Efficacy and tolerability of tirzepatide, a dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes: A 12-week, randomized, double-blind, placebo-controlled study to evaluate different dose-escalation regimens.

ABSTRACT: AIM:To assess the efficacy and tolerability of tirzepatide treatment using three different dose-escalation regimens in patients with type 2 diabetes. MATERIALS AND METHODS:In this double-blind, placebo-controlled study, patients were randomized (1:1:1:1) to receive either once-weekly subcutaneous tirzepatide or placebo. The tirzepatide dose groups and dose-escalation regimens were: 12?mg (4?mg?weeks 0-3; 8?mg?weeks 4-7; 12?mg?weeks 8-11), 15?mg-1 (2.5?mg?weeks 0-1; 5?mg?weeks 2-3; 10?mg?weeks 4-7; 15?mg?weeks 8-11) and 15?mg-2 (2.5?mg?weeks 0-3; 7.5?mg?weeks 4-7; 15?mg?weeks 8-11). The primary objective was to compare tirzepatide with placebo in HbA1c change from baseline at 12?weeks. RESULTS:Overall, 111 patients were randomized: placebo, 26; tirzepatide 12?mg, 29; tirzepatide 15?mg-1, 28; tirzepatide 15?mg-2, 28. The mean age was 57.4?years, HbA1c 8.4% and body mass index 31.9?kg/m2 . At week 12, absolute HbA1c change from baseline (SE) was greater in the tirzepatide treatment groups compared with placebo (placebo, +0.2% [0.21]; 12?mg, -1.7% [0.19]; 15?mg-1, -2.0% [0.20]; 15?mg-2, -1.8% [0.19]). The incidence of nausea was: placebo, 7.7%; 12?mg group, 24.1%; 15?mg-1 group, 39.3%; 15?mg-2 group, 35.7%. Three patients discontinued the treatment because of adverse events, one from each of the placebo, 12?mg and 15?mg-1 groups. CONCLUSIONS:Tirzepatide treatment for 12?weeks resulted in clinically significant reductions in HbA1c. This suggests that lower starting doses and smaller dose increments are associated with a more favourable side effect profile.

SUBMITTER: Frias JP 

PROVIDER: S-EPMC7318331 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature