\Safety/tolerability, efficacy and pharmacokinetics of 600-μg cotadutide in Japanese type 2 diabetes patients with a body mass index of 25 kg/m2 or higher: A phase I, randomized, double-blind, placebo-controlled study

Aim: To assess the safety/tolerability, efficacy and pharmacokinetics of once-daily, 600-mu g cotadutide in Japanese type 2 diabetes patients with a body mass index of 25 kg/m(2) or higher. Materials and Methods: This phase I, randomized, double-blind, placebo-controlled study (NCT04208620) enrolled patients to receive subcutaneous cotadutide at an escalating dose to determine the highest tolerated clinical dose (Cohort 1), then applied in Cohort 2. The primary endpoint was safety, including treatment-emergent adverse events (TEAEs); secondary endpoints included glycaemic control and body weight. Results: Sixteen patients were randomly allocated to receive cotadutide or placebo in a 3:1 ratio. All patients were Asian, 62.5% were male, and the median age and body mass index were 60 years and 27.2 kg/m(2), respectively. Through the follow-up period of the study, 11/12 (91.7%) patients in the cotadutide group experienced a TEAE versus 1/4 (25.0%) patients in the placebo group. All TEAEs were mild, except for one moderate event. There were no deaths, serious TEAEs or TEAEs leading to study discontinuation. Gastrointestinal-related events were the most common TEAEs. Cotadutide-treated patients achieved significantly improved 7-day mean glucose measured by continuous glucose monitoring; the 7-day mean (standard deviation) at the end of treatment (day 70) was 112.23 (20.79) versus 206.85 (3.62) mg/dL for placebo. Mean respective changes in HbA1c were similar to 1.13% (0.64%) and similar to 0.17% (0.65%); and mean percentage changes in body weight were -6.93% (3.44%) and -1.23% (1.20%). Conclusions: Cotadutide was well tolerated at doses up to 600 mu g; efficacy versus placebo for weight loss and glycaemic control was shown.