title: Effect of Semaglutide on the Pharmacokinetics of Metformin, Warfarin, Atorvastatin and Digoxin in Healthy Subjects.
abstract: Semaglutide is a glucagon-like peptide-1 analogue in development for the once-weekly treatment of type 2 diabetes mellitus. Its effect on the rate and extent of absorption of concomitant oral medications (metformin, warfarin, atorvastatin and digoxin) was evaluated in healthy subjects.
  
  
  
  Subjects received metformin (500 mg twice daily for 3.5 days), warfarin (25 mg, single dose), atorvastatin (40 mg, single dose) or digoxin (0.5 mg, single dose) before and with subcutaneous semaglutide treatment at steady state (1.0 mg). Lack of drug-drug interaction was concluded if the 90% confidence intervals for the area under the plasma concentration-time curve ratio before and with semaglutide were within a pre-specified interval (0.80-1.25).
  
  
  
  Overall, metformin, warfarin, atorvastatin and digoxin pharmacokinetics were not affected to a clinically relevant degree with semaglutide co-administration. Estimated area under the plasma concentration-time curve ratios for all concomitant medications before and with semaglutide treatment were within the pre-specified interval. In addition, semaglutide did not affect maximum plasma concentration of concomitant medications to a relevant degree. Furthermore, no clinically relevant change in international normalised ratio response to warfarin was observed with semaglutide co-administration. Most adverse events with semaglutide treatment were mild or moderate. Adverse events with semaglutide and co-administered medication were comparable to those reported during treatment with semaglutide alone, and were mostly gastrointestinal related.
  
  
  
  No clinically significant pharmacokinetic or pharmacodynamic interactions were identified and no new safety issues observed with combined treatment with semaglutide. This suggests that no dose adjustments should be required when semaglutide is administered concomitantly with these medications.
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark. hlhr@novonordisk.com.
authors.forename: Helene
authors.identifier: 0000-0003-4271-6018
authors.initials: H
authors.lastname: Hausner
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Julie
authors.initials: J
authors.lastname: Derving Karsbøl
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Anders G
authors.initials: AG
authors.lastname: Holst
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Jacob B
authors.initials: JB
authors.lastname: Jacobsen
authors.affiliation: Charité Research Organisation GmbH, Berlin, Germany.
authors.forename: Frank-Dietrich
authors.initials: FD
authors.lastname: Wagner
authors.affiliation: PAREXEL International GmbH, Berlin, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Golor
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Anderson
mesh_terms: D000293:Adolescent; D000328:Adult; D000069059:Atorvastatin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004077:Digoxin / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D004763:Glucagon-Like Peptides / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D064368:Healthy Volunteers; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D014859:Warfarin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult; D000099194:Semaglutide
chemical_list: D000069059:Atorvastatin; D004077:Digoxin; D004763:Glucagon-Like Peptides; D007004:Hypoglycemic Agents; D008687:Metformin; D014859:Warfarin; D000099194:Semaglutide