Volume 21, Issue 1 p. 120-128
ORIGINAL ARTICLE

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

Joachim Tillner PhD

Corresponding Author

Joachim Tillner PhD

Translational Medicine, Sanofi, Frankfurt, Germany

J.T. and M.G.P. two authors contributed equally.

Correspondence

Joachim Tillner PhD, Sanofi, Industriepark Hoechst, 65926 Frankfurt, Germany.

Email: joachim.tillner@sanofi.com

Search for more papers by this author
Maximilian G. Posch MD

Maximilian G. Posch MD

Charité Research Organisation GmbH, Berlin, Germany

J.T. and M.G.P. two authors contributed equally.Search for more papers by this author
Frank Wagner MD

Frank Wagner MD

Charité Research Organisation GmbH, Berlin, Germany

Search for more papers by this author
Lenore Teichert MSc

Lenore Teichert MSc

R&D Clinical Sciences, Sanofi, Frankfurt, Germany

Search for more papers by this author
Youssef Hijazi PhD

Youssef Hijazi PhD

Translational Medicine, Sanofi, Frankfurt, Germany

Search for more papers by this author
Christine Einig

Christine Einig

R&D Clinical Sciences, Sanofi, Frankfurt, Germany

Search for more papers by this author
Stefanie Keil PhD

Stefanie Keil PhD

R&D Diabetes Division, Sanofi, Frankfurt, Germany

Search for more papers by this author
Torsten Haack PhD

Torsten Haack PhD

R&D Diabetes Division, Sanofi, Frankfurt, Germany

Search for more papers by this author
Michael Wagner PhD

Michael Wagner PhD

R&D Diabetes Division, Sanofi, Frankfurt, Germany

Search for more papers by this author
Martin Bossart PhD

Martin Bossart PhD

R&D Diabetes Division, Sanofi, Frankfurt, Germany

Search for more papers by this author
Philip J. Larsen MD

Philip J. Larsen MD

R&D Diabetes Division, Sanofi, Frankfurt, Germany

Search for more papers by this author
First published: 08 August 2018
Citations: 135
Funding information The SAD and MAD trials were funded by Sanofi; Sanofi

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/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.