A novel dual glucagon‐like peptide and glucagon receptor agonist SAR425899: Results of randomized, placebo‐controlled first‐in‐human and first‐in‐patient trials

Aug 10, 2018Diabetes, obesity & metabolism

Effects of a new drug activating both blood sugar and energy control receptors: Results from early tests in healthy people and patients

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Abstract

SAR425899 led to a maximal reduction of 5.46 kg in body weight among overweight/obese patients with type 2 diabetes.

Gastrointestinal side effects were the most common adverse events reported.
Gastrointestinal side effects were less pronounced in patients with type 2 diabetes compared to healthy volunteers.
SAR425899 significantly reduced fasting plasma glucose levels in patients with type 2 diabetes.
A significant decrease in glycated hemoglobin levels was observed in patients with type 2 diabetes.
Healthy volunteers experienced a maximal body weight reduction of 5.32 kg after treatment.

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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/m; 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/m; n = 40) and overweight/obese patients with T2D (BMI 28-42 kg/m; n = 36) received daily doses of SAR425899 or placebo over 21 or 28 days, respectively. 2 2 2

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.

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A novel dual glucagon‐like peptide and glucagon receptor agonist SAR425899: Results of randomized, placebo‐controlled first‐in‐human and first‐in‐patient trials

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