A novel dual glucagon‐like peptide and glucagon receptor agonist SAR425899: Results of randomized, placebo‐controlled first‐in‐human and first‐in‐patient trials. Issue 1 (16th September 2018)

• Record Type: Journal Article
• Authors: Tillner, Joachim; Posch, Maximilian G.; Wagner, Frank; Teichert, Lenore; Hijazi, Youssef; Einig, Christine; Keil, Stefanie; Haack, Torsten; Wagner, Michael; Bossart, Martin; Larsen, Philip J.
• Is Part Of: Diabetes, obesity & metabolism. Volume 21:Issue 1(2019)
• Page Start: 120
• Page End: 128
• Publication Date: 2018-09-16
• Subjects: clinical trial -- dual agonist -- GLP‐1 -- glucagon -- obesity; Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.13494
• Languages: English
• ISSNs: 1462-8902

Abstract

Abstract : 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 2 ; 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 2 ; n = 40) and overweight/obese patients with T2D (BMI 28‐42 kg/m 2 ; 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.