To evaluate the safety, pharmacokinetics and pharmacodynamics of SAR425899, a novel polypeptide, active as an agonist at both the glucagon‐like peptide‐1 receptor (GLP‐1R) and the glucagon receptor (GCR), in healthy volunteers and in overweight/obese patients with type 2 diabetes (T2D).

Subcutaneous administrations of SAR425899 were tested in two randomized, placebo‐controlled, double‐blind clinical trials. In the first trial, healthy overweight volunteers (body mass index [BMI] 25‐30 kg/m²; n = 32) received single‐ascending doses (0.01‐0.1 mg) of SAR425899 or placebo. In the second, a multiple‐ascending‐dose trial (NCT02411825), healthy normal‐ to overweight volunteers (BMI 20‐30 kg/m²; n = 40) and overweight/obese patients with T2D (BMI 28‐42 kg/m²; n = 36) received daily doses of SAR425899 or placebo over 21 or 28 days, respectively.

The most frequently reported adverse events were gastrointestinal; gastrointestinal side effects were less pronounced in patients with T2D compared with healthy volunteers. SAR425899 significantly reduced levels of fasting plasma glucose (P < 0.05 vs. placebo) and glycated haemoglobin (P < 0.001 versus placebo) in patients with T2D. Additionally, SAR425899 led to reductions in body weight, with a maximal reduction of 5.32 kg in healthy volunteers and 5.46 kg in patients with T2D (P < 0.001 vs. placebo) at end of treatment.

SAR425899 was well tolerated and led to favourable glycaemic effects in patients with T2D and weight reduction in both healthy volunteers and patients. Whether dual GLP‐1R/GCR agonism represents a treatment method that is superior to pure GLP‐1R agonists for obesity and diabetes treatment remains to be confirmed.