3000 EFFICACY AND SAFETY OF COTADUTIDE, A DUAL GLP1-GLUCAGON RECEPTOR AGONIST, IN PATIENTS WITH CHRONIC KIDNEY DISEASE AND T2DM

Abstract Background and Aims Cotadutide is a dual GLP1-glucagon receptor agonist under development for NASH and CKD with T2DM. Incretin-based therapies have been shown to promote improvements in albuminuria while the addition of glucagon has been suggested to provide hepatic benefits; the renal benefits of dual GLP1-glucagon receptor agonism are unknown but kidney and liver are the organs with highest expression of glucagon receptor. We sought to evaluate the efficacy and safety of cotadutide in patients with CKD and T2DM. Method In this randomised, double-blind, phase 2b study, patients with T2DM and CKD on insulin and/or oral therapy including ≥ 40% treated with SGLT-2i (HbA1c ≥ 6.5 and ≤ 10.5%), eGFR ≥ 20 and < 90 ml/min/1.73m2 and BMI ≥ 25 (23 in Japan) kg/m2 were treated for 26 weeks. Participants were randomised (n = 45 per arm) to receive once-daily SC cotadutide titrated up to 100, 300 or 600 µg, or placebo. The primary endpoint was percentage change in UACR (log-transformed) at 14 weeks. Secondary endpoints evaluated urinary albumin creatinine ratio (UACR) at 26 weeks, safety and tolerability. Changes in renal function was evaluated as an exploratory endpoint. Results A total of 248 Participants were randomised. Approximately 47% were on SGLT-2i and 97% were on ACE inhibitors or ARBs at baseline. The primary endpoint was met. Dose dependent reductions in UACR from baseline were observed after 26 weeks treatment with 300 and 600 µg of cotadutide, -39.9% (95% CI -52,5, -23.9) and -46.0% (95% CI -57.1, -32.1) vs placebo (P