SURPASS-2: Tirzepatide More Effective Than Semaglutide For Reducing Glycated Hemoglobin in T2D?

In an open-label, phase 3 trial, tirzepatide was found to provide a greater reduction in glycated hemoglobin levels than semaglutide in patients with type 2 diabetes (T2D) treated with metformin, according to a study published June 25 in the New England Journal of Medicine in conjunction with the American Diabetes Association’s Annual Scientific Sessions.

Tirzepatide is a novel glucose-dependent insulinotropic polypeptide combined with a GLP1-RA for treatment of T2D. Juan P. Frías, MD, et al., randomly assigned 1,879 patients to tirzepatide 5 mg, 10 mg or 15 mg or semaglutide 1 mg, both once weekly. At baseline, the mean age of patients was 56.6 years, mean weight was 93.7 kg and mean glycated hemoglobin level was 8.28%.

Results showed that for the primary outcome of change in glycated hemoglobin from baseline to 40 weeks tirzepatide was associated with a greater reduction with each dose compared with semaglutide. The estimated mean change was –2.01% with 5 mg, –2.24% with 10 mg and –2.30% with 15 mg tirzepatide and –1.86% with semaglutide. The estimated differences between the 5 mg, 10 mg and 15 mg tirzepatide groups and the semaglutide group were −0.15% (95% confidence interval [CI], −0.28 to −0.03; p=0.02), −0.39% (95% CI, −0.51 to −0.26; p<0.001), and −0.45% (95% CI, −0.57 to −0.32; p<0.001), respectively. Tirzepatide at all doses was noninferior and superior to semaglutide.

In the tirzepatide group, hypoglycemia was identified in 0.6% of patients taking 5 mg, 0.2% of those taking 10 mg and 1.7% for those taking 15 mg. For patients in the semaglutide group, hypoglycemia was reported for 0.4%. Weight loss was significantly greater with tirzepatide, and increased in a linear fashion with each dose, compared with semaglutide. Gastrointestinal adverse events were the most common and were mostly mild to moderate in both groups.

In a related editorial comment, Katherine R. Tuttle, MD, highlights the rapid increase in diabetes worldwide and the urgent need for “effective therapies for diabetes – especially those that reduce the risks of serious complications – across populations.” She notes the novel concept of combining a glucose-dependent insulinotropic polypeptide with a GLP1-RA “takes incretin therapeutic agents to a new level.

Tuttle also notes the trial lacked adequate representation for racial and ethnic groups. She writes, “improvements in demographic representation across races and ethnic groups, geographic areas, sexes and genders, and age groups are important concerns to be addressed by the clinical-trial enterprise overall,” and “in the quest to deliver better care for persons with diabetes across the globe, the promotion of equity, diversity, and inclusion is critical.”

Clinical Topics: Cardiovascular Care Team

Keywords: Incretins, Metformin, Diabetes Mellitus, Type 2, Weight Loss, Ethnic Groups, Glucagon-Like Peptides, Hypoglycemia, Glucose, Gastric Inhibitory Polypeptide, Confidence Intervals

< Back to Listings