1013-P: Effect of Upper Gastrointestinal Disease on the Pharmacokinetics of Oral Semaglutide in Subjects with Type 2 Diabetes

Abstract

The GLP-1 analog semaglutide has been co-formulated with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC) to allow oral administration. Since oral semaglutide is absorbed in the stomach, the effect of upper gastrointestinal disease (UGD) on exposure to oral semaglutide has been investigated in an open-label, parallel-group trial (NCT02877355). Subjects aged 18-80 years with T2D and with UGD (N=36; chronic gastritis [n=5], gastroesophageal reflux disease [GERD; n=8] or both [n=23]) or without UGD (N=19) received oral semaglutide 3 mg once-daily for 5 days followed by 7 mg for 5 days. Key endpoints were area under the semaglutide plasma concentration-time curve (AUC) (primary) and maximum semaglutide plasma concentration (Cmax) from 0-24 h after the 10th dose. Semaglutide exposure was not statistically significantly different in subjects with vs. without UGD (Figure; estimated group ratios with/without UGD [95% CI] AUC: 1.18 [0.80; 1.75]and Cmax: 1.16 [0.77; 1.76]). Time to maximum plasma concentration and half-life of semaglutide were similar in subjects with vs. without UGD. Oral semaglutide was well tolerated. All adverse events (AEs) were mild or moderate with no withdrawals due to AEs. In conclusion, no significant difference in exposure to oral semaglutide in subjects with vs. without UGD was found; hence, no dose adjustment is expected to be required. Disclosure J.J. Meier: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. C. Granhall: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. U. Hoevelmann: None. A. Navarria: Employee; Self; Novo Nordisk A/S. Employee; Spouse/Partner; Novo Nordisk A/S. L. Plum-Moerschel: None. C. Ramesh: None. A. Tannapfel: None. C. Kapitza: Research Support; Self; ADOCIA, Biocon, Boehringer Ingelheim Pharmaceuticals, Inc., Dance Biopharm Holdings Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, MedImmune, Mylan, Nestlé, Nordic Bioscience, Novo Nordisk A/S, Poxel SA, Sanofi-Aventis, Wockhardt, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. Funding Novo Nordisk A/S