Glycaemic and nonglycaemic effects of pioglitazone in triple oral therapy of patients with type 2 diabetes

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To examine pioglitazone as add-on to metformin and insulin secretagogues in patients with type 2 diabetes and inadequate glycaemic control and its effect on glycaemic control, surrogate measures of insulin sensitivity (adiponectin) and β-cell function (proinsulin/insulin) and fluid retention.

Design and setting

Prospective open-label study of 54 patients with type 2 diabetes and HbA1c≥6.5% admitted to outpatient unit at Malmö University Hospital. The patients received 30–45 mg pioglitazone daily during 26 weeks in addition to their existing antidiabetic medication. After 26 weeks, one-third of patients were followed for 3 months without pioglitazone.


HbA1c decreased (7.8 ± 0.9–6.3 ± 0.9%, P < 0.001) with 61% of patients achieving levels <6.5%. However, in the group followed for another 3 months HbA1c increased (6.1 ± 0.73–7.1 ± 0.9, n = 18, P < 0.001) after pioglitazone withdrawal. Adiponectin increased (6.1 ± 2.8–13.2 ±5.8 μg mL−1, P < 0.001) and the proinsulin to insulin ratio decreased (0.89 ± 0.66–0.66 ± 0.53, P < 0.001). Nt-proBNP increased from 487.3 ± 252.2 to 657.8 ± 392.1 pmol L−1 (P < 0.001).


Pioglitazone is effective in achieving glycaemic targets and reducing risk factors involved in atherosclerosis and improving β-cell function when used as part of triple oral therapy in patients with type 2 diabetes and secondary drug failure. Nt-proBNP increase with concomitant decrease in haemoglobin suggests a subclinical sign of fluid retention.

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