Efficacy and Safety of Once Weekly Tirzepatide, a Dual GIP/GLP-1 Receptor Agonist Versus Placebo as Monotherapy in People with Type 2 Diabetes (SURPASS-1)

Is tirzepatide efficacious and safe in people with type 2 diabetes (T2D) inadequately controlled with diet and exercise alone, compared with placebo? Methodology: In this double-blind, placebo-controlled, 40-week Phase 3 study, people with T2D (N=478; mean baseline HbA1c 7.94%; age 54.1 years; T2D duration 4.7 years; BMI 31.9kg/m2) were randomized (1:1:1:1) to tirzepatide (5, 10, 15mg) or placebo. Primary efficacy measure was LSM mean change in HbA1c from baseline at 40-weeks. Secondary measures included LSM mean change in body weight as well as proportions achieving HbA1c and body weight goals at 40-weeks. Results: Tirzepatide 5, 10 and 15mg were superior to placebo in 1) mean change in HbA1c (difference vs placebo [95% CI]: -1.91% [-2.18, -1.63], -1.93% [-2.21, -1.65], -2.11% [-2.39, -1.83], respectively, p<0.001 all doses); 2) achieving HbA1c<7.0% (n [%]: 105 [86.8], 108 [91.5], 102 [87.9], respectively, placebo 22 [19.6]) and < 5.7% (41 [33.9], 36 [30.5], 60[51.7], respectively, placebo 1 [0.9]); and 3) meaningful body weight loss (difference vs placebo [95% CI]: -6.3kg [-7.8, -4.7], -7.1kg [-8.6, -5.5], -8.8kg [-10.3, -7.2], respectively, p<0.001 all doses]). Tirzepatide was well tolerated, and the most common adverse events were gastrointestinal and mild to moderate in severity. There was no severe or clinically significant hypoglycemia (blood glucose [BG]<54mg/dL) with tirzepatide. Conclusion: Tirzepatide as T2D monotherapy demonstrated robust clinically meaningful reductions in HbA1c and body weight without hypoglycemia (BG<54mg/dL). Among those taking tirzepatide 15mg, 52% achieved normoglycemia and 27% achieved ≥ 15% weight loss.

Conflict of Interest

1. This study was funded by Eli Lilly and Company.

2. Julio Rosenstock, MD: Research Support: Merck, Pfizer, Sanofi, Novo Nordisk, Eli Lilly, Lexicon, AstraZeneca, Genentech, Oramed, Boehringer Ingelheim, Hanmi, Applied Therapeutics and Intarcia; Advisory Boards, Consulting Honorarium: Novo Nordisk, Sanofi, Eli Lilly, Oramed, Boehringer Ingelheim, Hanmi, Applied Therapeutics and Intarcia. Carol Wysham: Received consulting and advisory board fees from AstraZeneca, Janssen, and Sanofi; research support from AstraZeneca and Novo Nordisk; and speaker fees from AstraZeneca,Boehringer Ingelheim, Eli Lilly and Company, Janssen, Novo Nordisk, and Sanofi. Juan P. Frias: Research Support: Allergan, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Intercept, Janssen, Madrigal, Metacrine, Merck, NorthSea Therapeutics, Novartis, Novo Nordisk, Oramed, Pfizer, Poxel, Sanofi, Theracos; Advisory Boards and Consulting: Altimmune, Axcella Health, Boehringer Ingelheim, Coherus Therapeutics, Echosens, 89bio, Eli Lilly, Gilead, Intercept, Merck, Novo Nordisk, Sanofi; Speaker Bureau: Merck, Sanofi. Shizuka Kaneko: Received honoraria for lectures from Sumitomo Dainippon Pharma Co., Ltd., Novo Nordisk Pharma Ltd., Eli Lilly Japan K.K., AstraZeneca K.K., Boehringer Ingelheim and Mitsubishi Tanabe Pharma Corporation and received consulting and advisory board fees from Novo Nordisk Pharma Ltd. Clare J. Lee, Laura Fernández Landó, Huzhang Mao, XueweiCui, Vivian T. Thieu are Employees and shareholder of Eli Lilly and Company.

3. Previously presented at American Diabetes Association – 81st Annual Scientific Sessions; Virtual; 25-29 June 2021.

Publication History

Article published online:
26 May 2022