Pharmacokinetics, safety, tolerability and efficacy of cotadutide, a glucagon‐like peptide‐1 and glucagon receptor dual agonist, in phase 1 and 2 trials in overweight or obese participants of A sian descent with or without type 2 diabetes

Abstract Aim To evaluate the safety and pharmacokinetics of cotadutide, a dual glucagon‐like peptide‐1 (GLP‐1) and glucagon receptor agonist, in overweight Asian participants with or without type 2 diabetes (T2D). Materials and Methods In the phase 1, randomized, blinded, single‐ascending dose study, 24 Japanese and eight Chinese healthy adults (body mass index BMI 23‐40 kg/m 2 ) received one subcutaneous dose of cotadutide (50‐150 or 100 μg, respectively) or placebo. The primary endpoint was safety. In the phase 2a, randomized, double‐blinded, parallel dose‐ranging study with forced uptitration, 61 Japanese adults with T2D (BMI 24‐40 kg/m 2 ; HbA1c 7.0%‐10.5%) received cotadutide (100, 200, 300 μg) or placebo for 48 days. Co‐primary endpoints were safety/tolerability, change in glucose AUC 0‐4h and body weight. Results Significant reductions from baseline to day 48 were observed with cotadutide for glucose AUC 0‐4h (33.6%‐42.1% reduction vs. +2.5% with placebo; 95% CIs: 100 μg −45.7%, −33.7%; 200 μg −35.6%, −23.7%; 300 μg −45.0%, −30.8%; placebo 3.4%, 8.3%) and body weight (1.3%‐2.5% decrease vs. +0.8% with placebo; 95% CIs: 100 μg −3.4%, −0.8%; 200 μg −4.7%, −2.0%; 300 μg −4.6%, −2.1%; placebo −2.1%, 0.4%). The most common adverse events with cotadutide were mild gastrointestinal symptoms with no serious adverse events. Increased pulse rate with cotadutide versus placebo is consistent with GLP‐1 monoagonists. Conclusions Once‐daily cotadutide was effective and well tolerated up to 300 μg in overweight Japanese patients with T2D. Further evaluation in Asian populations is warranted.