SILVER SPRING, MD — Are drugs used to treat overactive bladders a risk factor for development of Type 2 diabetes mellitus (T2DM)?

That was the question explored in a retrospective cohort study of females 18 years or older within the Military Health System from 2006 to 2016. Walter Reed Army Institute of Research, Experimental Therapeutics-led researchers used administrative and claims data to select patients who initiated therapy with tolterodine, fesoterodine, oxybutynin, darifenacin, solifenacin or trospium.

They then followed patients with no documented history of T2DM for the occurrence of diabetes, the end of the study or loss of eligibility. The study team also calculated rates of T2DM for the overall population, by duration of therapy and by individual drugs.

The report in Pharmacoepidemiology & Drug Safety notes that more than 2.6 million antimuscarinic prescriptions were dispensed to 241, 829 female MHS beneficiaries, with a mean age of 62. Results indicate that patients exposed to M3 selective antagonists (i.e., antimuscarinic drugs), had the highest risk of developing T2DM vs. those exposed to nonselective antagonists. 1

The study points out that 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 of the drugs are M3 selective, it adds.

“We found exposure to M3 selective antagonists darifenacin and solifenacin had the highest risk of developing T2DM compared to nonselective antagonist oxybutynin,” the authors conclude. “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.”


  1. Selig DJ, Brown AJ, DeLuca JP, Kress AT, Livezey JR, Oliver TG, Por ED, Thelus Jean R. Risk of Type 2 diabetes mellitus by antimuscarinic agents among adult females receiving care in the military health system. Pharmacoepidemiol Drug Saf. 2020 Dec;29(12):1605-1615. doi: 10.1002/pds.5090. Epub 2020 Sep 8. PMID: 32897626.