Volume 16, Issue 2 (volume 16, number 2 2024)                   IJDO 2024, 16(2): 66-77 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Zeinabadi Noghabi R, Rouintan R, Sabaghian T, Khalili S. A Comparison of Renal Effects between Empagliflozin and Linagliptin in Diabetic Patients with Chronic Kidney Disease: A Randomized Clinical Trial. IJDO 2024; 16 (2) :66-77
URL: http://ijdo.ssu.ac.ir/article-1-870-en.html
Department of Internal Medicine, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract:   (189 Views)
Objective: The current study aimed to compare the renal effects of Empagliflozin with Linagliptin combined with Metformin in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease.
Materials and Methods: We conducted a randomized clinical trial on diabetic patients aged over 18 years with chronic renal failure and an EGFR between 20 to 60 ml/minutes/1.73 m2 corrected with the MDRD equation. Between January and December 2023, a total of 150 cases in Imam Hossein Hospital were randomized into two study arms of 75 cases receiving Empagliflozin (10 mg/day) and metformin or Linagliptin (5mg/day) and metformin for 6 months. The primary outcome was a change in chronic kidney disease (CKD) stage, while serum creatinine, fasting blood sugar (FBS), proteinuria, and blood pressure were evaluated at baseline, 3 and 6 months later.
Results: The mean age of participants was 62.20 (± 4.45) years and 50% of them were females. Study indices including serum creatinine (P: 0.001), estimated glomerular filtration rate (eGFR) (P: 0.001), FBS (P: 0.001), HgA1c (P: 0.001), proteinuria (P: 0.001), and blood pressure (P: 0.001) reduced significantly over time in both groups. After adjustment for potential confounders, Empagliflozin reduced the level of serum creatinine independent of other factors.
Conclusion: Empagliflozin significantly reduces the level of serum creatinine compared to Linagliptin in patients with T2DM and chronic renal failure.
Full-Text [PDF 579 kb]   (126 Downloads)    
Type of Study: Research | Subject: Special
Received: 2023/12/28 | Accepted: 2024/03/21 | Published: 2024/06/21

1. Thomas MC, Brownlee M, Susztak K, Sharma K, Jandeleit-Dahm KA, Zoungas S, et al. Diabetic kidney disease. Nature reviews Disease primers. 2015;1(1):1-20. [DOI:10.1038/nrdp.2015.18]
2. Federation ID. IDF Diabetes Atlas, 9th edn.2019.https://diabetesatlas.org/atlas/ninth-edition/
3. Mohammad zadeh 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. Clinical Diabetes and Endocrinology. 2022;8(1):5. [DOI:10.1186/s40842-022-00142-1]
4. Bello AK, Alrukhaimi M, Ashuntantang GE, Basnet S, Rotter RC, Douthat WG, e. Complications of chronic kidney disease: current state, knowledge gaps, and strategy for action. Kidney international supplements. 2017;7(2):122-9. [DOI:10.1016/j.kisu.2017.07.007]
5. Au PC, Tan KC, Cheung BM, Wong IC, Li HL, Cheung CL. Association between SGLT2 inhibitors vs DPP4 inhibitors and renal outcomes among patients with type 2 diabetes. The Journal of Clinical Endocrinology & Metabolism. 2022;107(7):e2962-70.
6. Lee YT, Hsu CN, Fu CM, Wang SW, Huang CC, Li LC. Comparison of adverse kidney outcomes with empagliflozin and linagliptin use in patients with type 2 diabetic patients in a real-world setting. Frontiers in Pharmacology. 2021;12:781379. [DOI:10.3389/fphar.2021.781379]
7. Chan GC, Tang SC. SGLT2 inhibitor empagliflozin: finally at the latter stage of understanding?. Kidney International. 2018;93(1):22-4. [DOI:10.1016/j.kint.2017.07.008]
8. Rosenstock J, Jelaska A, Zeller C, Kim G, Broedl UC, Woerle HJ, et al. Impact of empagliflozin added on to basal insulin in type 2 diabetes inadequately controlled on basal insulin: a 78‐week randomized, double‐blind, placebo‐controlled trial. Diabetes, Obesity and Metabolism. 2015;17(10):936-48. [DOI:10.1111/dom.12503]
9. Rosenstock J, Jelaska A, Frappin G, Salsali A, Kim G, Woerle HJ, et al. Improved glucose control with weight loss, lower insulin doses, and no increased hypoglycemia with empagliflozin added to titrated multiple daily injections of insulin in obese inadequately controlled type 2 diabetes. Diabetes care. 2014;37(7):1815-23. [DOI:10.2337/dc13-3055]
10. Jung S, Bosch A, Kannenkeril D, Karg MV, Striepe K, Bramlage P, et al. Combination of empagliflozin and linagliptin improves blood pressure and vascular function in type 2 diabetes. European heart journal-Cardiovascular pharmacotherapy. 2020;6(6):364-71. [DOI:10.1093/ehjcvp/pvz078]
11. Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. New England Journal of Medicine. 2020;383(15):1413-24. [DOI:10.1056/NEJMoa2022190]
12. Li J, Albajrami O, Zhuo M, Hawley CE, Paik JM. Decision algorithm for prescribing SGLT2 inhibitors and GLP-1 receptor agonists for diabetic kidney disease. Clinical Journal of the American Society of Nephrology. 2020;15(11):1678-88. [DOI:10.2215/CJN.02690320]
13. Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, et al. Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes care. 2022;45(11):2753-86. [DOI:10.2337/dci22-0034]
14. de Boer IH, Khunti K, Sadusky T, Tuttle KR, Neumiller JJ, Rhee CM, et al. Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO). Diabetes care. 2022;45(12):3075-90. [DOI:10.2337/dci22-0027]
15. DeFronzo RA, Lewin A, Patel S, Liu D, Kaste R, Woerle HJ, et al. Combination of empagliflozin and linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin. Diabetes care. 2015;38(3):384-93. [DOI:10.2337/dc14-2364]
16. 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. [DOI:10.1001/jama.2018.18269]
17. Sone H, Mizuno S, Fujii H, Yoshimura Y, Yamasaki Y, Ishibashi S, et al. Is the diagnosis of metabolic syndrome useful for predicting cardiovascular disease in Asian diabetic patients? Analysis from the Japan Diabetes Complications Study. Diabetes care. 2005;28(6):1463-71. [DOI:10.2337/diacare.28.6.1463]
18. Fujihara K, Matsubayashi Y, Yamamoto M, Osawa T, Ishizawa M, Kaneko M, et al. Impact of body mass index and metabolic phenotypes on coronary artery disease according to glucose tolerance status. Diabetes & metabolism. 2017;43(6):543-6. [DOI:10.1016/j.diabet.2017.08.002]
19. Look Ahead Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. New England journal of medicine. 2013;369(2):145-54. [DOI:10.1056/NEJMoa1212914]
20. Staplin N, Haynes R, Judge PK, Wanner C, Green JB, Emberson J, et al. Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the Empa-Kidney trial. The Lancet Diabetes & Endocrinology. 2024;12(1):39-50. [DOI:10.1016/S2213-8587(23)00321-2]
21. Perkovic V, Toto R, Cooper ME, Mann JF, Rosenstock J, McGuire DK, et al. Effects of linagliptin on cardiovascular and kidney outcomes in people with normal and reduced kidney function: secondary analysis of the Carmelina randomized trial. Diabetes care. 2020;43(8):1803-12. [DOI:10.2337/dc20-0279]
22. Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Bonaca MP, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. The Lancet. 2019;393(10166):31-9. [DOI:10.1016/S0140-6736(18)32590-X]
23. 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):752-72. [DOI:10.1161/CIRCULATIONAHA.116.021887]
24. D'Andrea E, Wexler DJ, Kim SC, Paik JM, Alt E, Patorno E. Comparing effectiveness and safety of SGLT2 inhibitors vs DPP-4 inhibitors in patients with type 2 diabetes and varying baseline HbA1c levels. JAMA Internal Medicine. 2023;183(3):242-54. [DOI:10.1001/jamainternmed.2022.6664]
25. Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJ, Charytan DM, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. New England journal of medicine. 2019;380(24):2295-306. [DOI:10.1056/NEJMoa1811744]
26. Neuen BL, Young T, Heerspink HJ, Neal B, Perkovic V, Billot L, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. The lancet Diabetes & endocrinology. 2019;7(11):845-54. [DOI:10.1016/S2213-8587(19)30256-6]
27. Xie Y, Bowe B, Gibson AK, McGill JB, Yan Y, Maddukuri G, et al. Comparative effectiveness of the sodium-glucose cotransporter 2 inhibitor empagliflozin versus other antihyperglycemics on risk of major adverse kidney events. Diabetes Care. 2020;43(11):2785-95. [DOI:10.2337/dc20-1231]
28. Heerspink HJ, Karasik A, Thuresson M, Melzer-Cohen C, Chodick G, Khunti K, et al. Kidney outcomes associated with use of SGLT2 inhibitors in real-world clinical practice (CVD-REAL 3): a multinational observational cohort study. The lancet Diabetes & endocrinology. 2020;8(1):27-35. [DOI:10.1016/S2213-8587(19)30384-5]
29. Son C, Makino H, Kasahara M, Tanaka T, Nishimura K, Taneda S, et al. Comparison of efficacy between dipeptidyl peptidase-4 inhibitor and sodium-glucose cotransporter 2 inhibitor on metabolic risk factors in Japanese patients with type 2 diabetes mellitus: Results from the CANTABILE study. Diabetes Research and Clinical Practice. 2021;180:109037. [DOI:10.1016/j.diabres.2021.109037]
30. Baker WL, Smyth LR, Riche DM, Bourret EM, Chamberlin KW, White WB. 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):262-75. [DOI:10.1016/j.jash.2014.01.007]
31. Cherney DZ, Zinman B, Inzucchi SE, Koitka-Weber A, Mattheus M, von Eynatten M, et al. Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease: an exploratory analysis from the EMPA-REG OUTCOME randomised, placebo-controlled trial. The lancet Diabetes & endocrinology. 2017;5(8):610-21. [DOI:10.1016/S2213-8587(17)30182-1]
32. Neal B, Perkovic V, Mahaffey KW, De Zeeuw D, Fulcher G, Erondu N, Shaw W, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. New England Journal of Medicine. 2017;377(7):644-57. [DOI:10.1056/NEJMoa1611925]
33. Perkovic V, de Zeeuw D, Mahaffey KW, Fulcher G, Erondu N, Shaw W, et al. Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials. The lancet Diabetes & endocrinology. 2018;6(9):691-704. [DOI:10.1016/S2213-8587(18)30141-4]
34. Heerspink HJ, Jongs N, Chertow GM, Langkilde AM, McMurray JJ, Correa-Rotter R, et al. Effect of dapagliflozin on the rate of decline in kidney function in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial. The lancet Diabetes & endocrinology. 2021;9(11):743-54. [DOI:10.1016/S2213-8587(21)00242-4]
35. Lyu YS, Oh S, Kim JH, Kim SY, Jeong MH. Comparison of SGLT2 inhibitors with DPP-4 inhibitors combined with metformin in patients with acute myocardial infarction and diabetes mellitus. Cardiovascular Diabetology. 2023;22(1):185. [DOI:10.1186/s12933-023-01960-y]
36. Inzucchi SE, Fitchett D, Jurišić‐Eržen D, Woo V, Hantel S, Janista C, et al. Are the cardiovascular and kidney benefits of empagliflozin influenced by baseline glucose‐lowering therapy?. Diabetes, Obesity and Metabolism. 2020;22(4):631-9. [DOI:10.1111/dom.13938]
37. Anker SD, Butler J, Filippatos G, Khan MS, Marx N, Lam CS, et al. Effect of empagliflozin on cardiovascular and renal outcomes in patients with heart failure by baseline diabetes status: results from the EMPEROR-reduced trial. Circulation. 2021;143(4):337-49. [DOI:10.1161/CIRCULATIONAHA.120.051824]

Add your comments about this article : Your username or Email:

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2024 CC BY-NC 4.0 | Iranian Journal of Diabetes and Obesity

Designed & Developed by : Yektaweb