Effectiveness and safety of SGLT2 inhibitors in aged patients (≥ 75 Years) with diabetes: a multi-center retrospective cohort study

The prevalence of diabetes mellitus (DM) is rising globally, especially among older adults, creating unique management challenges due to increased susceptibility to adverse drug reactions and multiple comorbidities. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown cardioprotective and renoprotective effects, but their safety and efficacy in aged populations, particularly those aged ≥ 75 years, remain under-explored. In this multi-center retrospective cohort study, we analyzed data from the Chang Gung Memorial Hospital Medical System in Taiwan, focusing on diabetic patients aged ≥ 75 years between 2012 and 2021. Initially, 33,964 patients were screened. After serial exclusions, a total of 3000 patients were included, with 1,000 in the SGLT2i group and 2,000 in the non-SGLT2i group, matched 1:2 by key variables. Clinical outcomes, including all-cause mortality, cardiovascular (CV) death, heart failure (HF) hospitalization, worsening renal function, and urinary tract infections (UTIs), were compared between groups over a maximum 5-year follow-up, with a minimum follow-up of one year. The final cohort had a mean age of 83.5 ± 4.2 years, with 78.7% of patients aged 75–85 and 6.6% aged > 90 years. After inverse probability of treatment weighting (IPTW), SGLT2i use was associated with a significant reduction in all-cause mortality (6.1% vs. 11.3%, p < 0.05) and a lower incidence of worsening renal function (12.9% vs. 16.3%, p < 0.05). Cardiovascular mortality (1.6% vs. 2.4%, p = 0.08) and HF hospitalization rates (8.9% vs. 9.1%, p = 0.75) showed no significant differences between the groups. Notably, the reduced risk of renal decline was more pronounced in those aged 75–85 years, while benefits appeared to diminish in patients over 85 years. UTI incidence was similar between SGLT2i and non-SGLT2i users (5.7% vs. 6.3%, p = 0.64), suggesting no increased risk. Subgroup analysis highlighted that SGLT2i maintained benefits on all-cause mortality and renal outcomes in most aged subgroups, but careful consideration is needed for the very aged patients (> 85 years). SGLT2i treatment in DM patients aged ≥ 75 years seems associated with improved all-cause mortality and renal outcomes without increasing the risk of UTIs. The effectiveness of SGLT2i may decrease in very aged patients (> 85 years), suggesting careful patient selection is required in this subgroup.