Efficacy and safety of cotadutide, a dual glucagon-like peptide-1 and glucagon receptor agonist, in a randomized phase 2a study of patients with type 2 diabetes and chronic kidney disease

Aim: To assess the efficacy, safety and tolerability of cotadutide in patients with type 2 diabetes mellitus and chronic kidney disease.Materials and Methods: In this phase 2a study (NCT03550378), patients with body mass index 25-45 kg/m2, estimated glomerular filtration rate 30-59 ml/min/1.73 m2 and type 2 diabetes [glycated haemoglobin 6.5-10.5% (48-91 mmol/mol)] controlled with insulin and/or oral therapy combination, were randomized 1:1 to once-daily subcutaneous cotadutide (50-300 μg) or placebo for 32 days. The primary endpoint was plasma glucose concentration assessed using a mixed-meal tolerance test.Results: Participants receiving cotadutide (n = 21) had significant reductions in the mixed-meal tolerance test area under the glucose concentration-time curve (–26.71% vs. +3.68%, p Conclusions: We established the efficacy of cotadutide in this patient population, with significantly improved postprandial glucose control and reduced bodyweight versus placebo. Reductions in urinary albumin-to-creatinine ratios suggest potential benefits of cotadutide on kidney function, supporting further evaluation in larger, longer-term clinical trials.