Does Dapagliflozin ameliorate kidney function in Saudi type II diabetic patients with chronic kidney diseases?
Abstract
Background: In recent years, type 2 diabetes mellitus (T2DM) has become increasingly prevalent and is associated with numerous cardiovascular and renal complications. Various drug classes are utilized for treating and preventing complications in patients with T2DM. Dapagliflozin, a selective sodium-glucose cotransporter-2 inhibitor, has recently been approved for treating chronic kidney disease (CKD), whether DM is present. This study evaluates dapagliflozin effectiveness in managing T2DM patients with CKD.
Methods: Adult diabetic patients with CKD who received 10 mg dapagliflozin once daily for 12 months were compared with another group on a glucose-lowering regimen without dapagliflozin. Data of HbA1C and kidney function tests, including eGFR, serum creatinine, blood urea nitrogen (BUN), sodium, potassium, calcium, and albumin levels were retrieved before starting dapagliflozin treatment and then every three months for a total of 12 months.
Results: 159 diabetic patients with varying CKD stages received a glucose-lowering regimen. Group I (n=84) included 51 males and 33 females who were administered dapagliflozin, while group II (n =75) comprised 35 males and 40 females who received different glucose-lowering regimens without dapagliflozin. Furthermore, during the 12-month study period, a higher proportion of patients in the dapagliflozin group were identified as having retinopathy, cataracts, and glaucoma (29.8%, 11.9%, and 4.8%, respectively).
Conclusion: The present findings indicate that dapagliflozin did not demonstrate a significant renal protective effect during the first 12 months in this cohort. Further research is warranted to assess the long-term impact of dapagliflozin.
Keywords: Dapagliflozin, Diabetes Mellitus, Chronic Kidney Disease, Renal Failure
Full Text:
PDFReferences
Webster AC, Nagler EV, Morton RL, Masson P. Chronic kidney disease. The Lancet, (2017); 389(10075): 1238–1252.
Nasri H, Rafieian-Kopaei M. Diabetes mellitus and renal failure: Prevention and management. Journal of Research in Medical Sciences, (2015); 20(11): 1112–1120.
Robert AA, Al Dawish MA, Braham R, Musallam MA, Al Hayek AA, et al. Type 2 diabetes mellitus in Saudi Arabia: major challenges and possible solutions. Current Diabetes Reviews, (2017); 13(1): 59–64.
Alshaya OA, Korayem GB, Alghwainm M, Alyami W, Alotaibi A, et al. The prevalence of cardiovascular diseases, chronic kidney disease, and obesity in patients with type 2 diabetes mellitus and the description of concurrent treatments: A two-center retrospective cross-sectional study in Saudi Arabia. Saudi Pharmaceutical Journal, (2024); 32(5): 102054.
van den Brand JA. Diabetes mellitus as a cause of end-stage renal disease in Europe: signs of improvement. Clinical Kidney Journal, (2016); 9(3): 454–456.
Ruggenenti P, Perna A, Gherardi G, Garini G, Zoccali C, et al. Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria. The Lancet, (1999); 354(9176): 359–364.
Brenner BM, Cooper ME, De Zeeuw D, Keane WF, Mitch WE, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. New England Journal of Medicine, (2001); 345(12): 861–869.
Hou FF, Zhang X, Zhang GH, Xie D, Chen PY, et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. New England Journal of Medicine, (2006); 354(2): 131–140.
Chatzimanouil MKT, Wilkens L, Anders H-J. Quantity and reporting quality of kidney research. Journal of the American Society of Nephrology, (2019); 30(1): 13–22.
Wang H, Liu D, Zheng B, Yang Y, Qiao Y, et al. Emerging role of ferroptosis in diabetic kidney disease: molecular mechanisms and therapeutic opportunities. International Journal of Biological Sciences, (2023); 19(9): 2678.
Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. New England Journal of Medicine, (2001); 345(12): 851–860.
Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. New England Journal of Medicine, (2016); 375(4): 323–334.
Hsia DS, Grove O, Cefalu WT. An update on sodium-glucose co-transporter-2 inhibitors for the treatment of diabetes mellitus. Current Opinion in Endocrinology, Diabetes and Obesity, (2017); 24(1): 73–79.
Neal B, Perkovic V, Mahaffey KW, De Zeeuw D, Fulcher G, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. New England Journal of Medicine, (2017); 377(7): 644–657.
Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. New England Journal of Medicine, (2019); 380(4): 347–357.
Heerspink HJ, Kosiborod M, Inzucchi SE, Cherney DZ. Renoprotective effects of sodium-glucose cotransporter-2 inhibitors. Kidney International, (2018); 94(1): 26–39.
Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJ, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. New England Journal of Medicine, (2019); 380(24): 2295–2306.
Cherney DZ, Dekkers CC, Barbour SJ, Cattran D, Gafor AHA, et al. Effects of the SGLT2 inhibitor dapagliflozin on proteinuria in non-diabetic patients with chronic kidney disease (DIAMOND): a randomised, double-blind, crossover trial. The Lancet Diabetes & Endocrinology, (2020); 8(7): 582–593.
Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. New England Journal of Medicine, (2015); 373(22): 2117–2128.
Heerspink HJ, Stefansson BV, Chertow GM, Correa-Rotter R, Greene T, et al. Rationale and protocol of the Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial. Nephrology Dialysis Transplantation, (2020); 35(2): 274–282.
Heerspink HJ, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, et al. Dapagliflozin in patients with chronic kidney disease. New England Journal of Medicine, (2020); 383(15): 1436–1446.
Nashar K, Khalil P. Clinical evaluation of dapagliflozin in the management of CKD: focus on patient selection and clinical perspectives. International Journal of Nephrology and Renovascular Disease, (2022); 289–308.
Fioretto P, Del Prato S, Buse JB, Goldenberg R, Giorgino F, et al. Efficacy and safety of dapagliflozin in patients with type 2 diabetes and moderate renal impairment (chronic kidney disease stage 3A): The DERIVE Study. Diabetes, Obesity and Metabolism, (2018); 20(11): 2532–2540.
Duo Y, Gao J, Yuan T, Zhao W. Effect of sodium‐glucose cotransporter 2 inhibitors on the rate of decline in kidney function: A systematic review and meta‐analysis. Journal of Diabetes, (2023); 15(1): 58–70.
Chertow GM, Vart P, Jongs N, Toto RD, Gorriz JL, et al. Effects of dapagliflozin in stage 4 chronic kidney disease. Journal of the American Society of Nephrology, (2021); 32(9): 2352–2361.
Filippatos TD, Elisaf MS. Combination drug treatment in obese diabetic patients. World Journal of Diabetes, (2010); 1(1): 8.
Gosmanov AR, Wall BM, Gosmanova EO. Diagnosis and treatment of diabetic kidney disease. The American Journal of the Medical Sciences, (2014); 347(5): 406–413.
De Nicola L, Gabbai FB, Liberti ME, Sagliocca A, Conte G, et al. Sodium/glucose cotransporter 2 inhibitors and prevention of diabetic nephropathy: targeting the renal tubule in diabetes. American Journal of Kidney Diseases, (2014); 64(1): 16–24.
Terami N, Ogawa D, Tachibana H, Hatanaka T, Wada J, et al. Long-term treatment with the sodium glucose cotransporter 2 inhibitor, dapagliflozin, ameliorates glucose homeostasis and diabetic nephropathy in db/db mice. PLoS One, (2014); 9(6): e100777.
Fioretto P, Zambon A, Rossato M, Busetto L, Vettor R. SGLT2 inhibitors and the diabetic kidney. Diabetes Care, (2016); 39(Supplement_2): S165–S171.
Heerspink HJ, Perkins BA, Fitchett DH, Husain M, Cherney DZ. Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications. Circulation, (2016); 134(10): 752–772.
de Albuquerque Rocha N, Neeland IJ, McCullough PA, Toto RD, McGuire DK. Effects of sodium glucose co-transporter 2 inhibitors on the kidney. Diabetes and Vascular Disease Research, (2018); 15(5): 375–386.
Baker WL, Smyth LR, Riche DM, Bourret EM, Chamberlin KW, et al. Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: a systematic review and meta-analysis. Journal of the American Society of Hypertension, (2014); 8(4): 262–275.
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.
Filippatos TD, Liberopoulos EN, Elisaf MS. Dapagliflozin in patients with type 2 diabetes mellitus. Therapeutic Advances in Endocrinology and Metabolism, (2015); 6(1): 29–41.
Beernink JM, Persson F, Jongs N, Laverman GD, Chertow GM, et al. Efficacy of dapagliflozin by baseline diabetes medications: a prespecified analysis from the DAPA-CKD study. Diabetes Care, (2023); 46(3): 602–607.
Chertow GM, Correa‐Rotter R, Vart P, Jongs N, McMurray JJ, et al. Effects of Dapagliflozin in Chronic Kidney Disease, With and Without Other Cardiovascular Medications: DAPA‐CKD Trial. Journal of the American Heart Association, (2023); 12(9): e028739.
DOI: http://dx.doi.org/10.62940/als.v12i3.3699
Refbacks
- There are currently no refbacks.