Advertisement

Drugs

, Volume 69, Issue 15, pp 2103–2114 | Cite as

Saxagliptin

  • Sohita Dhillon
  • Juliane Weber
Adis Drug Profile

Abstract

  • ▲ Saxagliptin and its active metabolite M2 are dipeptidyl peptidase-4 inhibitors that improve glycaemic control by preventing the inactivation of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide. This increases GLP-1 levels, stimulates insulin secretion and reduces postprandial glucagon and glucose levels.

  • ▲ In well designed, 24-week trials in treatmentnaive patients with type 2 diabetes mellitus, monotherapy with oral saxagliptin 2.5 or 5mg once daily significantly improved glycaemic control, as measured by mean glycosylated haemoglobin (HbA1c) levels, relative to placebo.

  • ▲ In large, well designed, 24-week trials, combination therapy with saxagliptin 5 mg once daily plus metformin significantly improved HbA1c levels relative to single-agent saxagliptin or metformin in treatment-naive patients; in treatment-experienced patients with inadequate glycaemic control, the addition of saxagliptin 2.5 or 5 mg once daily to metformin, glyburide or a thiazolidinedione, significantly improved HbA1c levels relative to continued use of existing monotherapy.

  • ▲ Saxagliptin as monotherapy or in combination with other oral antihyperglycaemics was generally well tolerated, with most adverse events being of mild to moderate severity. In clinical trials, the incidence of hypoglycaemic events in patients receiving saxagliptin was generally similar to that in patients receiving placebo or other oral antihyperglycaemic agents.

  • ▲ Saxagliptin therapy was not associated with an increased risk of cardiovascular events according to pooled data from eight clinical trials. Saxagliptin generally had a weight-neutral effect.

Keywords

Metformin Pioglitazone Glycaemic Control HbA1c Level Vildagliptin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements and Disclosures

The manuscript was reviewed by: R.K. Campbell, College of Pharmacy, Washington State University, Pullman, Washington, USA; J. Eriksson, Department of General Practice and Primary Health Care, University of Helsinki, and Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland.

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was also offered an opportunity to comment on this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

References

  1. 1.
    American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2009 Jan; 32 Suppl. 1: S62–7CrossRefGoogle Scholar
  2. 2.
    World Health Organization. Diabetes: fact sheet (no. 312) [online]. Available from URL: http://www.who.int/mediacentre/factsheets/fs312/en/ [Accessed 2009 Jun 24]
  3. 3.
    Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009 Jan; 32(1): 193–203PubMedCrossRefGoogle Scholar
  4. 4.
    Rosenstock J, Zinman B. Dipeptidyl peptidase-4 inhibitors and the management of type 2 diabetes mellitus. Curr Opin Endocrinol Diabetes Obes 2007 Apr; 14(2): 98–107PubMedCrossRefGoogle Scholar
  5. 5.
    Turner RC, Cull CA, Frighi V, et al. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA 1999 Jun 2; 281(21): 2005–12Google Scholar
  6. 6.
    Campbell RK. Rationale for dipeptidyl peptidase 4 inhibitors: a new class of oral agents for the treatment of type 2 diabetes mellitus. Ann Pharmacother 2007 Jan; 41(1): 51–60PubMedGoogle Scholar
  7. 7.
    Ahren B. Dipeptidyl peptidase-4 inhibitors: clinical data and clinical implications. Diabetes Care 2007 Jun; 30(6): 1344–50PubMedCrossRefGoogle Scholar
  8. 8.
    Inzucchi SE, McGuire DK. New drugs for the treatment of diabetes. Part II: incretin-based therapy and beyond. Circulation 2008 Jan 29; 117(4): 574–84Google Scholar
  9. 9.
    Bristol-Myers Squibb. Onglyza (saxagliptin) tablets: US prescribing information [online]. Available from URL: http://packageinserts.bms.com/pi/pi_onglyza.pdf [Accessed 2009 Aug 6]
  10. 10.
    Boulton DW, Geraldes M. Safety, tolerabilty, pharmacokinetics and pharmacodynamics of once-daily oral doses of saxagliptin for 2 weeks in type 2 diabetic and healthy subjects [abstract no. 606-P plus poster]. 67th Scientific Sessions of the American Diabetes Association; 2007 Jun 22–26; Chicago (IL)Google Scholar
  11. 11.
    Henry R, Smith S, Schwartz S, et al. β-cell stimulation by saxagliptin in patients with T2D [abstract no. 447-P plus poster]. 69th Annual Scientific Sessions of the American Diabetes Association; 2009 Jun 5–9; New Orleans (LA)Google Scholar
  12. 12.
    Patel CG, Li L, Komoroski BJ, et al. No effect of saxagliptin on QTc interval in healthy subjects [abstract no. 2072-PO]. 69th Annual Scientific Sessions of the American Diabetes Association; 2009 Jun 5–9; New Orleans (LA)Google Scholar
  13. 13.
    Wang A, Dorso C, Kopcho L, et al. Implications of the prolonged dissociation rate of saxagliptin, a highly potent and selective DPP4 inhibitor, on plasma DPP measurements [abstract no. 2088-PO]. Diabetes 2008 Jun; 57 Suppl. 1: A576–7Google Scholar
  14. 14.
    Fura A, Khanna A, Vyas V, et al. Pharmacokinetics of the dipeptidyl peptidase 4 inhibitor saxagliptin in rats, dogs, and monkeys and clinical projections. Drug Metab Dispos 2009 Jun; 37(6): 1164–71PubMedCrossRefGoogle Scholar
  15. 15.
    Boulton D, Tang A, Patel C, et al. Pharmacokinetics of dipeptidyl pepetidase-4 inhibitor saxagliptin in subjects with renal impairment [abstract no. P357]. 11th European Congress of Endocrinology; 2009 Apr 25–29; IstanbulGoogle Scholar
  16. 16.
    Patel C, Castaneda L, Frevert U, et al. Single-dose pharmacokinetics and safety of saxagliptin in subjects with hepatic impairment compared with healthy subjects [abstract no. 537-P] Diabetes 2008 Jun; 57 Suppl. 1: A160Google Scholar
  17. 17.
    Boulton DW, Goyal A, Li L, et al. The effects of age and gender on the single-dose pharmacokinetics and safety of saxagliptin in healthy subjects [abstract no. 551-P] Diabetes 2008 Jun; 57 Suppl. 1: A164Google Scholar
  18. 18.
    Boulton DW, Adams D, Li L, et al. Magnesium and aluminum hydroxides plus simethicone, famotidine, or omeprazole do not meaningfully affect the pharmacokinetics of saxagliptin in healthy subjects [abstract no. PIII-68] Clin Pharmacol Ther 2008 Mar; 83 Suppl. 1: S92–3Google Scholar
  19. 19.
    Boulton DW, Li L, Patel CG, et al. No pharmacokinetic interaction between saxagliptin and digoxin in healthy subjects [abstract no. PIII-69] Clin Pharmacol Ther2008 Mar; 83 Suppl. 1: S93Google Scholar
  20. 20.
    Girgis S, Patel CG, Li L, et al. The effect of diltiazem on the pharmacokinetics of saxagliptin in healthy volunteers [abstract no. 72] J Clin Pharmacol 2007; 47(9): 1199Google Scholar
  21. 21.
    Boulton DW, Brenner E, Royzman K, et al. Effect of ketoconazole on the pharmacokinetics of saxagliptin in healthy sunjects [abstract no. 89] J Clin Pharmacol 2007; 47(9): 1203Google Scholar
  22. 22.
    Patel C, Li L, Komoroscki B, et al. No meaningful drug-drug interaction between saxagliptin and glyburide in healthy subjects [abstract no. 212]. 36th Annual Meeting of the American College of Clinical Pharmacology; 2007 Sep 9–11; San Fransisco (CA)Google Scholar
  23. 23.
    Patel C, Li L, Komoroscki B, et al. No meaningful drug-drug interaction between saxagliptin and metformin in healthy subjects [abstract no. 213]. 36th Annual Meeting of the American College of Clinical Pharmacology; 2007 Sep 9–11; San Fransisco (CA)Google Scholar
  24. 24.
    Patel C, Li L, Komoroscki B, et al. No meaningful drug-drug interaction between saxagliptin and pioglitazone subjects [abstract no. 226]. 36th Annual Meeting of the American College of Clinical Pharmacology; 2007 Sep 9–11; San Fransisco (CA)Google Scholar
  25. 25.
    Girgis S, You X, Maurer C, et al. The effect of simvastatin on the pharmacokinetics of saxagliptin in healthy volunteers [abstract no. 28]. J Clin Pharmacol 2007; 47(9): 1188Google Scholar
  26. 26.
    Rosenstock J, Aguilar-Salinas C, Klein E, et al. Effect of saxagliptin monotherapy in treatment-naive patients with type 2 diabetes. Curr Med Res Opin 2009; 25(10): 2401–11PubMedCrossRefGoogle Scholar
  27. 27.
    Rosenstock J, Sankoh S, List JF. Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drugnaive patients with type 2 diabetes. Diabetes Obes Metab 2008 May; 10(5): 376–86PubMedCrossRefGoogle Scholar
  28. 28.
    Jadzinsky M, Pfutzner A, Paz-Pacheco E, et al. Saxagliptin given in combination with metformin as initial therapy improves glycaemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trial. Diabetes Obes Metab 2009 Jun; 11(6): 611–22PubMedCrossRefGoogle Scholar
  29. 29.
    DeFronzo RA, Hissa MN, Garber AJ, et al. The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes on metformin alone. Diabetes Care 2009; 32(9): 1649–55PubMedCrossRefGoogle Scholar
  30. 30.
    Chacra AR, Tan GH, Apanovitch A, et al. 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 Jul 15; 63(9): 1395–406PubMedCrossRefGoogle Scholar
  31. 31.
    Allen E, Hollander P, Li J, et al. Saxagliptin added to a thiazolidinedione improves glycaemic control in patients with inadequately controlled type 2 diabetes [abstract no. 859]. Diabetologia 2008; 51 Suppl. 1: S342–3Google Scholar
  32. 32.
    Defronzo RA, Hissa MN, Garber AJ, et al. Once-daily saxagliptin added to metformin provides sustained glycemic control and is well tolerated over 102 weeks in patients with T2D [abstract no. 547-P]. 69th Annual Scientific Sessions of the American Diabetes Association; 2009 Jun 5–9; New Orleans (LA)Google Scholar
  33. 33.
    Chen R, Donovan M, Rusnak JM, et al. Saxagliptin used as monotherapy or in combination with other anti-hyperglycaemic agents does not significantly increase risk of hypoglycaemia [abstract no. 2082-PO]. 69th Annual Scientific Sessions of the American Diabetes Association; 2009 Jun 5–9; New Orleans (LA)Google Scholar
  34. 34.
    Wolf R, Frederich R, Fiedorek F, et al. Evaluation of CV risk in saxagliptin clinical trials [abstract no. 8-LB plus poster]. 69th Annual Scientific Sessions of the American Diabetes Association; 2009 Jun 5–9; New Orleans (LA)Google Scholar

Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  1. 1.Adis, a Wolters Kluwer BusinessMairangi Bay, North Shore 0754, AucklandNew Zealand

Personalised recommendations