Effect of upper gastrointestinal disease on the pharmacokinetics of oral semaglutide in subjects with type 2 diabetes.

Abstract

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. 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 7mg 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. 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. There was no significant difference in exposure to oral semaglutide in subjects with or without upper GI disease, hence no dose adjustment is required.