GLP-1 Receptor Agonist Therapy and Cardiorenal Outcomes in Patients ≥ 80 Years Old With Type 2 Diabetes

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated potential in improving glycemic control and reducing adverse outcomes in patients with Type 2 diabetes mellitus (T2DM); however, their efficacy in individuals aged 80 years and older remains understudied. To evaluate the efficacy of GLP-1 RAs compared with dipeptidyl peptidase-4 inhibitors (DPP4i) in patients aged ≥ 80 years with T2DM.

De-identified records from the TriNetX United States database identified 284,417 patients aged ≥ 80 years with T2DM, including 12,032 new GLP-1 RA users and 28,230 new DPP4i users, analyzed from January 2018 to December 2022.

This retrospective cohort study utilized a new-user and active comparator design to evaluate clinical outcomes between GLP-1 RA and DPP4i users during a follow-up period of up to 5 years. Propensity score matching, incorporating all the baseline covariates, was used to minimize baseline differences. The Cox proportional hazards regression model was used to estimate hazard ratios (HRs) for clinical outcomes. Sensitivity analyses were performed to validate the findings.

After 1:1 propensity score matching, 11,464 patients were included in each group. Both cohorts had a mean age of 81.6 years; 47.7% were female, and 67% were White. GLP-1 RA users had significantly lower risks of major adverse cardiovascular events (HR: 0.86, 95% CI: 0.81-0.91), major adverse kidney events (HR: 0.86, 95% CI: 0.82-0.91), all-cause hospitalization (HR: 0.91, 95% CI: 0.84-0.97), and all-cause mortality (HR: 0.82, 95% CI: 0.77-0.88) compared with DPP4i users. No significant differences were observed between the groups in the rate of heart failure or bone fractures.

GLP-1 RAs may offer substantial cardiorenal and survival benefits in patients aged 80 years and older with T2DM. These findings support the use of GLP-1 RAs as a therapeutic option in this high-risk, older population.