Clinical utility in the treatment of type 2 diabetes with the saxagliptin/metformin fixed combination

Patient Preference and Adherence

Volumn 8, Issue , 2014, Pages 227-236

  Panagoulias, George S ^a   Doupis, John ^b,c  

^a UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

^b ATHENS NAVAL HOSPITAL   (Greece)

^c Diabetes Division Iatriko Paleou Falirou Medical Center   (Greece)

Author keywords

DPP 4 inhibitors; FDC products; Fixed dose combination products; Metformin; Saxagliptin

Indexed keywords

EID: 84894259582     PISSN: None     EISSN: 1177889X     Source Type: Journal    
DOI: 10.2147/PPA.S34089     Document Type: Review

References (97)

1. 2011 National Diabetes Fact Sheet [webpage on the Internet]. Atlanta, GA: Centers for Disease Control and Prevention; 2013. Available from: http://www.cdc.gov/diabetes/pubs/factsheet11.htm. Accessed August 27, 2013.
2. American Diabetes Association. Standards of medical care in diabetes 2013. Diabetes Care. 2013;36 Suppl 1:S11-S66.
3. [No authors listed]. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective DiabetesStudy (UKPDS) Group. Lancet. 1998;352(9131):837-853.
4. [No authors listed]. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulindependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993;329(14):977-986.
5. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359(15):1577-1589.
6. IDF Diabetes Atlas Update 2012 [webpage on the Internet]. Brussels: International Diabetes Federation; 2012. Available from: http://www.idf.org/diabetesatlas/5e/Update2012. Accessed August 27, 2013.
7. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA. 2002;287(3):360-372.
8. Fox KM, Gerber Pharmd RA, Bolinder B, Chen J, Kumar S. Prevalence of inadequate glycemic control among patients with type 2 diabetes in the United Kingdom general practice research database: a series of retrospective analyses of data from 1998 through 2002. Clin Ther. 2006;28(3):388-395.
9. Barnett AH. Redefining the role of thiazolidinediones in the management of type 2 diabetes. Vasc Health Risk Manag. 2009;5(1):141-151.
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 patientcentered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35(6):1364-1379.
11. Rodbard HW, Jellinger PS, Davidson JA, etal. 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(6): 540-559.
12. Blackburn DF, Swidrovich J, Lemstra M. Non-adherence in type 2 diabetes: practical considerations for interpreting the literature. Patient Prefer Adherence. 2013;7:183-189.
13. Cramer JA. A systematic review of adherence with medications for diabetes. Diabetes Care. 2004;27(5):1218-1224.
14. Asche C, LaFleur J, Conner C. A review of diabetes treatment adherence and the association with clinical and economic outcomes. Clin Ther. 2011;33(1):74-109.
15. Koliaki C, Doupis J. Linagliptin/metformin fixed-dose combination treatment: a dual attack to type 2 diabetes pathophysiology. Adv Ther. 2012;29(12):993-1004.
16. Oral Diabetes Medications Summary Chart [webpage on the Internet]. Boston, MA: Joslin Diabetes Center; 2013. Available from: http://www.joslin.org/info/oral_diabetes_medications_summary_chart.html. Accessed August 27, 2013.
17. Brazg R, Xu L, Dalla Man C, Cobelli C, Thomas K, Stein PP. Effect of adding sitagliptin, a dipeptidyl peptidase-4inhibitor, to metformin on 24-h glycaemic control and beta-cell function in patients with type 2 diabetes. Diabetes Obes Metab. 2007;9(2):186-193.
18. Bosi E, Dotta F, Jia Y, Goodman M. Vildagliptin plus metformin combination therapy provides superior glycaemic control to individual monotherapy in treatment-naive patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2009;11(5):506-515.
19. Patlak M. New weapons to combat an ancient disease: treating diabetes. FASEB J. 2002;16(14):1853.
20. Proks P, Reimann F, Green N, Gribble F, Ashcroft F. Sulfonylurea stimulation of insulin secretion. Diabetes. 2002;51 Suppl 3: S368-S376.
21. Cruzan SM. FDA approves new diabetes drug [press release]. 1994 [December 30]. Available from: http://web.archive.org/web/20070929152824/http://www.fda.gov/bbs/topics/ANSWERS/ANS00627.html. Accessed July 26, 2013.
22. Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2006;29(8):1963-1972.
23. Van de Laar FA, Lucassen PL, Akkermans RP, Van de Lisdonk EH, Rutten GE, Van Weel C. Alpha-glucosidase inhibitors for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2005;(2):CD003639.
24. Lamanna C, Monami M, Marchionni N, Mannucci E. Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2011;13(3):221-228.
25. Idris I, Warren G, Donnelly R. Association between thiazolidinedione treatment and risk of macular edema among patients with type 2 diabetes. Arch Intern Med. 2012;172(13):1005-1011.
26. Nissen SE, Wolski K. Rosiglitazone revisited: an updated metaanalysis of risk for myocardial infarction and cardiovascular mortality. Arch Intern Med. 2010;170(14):1191-1201.
27. Lewis JD, Ferrara A, Peng T, et al. Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. Diabetes Care. 2011;34(4):916-922.
28. Symlin [webpage on the Internet]. Drugs.com; 2013 [revised December 3, 2010]. Available from: http://www.drugs.com/symlin.html. Accessed August 27, 2013.
29. Kleppinger EL, Vivian EM. Pramlintide for the treatment of diabetes mellitus. Ann Pharmacother. 2003;37(7-8):1082-1089.
30. Hollander PA, Levy P, Fineman MS, et al. Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type 2 diabetes: a 1-year randomized controlled trial. Diabetes Care. 2003;26(3):784-790.
31. Jones MC. Therapies for diabetes: pramlintide and exenatide. Am Fam Physician. 2007;75(12):1831-1835.
32. Ferrannini E, Ramos SJ, Salsali A, Tang W, List JF. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care. 2010;33(10):2217-2224.
33. Abrahamson MJ, Peters A. Intensification of insulin therapy in patients with type 2 diabetes mellitus: an algorithm for basal-bolus therapy. Ann Med. 2012;44(8):836-846.
34. Campbell RK. Recommendations for improving adherence to type 2 diabetes mellitus therapy focus on optimizing insulin-based therapy. Am J Manag Care. 2012;18(Suppl 3):S55-S61.
35. Jonassen I, Havelund S, Hoeg-Jensen T, Steensgaard DB, Wahlund PO, Ribel U. Design of the novel protraction mechanism of insulin degludec, an ultra-long-acting basal insulin. Pharm Res. 2012;29(8): 2104-2114.
36. Bergenstal RM, Rosenstock J, Arakaki RF, et al. A randomized, controlled study of once-daily LY2605541, a novel long-acting basal insulin, versus insulin glargine in basal insulin-treated patients with type 2 diabetes. Diabetes Care. 2012;35(11):2140-2147.
37. Pories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg. 1995;222(3):339-350; discussion 350-332.
38. Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009;122(3):248-256. e245.
39. Cao Y, Li Y, Kim J, et al. Orally efficacious novel small molecule 6-chloro-6-deoxy-1,2,3,4-tetra-O-galloyl-alpha-D-glucopyranose selectively and potently stimulates insulin receptor and alleviates diabetes. J Mol Endocrinol. 2013;51(1):15-26.
40. Ganugapati J, Baldwa A, Lalani S. Molecular docking studies of banana flower flavonoids as insulin receptor tyrosine kinase activators as a cure for diabetes mellitus. Bioinformation. 2012;8(5):216-220.
41. Elrick H, Stimmler L, Hlad CJ Jr, Arai Y. Plasma insulin response to oral and intravenous glucose administration. J Clin Endocrinol Metab. 1964;24:1076-1082.
42. Nauck MA, Homberger E, Siegel EG, et al. Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J Clin Endocrinol Metab. 1986;63(2):492-498.
43. Kumar A. Second line therapy: type 2 diabetic subjects failing on metformin GLP-1/DPP-IV inhibitors versus sulphonylurea/insulin: for GLP-1/DPP-IV inhibitors. Diabetes Metab Res Rev. 2012;28 (Suppl 2): 21-25.
44. Peters A. Incretin-based therapies: review of current clinical trial data. Am J Med. 2010;123(Suppl 3):S28-S37.
45. Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 11 2006;368(9548):1696-1705.
46. Mentis N, Vardarli I, Köthe LD, et al. GIP does not potentiate the antidiabetic effects of GLP-1 in hyperglycemic patients with type 2 diabetes. Diabetes. 2011;60(4):1270-1276.
47. Wysham CH, Blevins TC, Arakaki R et al. Efficacy and safety of dulaglutide vs placebo and exenatide in type 2 diabetes (AWARD-1). Efficacy and safety of dulaglutide vs placebo and exenatide in type 2 diabetes (AWARD-1). Abstract 66-OR. Presented at: American {Eth}iabetes Association (ADA) 73rd Scientific Sessions; June 21-25, 2013; Chicago, IL.
48. Europe approval status for Albiglutide: [webpage on the Internet]. Available from http://www.gsk.com/media/press-releases/2013/regulatory-update--gsk-announces-regulatory-submission-for-albig.html. Accessed December 17, 2013.
49. US approval status for Albiglutide: [webpage on the Internet]. Available from http://google2.fda.gov/searchq=Albiglutide&client=FDAgov&site=FDAgov&lr=&proxystylesheet=FDAgov&output=xml_no_dtd&getfields=. Accessed December 17, 2013.
50. Lovshin JA, Drucker DJ. Incretin-based therapies for type 2 diabetes mellitus. Nat Rev Endocrinol. 2009;5(5):262-269.
51. Martin JH, Deacon CF, Gorrell MD, Prins JB. Incretin-based therapies review of the physiology, pharmacology and emerging clinical experience. Intern Med J. 2011;41(4):299-307.
52. Victoza (liraglutide [rDNA origin]) injection: Rems risk of thyroid C-cell tumors, acute pancreatitis [wepage on the Internet]. Silver Spring, MD: US Food and Drug Administration; 2011 [updated June 13, 2011]. Available from: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm258826.htm. Accessed August 27, 2013.
53. Phenomix. Safety and Efficacy study of dutogliptin/PHX1149T to treat type 2 diabetes mellitus. Availabe from http://clinicaltrials.gov/ct2/show/NCT00690638?term=Dutogliptin&rank=9. Identifier NCT00690638.
54. Nathan DM, Buse JB, Davidson MB, et al; American Diabetes Association; European Association for Study of Diabetes. 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;32(1):193-203.
55. Mazzola N. Review of current and emerging therapies in type 2 diabetes mellitus. Am J Manag Care. 2012;18(Suppl 1):S17-S26.
56. Onglyza™ (Saxagliptin), a New Treatment for Type 2 Diabetes Mellitus in Adults, Now Available in US Pharmacies [press release]. Bristol-Myers Squibb Company; AstraZeneca; 2009 [August 14]. Available from: http://www.bms.com/Documents/news/onglyza_ available.pdf. Accessed July 29, 2013.
57. CHMP Assessment Report for Onglyza. London: European Medicines Agency; 2009. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/001039/WC500044319.pdf. Accessed July 29, 2013.
58. Onglyza FAQs [webpage on the Internet]. Bristol-Myers Squibb Company; AstraZeneca Pharmaceuticals LP; 2013. Available from: http://www.onglyza.com/about/faq.aspx. Accessed July 29, 2013.
59. Onglyza (saxagliptin) tablets [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company; Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2013. Available from: http://packageinserts.bms.com/pi/pi_onglyza.pdf. Accessed July 29, 2013.
60. 74 studies found for: saxagliptin [webpage on the Internet]. ClinicalTrials.gov; 2013. Available from: http://clinicaltrials.gov/ct2/results?term=saxagliptin&Search=Search. Accessed July 29, 2013.
61. Dickersin K, Scherer R, Lefebvre C. Identifying relevant studies for systematic reviews. BMJ. 1994;309(6964):1286-1291.
62. Ho PM, Rumsfeld JS, Masoudi FA, et al. Effect of medication nonadherence on hospitalization and mortality among patients with diabetes mellitus. Arch Intern Med. 2006;166(17):1836-1841.
63. Adherence to long-term therapies: evidence for action [webpage on the Internet]. Geneva: World Health Organization; 2013; Available from: http://www.who.int/chp/knowledge/publications/adherence_report/en/. Accessed July 27, 2013.
64. Melikian C, White TJ, Vanderplas A, Dezii CM, Chang E. Adherence to oral antidiabetic therapy in a managed care organization: a comparison of monotherapy, combination therapy, and fixed-dose combination therapy. Clin Ther. 2002;24(3):460-467.
65. Hermans MP, Delibasi T, Farmer I, et al. Effects of saxagliptin added to sub-maximal doses of metformin compared with uptitration of metformin in type 2 diabetes: the PROMPT study. Curr Med Res Opin. 2012;28(10):1635-1645.
66. Upreti VV, Keung CF, Boulton DW, et al. Bioequivalence of saxagliptin/ metformin immediate release (IR) fixed-dose combination tablets and single-component saxagliptin and metformin IR tablets in healthy adult subjects. Clin Drug Investig. 2013;33(5):365-374.
67. Boulton DW, Smith CH, Li L, Huang J, Tang A, LaCreta FP. Bioequivalence of saxagliptin/metformin extended-release (XR) fixed-dose combination tablets and single-component saxagliptin and metformin XR tablets in healthy adult subjects. Clin Drug Investig. 2011;31(9):619-630.
68. De Fronzo RA, Hissa MN, Garber AJ, et al; 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(9):1649-1655.
69. Liu Y, Hong T. Combination therapy of dipeptidyl peptidase-4 inhibitors and metformin in type 2 diabetes: rationale and evidence. Diabetes Obes Metab. Epub May 13, 2013.
70. Chacra AR, Tan GH, Ravichandran S, List J, Chen R; CV181040 Investigators. Safety and efficacy of saxagliptin in combination with submaximal sulphonylurea versus up-titrated sulphonylurea over 76 weeks. Diab Vasc Dis Res. 2011;8(2):150-159.
71. Fass AD, Gershman JA. Efficacy and safety of dipeptidyl peptidase-4 inhibitors in combination with metformin. Adv Ther. 2013;30(4): 337-353.
72. Cook W, Bryzinski B, Slater J, Frederich R, Allen E. Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus and cardiovascular disease history or cardiovascular risk factors: results of a pooled analysis of phase 3 clinical trials. Postgrad Med. 2013;125(3):145-154.
73. Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545-2559.
74. Scirica BM, Bhatt DL, Braunwald E, et al. The design and rationale of the saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus-thrombolysis in myocardial infarction (SAVOR-TIMI) 53 study. Am Heart J. 2011;162(5):818-825. e6.
75. AstraZeneca and Bristol-Myers Squibb announce top line results for SAVOR-TIMI-53 cardiovascular outcomes trial of Onglyza® (saxagliptin) [press release]. Princeton, NJ: Bristol-Myers Squibb; Wilmington, DE: AstraZeneca; 2013 [June 19]. Available from: http://news.bms.com/ press-release/astrazeneca-and-bristol-myers-squibb-announce-top-line-results-savor-timi-53-cardiovas. Accessed July 29, 2013.
76. Karyekar CS, Ravichandran S, Allen E, Fleming D, Frederich R. Tolerability and efficacy of glycemic control with saxagliptin in older patients (aged $65 years) with inadequately controlled type 2 diabetes mellitus. Clin Interv Aging. 2013;8:419-430.
77. Jerums G, Panagiotopoulos S, Premaratne E, MacIsaac RJ. Integrating albuminuria and GFR in the assessment of diabetic nephropathy. Nat Rev Nephrol. 2009;5(7):397-406.
78. Lipska KJ, Bailey CJ, Inzucchi SE. Use of metformin in the setting of mild-to-moderate renal insufficiency. Diabetes Care. 2011;34(6): 1431-1437.
79. Zanchi A, Lehmann R, Philippe J. Antidiabetic drugs and kidney disease - recommendations of the Swiss Society for Endocrinology and Diabetology. Swiss Med Wkly. 2012;142:w13629.
80. Nowicki M, Rychlik I, Haller H, et al. Long-term treatment with the dipeptidyl peptidase-4 inhibitor saxagliptin in patients with type 2 diabetes mellitus and renal impairment: a randomised controlled 52-week efficacy and safety study. Int J Clin Pract. 2011;65(12):1230-1239.
81. Cornell SA. A patient-centred approach to treatment with incretin-based agents in patients with type 2 diabetes. J Clin Pharm Ther. 2013;38(3): 181-189.
82. Peyrot M, Rubin RR, Lauritzen T, Snoek FJ, Matthews DR, Skovlund SE. Psychosocial problems and barriers to improved diabetes management: results of the Cross-National Diabetes Attitudes, Wishes and Needs (DAWN) Study. Diabet Med. 2005;22(10):1379-1385.
83. Cornell S. Differentiating among incretin therapies: a multiple-target approach to type 2 diabetes. J Clin Pharm Ther. 2012;37(5):510-524.
84. Nau DP. Recommendations for improving adherence to type 2 diabetes mellitus therapy focus on optimizing oral and non-insulin therapies. Am J Manag Care. 2012;18(Suppl 3):S49-S54.
85. Goke B, Gallwitz B, Eriksson J, Hellqvist A, Gause-Nilsson I. Saxagliptin is non-inferior to glipizide in patients with type 2 diabetes mellitus inadequately controlled on metformin alone: a 52-week randomised controlled trial. Int J Clin Pract. 2010;64(12):1619-1631.
86. Nadeau DA. Partnering with patients to improve therapeutic outcomes: incretin-based therapy for type 2 diabetes. Postgrad Med. 2010;122(3): 7-15.
87. Jendle J, Torffvit O, Ridderstrale M, Lammert M, Ericsson A, Bogelund M. Willingness to pay for health improvements associated with anti-diabetes treatments for people with type 2 diabetes. Curr Med Res Opin. 2010;26(4):917-923.
88. Erhardt W, Bergenheim K, Duprat-Lomon I, McEwan P. Cost effectiveness of saxagliptin and metformin versus sulfonylurea and metformin in the treatment of type 2 diabetes mellitus in Germany: a Cardiff diabetes model analysis. Clin Drug Investig. 2012;32(3): 189-202.
89. Hansen RA, Farley JF, Droege M, Maciejewski ML. A retrospective cohort study of economic outcomes and adherence to monotherapy with metformin, pioglitazone, or a sulfonylurea among patients with type 2 diabetes mellitus in the United States from 2003 to 2005. Clin Ther. 2010;32(7):1308-1319.
90. Elgart JF, Caporale JE, Gonzalez L, Aiello E, Waschbusch M, Gagliardino JJ. Treatment of type 2 diabetes with saxagliptin: a pharmacoeconomic evaluation in Argentina. Health Econ Rev. 2013;3(1):11.
91. Nita ME, Eliaschewitz FG, Ribeiro E, et al. Cost-effectiveness and budget impact of saxagliptine as additional therapy to metformin for the treatment of diabetes mellitus type 2 in the Brazilian private health system. Rev Assoc Med Bras. 2012;58(3):294-301.
92. Aphorisms [webpage on the Internet]. Available from: http://classics.mit.edu/Hippocrates/aphorisms.1.i.html. Accessed July 27, 2013.
93. Montori VM, Gafni A, Charles C. A shared treatment decision-making approach between patients with chronic conditions and their clinicians: the case of diabetes. Health Expect. 2006;9(1):25-36.
94. Porzsolt F, Clouth J, Deutschmann M, Hippler HJ. Preferences of diabetes patients and physicians: a feasibility study to identify the key indicators for appraisal of health care values. Health Qual Life Outcomes. 2010;8:125.
95. Drugs.com [homepage on the Internet]. Drugs.com; 2013. Available from: http://www.drugs.com. Accessed July 21, 2013.
96. Frederich R, McNeill R, Berglind N, Fleming D, Chen R. The efficacy and safety of the dipeptidyl peptidase-4 inhibitor saxagliptin in treatmentnaïve patients with type 2 diabetes mellitus: a randomized controlled trial. Diabetol Metab Syndr. 2012;4(1):36.
97. Dave DJ. Saxagliptin: a dipeptidyl peptidase-4 inhibitor in the treatment of type 2 diabetes mellitus. J Pharmacol Pharmacother. 2011;2(4): 230-235.