AIMS: 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).
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.