Dual glucagon-like peptide-1 receptor/glucagon receptor agonist SAR425899 improves beta-cell function in type 2 diabetes.

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. 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. 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. After 28 days of treatment, SAR425899 improved postprandial glucose control by significantly enhancing β-cell function and slowing glucose absorption rate. © 2019 John Wiley & Sons Ltd.

Citation

Roberto Visentin, Michele Schiavon, Britta Göbel, Michela Riz, Claudio Cobelli, Thomas Klabunde, Chiara Dalla Man. Dual glucagon-like peptide-1 receptor/glucagon receptor agonist SAR425899 improves beta-cell function in type 2 diabetes. Diabetes, obesity & metabolism. 2020 Apr;22(4):640-647

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PMID: 31808298

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