Pioglitazone for type 2 diabetes mellitus

Although pioglitazone appears to improve glycaemic control compared to placebo, there is only little evidence on benefit for patient-oriented outcomes. Pioglitazone is associated with an increase in heart failure, and its risk-benefit ratio remains unclear.

A Cochrane review included 22 studies with a total of 6200 subjects. Published studies of at least 24 weeks pioglitazone treatment in people with type 2 diabetes mellitus did not provide convincing evidence that patient-oriented outcomes like mortality, morbidity, adverse effects, costs and health-related quality of life are positively influenced by this compound. Metabolic control measured by HbA1c as a surrogate endpoint did not demonstrate clinically relevant differences to other oral antidiabetic drugs. Occurrence of oedema was significantly raised. The results of the single trial with relevant clinical endpoints (Prospective Pioglitazone Clinical Trial In Macrovascular Events - PROactive study) have to be regarded as hypothesis-generating and need confirmation. In the latter, the primary composite endpoint (time from randomisation to all-cause mortality, non-fatal myocardial infarction (including silent myocardial infarction), stroke, acute coronary syndrome, endovascular or surgical intervention on the coronary or leg arteries, or amputation above the ankle) did not show statistically significant differences between the pioglitazone and placebo group: The hazard ratio (HR) was 0.90 (95% CI 0.80 to 1.02, P=0.095). Of all secondary endpoints only the so-called "main" secondary endpoint (time to the first event of the composite endpoint of death from any cause, myocardial infarction (excluding silent myocardial infarction) and stroke) indicated a statistical significant difference between pioglitazone and placebo (HR 0.84 (95% CI 0.72 to 0.98, P=0.027)). HbA1c decreased significantly by 0.8% in the pioglitazone and 0.3% in the placebo group and levels of high-density lipoprotein cholesterol increased significantly by 19% and 10%, respectively. The median change in blood pressure was 3 mm Hg versus 0 mm Hg for pioglitazone compared to placebo (P = 0.03). Significantly more patients developed oedema and heart failure, including heart failure needing hospital admission, following administration of pioglitazone (6% versus 4% on placebo).

Comment: The quality of evidence is downgraded by indirectness (sparse data on patient-oriented outcomes).

Ədəbiyyat

1. Richter B, Bandeira-Echtler E, Bergerhoff K, Clar C, Ebrahim SH. Pioglitazone for type 2 diabetes mellitus. Cochrane Database Syst Rev 2006 Oct 18;(4):CD006060.