PPARγ Agonistic Activity of Sulphonylureas

Sulphonylureas (SU) are known to cause weight gain. Some investigators have reported increased insulin sensitivity with some sulphonylurea agents.

To review available evidence of SU agents having PPARγ agonist activity.

We searched online databases of PubMed®, Embase®, Google Scholar® and Web of Science® as per current guidance, published in English, between 1st January 1970 and 31st December 2017. The search found 6 articles.

None of the 1st generation SU drugs have any demonstrable PPARγ agonist activity. Most of the 2nd generation SU agents had a positive correlation between their concentration and PPARγ agonist activity except Gliclazide. The demonstrated PPARγ agonist activity was maximum in experiments with Glimepiride and Gliquidone and was seen in these in-vitro experiments at concentrations which were pharmacologically achievable in-vivo. The PPARγ agonist activity may be responsible for some sideeffect of the SU agents as weight gain. On the contrary, the clinical efficacy of the thiazolidinediones could theoretically be reduced when used in combination with the SUs with significant PPARγ agonist activity.

The PPARγ agonist activity demonstrated in vitro experiments may have clinical connotations.