Dapagliflozin in patients with chronic kidney disease: a systematic review and meta-analysis on randomized, double-blind, placebo-controlled multicenter trials

Hamidreza Khodabandeh ¹ , Hanieh Molaee ² , Ladan Ghashghaie ³ , Mohammad Reza Farnia ⁴ , Soleyman Alivand ⁵ , Faraz Zandiyeh ⁶ , Farshad Gharebakhshi ¹ , Elham Rashidi ⁷ , Nahid Mir ⁸^*

¹ Department of Radiology, Imam Hossein Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
² Department of Nursing, Faculty of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran
³ Department of Anesthesiology, Student Research Committee, Faculty of Nursing and Midwifery, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
⁴ Department of Emergency Medicine, Taleghani and Imam Reza Hospitals, School of Medicine, Kermanshah University of Medical Science, Kermanshah, Iran
⁵ Department of Biostatistical and Epidemiology, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
⁶ Department of Emergency Medicine, Shohadaye Salamat Hospital, Iran University of Medical Sciences, Tehran, Iran
⁷ Department of Critical Care, Razi School of Nursing and Midwifery, Kerman University of Medical Sciences, Kerman, Iran
⁸ Department of Nursing, Khatam al Anbia Hospital, Faculty of Nursing and Midwifery, Iranshahr University of Medical Sciences, Iranshahr, Iran

*Corresponding Author: Nahid Mir, Email: nahid.mir6641@gmail.com

Abstract

Introduction: Sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce the mortality rate, hospitalization, and cardiac morbidity in diabetic patients. However, their safety in chronic kidney disease (CKD) individuals is still debatable.

Objectives: The present study aims to evaluate the effect of dapagliflozin on primary composite outcomes and mortality rate in CKD patients using a systematic review and meta-analysis approach.

Materials and Methods: In this meta-analysis, Cochrane, Web of Science, Scopus, and PubMed databases, along with the Google Scholar search engine, were queried until March 2023. Data were analyzed by STATA software version 14 at a significance level of P<0.05.

Results: A total of nine randomized clinical trials (RCTs) articles were reviewed, with a sample size of 16720 in the dapagliflozin group and 13 476 in the placebo group. Dapagliflozin use (10 mg/d) compared to placebo improved primary composite outcomes in CKD patients by 39% (OR=0.61, 95% CI: 0.57, 0.65) while reducing the mortality rate by 31% (OR=0.69, 95% CI: 0.63, 0.76). In an analysis by treatment length, no statistically significant change was noted in early composite outcomes (OR=0.70, 95% CI: 0.48, 1.01) and mortality rate (OR=0.75, 95% CI: 0.39, 1.45) between patients who were on dapagliflozin for less than two years and the placebo group. However, patients receiving dapagliflozin for two years and above had significantly improved primary composite outcomes (OR=0.60, 95% CI: 0.55, 0.66) and mortality rate (OR=0.69, 95% CI: 0.61, 0.79) compared to the placebo group.

Conclusion: Dapagliflozin use, compared to placebo, improved the early composite outcomes and mortality rate in CKD patients. Prescribing a daily dose of 10 mg for a treatment duration of over two years seems safe in these patients.

Registration: This study has been compiled based on the PRISMA checklist, and its protocol was registered on the PROSPERO website (ID: CRD42023422186).

Keywords: Type 2 diabetes, SGLT2, Chronic kidney disease, Sodium-glucose cotransporter-2 inhibitors, Dapagliflozin

Implication for health policy/practice/research/medical education:

The results of combining nine randomized clinical trials studies showed that dapagliflozin administration (10 mg/d) compared to placebo improved primary composite outcomes in chronic kidney disease patients by 39% while reducing the mortality rate by 31%. In an analysis by treatment length, no statistically significant change was noted in early composite outcomes and mortality rate between patients who were on dapagliflozin for less than two years and the placebo group. However, patients receiving dapagliflozin for two years and above had significantly improved primary composite outcomes and mortality rates compared to the placebo group.

Please cite this paper as: Khodabandeh H, Molaee H, Ghashghaie L, Farnia MR, Alivand S, Zandiyeh F, Gharebakhshi F, Rashidi E, Mir N. Dapagliflozin in patients with chronic kidney disease: a systematic review and meta-analysis on randomized, double-blind, placebocontrolled multicenter trials. J Nephropathol. 2023;x(x):e21472. DOI: 10.34172/jnp.2023.21472.