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Meta-Analysis
. 2017 Jan 5;7(1):e013927.
doi: 10.1136/bmjopen-2016-013927.

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

Hung-Wei Liao  1 , Jeffrey L Saver  2 , Yi-Ling Wu  3 , Tso-Hsiao Chen  4 , Meng Lee  5 , Bruce Ovbiagele  6
Affiliations
Meta-Analysis

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

Hung-Wei Liao et al. BMJ Open. .

Abstract

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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Conflict of interest statement

Conflicts of Interest: None declared.

Figures

Figure 1
Figure 1
Separate and pooled relative risk and 95% CIs estimates for cardiovascular outcomes among patients with pre-diabetes or insulin resistance (pioglitazone vs control).
Figure 2
Figure 2
Trial sequential analysis for (A) MACE, (B) myocardial infarction, (C) stroke, among patients with pre-diabetes or insulin resistance. (A) A full blue cumulative Z-curve did not cross the required information size boundary but did cross boundary for benefit. (B) and (C) the required information size has not been reached and none of the boundaries for benefit, harm or futility has been crossed. MACE, major adverse cardiovascular events.
Figure 3
Figure 3
Separate and pooled relative risk and 95% CIs estimates for cardiovascular outcomes among patients with type 2 diabetes mellitus (pioglitazone vs control).
Figure 4
Figure 4
Trial sequential analysis for (A) MACE, (B) myocardial infarction, (C) stroke, among patients with diabetes mellitus. (A), (B) and (C): the required information size has not been reached and none of the boundaries for benefit, harm or futility has been crossed. MACE, major adverse cardiovascular events.
Figure 5
Figure 5
Separate and pooled relative risk and 95% CIs estimates for safety outcomes among all included trials (pioglitazone vs control).
See this image and copyright information in PMC

References

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