Saxagliptin, a potent, selective inhibitor of DPP-4, does not alter the pharmacokinetics of three oral antidiabetic drugs (metformin, glyburide or pioglitazone) in healthy subjects

Diabetes, Obesity and Metabolism

Volumn 13, Issue 7, 2011, Pages 604-614

  Patel, C G ^a   Kornhauser, D ^a   Vachharajani, N ^a   Komoroski, B ^a   Brenner, E ^a   Handschuh del Corral, M ^a   Li, L ^a   Boulton, D W ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

Diabetes mellitus; Drug drug interaction; Glyburide; Metformin; Pharmacokinetics; Pharmacology; Pioglitazone; Saxagliptin; Type 2 diabetes

Indexed keywords

5 HYDROXYSAXAGLIPTIN; DIPEPTIDYL PEPTIDASE IV; DRUG METABOLITE; GLIBENCLAMIDE; GLUCOSE; HYDROXYPIOGLITAZONE; METFORMIN; PIOGLITAZONE; SAXAGLIPTIN; UNCLASSIFIED DRUG;

ADULT; AREA UNDER THE CURVE; ARTICLE; ASTHENIA; BLURRED VISION; CHILL; CHLAMYDIAL URETHRITIS; CROSSOVER PROCEDURE; DIZZINESS; DRUG BLOOD LEVEL; DRUG DOSE SEQUENCE; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ECCHYMOSIS; FLU LIKE SYNDROME; HEADACHE; HUMAN; HUMAN EXPERIMENT; HYPOGLYCEMIA; MALE; MAXIMUM PLASMA CONCENTRATION; NERVOUSNESS; NORMAL HUMAN; OPEN STUDY; PHLEBITIS; RANDOMIZED CONTROLLED TRIAL; RECOMMENDED DRUG DOSE; SIDE EFFECT; SINGLE DRUG DOSE; STREPTOCOCCAL PHARYNGITIS; UPPER RESPIRATORY TRACT INFECTION;

EID: 79956336684     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/j.1463-1326.2011.01381.x     Document Type: Article

References (29)

1. Onglyza [package insert]. Princeton, NJ/Wilmington, DE: Bristol-Myers Squibb Company/AstraZeneca Pharmaceuticals LP; February 2011.
2. Zander M, Madsbad S, Deacon CF, Holst JJ. The metabolite generated by dipeptidyl-peptidase 4 metabolism of glucagon-like peptide-1 has no influence on plasma glucose levels in patients with type 2 diabetes. Diabetologia 2006; 49: 369-374.
3. Deacon CF. Incretin-based treatment of type 2 diabetes: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Diabetes Obes Metab 2007; 9(Suppl. 1): 23-31.
4. Rodbard HW, Jellinger PS, Garber AJ et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract 2009; 15: 540-558.
5. Rosenstock J. Clinical overview of saxagliptin for Type 2 diabetes management. Exp Rev Endocrinol Metab 2010; 5: 809-823.
6. Efendic S, Alvarsson M, Brismar K, Wagner H. Pathophysiology and treatment of patients with type 2 diabetes exhibiting failure to oral drugs. Acta Physiol (Oxf) 2008; 192: 117-125.
7. Hermansen K, Kipnes M, Luo E, Fanurik D, Khatami H, Stein P. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes Metab 2007; 9: 733-745.
8. Chacra AR, Tan GH, Apanovitch A, et al, for the CV181-040 Investigators. Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial. Int J Clin Pract 2009; 63: 1395-1406.
9. Garber AJ, Schweizer A, Baron MA, Rochotte E, Dejager S. Vildagliptin in combination with pioglitazone improves glycaemic control in patients with type 2 diabetes failing thiazolidinedione monotherapy: a randomized, placebo-controlled study. Diabetes Obes Metab 2007; 9: 166-174.
10. Rosenstock J, Kim SW, Baron MA et al. Efficacy and tolerability of initial combination therapy with vildagliptin and pioglitazone compared with component monotherapy in patients with type 2 diabetes. Diabetes Obes Metab 2007; 9: 175-185.
11. Rosenstock J, Brazg R, Andryuk PJ, Lu K, Stein P. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther 2006; 28: 1556-1568.
12. Hollander P, Li J, Allen E, Chen R for the CV181-013 Investigators. Saxagliptin added to a thiazolidinedione improves glycemic control in patients with type 2 diabetes and inadequate control on thiazolidinedione alone. J Endocrinol Metab 2009; 94: 4810-4819.
13. Glucophage [package insert]. Princeton, NJ: Bristol-Myers Squibb Company, January 2009.
14. ACTOS [package insert]. Deerfield, IL: Takeda Pharmaceuticals America, Inc., September 2009.
15. Micronase [package insert]. New York, NY: Pfizer Inc, May 2010.
16. Bristol-Myers Squibb Research and Development, Princeton, NJ. Data on file; 2007.
17. Scheen AJ. Clinical pharmacokinetics of metformin. Clin Pharmacokinet 1996; 30: 359-371.
18. Bristol-Myers Squibb Research and Development, Princeton, NJ. Data on file; 2006.
19. Kimura N, Masuda S, Tanihara Y et al. Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet 2005; 20: 379-386.
20. DeFronzo RA, Hissa MN, Garber AJ et al, for the Saxagliptin 014 Study Group. The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone. Diabetes Care 2009; 32: 1649-1655.
21. Brian WR. Hypoglycemic agents. In: Levy RH, Thummel KE, Trager WF, Hansten PD, Eichelbaum M eds. Metabolic Drug Interactions. Philadelphia, PA: Lippincott Williams & Wilkins, 2000; 529-543.
22. Kim KA, Park JY. Inhibitory effect of glyburide on human cytochrome p450 isoforms in human liver microsomes. Drug Metab Dispos 2003; 31: 1090-1092.
23. UKPDS Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837-853.
24. Hanefeld M. Pharmacokinetics and clinical efficacy of pioglitazone. Int J Clin Pract 2001; 121(Suppl. 121): 19-25.
25. Kirchheiner J, Roots I, Goldammer M et al. Effect of genetic polymorphisms in cytochrome p450 (CYP) 2C9 and CYP2C8 on the pharmacokinetics of oral antidiabetic drugs: clinical relevance. Clin Pharmacokinet 2005; 44: 1209-1225.
26. Krieter PA, Colletti AE, Doss GA et al. Disposition and metabolism of the hypoglycemic agent pioglitazone in rats. Drug Metab Dispos 1994; 22: 625-630.
27. Glazer NB, Cheatham WW. Thiazolidinediones for type 2 diabetes. No evidence exists that pioglitazone induces hepatic cytochrome P450 isoform CYP3A4. BMJ 2001; 322: 235-236.
28. Kajosaari LI, Jaakkola T, Neuvonen PJ et al. Pioglitazone, an in vitro inhibitor of CYP2C8 and CYP3A4, does not increase the plasma concentrations of the CYP2C8 and CYP3A4 substrate repaglinide. Eur J Clin Pharmacol 2006; 62: 217-223.
29. Nowak SN, Edwards DJ, Clarke A et al. Pioglitazone: effect on CYP3A4 activity. J Clin Pharmacol 2002; 42: 1299-1302.