Efficacy and safety of sodium glucose cotransporter 2 inhibitors plus standard care in diabetic kidney disease: A systematic review and meta-analysis

Abstract

Introduction: Many people with type 2 diabetes progress to end-stage diabetic kidney disease (DKD) despite blockade of the renin-angiotensin system, suggesting the need for innovative treatment options for DKD. To capture the findings of recent studies, we performed an updated systematic review and meta-analysis of the efficacy and safety of sodium glucose co-transporter 2 (SGLT2) inhibitors combined with standard care involving angiotensin converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers (ARBs) on the development and progression of DKD in people with type 2 diabetes compared with standard care alone.

Methods: The Cochrane Library, MEDLINE, EMBASE, PubMed and clinical trials registers were systematically searched for randomized controlled trials published before 1 September 2022. Primary outcomes were urine albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Secondary outcomes were glycated hemoglobin (HbA1c) and systolic blood pressure (SBP). Relative risk was calculated for adverse events.

Results: Eight studies enrolling 5512 participants were included. In the meta-analysis (n = 1327), SGLT2 inhibitors were associated with a statistically significant reduction in UACR (weighted mean difference [WMD] -105.61 mg/g, 95 % CI -197.25 to -13.98, I² = 99 %, p = 0.02). There was no statistically significant difference in relation to eGFR (n = 1375; WMD -0.23 mL/min/1.73m², 95 % CI -4.34 to 3.89, I² = 94 %, p = 0.91).

Conclusions: SGLT2 inhibitors in addition to standard care including ACE inhibitors and/or ARBs significantly reduced albuminuria, HbA1c and SBP when compared to standard care alone, supporting their routine use in people with type 2 diabetes.

Keywords: ACE inhibitors; ARBs; Diabetic kidney disease; SGLT2 inhibitors; Type 2 diabetes; Urine albumin-creatinine ratio.