Effect of upper gastrointestinal disease on the pharmacokinetics of oral semaglutide in subjects with type 2 diabetes. Issue 4 (17th January 2022)

• Record Type: Journal Article
• Authors: Meier, Juris J.; Granhall, Charlotte; Hoevelmann, Ulrike; Navarria, Andrea; Plum‐Moerschel, Leona; Ramesh, Chethana; Tannapfel, Andrea; Kapitza, Christoph
• Is Part Of: Diabetes, obesity & metabolism. Volume 24:Issue 4(2022)
• Page Start: 684
• Page End: 692
• Publication Date: 2022-01-17
• Subjects: GLP‐1RA -- pharmacokinetics -- type 2 diabetes; Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.14632
• Languages: English
• ISSNs: 1462-8902

Abstract

Abstract: Aim: To investigate whether upper gastrointestinal (GI) disease has any effect on the exposure of oral semaglutide, an important consideration given that its absorption occurs primarily in the stomach. Materials and Methods: In an open‐label, parallel‐group trial (NCT02877355), subjects aged 18‐80 years with type 2 diabetes with mild‐to‐moderate upper GI disease (N = 36; chronic gastritis [n = 5], gastroesophageal reflux disease [n = 8], and both [n = 23]) or without upper GI disease (N = 19) received oral semaglutide 3 mg once daily for 5 days, followed by 7 mg for 5 days. The primary and key supportive endpoints were the area under the semaglutide plasma concentration–time curve (AUC) from 0 to 24 hours after last trial product administration on day 10 (AUC0−24h, day10 ) and the maximum semaglutide plasma concentration (Cmax, day10 ), respectively. Results: Semaglutide exposure was not statistically significantly different between subjects with and without upper GI disease. Estimated group ratios (subjects with/without upper GI disease) were 1.18 (95% confidence interval [CI], 0.80, 1.75) for AUC0−24h, day10 and 1.16 (95% CI, 0.77, 1.76) for Cmax . Time to Cmax and semaglutide half‐life were similar in subjects with and without upper GI disease. Oral semaglutide was well tolerated; all adverse events were mild‐to‐moderate, with no withdrawals because of adverse events. Conclusions: There was no significant difference in exposure to oral semaglutide in subjects with or without upper GI disease, hence no dose adjustment is required.