The Effect of Sodium–Glucose Cotransporter Inhibitors on Renal Function as Adjunctive to Insulin in Adults with Type 1 Diabetes: An Updated Multilevel Meta-analysis of Randomized Controlled Trials

Abstract

Introduction: This systematic review aimed to summarize the existing evidence from published randomized controlled trials (RCTs) on the impact of sodium–glucose cotransporter (SGLT) inhibitors on albuminuria levels and renal function in patients with type 1 diabetes mellitus (T1D). Methods: The literature search was performed through Medline (via PubMed), Cochrane Library, and Scopus until November 11, 2023. Double-independent study selection, data extraction, and quality assessment were performed. Evidence was pooled with three-level mixed-effects meta-analysis. Results: In total, 5221 participants with T1D among 11 RCTs were analyzed. All RCTs had low risk of bias according to the Cochrane Collaboration tool (RoB 2). SGLT inhibitors were associated with a significantly greater reduction in urine albumin-to-creatinine ratio (UACR) compared to controls (MD = − 23.13%; 95% CI = [− 33.69, − 12.57]; P < 0.001; level of evidence high). On the basis of subgroup analysis, this effect was consistent across all available SGLT inhibitors, irrespective of the dosage. Finally, a neutral class effect was observed on the estimated glomerular filtration rate (eGFR, MD = − 1.03 mL/min/1.73 m2; 95% CI = [− 2.26, 0.19]; P = 0.1; level of evidence moderate). Only empagliflozin was associated with a significant reduction in eGFR compared to placebo (MD = − 2.23 mL/min/1.73 m2; 95% CI = [− 3.62, − 0.84]; P = 0.002). Conclusion: Our findings suggest that adjunctive therapy with SGLT inhibitors results in a significant reduction in albuminuria, while their use is associated with a neutral effect on creatinine clearance, as a measure of renal function. Future renal outcome trials are needed to assess SGLT inhibitors’ role in the pharmacological armamentarium against diabetic nephropathy in T1D.