335-OR: Dapiglutide, a Once-Weekly GLP-1R/GLP-2R Dual Agonist, Was Safe and Well Tolerated and Showed Dose-Dependent Body Weight Loss over Four Weeks in Healthy Subjects

Dapiglutide is a first-in-class peptide with dual activity on the GLP-1 and GLP-2 receptors and with potential to treat several metabolic/gastrointestinal (GI) diseases. In a multiple ascending dose cohort trial, 40 healthy subjects (mean BMI 24.6 kg/m2) received once weekly s.c. injections of dapiglutide (1, 2.25, 3.5 or 6 mg) or placebo for 4 weeks. There were no serious or severe adverse events (AEs) and no withdrawals. The most frequent related AEs reported were GI disorders and metabolism and nutrition disorders similar to marketed GLP-1RAs. No subject developed anti-drug antibodies. The pharmacokinetics (PK) showed dose proportionality with a low inter-subject variability and a mean half-life of 123-129 hours across the 4 dose cohorts. Dose-response was shown for plasma glucose, insulin, triglycerides, and gastric emptying after a mixed meal test. Mean body weight loss was 0.1%, 0.5%, 2.4% and 4.5% after 4 weeks of treatment in each cohort (fig 1) . Multiple doses of dapiglutide were well-tolerated and the safety profile is similar to GLP-1 and GLP-2 receptor agonists. The PK results support that dapiglutide is suitable for once-weekly dosing. The clinical potential of dapiglutide as a novel treatment for obesity and NASH should be explored in trials of longer duration. Disclosure M.B.Olsen: Employee; Zealand Pharma A/S, Stock/Shareholder; Novo Nordisk A/S, Zealand Pharma A/S. U.Hövelmann: None. J.Griffin: Employee; Zealand Pharma A/S, Stock/Shareholder; Zealand Pharma A/S. K.M.Knudsen: Employee; Zealand Pharma A/S. P.Eriksson: Employee; Zealand Pharma A/S. M.A.Agersnap: Employee; Zealand Pharma A/S.