Change in pharmacodynamic variables following once-weekly tirzepatide treatment versus dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono substudy).

Aim: To evaluate the pharmacodynamic effects of tirzepatide, a novel dual glucagon-like peptide-1 receptor and glucose-dependent insulinotropic polypeptide receptor agonist, compared with dulaglutide in patients with type 2 diabetes.

Materials And Methods: SURPASS J-mono was a 52-week, multicentre, randomized, double-blind, parallel, active-controlled, Phase 3 study, conducted in Japan. This substudy of SURPASS J-mono evaluated postprandial metabolic variables and appetite after a meal tolerance test, and body composition measured by bioelectrical impedance analysis.

Results: Of 636 participants in SURPASS J-mono, 48 were included in this substudy and assigned to tirzepatide 5 mg (n = 9), tirzepatide 10 mg (n = 11), tirzepatide 15 mg (n = 9), or dulaglutide 0.75 mg (n = 19). Participants had a mean (standard deviation) age of 58.6 (7.5) years, duration of diabetes of 6.0 (6.3) years, and body mass index of 27.5 (3.5) kg/m . Mean glycated haemoglobin at baseline was 66 mmol/mol (8.22%). Following a standardized meal test, statistically significant differences in change from baseline in area under the concentration versus time curve from time zero to 6 h after dose for glucose, insulin, glucagon, C-peptide and triglycerides were observed in all tirzepatide treatment arms, except triglycerides at 10 mg, compared with dulaglutide at Week 32. For body composition, tirzepatide 10 mg and 15 mg resulted in a significant reduction in body weight, and all doses of tirzepatide resulted in a significant reduction in body fat mass at Week 52.

Conclusions: Compared with dulaglutide, tirzepatide showed greater potential for normalizing metabolic factors after a standardized meal. Tirzepatide reduced body weight and body fat mass.