Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes

This phase 3 trial (SURPASS-2) compared the efficacy and safety of once-weekly tirzepatide—a dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist with semaglutide (a selective GLP-1 receptor agonist) in patients with type 2 diabetes inadequately controlled with metformin. A total of 1879 participants were randomized to three tirzepatide doses (5 mg, 10 mg, 15 mg) or semaglutide 1 mg over 40 weeks. Tirzepatide showed greater reductions in glycated hemoglobin (-2.01 to -2.30%) versus semaglutide (-1.86%), with all doses being noninferior and superior. Weight loss was also significantly greater with tirzepatide (up to -11.2 kg) than semaglutide (-5.7 kg). Gastrointestinal adverse events were common but mostly mild to moderate. Serious adverse events occurred in 5–7% (tirzepatide) and 3% (semaglutide) groups. The study concluded tirzepatide offers superior glycemic and weight control with acceptable safety, supporting its potential as a next-generation incretin-based therapy.

This phase 3 trial (SURPASS-2) compared the efficacy and safety of once-weekly tirzepatide—a dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist with semaglutide (a selective GLP-1 receptor agonist) in patients with type 2 diabetes inadequately controlled with metformin. A total of 1879 participants were randomized to three tirzepatide doses (5 mg, 10 mg, 15 mg) or semaglutide 1 mg over 40 weeks. Tirzepatide showed greater reductions in glycated hemoglobin (-2.01 to -2.30%) versus semaglutide (-1.86%), with all doses being noninferior and superior. Weight loss was also significantly greater with tirzepatide (up to -11.2 kg) than semaglutide (-5.7 kg). Gastrointestinal adverse events were common but mostly mild to moderate. Serious adverse events occurred in 5–7% (tirzepatide) and 3% (semaglutide) groups. The study concluded tirzepatide offers superior glycemic and weight control with acceptable safety, supporting its potential as a next-generation incretin-based therapy.