Assessment of the Drug Interaction Potential of Ertugliflozin With Sitagliptin, Metformin, Glimepiride, or Simvastatin in Healthy Subjects. Issue 3 (22nd May 2018)

• Record Type: Journal Article
• Authors: Dawra, Vikas Kumar; Cutler, David L.; Zhou, Susan; Krishna, Rajesh; Shi, Haihong; Liang, Yali; Alvey, Christine; Hickman, Anne; Saur, Didier; Terra, Steven G.; Sahasrabudhe, Vaishali
• Is Part Of: Clinical pharmacology in drug development. Volume 8:Issue 3(2019)
• Page Start: 314
• Page End: 325
• Publication Date: 2018-05-22
• Subjects: diabetes -- drug‐drug interaction -- ertugliflozin -- glimepiride -- metformin -- pharmacokinetics -- SGLT2i -- simvastatin -- sitagliptin; Drugs -- Testing -- Periodicals; Drug development -- Periodicals; Clinical pharmacology -- Periodicals; 615.580724
• DOI: 10.1002/cpdd.472
• Languages: English
• ISSNs: 2160-7648

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 (AUCinf ) or maximum observed plasma concentration (Cmax ) of ertugliflozin (per standard bioequivalence boundaries, 80% to 125%). Similarly, ertugliflozin did not have any impact on AUCinf or Cmax of sitagliptin, metformin, or glimepiride. AUCinf 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.