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Evidence summaries

Pioglitazone for Type 2 Diabetes Mellitus

Pioglitazone appears to improve glycaemic control compared to placebo. However, there is only little evidence on benefit for patient-oriented outcomes. Pioglitazone appears to be associated with an increase in heart failure. Level of evidence: "B"

A Cochrane review [Abstract] 1 included 22 studies with a total of 6200 subjects. 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. 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. Significantly more patients developed oedema and heart failure, including heart failure needing hospital admission, following administration of pioglitazone (6% versus 4% on placebo). There were no convincing data that patient-oriented outcomes like mortality, morbidity, adverse effects, costs and health-related quality of life were positively influenced.

A network meta-analysis 2 included 39 RCTs involving 17 860 individuals. Glucagon-like peptide-1 (GLP-1) analogues resulted in greater decrease in HbA1c compared with sulfonylureas, glinides, thiazolidinediones, α-glucosidase inhibitors and DPP-4 inhibitors [-0.20% (95% CI -0.34 to -0.04%), -0.31% (95% CI -0.61 to -0.02%), -0.20% (95% CI -0.38 to -0.00), -0.36% (95% CI -0.64 to -0.07%), -0.32% (95% CI -0.47 to -0.17%), respectively]. Weight increase was seen with sulfonylureas, glinides, thiazolidinediones, basal insulin and biphasic insulin.

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

References

  • 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. [PubMed]
  • Liu SC, Tu YK, Chien MN et al. Effect of antidiabetic agents added to metformin on glycaemic control, hypoglycaemia and weight change in patients with type 2 diabetes: a network meta-analysis. Diabetes Obes Metab 2012;14(9):810-20. [PubMed]

Primary/Secondary Keywords