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Drugs

, Volume 72, Issue 2, pp 229–248 | Cite as

Saxagliptin

A Review of its Use as Combination Therapy in the Management of Type 2 Diabetes Mellitus in the EU
  • Lily P. H. YangEmail author
Adis Drug Evaluation

Abstract

Saxagliptin (Onglyza™) is a dipeptidyl peptidase 4 inhibitor widely approved for the treatment of type 2 diabetes mellitus. In the EU, saxagliptin is indicated as combination therapy with metformin, a sulfonylurea, a thiazolidinedione, or insulin (with or without metformin) for the treatment of adult patients with type 2 diabetes, including those with mild to severe renal impairment. This article reviews the clinical efficacy and tolerability of add-on saxagliptin therapy in patients with type 2 diabetes, in line with its approved indications in the EU, and summarizes the drug’s pharmacological properties.

The clinical efficacy of saxagliptin 5 mg/day in combination with metformin, glibenclamide (glyburide), a thiazolidinedione, or insulin (with or without metformin) has been demonstrated in several randomized, double-blind, placebo-controlled, multicentre, phase III trials (18–104 weeks in duration) in patients with type 2 diabetes. In these trials, glycosylated haemoglobin (HbA1c) was changed from baseline (primary endpoint) by a greater extent with add-on saxagliptin 5 mg/day (−1.09% to +0.03%) than with comparator regimens (−0.44% to +0.69%). Two other randomized, double-blind trials showed that saxagliptin 5 mg/day as add-on therapy to metformin was noninferior to uptitrated glipizide in terms of lowering HbA1c (−0.74% vs −0.80%) at 52 weeks, or sitagliptin (−0.52% vs −0.62%) at 18 weeks. Saxagliptin 2.5 mg/day as add-on to existing anti-diabetic therapy was also effective for up to 52 weeks in a randomized, double-blind, placebo-controlled, multicentre trial in patients with type 2 diabetes and renal impairment (HbA1c was reduced by 1.08% vs 0.36%; p ≤ 0.007).

Saxagliptin as add-on therapy for up to 4 years was generally well tolerated in clinical trials. Treatment with saxagliptin did not increase the risk of hypoglycaemia or cardiovascular outcomes relative to placebo or active comparators, and was generally weight neutral.

In conclusion, saxagliptin is a useful option as add-on therapy to metformin, a sulfonylurea, a thiazolidinedione, or insulin (with or without metformin) in patients with type 2 diabetes who require combination therapy.

Keywords

Metformin Glycaemic Control Sulfonylurea Glibenclamide Sitagliptin 
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.

References

  1. 1.
    Tahrani AA, Bailey CJ, Del Prato S, et al. Management of type 2 diabetes: new and future developments in treatment. Lancet 2011 Jul 9; 378(9786): 182–97PubMedCrossRefGoogle Scholar
  2. 2.
    Nolan CJ, Damm P, Prentki M. Type 2 diabetes across generations: from pathophysiology to prevention and management. Lancet 2011 Jul 9; 378(9786): 169–81PubMedCrossRefGoogle Scholar
  3. 3.
    Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010 Jan; 87(1): 4–14PubMedCrossRefGoogle Scholar
  4. 4.
    Roglic G, Unwin N. Mortality attributable to diabetes: estimates for the year 2010. Diabetes Res Clin Pract 2010 Jan; 87(1): 15–9PubMedCrossRefGoogle Scholar
  5. 5.
    American Association of Clinical Endocrinologists. State of diabetes complications in America: a comprehensive report issued by the American Association of Clinical Endocrino logists [online]. Available from URL: http://harrisschool.uchicago.edu/News/press-releases/media/Diabetes%20Complications%20Report_FINAL.PDF [Accessed 2011 Dec 19]
  6. 6.
    Hollander PA, Kushner P. Type 2 diabetes comorbidities and treatment challenges: rationale for DPP-4 inhibitors. Postgrad Med 2010 May; 122(3): 71–80PubMedCrossRefGoogle Scholar
  7. 7.
    Rodbard HW, Jellinger PS, Davidson JA, 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 [published erratum appears in EndocrPract 2009 Nov–Dec; 15 (7): 768–70]. Endocr Pract 2009 Sep–Oct; 15(6): 540–59PubMedCrossRefGoogle Scholar
  8. 8.
    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): 193–203PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Handelsman Y, Mechanick JI, Blonde L, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract 2011 Mar–Apr; 17 Suppl. 2: 1–53PubMedCrossRefGoogle Scholar
  10. 10.
    National Institute for Health and Clinical Excellence. Type 2 diabetes: the management of type 2 diabetes (NICE clinical guideline 87) [online]. Available from URL: http://www.nice.org.uk/nicemedia/live/12165/44320/44320.pdf [Accessed 2011 Dec 19]
  11. 11.
    Bristol-Myers Squibb and AstraZeneca EEIG. Onglyza (saxagliptin) 2.5, 5mg film-coated tablets: summary of product characteristics [online]. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001039/WC500044316.pdf [Accessed 2011 Dec 19]
  12. 12.
    Bristol Myers Squibb-AstraZeneca EEIG. Onglyza (saxagliptin) 2.5, 5mg film-coated tablets: summary of product characteristics [online]. Available from URL: http://www.medicines.org.uk/EMC/medicine/22315/SPC/Onglyza+2.5mg+%26+5mg+film-coated+tablets/ [Accessed 2011 Dec 19]
  13. 13.
    Dhillon S, Weber J. Saxagliptin. Drugs 2009; 69(15): 2103–14PubMedCrossRefGoogle Scholar
  14. 14.
    Chacra AR. Saxagliptin for type 2 diabetes. Diabetes Metab Syndr Obes 2010 Sep 22; 3: 325–35PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Gallwitz B. New treatments in the management of type 2 diabetes: a critical appraisal of saxagliptin. Diabetes Metab Syndr Obes 2010 May 10; 3: 117–24PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    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
  17. 17.
    Patel CG, Li L, Komoroski BJ, et al. No effect of saxagliptin on QTc interval in healthy subjects [abstract no. 2072-PO]. 69th Scientific Sessions of the American Diabetes Association; 2009 Jun 5–9; New Orleans (LA)Google Scholar
  18. 18.
    Boulton DW, Geraldes M. Safety, tolerability, pharmacokinetics and pharmacodynamics of once-daily oral doses of saxagliptin for 2 weeks in type 2 diabetic and healthy subjects [abstract no. 0606-P plus poster]. 67th Scientific Sessions of the American Diabetes Association; 2007 Jun 22–26; Chicago (IL)Google Scholar
  19. 19.
    Deacon CF. Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: a comparative review. Diabetes Obes Metab 2011 Jan; 13(1): 7–18PubMedCrossRefGoogle Scholar
  20. 20.
    Augeri DJ, Robl JA, Betebenner DA, et al. Discovery and preclinical profile of saxagliptin (BMS-477118): a highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem 2005 Jul 28; 48(15): 5025–37PubMedCrossRefGoogle Scholar
  21. 21.
    Drucker DJ. The role of gut hormones in glucose homeostasis. J Clin Invest 2007 Jan; 117(1): 24–32PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Kirby M, Yu DMT, O’Connor SP, et al. Inhibitor selectivity in the clinical application of dipeptidyl peptidase-4 inhibition. Clin Sci (Lond) 2010 Jan; 118(1): 31–41CrossRefGoogle Scholar
  23. 23.
    Baetta R, Corsini A. Pharmacology of dipeptidyl peptidase-4 inhibitors: similarities and differences. Drugs 2011; 71(11): 1441–67PubMedCrossRefGoogle Scholar
  24. 24.
    Rosenstock J, Aguilar-Salinas C, Klein E, et al. Effect of saxagliptin monotherapy in treatment-naïve patients with type 2 diabetes. Curr Med Res Opin 2009 Aug 4; 25(10): 2401–11PubMedCrossRefGoogle Scholar
  25. 25.
    Jadzinsky M, Pfützner 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 [published erratum appears in Diabetes Obes Metab 2010 May; 12 (5): 462]. Diabetes Obes Metab 2009 Jun; 11(6): 611–22PubMedCrossRefGoogle Scholar
  26. 26.
    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 with metformin alone. Diabetes Care 2009 Sep; 32(9): 1649–55PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    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 [published erratum appears in Int J Clin Pract 2010 Jan; 64 (2): 277]. Int J Clin Pract 2009 Sep; 63(9): 1395–406PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Hollander P, Li J, Allen E, et al. Saxagliptin added to a thiazolidinedione improves glycemic control in patients with type 2 diabetes and inadequate control on thiazolidinedione alone. J Clin Endocrinol Metab 2009 Dec; 94(12): 4810–9PubMedCrossRefGoogle Scholar
  29. 29.
    Rosenstock J, Sankoh S, List JF. Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes. Diabetes Obes Metab 2008 May; 10(5): 376–86PubMedCrossRefGoogle Scholar
  30. 30.
    Yang W, Pan CY, Tou C, et al. Efficacy and safety of saxagliptin added to metformin in Asian patients with type 2 diabetes mellitus: a randomized controlled trial. Diabetes Res Clin Pract 2011 Nov; 94(2): 217–24PubMedCrossRefGoogle Scholar
  31. 31.
    Göke B, Gallwitz B, Eriksson J, et al. 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 Nov; 64(12): 1619–31PubMedCrossRefGoogle Scholar
  32. 32.
    Scheen AJ, Charpentier G, Östgren CJ, et al. Efficacy and safety of saxagliptin in combination with metformin compared with sitagliptin in combination with metformin in adult patients with type 2 diabetes mellitus. Diabetes Metab Res Rev 2010 Oct; 26(7): 540–9PubMedCrossRefGoogle Scholar
  33. 33.
    European Medicines Agency. CHMP assessment report for Onglyza [online]. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/001039/WC500044319.pdf [Accessed 2011 Dec 19]
  34. 34.
    Patel CG, Zhang J, Li L, et al. Effect of a high-fat meal on the pharmacokinetics of saxagliptin in healthy subjects. J Clin Pharmacol 2010 Oct; 50(10): 1211–6PubMedCrossRefGoogle Scholar
  35. 35.
    Boulton DW, Li L, Frevert EU, et al. Influence of renal or hepatic impairment on the pharmacokinetics of saxagliptin. Clin Pharmacokinet 2011; 50(4): 253–65PubMedCrossRefGoogle Scholar
  36. 36.
    Scheen AJ. Dipeptidylpeptidase-4 inhibitors (gliptins): focus on drug-drug interactions [published erratum appears in Clin Pharmacokinet 2011; 50 (1): 74]. Clin Pharmacokinet 2010; 49(9): 573–88PubMedCrossRefGoogle Scholar
  37. 37.
    Patel CG, Kornhauser D, Vachharajani N, et al. 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 Obes Metab 2011 Jul; 13(7): 604–14PubMedCrossRefGoogle Scholar
  38. 38.
    Patel CG, Li L, Girgis S, et al. Two-way pharmacokinetic interaction studies between saxagliptin and cytochrome P450 substrates or inhibitors: simvastatin, diltiazem extended-release, and ketoconazole. Clin Pharmacol Adv Appl 2011 Jun; 3: 13–25CrossRefGoogle Scholar
  39. 39.
    Upreti VV, Boulton DW, Li L, et al. Effect of rifampicin on the pharmacokinetics and pharmacodynamics of saxagliptin, a dipeptidyl peptidase-4 inhibitor, in healthy subjects. Br J Clin Pharmacol 2011 Jul; 72(1): 92–102PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Pan CY, Yang W, Tou C, et al. Efficacy and safety of saxagliptin in drug-naïve Asian patients with type 2 diabetes mellitus: a randomized controlled trial. Diabetes Metab Res Rev. Epub 2011 Nov 12Google Scholar
  41. 41.
    Pfützner A, Paz-Pacheco E, Allen E, et al. Initial combination therapy with saxagliptin and metformin provides sustained glycaemic control and is well tolerated for up to 76 weeks. Diabestes Obes Metab 2011; 13(6): 567–76CrossRefGoogle Scholar
  42. 42.
    Ravichandran S, DeFronzo R, Garber AJ, et al. Once-daily saxagliptin added to metformin is well tolerated and provides sustained glycaemic control over 102 weeks in patients with type 2 diabetes [abstract no. 132]. Diabetologia 2009 Sep; 52 Suppl. 1: S60CrossRefGoogle Scholar
  43. 43.
    Göke B, Gallwitz B, Eriksson J, et al. Saxagliptin vs glipizide as add-on therapy to metformin for type 2 diabetes mellitus (T2DM): long-term safety and efficacy [abstract no. 1110-P]. 71st Scientific Sessions of the American Diabetes Association; 2011 Jun 24–28; San Diego (CA)Google Scholar
  44. 44.
    Hermans MP, Delibasi T, Farmer I, et al. Effects of saxagliptin added to sub-maximal doses of metformin compared with dose escalation of metformin in type 2 diabetes: results from the PROMPT study [abstract no. 828]. 47th Annual Meeting of the European Association for the Study of Diabetes; 2011 Sep 12–16; LisbonGoogle Scholar
  45. 45.
    Chacra AR, Tan GH, Ravichandran S, et al. Safety and efficacy of saxagliptin in combination with submaximal sulphonylurea versus up-titrated sulphonylurea over 76 weeks. Diab Vasc Dis Res 2011 Apr; 8(2): 150–9PubMedCrossRefGoogle Scholar
  46. 46.
    Hollander PL, Li J, Frederich R, et al. Safety and efficacy of saxagliptin added to thiazolidinedione over 76 weeks in patients with type 2 diabetes mellitus. Diab Vasc Dis Res 2011 Apr; 8(2): 125–35PubMedCrossRefGoogle Scholar
  47. 47.
    Charbonnel B, Barnett AH, Donovan M, et al. Saxagliptin (SAXA) add-on therapy improves glycemic control in patients (pts) with poorly controlled type 2 diabetes (T2D) on insulin (INS) alone or INS combined with metformin (MET) [abstract no. 1108-P]. 71st Scientific Sessions of the American Diabetes Association; 2011 Jun 24–28; San Diego (CA)Google Scholar
  48. 48.
    Barnett AH, Charbonnel B, Li J, et al. Saxagliptin addon therapy to insulin with or without metformin for type 2 diabetes mellitus: 52-week safety and efficacy [abstract no. 243]. 47th Annual Meeting of the European Association for the Study of Diabetes; 2011 Sep 12–16; LisbonGoogle Scholar
  49. 49.
    Nowicki M, Rychlik I, Haller H, et al. Saxagliptin improves glycaemic control and is well tolerated in patients with type 2 diabetes mellitus and renal impairment. Diabetes Obes Metab 2011; 13(6): 523–32PubMedCrossRefGoogle Scholar
  50. 50.
    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 Dec; 65(12): 1230–9PubMedCrossRefGoogle Scholar
  51. 51.
    Rosenstock J, Gross JL, Aguilar Salinas CA, et al. Long-term safety and efficacy of saxagliptin after 4-year follow-up of patients with type 2 diabetes [abstract no. 1086-P]. 71st Scientific Sessions of the American Diabetes Association; 2011 Jun 24–28; San Diego (CA)Google Scholar
  52. 52.
    Doucet J, Chacra A, Maheux P, et al. Efficacy and safety of saxagliptin in older patients with type 2 diabetes mellitus. Curr Med Res Opin 2011 Apr; 27(4): 863–9PubMedCrossRefGoogle Scholar
  53. 53.
    Frederich R, Alexander JH, Fiedorek FT, et al. A systematic assessment of cardiovascular outcomes in the saxagliptin drug development program for type 2 diabetes. Postgrad Med 2010 May; 122(3): 16–27PubMedCrossRefGoogle Scholar
  54. 54.
    Erhardt W, Bergenheim K, Townsend R, et al. The cost-effectiveness of saxagliptin versus sulfonylurea (SU) in the treatment of type 2 diabetes mellitus (T2DM) in Germany [abstract no. PDB44]. Value Health 2010 Nov; 13(7): A291–2. Plus poster presented at the 13th Annual European Congress of the International Society for Pharmacoeconomics and Outcomes Research; 2010 Nov 6–9; PragueCrossRefGoogle Scholar
  55. 55.
    Granström O, Bergenheim K, McEwan P, et al. Cost-effectiveness of saxagliptin (Onlyza®) in type 2 diabetes in Sweden. Prim Care Diabetes. Epub 2011 Oct 14Google Scholar
  56. 56.
    Grzeszczak W, Czupryniak L, Kolasa K, et al. The cost-effectiveness of saxagliptin versus NPH insulin when used in combination with other oral antidiabetes agents in the treatment of type 2 diabetes mellitus in Poland. Diabetes Technol Ther. Epub 2011 Nov 8Google Scholar
  57. 57.
    Hutchings A, Tolley K, Achana F, et al. Cost-effectiveness of saxagliptin compared to sitagliptin for the treatment of patients with type 2 diabetes mellitus (T2DM) [abstract no. PDB39]. Value Health 2011 Nov; 14(7): A478CrossRefGoogle Scholar
  58. 58.
    Ramirez de Arellano A, Brosa M, Franch J, et al. Cost-effectiveness analysis of saxagliptin in the treatment of diabetes mellitus type 2 in Spain [abstract no. PDB45]. Value Health 2010 Nov; 13(7): A292CrossRefGoogle Scholar
  59. 59.
    Bergenheim K, Williams SA, Bergeson JG, et al. Cost-effectiveness of saxagliptin in type 2 diabetes in the United States [abstract no. 2369-PO]. 71st Scientific Sessions of the American Diabetes Association; 2011 Jun 24–28; San Diego (CA)Google Scholar
  60. 60.
    Elgart JF, Caporale JE, Aiello EC, et al. Cost-effectiveness of saxagliptin treatment in three Latin American countries [abstract no. PDB7]. Value Health 2011 Nov; 14(7): A47Google Scholar
  61. 61.
    Eliaschewitz FG, Asano E, Nita ME, et al. Cost-utility analysis of saxagliptin as an add-on therapy to metformin in type 2 diabetes patients from the Brazilian private health system [abstract no. PDB62]. Value Health 2010 Nov; 13(7): A295CrossRefGoogle Scholar
  62. 62.
    Clarke PM, Gray AM, Briggs A, et al. A model to estimate the lifetime health outcomes of patients with type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model (UKPDS no. 68). Diabetologia 2004 Oct; 47(10): 1747–59PubMedCrossRefGoogle Scholar
  63. 63.
    McEwan P, Peters JR, Bergenheim K, et al. Evaluation of the costs and outcomes from changes in risk factors in type 2 diabetes using the Cardiff stochastic simulation cost-utility model (DiabForecaster). Curr Med Res Opin 2006 Jan; 22(1): 121–9PubMedCrossRefGoogle Scholar
  64. 64.
    LaSalle JR. Reaching HbA1c goals with saxagliptin in combination with other oral antidiabetic drugs. Postgrad Med 2010 Jan; 122(1): 144–52PubMedCrossRefGoogle Scholar
  65. 65.
    Matthaei S, Bierwirth R, Fritsche A, et al. Pharmacological antihyperglycemia therapy of type 2 diabetes mellitus: update of the evidence-based guidelines of the German Diabetes Association [in German]. Diabetologie 2009; 4: 32–64CrossRefGoogle Scholar
  66. 66.
    Scheen AJ. Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab 2010 Aug; 12(8): 648–58PubMedCrossRefGoogle Scholar
  67. 67.
    Scott LJ. Linagliptin: in type 2 diabetes mellitus. Drugs 2011; 71(5): 611–24PubMedCrossRefGoogle Scholar
  68. 68.
    Keating GM. Vildagliptin: a review of its use in type 2 diabetes mellitus. Drugs 2010; 70(16): 2089–112PubMedCrossRefGoogle Scholar
  69. 69.
    Scott LJ. Alogliptin: a review of its use in the management of type 2 diabetes mellitus [published erratum appears in Drugs 2010; 70 (18): 2475]. Drugs 2010; 70(15): 2051–72PubMedCrossRefGoogle Scholar
  70. 70.
    Dhillon S. Sitaliptin: a review of its use in the management of type 2 diabetes mellitus. Drugs 2010; 70(4): 489–512PubMedCrossRefGoogle Scholar
  71. 71.
    DeFronzo RA. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 2009 Apr; 58(4): 773–95PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    AstraZeneca. Komboglyze receives marketing authorisation in the European Union for adult patients with type 2 diabetes [online]. Available from URL: http://www.astrazeneca.com/Media/Press-releases/Article/20111129-komboglyze-authorisation-in-the-eu [Accessed 2011 Dec 19]
  73. 73.
    Fonseca V, Zhu T, Karyekar C, et al. Adding saxagliptin (SAXA) 5 mg is superior to uptitrating metformin extended release (MET XR) in type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control on a stable dose of MET XR 1500mg [abstract no. 1018-P]. 71st Scientific Sessions of the American Diabetes Association; 2011 Jun 24–28; San Diego (CA)Google Scholar
  74. 74.
    Goldfine AB. Assessing the cardiovascular safety of diabetes therapies. N Engl J Med 2008 Sep 11; 359(11): 1092–5PubMedCrossRefGoogle Scholar
  75. 75.
    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 Incarction (SAVOR-TIMI) 53 Study. Am Heart J 2011 Nov; 162(5): 818–25.e6PubMedCrossRefGoogle Scholar
  76. 76.
    Monami M, Dicembrini I, Martelli D, et al. Safety of dipeptidyl peptidase-4 inhibitors: a meta-analysis of randomized clinical trials. Curr Med Res Opin 2011 Nov; 27 Suppl. 3: 57–64PubMedGoogle Scholar
  77. 77.
    Elashoff M, Matveyenko AV, Gier B, et al. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology 2011 Jul; 141(1): 150–6PubMedCrossRefGoogle Scholar

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