Pioglitazone use associated with reduced mortality risk, cohort analysis finds

The study did not find any consistent trend in mortality risk with increasing duration or dose, and the effect of pioglitazone on mortality was significantly modified by history of diabetes complications, chronic kidney disease, and macrovascular disease.


Patients with type 2 diabetes who took pioglitazone had reduced risk of mortality, according to a new European database study.

The cohort analysis used pooled health and mortality data from Finland, Sweden, and the United Kingdom. Researchers matched 31,133 patients with type 2 diabetes who were first prescribed pioglitazone between 2000 and 2011 to 31,133 patients who were never prescribed pioglitazone. They were matched by propensity score as well as the exact variables of treatment stage; history of diabetes, diabetes complications, and cardiovascular disease; and year of cohort entry. Mean follow-up was more than two years in both groups. Results were published by BMJ Open Diabetes Research & Care on Jan. 20.

The crude and adjusted mortality rates were lower in the pioglitazone group than in the no-pioglitazone patients. Adjusted hazard ratios in patients taking pioglitazone rather than any alternative diabetes medication were 0.58 (95% CI, 0.52 to 0.63) for cardiovascular mortality and 0.63 (95% CI, 0.58 to 0.68) for noncardiovascular mortality. A significant protective effect from pioglitazone was also found for specific cardiovascular causes of mortality, including myocardial infarction, stroke, and heart failure.

The study did not find any consistent trend in mortality risk with increasing duration or dose of pioglitazone. The effect of pioglitazone on both cardiovascular and noncardiovascular mortality was significantly modified by history of diabetes complications, chronic kidney disease, and macrovascular disease; a weaker risk reduction was seen in patients with a history of any of these conditions. The study authors noted several possible mechanisms for the observed benefit of pioglitazone, including reduced insulin resistance, decreased hyperglycemia, fat redistribution, renoprotection, and improved liver function.

Strengths of the study included the large number of patients, the long follow-up period (up to 10 years), and multiple efforts to reduce potential biases, the authors said. However, it also had a number of limitations, particularly the risk of confounding from its observational design. “Results should be interpreted with caution due to the potential for residual confounding in this exploratory analysis. Further studies, specifically designed to test the association between pioglitazone use and patient-focused outcomes, are suggested,” the authors concluded.