Visual Abstract
Background: This study examined the safety and efficacy of cotadutide, a dual receptor agonist with activity on receptors for glucagon-like peptide-1 and glucagon, at doses up to and including 600 µg in patients with T2DM and obesity in Japan.
Methods: During this double-blind, phase 1b study, adults with T2DM (HbA1c 6.5-8.5%) and obesity were randomized to two cohorts of once-daily cotadutide (n = 6 each) or placebo (n = 2 each) for 70 days. A dose-escalation committee (DEC) approved titrations > 400 µg following a safety data review.
Results: The DEC approved titrations up to 600 µg. Gastrointestinal disorders were the most frequently reported AE with 9 patients on cotadutide (75%) reporting at least 1 event. No SAEs were reported. There was a significant reduction from baseline in 7-day average glucose measured by CGM with cotadutide: mean change (SD) to final week of treatment -62.79 mg/dL (35.66) vs. an increase of 28.52 mg/dL (9.16) with placebo. Cotadutide treatment reduced HbA1c by 1.13% (0.64) at end of treatment from a baseline of 7.41% (0.67). On day 70, the cotadutide group demonstrated a -6.93% (3.44) reduction from baseline in body weight, compared with -1.23% (1.2) in the placebo group.
Conclusions: Cotadutide was well tolerated at doses up to 600 µg in Japanese patients and promoted a generalized reduction in blood glucose and body weight.
M. Asano: Employee; Self; AstraZeneca K. K. A. Sekikawa: Employee; Self; AstraZeneca K. K. M. Sugeno: Employee; Self; AstraZeneca K. K. H. Shimada: None. D. Robertson: Employee; Self; AstraZeneca, Employee; Spouse/Partner; GlaxoSmithKline plc., Stock/Shareholder; Self; AstraZeneca. L. Hansen: Employee; Self; AstraZeneca.
