Sodium-Glucose Cotransporter-2 Inhibitors versus Glucagon-Like Peptide 1 Receptor Agonists Effects on Kidney and Clinical Outcomes in Veterans with Type 2 Diabetes

Key Points Using data on veterans with type 2 diabetes (T2D), we evaluated the clinical end points of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) in preserving kidney function over a 3-year period. Veterans with T2D initiated on an SGLT2i experienced a 35% reduced hazard of the composite endpoint compared with GLP-1RA. Further research on combination therapy of SGLT2i and GLP-1RA is warranted to better understand the potential of CKD guideline-directed medical therapy. Background The primary aim of this study was to compare kidney end points between patients with type 2 diabetes (T2D) 36 months after initiation on a sodium-glucose cotransporter-2 inhibitor (SGLT2i) or a glucagon-like peptide 1 receptor agonist (GLP-1RA). Secondary aims compared eGFR, hemoglobin A1c (HbA1c), weight, and urine albumin-creatinine ratio (UACR) changes. Methods We conducted a retrospective cohort study of propensity score–matched veterans with T2D, baseline eGFR >20 ml/min per 1.73 m 2 , and initiated on a SGLT2i versus GLP-1RA between April 1, 2009 and September 1, 2020. Cox proportional hazard models were constructed to evaluate effectiveness between both groups on composite endpoint (decline of ≥40% in eGFR from baseline, ESKD event, and all-cause mortality) and its components, adjusting for baseline characteristics. Spline models were constructed to evaluate eGFR change, and linear mixed effects models were constructed to evaluate changes in HbA1c, weight, and UACR. We used an intent-to-treat (ITT) approach as our main analysis followed by a per-protocol (PP) approach excluding veterans who discontinued or switched therapy during the study period. Results A total of 29,146 propensity score–matched veterans were included in SGLT2i and GLP-1RA groups (14,573 per group). In the ITT and PP analyses, veterans initiated on SGLT2i had a 35% (hazard ratio, 0.65; 95% confidence interval [CI], 0.62 to 0.68) and 34% (hazard ratio, 0.66; 95% CI, 0.62 to 0.69) reduction in the hazard of experiencing the composite endpoint compared with veterans initiated on GLP-1RA adjusting for baseline characteristics, respectively. Between 6 and 36 months, we found an improved chronic eGFR slope with SGLT2i compared with GLP-1RA in both ITT and PP analyses; +1.19 ml/min per 1.73 m 2 (95% CI, 0.93 to 1.45) and +1.29 ml/min per 1.73 m 2 (95% CI, 1.01 to 1.57), respectively. The annual difference in chronic eGFR slope in both ITT and PP analyses were +0.97 ml/min per 1.73 m 2 per year (95% CI, 0.82 to 1.11) and +1.08 ml/min per 1.73 m 2 per year (95% CI, 0.92 to 1.25). Improved HbA1c, weight loss, and UACR were reported for both groups. Conclusions In this real-world study, veterans with T2D initiated on SGLT2i were associated with reduced hazard of experiencing mortality, worsening eGFR, or developing ESKD and improved glycemic, metabolic, and renal end points compared with GLP-1RA use.