The addition of pioglitazone in type 2 diabetics poorly controlled on insulin therapy: a meta-analysis

To quantify the effect of a pioglitazone on glycemic control and lipid parameters, as well as the risk of adverse events when incorporated into the treatment regimen of patients with type 2 diabetes inadequately controlled on insulin.

The electronic databases PubMed, Embase and The Cochrane Library were searched systematically to identify randomized controlled trials (RCTs) of pioglitazone therapy in patients with type 2 diabetes mellitus (DM) inadequately controlled after treatment with insulin. Data on change of haemoglobin A1C (HbA1c), fasting plasma glucose (FPG), lipid parameters and risk of hypoglycemic, edema events were extracted from each study and pooled according to fixed effect model or random effect model in meta-analyses.

Four RCTs including 1767 patients were included. The pooled estimate of change in HbA1c from baseline was 1.22% (95% CI 1.01-1.44, p<0.001 vs. baseline) and of change in FPG from baseline was 1.63 mmol/l (95% CI 0.75-2.50, p<0.001 vs. baseline). Pioglitazone significantly increased high-density lipoprotein cholesterol (HDL-c) level (0.2 mmol/L, 95%CI: 0.13-0.28) and low-density lipoprotein cholesterol (LDL-c) level (0.10 mol/L, 95%CI: 0.09-0.17), and lowered triglyceride (TG) level (0.05 mmol/L, 95%CI: 0.01-0.09). The odds of experiencing a hypoglycemic event in pioglitazone-treated arms was significantly higher than comparator treatments (RR=1.57, 95% CI 1.12-2.20, p<0.001). The case was the same with edema (RR=2.42, 95% CI 1.67-3.50, p<0.001).

Our study implied that in patients with type 2 DM whose control is inadequate on insulin therapy, the additional pioglitazone could significantly improve glucose metabolism and might have a positive effect on important components of the lipid profile, which may have important implications in reducing the risk of cardiovascular disease, a major long-term complication in type 2 diabetes mellitus. Besides, the adverse events (AEs) were well tolerated.