg (GLP-1 agonist) in 1,879 patients with type 2 diabetes inadequately controlled with metformin. Treatment lasted 40 weeks.

Tirzepatide demonstrated statistical superiority over semaglutide 1 mg at all three doses tested. HbA1c reductions were -2.01% (5 mg), -2.24% (10 mg), and -2.30% (15 mg) versus -1.86% with semaglutide (p<0.05 for all comparisons). Body weight reductions were also significantly greater with tirzepatide.

• Tirzepatide 5 mg: weight loss of -7.6 kg vs -5.7 kg with semaglutide
• Tirzepatide 10 mg: weight loss of -9.3 kg
• Tirzepatide 15 mg: weight loss of -11.2 kg
• More patients achieved HbA1c < 7% with tirzepatide (82-92%) vs semaglutide (81%)

This study was the first direct head-to-head comparison between tirzepatide and semaglutide, establishing the superiority of dual GIP/GLP-1 agonism over GLP-1 agonism alone. The results contributed to positioning tirzepatide as a new reference therapeutic class in the treatment of type 2 diabetes and accelerated the development of the SURMOUNT program for obesity.