Comparative Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Classes of Glucose-Lowering Medications on Renal Outcome in Type 2 Diabetes

Abstract

Objective: To assess whether sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy is associated with a favorable renal prognosis for patients with type 2 diabetes melllitus (T2DM) outside the clinical trials setting. Participants and Methods: This retrospective study analyzed routinely collected health care records of ∼160 medical institutions in Japan from April 1, 2014, to December 31, 2017/2018 (varying at the institutional level). Adults with T2DM but without end-stage renal disease who initiated either SGLT2i or other classes of glucose-lowering medications (o-GLM) were matched using propensity score. The primary outcome was the time course of estimated glomerular filtration rate (eGFR) displayed in spline curve. The composite of renal worsening (>40% decline in eGFR) and the development of eGFR<30 mL/1.73 m2 per minute was evaluated as a secondary outcome. Two sensitivity analyses were conducted to determine the robustness of results. Results: We compared a matched cohort of 1433 SGLT2i users and 2739 o-GLM users (mean age: 61 years). The eGFR declined over time in both groups during the observation period (median: 17 months; maximum: 54 months), with a slower eGFR slope observed in SGLT2i users. This slower decline was consistently observed across different SGLT2i agents and different baseline eGFR groups. The cumulative incidence of composite renal endpoints was lower in the SGLT2i group with a hazard ratio of 0.70 (95% CI, 0.50-0.98; P=.039). Those findings were consistent in sensitivity analyses limited to the period adherent to the initial drug regimen and with a different approach for propensity score calculation. Conclusion: In a matched cohort of T2DM patients, SGLT2i use was associated with preserved renal function relative to o-GLM use over 2 to 4 years.