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.