Pioglitazone and cardiovascular outcomes in patients with insulin resistance, pre-diabetes and type 2 diabetes: a systematic review and meta-analysis

Objectives

To evaluate the effect of pioglitazone in people with insulin resistance, pre-diabetes and type 2 diabetes.

Design and setting

Systematic review and meta-analysis of randomised, controlled trials.

Data sources

Literature searches were performed across PubMed, EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials from 1966 to May 2016 to identify randomised, controlled trials with more than 1 year follow-up.

Outcome measures

Relative risk (RR) with 95% CI was used to evaluate the association between pioglitazone and the risk of major adverse cardiovascular events (MACE: composite of non-fatal myocardial infarction, non-fatal stroke and cardiovascular death) and safety outcomes, after pooling data across trials in a fixed-effects model.

Results

Nine trials with 12 026 participants were enrolled in the current meta-analysis. Pioglitazone therapy was associated with a lower risk of MACE in patients with pre-diabetes or insulin resistance (RR 0.77, 95% CI 0.64 to 0.93), and diabetes (RR 0.83, 95% CI 0.72 to 0.97). Risks of heart failure (RR 1.32; CI 1.14 to 1.54), bone fracture (RR 1.52, 95% CI 1.17 to 1.99), oedema (RR, 1.63; CI 1.52 to 1.75) and weight gain (RR 1.60; CI 1.50 to 1.72) increased in pioglitazone group.

Conclusions

Pioglitazone was associated with reduced risk of MACE in people with insulin resistance, pre-diabetes and diabetes mellitus. However, the risks of heart failure, bone fracture, oedema and weight gain were increased.

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