Saxagliptin and Dapagliflozin for type 2 Diabetes mellitus: A Review

  • Deepshi Ranjan M.Pharm Scholar
  • Akanksha Sharma
  • Ramesh Babu Bodla

Abstract

Qtern® is a fixed dose combination tablet of Saxagliptin and Dapagliflozin which is indicated for the advancement of glycaemic control in adults with type 2 diabetes mellitus (T2DM). It can be done either when medication with metformin and/or a sulfonylurea with a monocomponent of either Saxagliptin or Dapagliflozin render poor glycaemic control, or when the subject is treated with the free combination of Saxagliptin and Dapagliflozin. This review compiles pathophysiology of type 2 diabetes mellitus (T2DM) along with pharmacological properties, mechanism of action, and side effects of both the drugs. Furthermore, the method of determination of combination is described in this review. The agents have corresponding mechanisms of action, which further adds to the benefit of using this combination. The mixture is associated with reduced body weight and a low risk of hypoglycaemia. It is the first dipeptidyl peptidase-4 (DPP-4) inhibitor and sodium-glucose cotransporter (SGLT2) inhibitor fixed-dose combination available in the EU therefore can act as potent option for glycaemic control in patients with T2DM.

Keywords: Qtern,, Saxagliptin, Pharmacodynamics., Dapagliflozin, Pharmacokinetics, Type 2 diabetes mellitus

Downloads

Download data is not yet available.

References

1. King, H. and Rewers M. Global estimates for prevalence of diabetes mellitus and impaired glucose tolerance in adults. WHO Ad Hoc Diabetes Reporting Group. Diabetes Care. 1993; 16:157-77.
2. King H. Aubert RE and Herman WH. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998; 21: 1414–31.
3. Wild S, Roglic G, Green A, Sicree R and King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004; 27: 1047-53.
4. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes-estimates for the year 2000 and projections for 2030. Diabetes Care. 2004; 27(3):1047–53.
5. Whiting Dr, Guariguata L, Weil C, Shawj. IDF Diabetes Atlas: Global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract. 2011;94:311–21.
6. WHO About diabetes [Internet]. Web.archive.org; 2018 [cited 2018 May 21]. Available from:
https://web.archive.org/web/20140331094533/http://www.who.int/diabetes/action_online/basics/en/
7. Kahn CR. Banting Lecture. Insulin action, diabetogenes, and the cause of type II diabetes. Diabetes. 1994 Aug; 43(8):1066-84 [PubMed].
8. Robertson RP. Antagonist: diabetes and insulin resistance–philosophy, science, and the multiplier hypothesis. J Lab Clin Med. 1995 May;125(5):560-4.
9. Fujioka K. Pathophysiology of type 2 diabetes and the role of incretin hormones and beta-cell dysfunction. JAAPA 2007; suppl 3-8. [PubMed].
10. Inzucchi SE, Bergenstal RM, Buse JB, et al. American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD) Management of hyperglycemia in type 2 diabetes: a patient-centred approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012; 35:1364–79. pmid: 22517736.
11. Fonseca VA. Defining and characterizing the progression of type 2 diabetes. Diabetes Care. 2009; 32(Suppl. 2):S151–S156. pmid:19875543
12. Harper W, Clement M, Goldenberg R, et al. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee Canadian Diabetes Association 2013 clinical practice guidelines for the prevention and management of diabetes in Canada. Pharmacologic management of type 2 diabetes. Can J Diabetes. 2013;37 (Suppl.1): S61–S68. pmid: 24070926
13. Garber AJ, Abrahamson MJ, Barzilay JI, et al. American Association of Clinical Endocrinologists' comprehensive diabetes management algorithm 2013 consensus statement-executive summary. Endocr Pract. 2013;19:536–557. pmid:23816937.
14. Raz I, Riddle MC, Rosenstock J, et al. Personalized management of hyperglycaemia in type 2 diabetes: reflections from a Diabetes Care Editors’ Expert Forum. Diabetes Care. 2013; 36:1779–88. pmid: 23704680
15. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee Canadian Diabetes Association 2013. clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes. 2013; 37(suppl 1):S1–S212.
16. Inzucchi S, Bergenstal R, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centred approach - position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) Diabetes Care 2012. 2013; 3536(2):1364-79.
17. Garber AJ, Abrahamson MJ, Barzilay JI, et al. AACE/ACE Comprehensive Diabetes Management Algorithm 2015. Endocr Prac. 2015; 21(4):438-47.
18. Merovci A, Solis-Herrera C, Daniele G, et al. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest. 2014; 124(2):509-14.
19. Abdul-Ghani M. Where does combination therapy with an SGLT2 inhibitor plus a DPP-4 inhibitor fit in the management of type 2 diabetes? Diabetes Care. 2015; 38(3):373-75.
20. European Medicines Agency. Qtern: EPAR product information; 2016.
21. Thom S, Poulter N, Field J, et al. UMPIRE Collaborative Group Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD: The UMPIRE randomized clinical trial. JAMA. 2013; 310(9):918-29.
22. Thayer S, Arondekar B, Harley C, Darkow TE. Adherence to a fixed-dose combination of rosiglitazone/glimepiride in subjects switching from monotherapy or dual therapy with a thiazolidinedione and/or a sulfonylurea. Ann Pharmacother. 2010; 44(5):791-9.
23. Singh-Franco D. Potential for dipeptidyl peptidase-4 inhibitor and sodium glucose cotransporter 2 inhibitor single-pill combinations. Expert Rev Endocrinol Metab. 2015; 10(3):305-17.
24. European Medicines Agency Qtern. Summary of Product Characteristics [Internet]. EMEA; 2013 [Cited 2018 Jan 25]. Available from:
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004057/WC500211093.pdf.
25. U.S. Food and Drug Administration, editor. QTERN. Full Prescribing Information [Internet]. US FDA; 2011 [Cited 2018 Mar 17]. Available from:
https://www.accessdata.fda.gov/drug-satfda_docs/label/2017/209091s000lbl.pdf.
26. Sujana KP, Rani SG, Prasad MB, Reddy MS. Simultaneous estimation of Pioglitazone Hydrochloride and Metformin hydrochloride using UV Spectroscopic method. J Biomed Sci and Res. 2010; 2:110-5.
27. Dadhania KP, Nadpara PA, Agrawal YA. Development and validation of spectrophotometric method for simultaneous estimation of Gliclazide and Metformin hydrochloride in bulk and tablet dosage form by Simultaneous equation method. IJPSR. 2011; 2:1559-63.
28. Shah AS, Sen DB, Sen AB. Simultaneous UV Spectrophotometric Method for Estimation of Fenofibrate and Metformin Hydrochloride in Tablet Dosage Form. Asian J Research in Chemistry. 2011; 4:1234-7.
29. Raj NP, Nargund RG, Kabra PS, Patel KA, Nargund LVG. Simultaneous Quantification of Voglibose and Metformin by Validated Analytical Method in Tablet Dosage Form. Int J Institute Pharmacy and Life Sciences. 2011; 1:58-63.
30. Grant RW, Devita NG, Singer DE, Meigs JB. Polypharmacy and medication adherence in patients with type 2 diabetes. Diabetes Care. 2003; 26(5) :1408-12.
31. Drug Bank: Dapagliflozin (DB06292) [Internet]. Drug bank; 2008 Mar 19 [Cited 2018 Jan 27]. Available from:
https://www.drugbank.ca/drugs/DB06292
32. Prentki M, Nolan CJ. Islet beta cell failure in type 2 diabetes. J Clin Invest. 2006; 116(7):1802-12.
33. Matthews DR, Cull CA, Stratton IM, Holman RR, Turner RC. UKPDS 26: Sulphonylurea failure in non-insulin-dependent diabetic patients over six years. UK Prospective Diabetes Study (UKPDS) Group. Diabet Med. 1998; 15(4):297-303.
34. Pratley RE, Salsali A. Inhibition of DPP-4: a new therapeutic approach for the treatment of type 2 diabetes. Curr Med Res Opin. 2007 Apr; 23(4):919-931.doi: 10.1185/030079906X162746
35. Barnett A. DPP-4 inhibitors and their potential role in the management of type 2 diabetes. Int J Clin Pract. 2006 Nov; 60(11):1454-70. doi: 10.1111/j.1742-1241.2006.01178.x.
36. Alpern RJ, Moe O, Caplan M, Seldin DW. Seldin and Giebisch’s The Kidney: Physiology and Pathophysiology. Oxford: Academic; 2012.
37. Drug Bank: Saxagliptin (DB06335) [Internet]. Drug bank; 2008 Mar 19 [Cited 2018 Jan 28]. Available from:
https://www.drugbank.ca/drugs/DB06335
38. Wright EM, Hirayama BA, Loo DF. Active sugar transport in health and disease. J Intern Med. 2007; 261(1): 32–43.
Statistics
386 Views | 794 Downloads
How to Cite
Ranjan, D., A. Sharma, and R. B. Bodla. “Saxagliptin and Dapagliflozin for Type 2 Diabetes Mellitus: A Review”. International Journal of Drug Regulatory Affairs, Vol. 6, no. 3, Sept. 2018, pp. 24-30, doi:10.22270/ijdra.v6i3.264.