Clinical relevance of dual agonist of glucagon and glucagon‐like peptide‐1 receptors to achieve functional restoration of first‐ and second‐phase insulin secretion

Abstract

The role of glucagon and GLP‐1 receptors in first and second phase insulin secretion

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

“…A recent review paper described glucagon's important role in glucose homeostasis with respect to the GLP‐1 receptor, 20 and a mechanistic study of cotadutide suggested its glucose‐lowering effects are mediated by enhanced insulin secretion together with delayed gastric emptying 12 . In our study, cotadutide reduced the time spent in hyperglycaemia as measured by CGM and reduced 7‐day mean glucose levels from the dose of 50 μg, with a maximal effect reached at the 200‐μg dose that was maintained up to the 600‐μg dose.…”

“…11,[16][17][18] A reduction in systolic BP and an increase in pulse rate were observed in this study, consistent with the results of a phase IIb study of cotadutide 13 and those of a study of semaglutide (a GLP-1 receptor mono-agonist). 19 A recent review paper described glucagon's important role in glucose homeostasis with respect to the GLP-1 receptor, 20 and a mechanistic study of cotadutide suggested its glucose-lowering effects are mediated by enhanced insulin secretion together with delayed gastric emptying. 12 In our study, cotadutide reduced the time spent in hyperglycaemia as measured by CGM and reduced 7-day mean glucose levels from the dose of 50 μg, with a maximal effect reached at the 200-μg dose that was maintained up to the 600-μg dose.…”