Ketoanalogue use is associated with a lower risk of worsening frailty among patients with diabetic kidney disease of advanced stage: A retrospective cohort study.

Background: Patients with diabetes kidney disease (DKD) are at risk of developing frailty, leading to functional impairment and poor outcomes. Medications are potential modifiers of such risk. Ketoanalogues have been shown to delay dialysis initiation in DKD patients. We investigated whether ketoanalogues use influenced the risk of worsening frailty in this population.

Methods: From 840,000 patients with diabetes, we identified those with DKD but without full-fledged frailty, and divided them into those with and without receiving ketoanalogue, followed by propensity score matching in 1:4 ratio. Worsening frailty was defined as ≥1 positive FRAIL item increase compared to baseline status (0, 1, or 2 items) during follow-up. We used Cox proportional hazard regression to estimate the probability of worsening frailty, adjusting for demographics, comorbidities, glycemic control, renal function, treatments and medications.

Results: Totally 183 and 732 ketoanalogue users and matched non-users were identified, respectively. The mean age of included patients was 57.4 years, with 91.3 % having non-dialysis stage 5 chronic kidney disease. Approximately two-thirds had pre-frailty (1 o2 items). After 3.72 years, 16.6 % patients had worsening frailty. Multivariate analyses, adjusting for confounders disclosed that ketoanalogue users (≥14 days) had a significantly lower risk of worsening frailty than non-users (hazard ratio (HR) 0.52, 95 % confidence interval (CI) 0.32-0.87). Sensitivity analysis including those received ketoanalogue ≥28 days showed even greater benefits (HR 0.45, 95 % CI 0.26-0.78).

Conclusions: Patients with DKD receiving ketoanalogues were less likely to have worsening frailty over time than non-users. Our findings uncover a new potential strategy of ameliorating frailty progression in this population carrying a high risk of accelerated aging.