Efficacy and safety of SGLT2 inhibitors in elderly patients with type 2 diabetes

Abstract

Abstract Objectives To evaluate the effectiveness and safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors in elderly patients with type 2 diabetes mellitus, with particular focus on renal and cardiovascular outcomes. Methods This retrospective cohort study analyzed data from 9,915 diabetic patients aged ≥65 years who received antihyperglycemic therapy at Changhua Christian Hospital, Taiwan, between January 2021 and September 2023. Patients were categorized as SGLT2 inhibitor users (n = 3,345) or non-users (n = 6,570). After 1:1 propensity score matching, 1,529 patients remained in each group. Primary outcomes included renal function (measured by eGFR decline), coronary artery disease, ischemic stroke, and heart failure. Secondary outcomes included urinary tract infection, genital infection, diabetic ketoacidosis, and hypoglycemia. Results SGLT2 inhibitor use was associated with significant renoprotective effects, demonstrated by reduced risk of 30% eGFR decline (HR 0.69, 95% CI 0.59–0.80, p < 0.001) and 50% eGFR decline (HR 0.60, 95% CI 0.45–0.80, p < 0.001). Subgroup analyses revealed that renoprotective effects were more pronounced in patients with higher baseline eGFR (≥50 mL/min/1.73 m2), suggesting greater benefit with early initiation of SGLT2 inhibitors for kidney protection. However, SGLT2 inhibitor use was associated with an increased risk of genital infections (HR 4.29, 95% CI 1.02–18.04, p = 0.047) in patients without prior history of such infections. Conclusions In elderly patients with type 2 diabetes, SGLT2 inhibitors demonstrate significant renal protective effects, particularly among those with preserved renal function (eGFR ≥50 mL/min/1.73 m2). These findings highlight the importance of considering patient characteristics when evaluating potential benefits of SGLT2 inhibitor therapy. The differential risk patterns suggest that clinicians should consider individual patient profiles and medical histories when prescribing these medications. The occurrence of major adverse cardiovascular events (MACE) did not exhibit a statistically significant difference between the cohort administered SGLT2 inhibitors and the cohort not receiving SGLT2 inhibitors (log-rank p-value = 0.160). Conversely, the recurrence of MACE was markedly reduced in the cohort receiving SGLT2 inhibitors (log-rank p-value < 0.001). These findings should be interpreted in the context of a single-center retrospective design and the inherent limitations of propensity-score-matched observational analyses.