Add-on saxagliptin improves glycemic status among uncontrolled type 2 diabetes mellitus
DOI:
https://doi.org/10.18203/2320-6012.ijrms20181758Keywords:
Add-on, Type-2 Diabetes Mellitus, Saxagliptin, UncontrolledAbstract
Background: Type 2 diabetes mellitus (T2DM) have multiple pathophysiologic defects contributing to hyperglycemia. T2DM patients have insulin resistance with progressive β-cell failure and progressive insulin secretion defect. Dipeptidyl peptidase-4 (DPP-4) inhibitors target the incretin system. saxagliptin is a DPP-4 inhibitor slowing the degradation of Glucagon-like peptide-1 (GLP-1) and Glucose-dependent insulinotropic peptide (GIP) sustain the incretin effects. Aim was to know the add-on effects of saxagliptin among uncontrolled T2DM.
Methods: A total of 71 uncontrolled T2DM patients on various antidiabetic therapies except incretin mimetic were consecutively selected for the study. Baseline fasting plasma glucose (FPG), 2hour postprandial glucose (PPG) and glycated hemoglobin (HbA1c) was measured. Saxagliptin orally 5mg/day was given after approval of ethical committee and FPG, 2hour PPG and HbA1c was measured at 12 weeks and 24 weeks. Data were collected and analyzed by ‘t’ test using SPSS software version 25.
Results: Baseline FPG, 2hour PPG and HbA1c was 158.4±13.9mg%, 252.6±24.4mg% and 8.6±1.3% respectively. Percentage of patients achieved HbA1c of <7% at 12 weeks was 16.9% and 43.6% at 24 weeks (P <0.05). Adjusted mean difference in HbA1c was 0.73% at 12 weeks and 1.2 % at 24 weeks (P <0.05). Reduction of mean FPG, 2hour PPG and HbA1c was 154.48±13.8mg%, 240.31±26.8mg% and 7.93±1.1% at 12 weeks and 151.15±13.7mg%, 231.7±27mg% and 7.38±1% at 24 weeks respectively (P <0.05). Patients on insulin were better responded.
Conclusions: Add-on saxagliptin improves all parameter of glycemic status in uncontrolled type 2 DM patients.
References
Boaz-Hirschberg S, Brian Bruzinski, John Xu and NayyerIqbal. A pooled analysis of the efficacy and safety of saxagliptin as monotherapy in patients with type 2 Diabetes. J Diabetes Metab. 2015;6:4-24.
Pradhan B, Majhi C. Pancreatic alpha cell dysfunction in diabetes mellitus and its management strategies. J Evid Based Med Health. 2017;4(54):2775-82.
Habner JF, Stanojevic V. Alpha cells come of age. Trend Endocrinol Metab. 2013;24:153-63.
Moon JS, Won KC. Pancreatic α-cell dysfunction in type 2 diabetes: old kids on the block. Diabetes metabolism J. 2015;39(1):1-9.
Dunning BE, Gerich JE. Role of alpha cell dysregulation in fasting and postprandial hyperglycemia in type 2 diabetes and therapeutic implications. Endocr Rev. 2007;28(3):253-83.
Walli AJ, Thomas HE. Pancreatic alpha cell hold the key to survival BIO Med. 2015;2(5):368-86.
Larson H, Ahren B. Islet dysfunction in insulin resistance involves impaired insulin secretion and increase glucagon secretion in postmenopausal women with impaired glucose tolerance. Diabetes Care. 2000;23(5)65-660.
Shah P, Vella A, Basu A, Basu R, Schwenk WF, Rizza RA. Lack of suppression of glucagon contributes to postprandial hyperglycemia in subjects with type 2 diabetes mellitus. J Clin Endocrinol Meta. 2000;85(11):4053-9.
Crye PE. Hypoglycemia: The limiting factor in the glycemic management of type-1 and type-2 diabetes. Diabetologia. 2002;45:(7):937-48.
Yoon KH, Ko SH, Cho JH, Lee JM, Ahn YB, Song KH, et al. Selective β-cell loss and α-cell expansion in patients with type 2 diabetes mellitus in Korea. J Clin Endocrinol Meta. 2003;88(5):2300-8.
Henquin RH, Rathier J. Pancreatic alpha cell mass in European subjects with type 2 diabetes. Diabetologia. 2011;54(7):1720-1725.
Lund A, Bagger JI, Christensen M, Knop FK, Vilsbøll T. Glucagon and type 2 diabetes: the return of the alpha cell. Current diabetes reports. 2014;14(12):555.
Menge BA, Grüber L, Jørgensen SM, Deacon CF, Schmidt WE, Veldhuis JD, et al. Loss of inverse relationship between pulsatile insulin and glucagon secretion in patients with type 2 diabetes. Diabetes. 2011;60(8):2160-8.
Pradhan B, Tripathy S. Pathophysiology and management strategies of postprandial hyperglycemia. Orissa Phys J. 2016;13(1):91-100.
Stratton IM, Adler AI, Neil HA, Mathews DR, Manley SE, et all. Association of glycemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS); Prospective observational study. BMJ. 2000;321:205-412.
Neumiller JJ, Cambell RK. Saxagliptin: a dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus. Am J Health Syst Pharm. 2010;67(18):1515-26.
Holst JJ, Gramada J. Role of incretin hormones in the regulation of insulin secretion in diabetes and nondiabetic humans. Am J Physiol Endocrinol Metab. 2004;287(2):E199-206.
Druker DJ. The role of gut hormones in glucose homeostasis. Cli Invest. 2007;112(1):24-32.
Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes care. 2013;36(2):490.
Garber A, Abrahamson M, Barzilay J, Blonde L, Bloomgarden Z, Bush M, et al. AACE comprehensive diabetes management algorithm 2013. Endocrine Practice. 2013;19(2):327-36.
Rosenstock J, Sankoh S, List JF. Glucose lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug naïve patients with type 2 diabetes. Diabates Obes Metab. 2008;10:376-86.
Defronzo RA, Hissa MN, Garber AJ, Luiz Gross, YuyanDuan R, Ravichandran S, 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;32:1645-55.
Jadzinsky M, Pfutzner A, Paz-Pacheo E, Xu Z, Allen E, Chen R. Saxagliptin given in combination with metformin as initial therapy improves glycemic control in type 2diabetes compared with either monotherapy: a randomized control trial. Diabetes Obes Metab. 2009;11:611-22.
Chacra AR, Tan GH, Apanovitch A, Rabichandran S, List J, Chen R. Saxagliptin added to suboptimal dose of sulfonylurea improves glycemic control compared with up titration of sulfonylurea in patients with type 2 diabetes: a randomized control trial. Int J Cli Pract. 2009;63:1395-406.
Hollander P, Li J, Allen E, Chen R, Investigator C. Saxagliptin added to a Thiazolindinediones improves glycemic control in patients with type 2 diabetes inadequately control on Thiazolindinediones alone. J Cli Endocrinol Metab. 2009;94:4810-9.
Barnett AH, Charbonne lB, Donovan M, Fleming DJ, Chen R. Effect of saxagliptin as add-on therapy in patients with poorly controlled type 2 diabetes on insulin alone or insulin combined with metformin. Curr Med Res Opin. 2012;28:513-23.
