Effect of Oral Semaglutide on the Pharmacokinetics of Lisinopril, Warfarin, Digoxin, and Metformin in Healthy Subjects

Apr 5, 2019Clinical pharmacokinetics

How Oral Semaglutide Affects the Blood Levels of Lisinopril, Warfarin, Digoxin, and Metformin in Healthy People

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Abstract

The area under the plasma concentration-time curve (AUC) of metformin increased by 32% with oral semaglutide coadministration.

Oral semaglutide did not alter the AUC or maximum plasma concentration for lisinopril, warfarin, or digoxin.
SNAC alone did not affect the exposure of lisinopril, warfarin, digoxin, or metformin.
The increase in AUC for metformin suggests that oral semaglutide may enhance its absorption.
The maximum plasma concentration of metformin remained unchanged with coadministration of oral semaglutide.
Adverse events related to oral semaglutide were consistent with those previously reported for GLP-1 receptor agonists.

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BACKGROUND: Oral semaglutide is a tablet co-formulation of the human glucagon-like peptide-1 (GLP-1) analog semaglutide with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC). The absorption of coadministered oral drugs may be altered due to enhancement by SNAC, potential gastric emptying delay by semaglutide, or other mechanisms. Two one-sequence crossover trials investigated the effect of oral semaglutide on the pharmacokinetics of lisinopril, warfarin, digoxin, and metformin.

METHODS: In trial 1, 52 healthy subjects received lisinopril (20 mg single dose) or warfarin (25 mg single dose) with subsequent coadministration with SNAC alone (300 mg single dose), followed by oral semaglutide 20 mg once daily (steady state). In trial 2, 32 healthy subjects received digoxin (500 μg single dose) or metformin (850 mg twice daily for 4 days), with subsequent coadministration with SNAC alone followed by oral semaglutide, as in trial 1.

RESULTS: There were no apparent effects of oral semaglutide on area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C) for lisinopril, warfarin, and digoxin. The AUC of metformin was increased by 32% (90% confidence interval 1.23-1.43) by oral semaglutide coadministration versus metformin alone, whereas the Cwas unaffected. SNAC alone did not affect exposure of lisinopril, warfarin, digoxin, or metformin. Adverse events were in line with those previously observed for GLP-1 receptor agonists. max max

CONCLUSIONS: Oral semaglutide or SNAC alone did not appear to affect the exposure of lisinopril, warfarin, or digoxin, and, based on its wide therapeutic index, the higher metformin exposure with oral semaglutide was not considered clinically relevant.

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Effect of Oral Semaglutide on the Pharmacokinetics of Lisinopril, Warfarin, Digoxin, and Metformin in Healthy Subjects

Abstract

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