Combined thiazolidinedione-insulin therapy: should we be concerned about safety?

Drug Safety : an International Journal of Medical Toxicology and Drug Experience
André Scheen

Abstract

Thiazolidinediones, also called glitazones, are insulin sensitisers that act as agonists of the peroxisome proliferator-activated receptors-gamma (PPARgamma). After the withdrawal of troglitazone due to hepatotoxicity, only pioglitazone and rosiglitazone can be used for treating patients with type 2 diabetes mellitus, either as monotherapy or in combination with metformin or with sulphonylureas (or glinides). The combination of glitazones with insulin is also appealing, as it allows improvement of glycaemic control while decreasing the daily insulin requirement. Insulin dosage has to be adjusted regularly to avoid hypoglycaemic episodes. However, some concerns have been raised about such combined glitazone-insulin therapy because it may favour weight gain due to both enhanced adipogenesis and fluid retention. Such adverse effects are commonly observed in all diabetic individuals receiving glitazones, whatever the mode of use, but they appear to be exacerbated in insulin-treated patients. Body fat gain is a major drawback of treatment with adipogenic compounds such as glitazones. However, some evidence suggests that the fat is redistributed in a favourable direction, that is, from visceral to subcutaneous depots, although no lon...Continue Reading

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