Juan P. Frías; Melanie J. Davies; Julio Rosenstock; Federico C. Pérez Manghi; Laura Fernández Landó; Brandon K. Bergman; Bing Liu; Xuewei Cui; Katelyn Brown · 2021 · New England Journal of Medicine
Paper
BACKGROUND: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist that is under development for the treatment of type 2 diabetes. The efficacy and safety of once-weekly tirzepatide as compared with semaglutide, a selective GLP-1 receptor agonist, are unknown. METHODS: In an open-label, 40-week, phase 3 trial, we randomly assigned 1879 patients, in a 1:1:1:1 ratio, to receive tirzepatide at a dose of 5 mg, 10 mg, or 15 mg or semaglutide at a dose of 1 mg. At baseline, the mean glycated hemoglobin level was 8.28%, the mean age 56.6 years, and the mean weight 93.7 kg. The primary end point was the change in the glycated hemoglobin level from baseline to 40 weeks. RESULTS: The estimated mean change from baseline in the glycated hemoglobin level was -2.01 percentage points, -2.24 percentage points, and -2.30 percentage points with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and -1.86 percentage points with semaglutide; the estimated differences between the 5-mg, 10-mg, and 15-mg tirzepatide groups and the semaglutide group were -0.15 percentage points (95% confidence interval [CI], -0.28 to -0.03; P = 0.02), -0.39 percentage points (95% CI, -0.51 to -0.26; P<0.001), and -0.45 percentage points (95% CI, -0.57 to -0.32; P<0.001), respectively. Tirzepatide at all doses was noninferior and superior to semaglutide. Reductions in body weight were greater with tirzepatide than with semaglutide (least-squares mean estimated treatment difference, -1.9 kg, -3.6 kg, and -5.5 kg, respectively; P<0.001 for all comparisons). The most common adverse events were gastrointestinal and were primarily mild to moderate in severity in the tirzepatide and semaglutide groups (nausea, 17 to 22% and 18%; diarrhea, 13 to 16% and 12%; and vomiting, 6 to 10% and 8%, respectively). Of the patients who received tirzepatide, hypoglycemia (blood glucose level, <54 mg per deciliter) was reported in 0.6% (5-mg group), 0.2% (10-mg group), and 1.7% (15-mg group); hypoglycemia was reported in 0.4% of those who received semaglutide. Serious adverse events were reported in 5 to 7% of the patients who received tirzepatide and in 3% of those who received semaglutide. CONCLUSIONS: In patients with type 2 diabetes, tirzepatide was noninferior and superior to semaglutide with respect to the mean change in the glycated hemoglobin level from baseline to 40 weeks. (Funded by Eli Lilly; SURPASS-2 ClinicalTrials.gov number, NCT03987919.).
Analysis
A phase 3 trial found tirzepatide to be noninferior and superior to semaglutide in improving glycemic control and reducing body weight in patients with type 2 diabetes over 40 weeks, with similar gastrointestinal side effects.
Discovery
Sean Wharton; Louis J. Aronne; Adam Stefański; Nasreen Alfaris; Andreea Ciudin; Koutaro Yokote; Bruno Halpern; Alpana P. Shukla; Chunmei Zhou; Lisa Macpherson; Sheryl Allen; Nadia N. Ahmad; Suzanne Klise
Nadia J Abbass; Raya Nahlawi; Jacqueline K. Shaia; Kevin Allan; David C. Kaelber; Katherine E. Talcott; Rishi P. Singh
Roger S. McIntyre; Rodrigo B. Mansur; Joshua D. Rosenblat; Angela T.H. Kwan
A. Michael Lincoff; Kirstine Brown‐Frandsen; Helen M. Colhoun; John Deanfield; Scott S. Emerson; Sille Esbjerg; Søren Hardt‐Lindberg; G. Kees Hovingh; Steven E. Kahn; Robert F. Kushner; Ildiko Lingvay; Tuğçe Kalaycı Oral; Marie Mide Michelsen; Jorge Plutzky; Christoffer W. Tornøe; Donna H. Ryan
Jingyue Wang; Quanwei Wang; Xinyu Yang; Wei Yang; Dong-Rui Li; Jingyu Jin; Hui-Cong Zhang; Xianfeng Zhang
Xin Zhao; Minghe Wang; Zhitong Wen; Zhihong Lu; Lijuan Cui; Chao Fu; Huan Xue; Yunfeng Liu; Yi Zhang
Source record