Mortality, kidney, and safety outcomes with SGLT2 inhibitors versus DPP4 inhibitors in patients with type 2 diabetes treated with systemic glucocorticoids: a real-world exploratory study

Background: Clinical trials that demonstrated sodium-glucose cotransporter-2 inhibitors (SGLT2) inhibitors benefits in patients with type 2 diabetes excluded patients treated with glucocorticoids. It is unknown whether SGLT2 inhibitors are safe and effective for these patients, limiting their clinical use. Methods: In a cohort study, we used TriNetX, a global real-world data network, and propensity-score matched (1:1) adults with type 2 diabetes and estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m², treated with oral glucocorticoids, who initiated treatment with SGLT2 inhibitors or dipeptidyl peptidase-4 (DPP4) inhibitors (2015–2021). Outcomes included all-cause death and a composite of chronic kidney disease stage 4 or worse, eGFR < 30 mL/min/1.73 m², or dialysis initiation. Safety outcomes included diabetic ketoacidosis and genital tract infections (in women). Results: The 9090 matched patients (3906 women) had a mean age 60.1 years and a mean eGFR 82.4 mL/min/1.73 m² at baseline. All-cause death occurred among 315 versus 433 patients with SGLT2 inhibitors versus DPP4 inhibitors, respectively (RR 0.73 [95 %CI 0.64–0.84]). The composite kidney outcome occurred in 421 versus 518 patients, respectively (RR 0.81 [0.72–0.92]). The respective numbers of patients with diabetic ketoacidosis and genital tract infections were 67 versus 59 and 125 versus 119. Conclusion: In a global real-world cohort of patients with type 2 diabetes treated with systemic glucocorticoids, SGLT2 inhibitors versus DPP4 inhibitors initiation was associated with a lower rate of all-cause death, with evidence suggesting kidney benefits.