Mortality and persistence in therapy in elderly subjects with type 2 diabetes receiving gliflozins or incretins

PURPOSE: Evidence supporting the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) in individuals aged ≥ 80 years remains limited, particularly regarding treatment persistence and real-world outcomes. METHODS: In this retrospective real-world study, 292 individuals with type 2 diabetes (T2D) aged ≥ 80 years who started SGLT2i (n = 155) or GLP1-RA (n = 137) after the age of 75 were stratified by age at treatment initiation (75-80 vs. > 80). Primary outcomes were all-cause mortality and treatment persistence; longitudinal renal function was also assessed. Survival analyses were performed using Cox models adjusted for confounders. RESULTS: Over a median follow-up of 40 (37-43) months, 47 deaths (16.1%) occurred. The incidence rate of mortality was 37.5 and 68.6 events/1000 person-years in the GLP1-RA and SGLT2i groups, respectively (adjusted HR = 0.58, 95% CI [0.28-1.21]; p = 0.148). Stratifying participants by age at first prescription, those starting either GLP1-RA or SGLT2i at age 75-80 showed similar mortality. In contrast, subjects starting GLP1-RA vs. SGLT2i after 80 years showed a higher survival rate (adjusted HR = 0.33, 95% CI [0.12-0.91]; p = 0.034); significance disappeared after further adjustment for cardiovascular burden. Treatment discontinuation was 14% with GLP1-RA and 20% with SGLT2i (HR 0.53, 95% CI [0.30-0.95]; p = 0.032), due to a better persistence in GLP1-RA of more elderly subjects. Longitudinal eGFR trajectories were similar between treatments. CONCLUSION: GLP1-RA and SGLT2i were associated with similar all-cause mortality risk when started in very late age. Kidney function over time was comparable. Persistence on SGLT2i was lower when therapy was started after the age of 80. These findings highlight the need for individualized treatment decisions in older, frail patients and for prospective studies on glucose-lowering therapies in very old populations.