Sustained Use of SGLT2 Inhibitors and Cardiovascular Outcomes in Older Adults: A Landmark Cohort Study

Aims To examine adjusted cardiovascular outcome associations among older adults with type 2 diabetes who had sustained sodium–glucose cotransporter 2 inhibitor (SGLT2i) or dipeptidyl peptidase‐4 inhibitor (DPP‐4i) therapy for ≥ 6 months, focusing on the maintenance phase and heterogeneity across body mass index (BMI) strata. Materials and Methods We conducted a nationwide‐scale landmark cohort study using linked claims and health examination data in Japan. Adults aged ≥ 65 years with type 2 diabetes who maintained SGLT2i or DPP‐4i for ≥ 6 months were included. Weighted discrete‐time hazard models with inverse probability of treatment and censoring weighting were applied. Results Among 24 380 participants (4223 SGLT2i; 20 157 DPP‐4i), sustained SGLT2i use was associated with lower hazards of heart failure hospitalisation (HR, 0.775; 95% CI, 0.628–0.958) and MACE (myocardial infarction, stroke or all‐cause mortality) (HR, 0.848; 95% CI, 0.753–0.955). Stroke hazard was lower (HR, 0.834; 95% CI, 0.721–0.965), whereas myocardial infarction and all‐cause mortality were not clearly different. The association for heart failure hospitalisation was directionally consistent across BMI strata ( p for interaction = 0.953), whereas MACE estimates differed across BMI strata ( p for interaction = 0.007), with no clear association in the lowest BMI group (< 22 kg/m 2 ; HR, 1.226; 95% CI, 0.931–1.615). Conclusions Among older adults who had maintained treatment for ≥ 6 months, sustained SGLT2i use was associated with lower subsequent risks of heart failure hospitalisation and MACE. Heart failure associations were directionally consistent across BMI strata, whereas BMI‐related MACE heterogeneity was exploratory and should not be interpreted as evidence to guide treatment by BMI alone.