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

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.

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.

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/m²; HR, 1.226; 95% CI, 0.931-1.615).

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.