Assessment of the Drug Interaction Potential of Ertugliflozin With Sitagliptin, Metformin, Glimepiride, or Simvastatin in Healthy Subjects

Abstract

Abstract Ertugliflozin, a sodium‐glucose cotransporter 2 inhibitor for the treatment of adults with type 2 diabetes mellitus, is expected to be coadministered with sitagliptin, metformin, glimepiride, and/or simvastatin. Four separate open‐label, randomized, single‐dose, crossover studies were conducted in healthy adults to assess the potential pharmacokinetic interactions between ertugliflozin 15 mg and sitagliptin 100 mg (n = 12), metformin 1000 mg (n = 18), glimepiride 1 mg (n = 18), or simvastatin 40 mg (n = 18). Noncompartmental pharmacokinetic parameters derived from plasma concentration–time data were analyzed using mixed‐effects models to assess interactions. Coadministration of sitagliptin, metformin, glimepiride, or simvastatin with ertugliflozin had no effect on area under the plasma concentration–time profile from time 0 to infinity (AUC inf ) or maximum observed plasma concentration (C max ) of ertugliflozin (per standard bioequivalence boundaries, 80% to 125%). Similarly, ertugliflozin did not have any impact on AUC inf or C max of sitagliptin, metformin, or glimepiride. AUC inf for simvastatin (24%) and simvastatin acid (30%) increased slightly after coadministration with ertugliflozin and was not considered clinically relevant. All treatments were well tolerated. The lack of clinically meaningful pharmacokinetic interactions demonstrates that ertugliflozin can be coadministered safely with sitagliptin, metformin, glimepiride, or simvastatin without any need for dose adjustment.