Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults With Overweight or Obesity and Type 2 Diabetes: A 54-Week Randomized Phase 2b Study

OBJECTIVE Cotadutide, a dual GLP-1 and glucagon receptor agonist, is under development for nonalcoholic steatohepatitis (NASH) and chronic kidney disease with type 2 diabetes. The effects of cotadutide on hepatic and metabolic parameters were evaluated in participants with overweight/obesity and type 2 diabetes. RESEARCH DESIGN AND METHODS In this phase 2b study, 834 adults with BMI >= 25 kg/m(2) and type 2 diabetes inadequately controlled with metformin (glycated hemoglobin A(1c) [HbA(1c)] of 7.0%-10.5% [53-91 mmol/mol]) were randomized to double-blind cotadutide 100 mu g (n = 100), 200 mu g (n = 256), or 300 mu g (n = 256); placebo (n = 110); or open-label liraglutide 1.8 mg (n = 110)-all administered subcutaneously. Coprimary end points were changes in HbA(1c) and body weight at week 14. The originally randomized interventions were continued to week 54. Liver damage biomarkers and liver fibrosis algorithms were assessed. RESULTS Cotadutide significantly decreased HbA(1c) and body weight at weeks 14 and 54 versus placebo (all P < 0.001). Improvements in lipid profile, AST and ALT levels, propeptide of type III collagen level, fibrosis-4 index, and nonalcoholic fatty liver disease fibrosis score were observed with cotadutide 300 mu g versus placebo, but not with liraglutide. Weight loss with cotadutide 200 mu g was similar to that with liraglutide 1.8 mg and greater with cotadutide 300 mu g versus liraglutide 1.8 mg. The most common adverse events with cotadutide (nausea, 35%; vomiting, 17%) decreased over time. CONCLUSIONS Cotadutide treatment for 54 weeks improved glycemic control and weight loss in participants with overweight/obesity and type 2 diabetes. Ad hoc analyses demonstrated improvements in hepatic parameters and support further evaluation of cotadutide in NASH.

Automated summary

Cotadutide treatment for 54 weeks improved glycemic control and weight loss in participants with overweight/obesity and type 2 diabetes. Ad hoc analyses demonstrated improvements in hepatic parameters and support further evaluation of cotadutide in NASH.