Allopurinol adherence, persistence and patterns of use in individuals with diabetes and gout: a retrospective, population-based cohort analysis

Objective — There has been growing interest in the potential role for allopurinol to reduce cardiovascular events in people with diabetes. While adherence to allopurinol is poor in those with gout, our aim was to characterize persistence, patterns of use, and predictors of allopurinol use in a population-based cohort of individuals with diabetes and gout.

Methods — Individuals with diabetes older than 66 (thus eligible for prescription medication coverage) and newly prescribed allopurinol were followed for up to three years in a retrospective cohort study. Allopurinol use patterns were categorized as adherer (used continuously throughout follow-up), interrupter (non-persistent but subsequently resumed), or discontinuer (non-persistent with no subsequent resumption). Main outcomes were allopurinol non-persistence (no subsequent prescription accounting for a grace period), and indicators of gout severity throughout follow-up (prescriptions for prednisone or colchicine, outpatient gout visits, hospitalization/emergency department visits for gout). Outcome frequencies were determined, a multivariable Cox proportional hazards model evaluated associations between predictors and non-persistence, and zero-inflated negative binomial (ZINB) models evaluated associations between allopurinol use pattern and indicators of gout severity.

Results — 22,056 individuals were followed for a maximum of 3.0 years (17,410 with 3 years of follow-up). 9092 (41.2%) were non-persistent with allopurinol. Higher risks of non-persistence were associated with female sex (HR, 95% CI: 1.28, 1.23–1.33), dementia (1.23, 1.11–1.35), and an outpatient visit for gout in the prior year (1.19, 1.09–1.29). There were 12,964 (58.8%) allopurinol adherers, 4618 interrupters (20.9%), and 4474 (20.3%) discontinuers. Allopurinol interrupters and discontinuers had indicators of more severe gout over time compared to adherers, including greater odds of being prescribed prednisone.

Conclusion — Allopurinol non-persistence and interruptions were frequent in individuals with diabetes and gout and were associated with prescriptions for prednisone. Suboptimal allopurinol adherence may not only increase the risk of gout complications in this population but also potentially diabetes complications through greater prednisone use and its negative effects on glycemic control.