Sitagliptin, a Dipeptidyl Peptidase-4 Inhibitor, Does Not Affect the Pharmacokinetics of Ethinyl Estradiol or Norethindrone in Healthy Female Subjects

Abstract

Sitagliptin is a dipeptidyl peptidase-IV (DPP-4) inhibitor used for the treatment of patients with type 2 diabetes mellitus. This randomized, placebo-controlled, 2-period, crossover study evaluated the effect of sitagliptin on the pharmacokinetics of 17 α-ethinyl estradiol (EE(2)) and norethindrone (NET) in healthy female subjects who were receiving oral contraceptives for >3 months prior to enrollment. A total of 18 subjects with normal menstrual cycles received the oral contraceptive pill ORTHO-NOVUM(®) 7/7/7 on days 1 to 28 for 2 successive cycles, and on days 1 to 21 were randomly assigned to receive sitagliptin 200 mg/day (2 × 100 mg tablets) or placebo using a computer-generated allocation schedule. Blood samples for determination of plasma EE(2) and NET concentrations were collected predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours postdose on day 20 or 21 of each treatment period. The GMRs (90% confidence interval [CI]) for the AUC(0-24 hr) of EE(2) and NET were 0.99 (0.93, 1.06) and 1.03 (0.97, 1.09), respectively, and for C(max) were 0.97 (0.86, 1.10) and 0.98 (0.89, 1.07), respectively. The coadministration of sitagliptin 200 mg/day with an oral contraceptive for 21 days did not lead to clinically meaningful alterations in the pharmacokinetics of EE(2) and NET.

Evaluation of Metformin + Sitagliptin versus Metformin + Glibenclamide on Glycemic Control in Iraqis Type 2 Diabetic Patients

“…In clinical trials, the DPP-4 inhibitor, sitagliptin, improved fasting and postprandial glycaemic control and measures of β-cell function in patients with type 2 diabetes, with minimal effects on measures of insulin resistance/ sensitivity (30,31) . Metformin has been found to increase GLP-1 levels in humans (32,33) . Sulfonylurea have the advantage of being quite effective in blood glucose lowering, with an almost instant onset of the effect after start of therapy.…”

Bioequivalence of Ertugliflozin/Sitagliptin Fixed‐Dose Combination Tablets and Coadministration of Respective Strengths of Individual Components

“…In phase 1 clinical pharmacology studies, sitagliptin was not found to meaningfully alter the PK of metformin, simvastatin, warfarin, oral contraceptives, rosiglitazone, or glyburide; these studies provide in vivo evidence for a low propensity of sitagliptin for perpetrating drug interactions with substrates of human organic cation transporter, CYP3A4, CYP2C8, and CYP2C9 . Multiple doses of sitagliptin slightly increased plasma immunoreactive digoxin concentrations; however, these increases are not considered likely to be clinically meaningful .…”

“…24 In phase 1 clinical pharmacology studies, sitagliptin was not found to meaningfully alter the PK of metformin, simvastatin, warfarin, oral contraceptives, rosiglitazone, or glyburide; these studies provide in vivo evidence for a low propensity of sitagliptin for perpetrating drug interactions with substrates of human organic cation transporter, CYP3A4, CYP2C8, and CYP2C9. [25][26][27][28][29][30][31] Multiple doses of sitagliptin slightly increased plasma immunoreactive digoxin concentrations; however, these increases are not considered likely to be clinically meaningful. 32 In a population PK analysis of phase 1 and phase 2b studies, 83 concomitantly administered medications were screened for potential effects on sitagliptin PK; none of the evaluated medications was found to meaningfully alter sitagliptin plasma concentrations.…”

Efficacy and Safety of Omarigliptin, a Novel Once-Weekly Dipeptidyl Peptidase-4 Inhibitor, in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

“…The hepatic metabolism of sitagliptin is minimal (mainly by cytochrome P450 3A4) and it is largely (70-80%) excreted by the urine in its unchanged form, with a halflife of around 12 hours [135]. As a result of its metabolism and elimination, dose adjustment is required in patients with severe renal impairment, but not in those with mild or moderate renal or hepatic impairment [136,137]. No dosage adjustment is necessary on the basis of age, gender, race, or body mass index; in addition, sitagliptin has a low propensity for pharmacokinetic drug interactions [93].…”