Premium
Dual glucagon‐like peptide‐1 receptor/glucagon receptor agonist SAR425899 improves beta‐cell function in type 2 diabetes
Author(s) -
Visentin Roberto,
Schiavon Michele,
Göbel Britta,
Riz Michela,
Cobelli Claudio,
Klabunde Thomas,
Dalla Man Chiara
Publication year - 2020
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13939
Subject(s) - postprandial , medicine , endocrinology , glucagon like peptide 1 receptor , glucagon , agonist , insulin , alpha cell , glucagon like peptide 1 , beta cell , type 2 diabetes , receptor , diabetes mellitus , meal , placebo , area under the curve , chemistry , islet , alternative medicine , pathology
Aim To evaluate the change in insulin sensitivity, β‐cell function and glucose absorption after 28 days of treatment with high and low doses of SAR425899, a novel dual glucagon‐like peptide‐1 receptor/glucagon receptor agonist, versus placebo. Materials and Methods Thirty‐six overweight to obese subjects with type 2 diabetes were randomized to receive daily subcutaneous administrations of low‐dose SAR425899 (0.03, 0.06 and 0.09 mg) and high‐dose SAR425899 (0.06, 0.12 and 0.18 mg) or placebo for 28 days; dose escalation occurred after days 7 and 14. Mixed meal tolerance tests were conducted before treatment (day −1) and on days 1 and 28. Oral glucose and C‐peptide minimal models were used to quantify metabolic indices of insulin sensitivity, β‐cell responsiveness and glucose absorption. Results With low‐dose SAR425899, high‐dose SAR425899 and placebo, β‐cell function from day −1 to day 28 increased by 163%, 95% and 23%, respectively. The change in area under the curve for the rate of meal glucose appearance between 0 and 120 minutes was −32%, −20% and 8%, respectively. Conclusions After 28 days of treatment, SAR425899 improved postprandial glucose control by significantly enhancing β‐cell function and slowing glucose absorption rate.