Polypharmacy Reflects Metabolic Burden Rather than Frailty in Older Adults with Type 2 Diabetes: A Comprehensive...

Background: Polypharmacy is highly prevalent among older adults with type 2 diabetes mellitus (T2DM) and is traditionally considered a marker of geriatric vulnerability. However, it remains unclear whether polypharmacy is more closely associated with multidimensional frailty or metabolic burden in this population. Methods: In this retrospective cross-sectional study, 278 adults aged ≥65 years with T2DM underwent comprehensive geriatric assessment (CGA), including evaluation of functional status, cognition, nutrition, depressive symptoms, frailty, and physical performance. Frailty was assessed using the Fried phenotype. Polypharmacy was defined as the concurrent use of ≥5 medications. Multivariable logistic regression and interaction analyses were performed to identify independent predictors of polypharmacy. Receiver operating characteristic (ROC) analyses were conducted to evaluate the discriminative performance of metabolic parameters. Results: Polypharmacy was present in 54.7% of participants. Patients with polypharmacy had significantly higher HbA1c and fasting glucose levels compared with those without polypharmacy (both p < 0.001). In multivariable analysis, higher HbA1c levels remained independently associated with polypharmacy (OR = 4.99, 95% CI: 3.18-7.84, p < 0.001), whereas frailty status was not significantly associated with polypharmacy (OR = 0.58, 95% CI: 0.15-2.21, p = 0.427). No significant interaction was observed between HbA1c and frailty status (p for interaction > 0.05). Among CGA domains, only functional status and gait speed differed in unadjusted analyses, while cognition, nutritional status, and depressive symptoms were not significantly associated with polypharmacy after adjustment. HbA1c demonstrated strong discriminative performance for polypharmacy (AUC = 0.898, 95% CI: 0.863-0.931), with an optimal cut-off of 6.81%. Conclusions: In older adults with T2DM, polypharmacy appeared to be more closely associated with markers of poor glycemic control, particularly HbA1c levels, than with frailty status itself. These findings suggest that medication burden in older adults with T2DM may reflect treatment intensification and suboptimal glycemic control in addition to geriatric vulnerability.