Pioglitazone was not found to be associated with a statistically significant increased risk of bladder cancer or 8 of 10 additional cancers in a recent study.
In a large, long-term study, researchers analyzed pioglitazone use and associated risks of the following cancers: bladder, prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma, pancreas, kidney/renal pelvis, rectum, and melanoma. Results were published on July 21 by the Journal of the American Medical Association.
Of 193,099 people studied, 34,181 (18%) received pioglitazone and 1,261 had incident bladder cancer. Crude incidences of bladder cancer in users and nonusers were 89.8 and 75.9 per 100,000 person-years, respectively, and ever having taken pioglitazone was not associated with bladder cancer risk (adjusted hazard ratio [HR], 1.06; 95% CI, 0.89 to 1.26). However, the study cannot exclude up to a 54% increased risk of bladder cancer, the authors noted.
Use of other diabetes medications, such as metformin, sulfonylureas, insulin, and other thiazolidinediones, was also not significantly associated with bladder cancer risk, with adjusted HRs ranging from 0.91 to 1.09, according to the study.
Although use of pioglitazone was not associated with 8 of 10 additional cancers in adjusted analyses of 236,507 people (HRs ranged from 0.81 to 1.15), use of the medication was associated with increased risk of prostate cancer (HR, 1.13; 95% CI, 1.02 to 1.26) and pancreatic cancer (HR, 1.41; 95% CI, 1.16 to 1.71). Crude incidences of the cancers in pioglitazone users and nonusers were 453.3 versus 449.3 for prostate and 81.1 versus 48.4 for pancreatic per 100,000 person-years. "The increased prostate and pancreatic cancer risks associated with ever use of pioglitazone merit further investigation to assess whether they are causal or are due to chance, residual confounding, or reverse causality," the study authors wrote.
Use of insulin was associated with a decreased risk of prostate cancer (HR, 0.90; 95% CI, 0.81 to 0.99). Use of metformin (HR, 1.21; 95% CI, 1.02 to 1.43), insulin (HR, 2.34; 95% CI, 1.97 to 2.78), and sulfonylureas (HR, 1.49; 95% CI, 1.22 to 1.81) and never having 2 prescriptions of a diabetes medication from the same class within 6 months (HR, 1.55; 95% CI, 1.02 to 2.36) were each associated with increased risk of pancreatic cancer. The fact that other diabetes medications were also associated with an increased risk of pancreatic cancer suggests reverse causality because hyperglycemia is an early manifestation of the cancer, the authors wrote.
The researchers noted that their observational study has potential for unmeasured confounding; has limited statistical power for subgroup analyses related to time since initiation, dose, and duration; and could not exclude all patients with type 1 diabetes (although they minimized this by excluding those under 40).