Combining pioglitazone with a sulphonylurea or metformin in the management of type 2 diabetes

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Abstract
Evidence suggests that strict control of both fasting and postprandial hyperglycaemia is essential to prevent chronic progression of diabetes and its complications. The UKPDS authors concluded that this goal may be achieved by using combination therapy rather than monotherapy after failure of dietary and lifestyle changes. This paper focuses on the role of pioglitazone in combination with other oral antihyperglycaemic agents in the treatment of type 2 diabetes. New long-term data from an interim analysis with respect to efficacy and safety of these combinations are also discussed. Sulphonylureas (SUs) are suitable for combination with pioglitazone based on their complementary mechanisms of action, while adding pioglitazone to metformin provides a useful synergistic combination when glucose levels are insufficiently controlled with monotherapy. Long-term combination therapy for up to 40 weeks with pioglitazone and an SU or metformin resulted in continued metabolic improvement. As an important adjunctive effect of pioglitazone combination therapy, a sustained improvement in the lipid profile was reported. Pioglitazone, in combination with either an SU or metformin, thus enhances glycaemic control and favourably affects the lipid profile in patients with type 2 diabetes. All effects are maintained over the long term. Combination therapy with an SU or metformin was well tolerated and did not show any drug-related hepatotoxicity. The continued improvement in glycaemic control was associated with weight gain of 3-4 kg over the 40-week study period.

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