OBJECTIVE-: Thiazolidinediones are known to increase the risk of heart failure in patients with type 2 diabetes. We aimed to evaluate the magnitude of the risk of heart failure with thiazolidinediones and classify this adverse effect under the novel Dose-Time-Susceptibility system.

RESEARCH DESIGN AND METHODS-: Evidence from randomized trials, controlled observational studies, anecdotal case reports, case-series and spontaneous reports in the Canadian Adverse Events Database (CADRMP) were analyzed in a teleo-analysis.

RESULTS-: Random effects meta-analysis of 3 randomized controlled trials showed an odds ratio of 2.1 (95% CI: 1.08 -- 4.08; p = 0.03) for the risk of heart failure in patients randomized to thiazolidinediones compared to placebo. 4 observational studies, revealed an odds ratio of 1.55 (95% CI: 1.33 -- 1.80; p <0.00001) for heart failure with thiazolidinediones. A Dose-Time-Susceptibility analysis of 28 published reports, and 214 spontaneous reports from the CADRMP database showed that heart failure was more likely to occur after several months, with median treatment duration of 24 weeks after initiation of therapy. Heart failure occurred equally at high and low doses. The adverse reaction was not limited to the elderly, with 42/162 (26%) of the reported cases occurring in patients below the age of 60 years.

CONCLUSIONS-: Our teleo-analysis confirms the increased magnitude of the risk of heart failure with thiazolidinediones. We estimate the Number-Needed-to-Harm with thiazolidinediones to be around 50 over 2.2 years. Existing guidelines and package inserts may have to be revised to incorporate these risk-characteristics of thiazolidinediones.