Sitagliptin, an dipeptidyl peptidase-4 inhibitor, does not alter the pharmacokinetics of the sulphonylurea, glyburide, in healthy subjects

AIMS

Sitagliptin, a dipeptidyl peptidase-4 inhibitor, is an incretin enhancer that is approved for the treatment of Type 2 diabetes. Sitagliptin is mainly renally eliminated and not an inhibitor of CYP450 enzymes in vitro. Glyburide, a sulphonylurea, is an insulin sensitizer and mainly metabolized by CYP2C9. Since both agents may potentially be co-administered, the purpose of this study was to examine the effects of sitagliptin on glyburide pharmacokinetics.

METHODS

In this open-label, randomized, two-period crossover study, eight healthy normoglycaemic subjects, 22–44 years old, received single 1.25-mg doses of glyburide alone in one period and co-administered with sitagliptin on day 5 following a multiple-dose regimen for sitagliptin (200-mg q.d. ×6 days) in the other period.

RESULTS

The geometric mean ratios and 90% confidence intervals [(glyburide + sitagliptin)/glyburide] for AUC_0–∞ and C_max were 1.09 (0.96, 1.24) and 1.01 (0.84, 1.23), respectively.

CONCLUSION

Sitagliptin does not alter the pharmacokinetics of glyburide in healthy subjects.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• No data are available on the potential drug interaction of sitagliptin and glyburide.
• Sitagliptin belongs to a new class of drugs called DPP-4 inhibitors recently approved for the treatment of Type 2 diabetes.

WHAT THIS STUDY ADDS

• Glyburide is a commonly used sulphonylurea medication to treat Type 2 diabetes.
• Combination therapy is often required to achieve adequate glucose control in Type 2 diabetes.
• Sitagliptin does not appear to interfere with glyburide pharmacokinetics and therefore may be potentially co-administered with glyburide for the treatment of Type 2 diabetes.