Association of GLP1-Receptor Agonist Use With Frailty and Falls in Adults With Type 2 Diabetes.

Objective

To evaluate the association of initiating glucagon-like peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors (as active comparator) with frailty progression and falls and whether associations differed by baseline frailty. RESEARCH

Design

AND

Methods

Five propensity score-matched retrospective cohorts using Veterans Health data (years 2006-2021), utilizing new-user, active-comparator design. The five matched cohorts were at progressive degrees of frailty at baseline and included adults with diabetes and 3 years of baseline data who initiated study medications with at least 90 days of therapy. MAIN OUTCOMES AND MEASURES Primary outcome was absolute change in Frailty Index from baseline to follow-up. Secondary outcomes were increase in the frailty index and fall rate during follow-up. Outcomes were assessed in an as-treated framework.

Results

The main matched cohort included 73 592 pairs. Over a mean follow-up of approximately 27 months, glucagon-like peptide-1 receptor agonists initiation was associated with less worsening in frailty index (regression coefficient: -0.0010; 95% CI: -0.0018 to -0.0002; p = 0.011), lower odds of frailty index progression (OR: 0.97; 95% CI: 0.95-0.99; p = 0.003), and a lower fall rate (incidence rate ratio: 0.87; 95% CI: 0.84-0.91; p < 0.001) compared to dipeptidyl peptidase-4 inhibitor initiation. Findings were generally consistent across the other four matched cohorts, with attenuation in the matched cohort with severe frailty at baseline.

Conclusions

Initiation of glucagon-like peptide-1 receptor agonist was associated with slightly less frailty progression and fewer falls compared with dipeptidyl peptidase-4 inhibitor initiation, but estimates were attenuated in severe frailty.