Purpose: To explore patterns of antimuscarinic medication as a risk factor for type 2 diabetes mellitus (T2DM).
Methods: This is a retrospective cohort study of females 18 years or older within the Military Health System from 2006 to 2016. Administrative and claims data were used to select patients who initiated therapy with tolterodine, fesoterodine, oxybutynin, darifenacin, solifenacin, or trospium. Patients with no documented history of T2DM were followed for the occurrence of T2DM, the end of the study or loss of eligibility. Rates of T2DM were calculated for the overall population, by duration of therapy and by individual drugs. Crude and adjusted Cox proportional hazards were calculated to assess differences by duration of use and specific muscarinic antagonist.
Results: Over 2.6 million antimuscarinic prescriptions were dispensed to 241 829 females (mean age/SD, 62 ± 18 years). Patients exposed to M3 selective antagonists had highest risk of developing T2DM compared to those exposed to nonselective antagonists. Using oxybutynin, a nonselective antagonist as a comparator, adjusted rate ratios of T2DM were 57% (HR 1.57, 95%CI 1.48-1.67) and 29% (HR 1.29, 95%CI 1.24-1.35) significantly higher for darifenacin and solifenacin, respectively (both M3 selective).
Conclusions: We found exposure to M3 selective antagonists darifenacin and solifenacin had the highest risk of developing T2DM compared to nonselective antagonist oxybutynin. This is supported by well described physiologic mechanisms and may allow for more informed prescribing decisions, particularly if minimizing risk of T2DM is a priority.
Keywords: darifenacin; diabetes mellitus type 2; muscarinic antagonists; oxybutynin; pharmacoepidemiology; tolterodine.
Published 2020. This article is a U.S. Government work and is in the public domain in the USA.