Effect of SGLT-2 inhibitor (remogliflozin) plus DPP4 inhibitor (vildagliptin) on diabetic nephropathy in patients with type 2 diabetes mellitus comparison with combination of metformin and sulphonylureas
DOI:
https://doi.org/10.18203/2349-3933.ijam20231450Keywords:
SGLT 2 inhibitors, DPP4 inhibitors, Remogliflozin and vildagliptin, Diabetic nephropathyAbstract
Background: Diabetes is leading cause of renal failure in entire world. Approximately 20-40 percent of patients with diabetes develop diabetic nephropathy. Newer drugs like SGLT-2 inhibitors and DPP-4 inhibitors are valuable option for Diabetic Nephropathy. Remogliflozin etabonate (RE) is the latest addition to the SGLT2 inhibitor class of drugs that have been recently approved in India for the management of T2DM.This study was conducted to elaborate effect of SGLT2 inhibitor (remogliflozin) plus DPP4 inhibitor (vildagliptin) on diabetic nephropathy in patients of Type 2 DM.
Methods: This hospital based, comparative, open label, randomized controlled trial has been carried out in our department during January 2020 to October 2022 on 60 patients. Group 1 was given metformin 500 mg BD and glimepiride 1 mg BD and group 2 was given FDC of remogliflozin 100 mg and vildagliptin 50 mg BD with 32 patients in group 1 and 28 patients in group 2. The study was approved by ethical committee of our institute.
Results: Mean (SD) of urine ACR in metformin and glimepiride group at screening, 12 weeks, 24 weeks, and at 36 weeks were 93.64 (53.92), 95.56 (52.76), 89.96 (50.22) and 90.9 (53.56) respectively mean (SD) of urine ACR in remogliflozin and vildagliptin group at screening, 12 weeks, 24 weeks, and at 36 weeks were 108.28 (68.5), 100.73 (55.5), 99.35 (55.71) and 75.1 (38.7) respectively. Mean (SD) of eGFR in metformin and glimepiride group at screening, 12 weeks, 24 weeks, and at 36 weeks were 59.62 (18.57), 61.2 (11.1), 60.06 (14.37) and 60.8 (13.3) respectively. Mean (SD) of eGFR in remogliflozin and vildagliptin group at screening, 12 weeks, 24 weeks, and at 36 weeks were 68.03 (16.35), 65.8 (7.96), 66.28 (15.13) and 68.4 (11.6) respectively.
Conclusions: Remogliflozin and vildagliptin combination has significant reduction of proteinuria and eGFR improvement when compared to metformin plus glimepiride.
Metrics
References
Loke A. Diabetes, 2022. Available at: https://www.who.int/newsroom/factsheets/detail/diabete. Accessed on 25 March 2023.
Tripathy JP. Burden and risk factors of diabetes and hyperglycemia in India: findings from the Global Burden of Disease Study 2016. Diabetes Metab Syndr Obes. 2018;11:381-7.
Swain SP, Samal S, Sahu KS, Rout SK. Out-of-pocket expenditure and drug adherence of patients with diabetes in Odisha. J Family Med Prim Care. 2018;7(6):1229-35.
Neal B, Perkovic V, Mahaffey KW, Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017;377(7):644-57.
Fitchett D, Inzucchi SE, Cannon CP, McGuire DK, Scirica BM, Johansen OE, et al. Empagliflozin Reduced Mortality and Hospitalization for Heart Failure Across the Spectrum of Cardiovascular Risk in the EMPA-REG OUTCOME Trial. Circulation. 2019;139(11):1384-95.
Mohan V, Mithal A, Joshi SR, Aravind SR, Chowdhury S. Remogliflozin Etabonate in the Treatment of Type 2 Diabetes: Design, Development, and Place in Therapy. Drug Des Devel Ther. 2020;14:2487-2501.
Gupta VK. Remogliflozin (SGLT2 Inhibitor) Significantly Reduces Albuminuria and Delays the Progression of Nephropathy in Type 2 Diabetes Mellitus Patients. Diabetes. 2020;1139.
Daza-Arnedo R, Rico-Fontalvo J, Pajaro-Galvis N, Leal-Martínez V, Abuabara-Franco E, Raad-Sarabia M, et al Dipeptidyl Peptidase-4 Inhibitors and Diabetic Kidney Disease: A Narrative Review Kidney Med. 2021;13(6).
Penno G, Garofolo M, Del Prato S. Dipeptidyl peptidase-4 inhibition in chronic kidney disease and potential for protection against diabetes-related renal injury. Nutr Metab Cardiovasc Dis. 2016;26(5):361-73.
Leiter LA, Yoon KH, Arias P, Langslet G, Xie J, Balis DA, et al. Canagliflozin provides durable glycemic improvements and body weight reduction over 104 weeks versus glimepiride in patients with type 2 diabetes on metformin: a randomized, double-blind, phase 3 study. Diabetes Care. 2015;38(3):355-64.
Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017;377(7):644-57.
Rosenstock J, Perkovic V, Johansen OE, Cooper ME, Kahn SE, Marx N, et al. Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk: The CARMELINA Randomized Clinical Trial. JAMA. 2019;321(1):69-79.
Gharabaghi MA, Rezvanfar MR, Saeedi N, Aghajani F, Alirezaei M, Yarahmadi P, et al. Comparison of effects of Empagliflozin and Linagliptin on renal function and glycaemic control: a double-blind, randomized clinical trial. Clin Diabetes Endocrinol. 2022 May 25;8(1):5.
Nag A, Dey PP. To Evaluate the Therapeutic Efficacy of Vildagliptin on Microalbuminuria in Type 2 Diabetes Mellitus. Int J Contemp Med Res. 2019;6(5):18-21.
Heerspink HJL, Cherney D, Postmus D, Stefánsson BV, Chertow GM, Dwyer JP, et al. A pre-specified analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial on the incidence of abrupt declines in kidney function. Kidney Int. 2022;101(1):174-84.
Chadha M, Das AK, Deb P, Gangopadhyay KK, Joshi S, Kesavadev J, et al. Expert Opinion: Optimum Clinical Approach to Combination-Use of SGLT2i + DPP4i in the Indian Diabetes Setting. Diabetes Ther. 2022;13(5):1097-114.