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.

中文翻译：

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双胰高血糖素样肽 1 受体/胰高血糖素受体激动剂 SAR425899 可改善 2 型糖尿病的 β 细胞功能。

目的 评估高剂量和低剂量 SAR425899（一种新型胰高血糖素样肽-1 受体/胰高血糖素受体双重激动剂）与安慰剂治疗 28 天后胰岛素敏感性、β 细胞功能和葡萄糖吸收的变化。材料和方法 36 名超重至肥胖的 2 型糖尿病受试者随机接受每日皮下注射低剂量 SAR425899（0.03、0.06 和 0.09 mg）和高剂量 SAR425899（0.06、0.12 和 0.18 mg）或安慰剂28天；在第 7 天和第 14 天后剂量增加。在治疗前（第 -1 天）和第 1 天和第 28 天进行混合膳食耐受试验。口服葡萄糖和 C 肽最小模型用于量化胰岛素敏感性、β 细胞的代谢指数反应性和葡萄糖吸收。结果 使用低剂量 SAR425899，大剂量 SAR425899 和安慰剂，β 细胞功能从第 -1 天到第 28 天分别增加了 163%、95% 和 23%。0 至 120 分钟膳食葡萄糖出现率的曲线下面积变化分别为 -32%、-20% 和 8%。结论 治疗 28 天后，SAR425899 通过显着增强 β 细胞功能和减慢葡萄糖吸收率来改善餐后血糖控制。