Factors associated with the effect-size of thiazolidinedione (TZD) therapy on HbA_1c:a meta-analysis of published randomized clinical trials

ABSTRACT

Objective: To examine factors affecting the size of the HbA^1c response to thiazolidinedione (TZD) therapy.

Research design and methods: Meta-analysis of randomized TZD controlled trials which were identified using PubMed, EBSCO and Sci-lit databases and were published in English. Sociodemographic and clinical data were extracted from each trial. HbA_1c effect size was defined as either a placebo-subtracted change in HbA_1c or a change in HbA_1c from baseline. Weighted multivariable regression was used to examine factors associated with changes in HbA_1c. Bootstrapped smearing estimates were computed to obtain reliable estimates of HbA_1c effect size.

Results: Forty-two trials yielded 60 trial arms which represented 8322 patients treated with thiazolidinediones. Weighted placebo-subtracted change in HbA_1c was –0.99% ± 0.02% with an average baseline HbA_1c of 9.1% ± 1.0%. Weighted bootstrapped smearing estimate of the placebo-subtracted change in HbA_1c was –1.02% ± 0.004%. After controlling for other variables, the baseline HbA_1c level had a significant negative association with placebo-subtracted HbA_1c change ( p = 0.004) and also with change in HbA_1c from baseline ( p = 0.002). Longer trial duration was associated with greater placebo-subtracted HbA_1c change ( p = 0.01) but not with the change in HbA_1c from baseline. The multivariable models explained 72% of the variation in placebo-subtracted HbA_1c change. It was not possible to estimate effects of the run-in period and obesity on TZD effect size.

Conclusion: Baseline HbA_1c and trial duration significantly impacted the effect size of TZD therapy on HbA_1c. Age, gender, duration of diabetes and prior use of anti-diabetic therapy were not associated with the TZD effect size.

Key words: :

• Baseline HbA1c
• Effect-size
• Placebo-subtracted change in HbA1c
• Thiazolidinediones