Main Article Content
This review highlights the potential indications of Saxagliptin and its combinations including several analytical aspects. The selective, reversible dipeptidyl peptidase-4 inhibitor Saxagliptin and its active metabolite M2 are used to improve the glycaemic control in type 2 diabetic patients. Saxagliptin prevents the inactivation of the incretin hormones namely glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. This increases glucagon-like peptide-1 levels, stimulates insulin secretion and reduces the postprandial glucagon and glucose levels in the body. Saxagliptin therapy in patient with type 2 diabetes are prescribed as monotherapy or as add-on therapy to Metformin, Sulphonyl urea and Thiazolidine-diones, without significant change in body weight while exhibiting a low risk of hypoglycaemia. There is a significant enhancement in the HbA1C levels relative to continued use of existing monotherapy. Some potential indications of Saxagliptin include metabolic disorders, inflammatory disorders, hepatic disorders, neurological disorders and as well as cardiac disease..
Ahren B. â€œDPP-4 inhibitorsâ€ Best Practice & Research Clinical Endocrinology & Etabolism, 2007, 21(4): 517-533. 2. Ali S, Fonseca V. â€œSaxagliptin overview: special focus on safety and adverse effects. Expert opinion on drug safetyâ€ 2013, 12(1): 103-109. 3. Anderson R, Hayes J, et al. â€œPharmacokinetic, pharmacodynamic and clinical evaluation of saxagliptin in type 2 diabetesâ€ Expert Opinion on Drug Metabolism & Toxicology, 2016, 12(4): 467-473.
Augeri DJ, Robl JA, et al. â€œDiscovery and preclinical profile of Saxagliptin (BMS-477118): a highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetesâ€ J Med Chem, 2005, 48: 5025â€“5037.
Barnett AH, Charbonnel B, et al. â€œEffect of saxagliptin as add-on therapy in patients with poorly controlled type 2 diabetes on insulin alone or insulin combined with metforminâ€ Curr Med Res Opin, 2012,28(4):513-23.
Barnett AH, Charbonnel B,et al. â€œSaxagliptin add-on therapy to insulin with or without metformin for type 2 diabetes mellitus: 52-week safety and efficacyâ€ Diabetologia,, 2011,54:S108-9. 7. Batta N, Pilli NR, et al. â€œA Rapid and Sensitive LC-MS/MS Assay for the Determination of Saxagliptin and its Active Metabolite 5-Hydroxy Saxagliptin in Human Plasma and its application to a pharmacokinetic studyâ€ Drug research, 2015, 65(03):133-408. Boulton David W, â€œClinical pharmacokinetics and pharmacodynamics of saxagliptin, a dipeptidyl peptidase-4 inhibitorâ€ Springer International Publishing Switzerland, 2016, 56(1): 11â€“24.
Boulton DW, Geraldes M, et al. â€œSafety, tolerability, pharmacokinetics and pharmacodynamics of once-daily oral doses of saxagliptin for 2 weeks in type 2 diabetic and healthy subjectsâ€ Presented at: 67th Scientific Sessions of the American Diabetes Association: Chicago, 2007, 606P. 10. Boulton DW. Clinical pharmacokinetics and pharmacodynamics of saxagliptin, a dipeptidyl peptidase-4 inhibitor. Clinical pharmacokinetics. 2017 Jan;56(1):11-24. 11. Caglar S, Alp AR. et al. â€œA validated high performance liquid chromatography method for the determination of saxagliptin and metformin in bulk, a stability indicating studyâ€ J Anal Bioanal Tech S, 2014, 12: 2.
Cole PSN, BolÃ³s J, et al. â€œSaxagliptinâ€ Drugs of the Future, 2008, 33(7):577-86. 13. Coskun ZM, et al. â€œER Stress Amelioration by Saxagliptin Protects the Liver Against Fructose-induced Insulin Resistanceâ€ Archives of Medical Research, 2020. 14. Deacon CF, Holst JJ, et al. â€œDipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes: comparison, efficacy and safetyâ€ Expert opinion on pharmacotherapy, 2013, 14(15): 2047-2058.
DeFronzo,RA, Hissa MN, et al. â€œThe efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin aloneâ€ Diabetes Care, 2009, 32(9):1649â€“55.
Dore DD, Seeger JD, et al. â€œUse of a claims-based active drug safety surveillance system to assess the risk of acute pancreatitis with exenatide or sitagliptin compared to metformin or glyburideâ€ Curr Med Res Opin, 2009, 25(4):1019-27.
Drucker DJ, â€œDipeptidyl peptidase-4 inhibition and the treatment of type 2 diabetes â€“ Preclinical biology and mechanisms of actionâ€ 2007, Diabetes Care, 30: 1335-43. 18. Drucker DJ, Nauck MA, et al. â€œThe incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetesâ€ The Lancet, 2006, 368(9548): 1696-1705.
Engel SS, Williams-Herman DE, et al. â€œSitagliptin: review of preclinical and clinical data regarding incidence of pancreatitisâ€ Int J Clin Pract, 2010, 64(7):984-90. 20. Gao JW, Yuan YM., et al. â€œDevelopment of a rapid UPLCâ€MS/MS method for quantification of saxagliptin in rat plasma and application to pharmacokinetic studyâ€ Biomedical Chromatography, 2012, 26(12): 1482-1487.
Goke B, Gallwitz B, et al. â€œSaxagliptin is non-inferior to glipizide in patients with type 2 diabetes mellitus inadequately controlled on metformin alone: a 52-week randomised controlled trialâ€ Int J Clin Pract, 2010, 64(12):1619-31.
Goke B, Gallwitz B, et al. â€œSaxagliptin vs glipizide as add-on therapy to metformin for type 2 diabetes mellitus (T2DM): long-term safety and efficacyâ€ Diabetes, 2011,60:A305 23. Helal MG, Megahed NA, et al. â€œSaxagliptin mitigates airway inflammation in a mouse model of acute asthma via modulation of NF-kB and TLR4â€ Life sciences, 2019, 239: 117017. 24. Hollander PA, Kushner P. Type 2 diabetes comorbidities and treatment challenges: rationale for DPP-4 inhibitors. Postgraduate medicine. 2010 May 1;122(3):71-80. 25. Jadzinsky M, Pfutzner A, et al. â€œSaxagliptin given in combination with metformin as initial therapy improves glycaemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trialâ€ Diabetes Obes Metab, 2009, 11(6):611-22. 26. Kagal UA, Angadi NB, et al. â€œEffect of dipeptidyl peptidase 4 inhibitors on acute and subacute models of inflammation in maleWistar rats: an experimental studyâ€ International Journal of Applied and Basic Medical Research, 2017, 7(1):26. 27. Koyani CN, Kolesnik E, et al. â€œMaechler H. Dipeptidyl peptidase-4 independent cardiac dysfunction links saxagliptin to heart failureâ€ Biochemical pharmacology, 2017, 145:64-80. 28. Langley AK, Suffoletta, TJ, et al. â€œDipeptidyl peptidase IV inhibitors and the incretin system in type 2 diabetes mellitusâ€ Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 2007, 27(8): 1163-1180. 29. Leibowitz G, Cahn A, et al. â€œImpact of treatment with saxagliptin on glycaemic stability and Î²-cell function in the SAVORâ€TIMI 53 studyâ€ Diabetes, Obesity and Metabolism, 2015, 17(5): 487-494. 30. Men P, Li XT, et al. â€œEfficacy and safety of saxagliptin in patients with type 2 diabetesâ€ a systematic review and meta-analysis. PloS One, 2018,13(5):
Monami M, Dicembrini I, et al. â€œSafety of dipeptidyl peptidase-4 inhibitors: a meta-analysis of randomized clinical trialsâ€ Curr Med Res Opin, 2011,27(Suppl 3):57-64. 32. Nassar NN, Al-Shorbagy MY, et al. â€œSaxagliptin: a novel antiparkinsonian approachâ€ Neuropharmacology, 2015, 89:308-17. 33. Neumiller JJ, Campbell RK. Saxagliptin: a dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus. American Journal of Health-System Pharmacy. 2010 Sep 15;67(18):1515-25.
Patel CG, Li L, et al. â€œNo effect of saxagliptin on QTc interval in healthy subjectsâ€ Presented at: American Diabetes Association 69th Scientific Sessions: New Orleans, LA, 2009. 35. Prasad PBN, Satyanaryana K, et al. â€œDevelopment and Validation of a Method for Simultaneous Determination of Metformin and Saxagliptin in a Formulation by RP-HPLCâ€ American Journal of Analytical Chemistry, 2015 6(11): 841.
Ranjan D, Sharma A, et al. â€œSaxagliptin and Dapagliflozin for type 2 Diabetes mellitusâ€ A Review. International Journal of Drug Regulatory Affairs, 2018,6(3): 24-30.
Rosenstock J, Aguilar-Salinas C, et al. â€œEffect of saxagliptin monotherapy in treatment-naive patients with type 2 diabetesâ€ Curr Med Res Opin, 2009, 25(10):2401.
Rosenstock J, Gross JL, et al. â€œLong-term safety and efficacy of saxagliptin after 4-year follow-up of patients with type 2 diabetesâ€ Diabetes, 2011,60:A298. 39. Rosenstock J, Sankoh S, List JF. Glucoseâ€lowering activity of the dipeptidyl peptidaseâ€4 inhibitor saxagliptin in drugâ€naive patients with type 2 diabetes. Diabetes, Obesity and Metabolism. 2008 May;10(5):376-86. 40. Savage SA, Jones GS, et al. â€œPreparation of saxagliptin, a novel DPP-IV inhibitorâ€ Organic Process Research & Development, 2009, 13(6): 1169-1176 41. Srividya S, Swetha E, et al. â€œDevelopment and validation of a high performance thin layer chromatographic method for quantitative analysis of saxagliptinâ€ American Journal of Analytical Chemistry, 2015, 6(10): 797.
Tekkeli SE, KÄ±zÄ±ltaÅŸ MV, et al.â€œAn HPLC method for the determination of saxagliptin in human plasma with fluorescence detectionâ€ Journal: Journal of Advances in Chemistry, 2013, 5(3): 43. Teleanu DM, Chircov C, et al. â€œNeuronanomedicine: An up-to-date overviewâ€ Pharmaceutics, 2019, 11(3): 101. 44. Tella SH, Rendell MS. DPP-4 inhibitors: focus on safety. Expert opinion on drug safety. 2015 Jan 2;14(1):127-40. 45. Wang A, Dorso C, et al. â€œPotency, selectivity and prolonged binding of saxagliptin to DPP4: maintenance of DPP4 inhibition by saxagliptin in vitro and ex vivo when compared to a rapidly-dissociating DPP4 inhibitorâ€ BMC pharmacology, 2012, 12(1):2.
Yazbeck R, Howarth GS, et al. â€œDipeptidyl peptidase inhibitors, an emerging drug class for inflammatory diseaseâ€ Trends Pharmacol Sci, 2009, 30(11):600-7.