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

Diabetes Obes Metab. 2022 Apr;24(4):684-692. doi: 10.1111/dom.14632. Epub 2022 Jan 17.


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.

Keywords: GLP-1RA; pharmacokinetics; type 2 diabetes.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Diabetes Mellitus, Type 2* / chemically induced
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Gastrointestinal Diseases* / chemically induced
  • Gastrointestinal Diseases* / drug therapy
  • Glucagon-Like Peptides
  • Humans
  • Hypoglycemic Agents
  • Middle Aged
  • Young Adult


  • Hypoglycemic Agents
  • semaglutide
  • Glucagon-Like Peptides