Main Article Content
Type 2 diabetes, atherosclerosis, dipeptidyl peptidase-4, statin, HMG-CoA reductase, drug interactions
Treatment with the combination of sitagliptin (a dipeptidyl peptidase 4 inhibitor which improves glycemic control) and simvastatin (a well characterized lipid-lowering agent) may be considered an appropriate approach to management of type 2 diabetes and its associated increased risk of cardiovascular disease.
An investigation of the effects of simvastatin on the pharmacokinetics of sitagliptin was conducted.
Ten healthy men and women were enrolled into an open-label, randomized, 2-period, crossover study. Pharmacokinetics of sitagliptin were measured after a single dose of sitagliptin 100-mg alone, and after a single dose of sitagliptin 100-mg administered on Day 5 of a 7 day course of simvastatin 80-mg once daily.
The geometric mean ratio of (sitagliptin + simvastatin) / sitagliptin and corresponding 90% confidence interval for sitagliptin AUC0-∞ andCmax were 1.01 (0.97, 1.05), and 1.12 (1.00, 1.26), respectively.
Simvastatin has no clinically important effect on sitagliptin pharmacokinetics. No dose adjustment for either sitagliptin or simvastatin is recommended when these drugs are coadministered.
2. Garcia MJ, McNamara PM, Gordon T, Kannel WB. Morbidity and mortality in diabetics in the Framingham population. Sixteen year follow-up study. Diabetes 1974;23:105-11.
3. Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. Brit Med J 2000; 321:405-12.
4. American Diabetes Association. Standards of Medical Care in Diabetes - 2011. Diabetes Care 2011;34:S11-S61.
5. Ryden L, Standl E, Bartnik M, et al. Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J 2007;28:88-136.
6. Karasik A, Aschner P, Katzeff H, Davies MJ, Stein PP. Sitagliptin, a DPP-4 inhibitor for the treatment of patients with type 2 diabetes: a review of recent clinical trials. Curr Med Res Opin 2008;24: 489-96.
7. Thornberry NA, Weber AE. Discovery of JANUVIA (Sitagliptin), a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Curr Top Med Chem 2007;7:557-68.
8. Pedersen TR, Tobert JA. Simvastatin: a review. Expert Opin Pharmacother 2004;5:2583-96.
9. Kearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomized trials of statins: a meta-analysis. Lancet 2008;371:117-25.
10. U.S. Food and Drug Administration. FDA approves combination therapy Juvisync [press release]. U.S. Food and Drug Administration. (October 7, 2011) http://www.fda.gov/NewsEvents/Newsroom/Pre ssAnnouncements/ucm274748.htm (Accessed April 3, 2012).
11. Bergman AJ, Cote J, Maes A, et al. Effect of sitagliptin on the pharmacokinetics of simvastatin. J Clin Pharmacol 2009;49:483-8.
12. Ayalasomayajula SP, Dole K, He YL, et al. Evaluation of the potential for steady-state pharmacokinetic interaction between vildagliptin and simvastatin in healthy subjects. Curr Med Res Opin 2007; 23:2913-20.
13. Zeng W, Xu Y, Constanzer M, Woolf EJ. Determination of sitagliptin in human plasma using protein precipitation and tandem mass spectrometry. J Chromatography B 2010;878:1817-23.
14. Herman GA, Stevens C, Van Dyck K, et al. Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses. Clin Pharmacol Ther 2005;78:675-88.
15. Vincent SH, Reed JR, Bergman AJ, et al. Metabolism and excretion of the dipeptidyl peptidase 4 inhibitor [14C]sitagliptin in humans. Drug Metab Dispos 2007;35:533-8.
16. Prueksaritanont T, Ma B, Yu N. The human hepatic metabolism of simvastatin hydroxy acid is mediated primarily by CYP3A, and not CYP2D6. Br J Clin Pharmacol 2003;56:120-4.
17. U.S. prescribing information for JANUVIA® (sitagliptin) Tablets. (September 2010) http://www.januvia.com/sitagliptin/januvia/cons umer/index.jsp (Accessed April 3, 2012).
18. Bergman A, Mistry GC, Luo WL, et al. Doseproportionality of a final market image sitagliptin formulation, an oral dipeptidyl peptidase-4 inhibitor, in healthy volunteers. Biopharm Drug Dispos 2007; 28:307-13.