Topiramate and Type 2 diabetes: an old wine in a new bottle

Abstract

Topiramate, a marketed antiepileptic drug, has been used to treat seizures and allied neurological problems since 1999. Recently, a series of newer findings for the use of topiramate have cropped up, which include Type 2 diabetes and obesity. In a series of clinical studies, a subset of neurological patients with Type 2 diabetes mellitus (T2DM) serendipitously showed better glycaemic control when treated with topiramate. It has since been demonstrated that topiramate can act both as an insulin secretagogue and sensitiser in T2DM animal models. Pathogenesis of Type 2 diabetes involves both β-cell dysfunction and insulin resistance. Therefore, an agent that has dual action (insulin secretagougue and sensitisation) is preferred for T2DM. Topiramate seems to act through multiple mechanisms to ameliorate diabetic symptoms, some of them unknown. Hence, it becomes imperative to discuss its probable modes of action. Topiramate raises new hope as an antidiabetic agent or a potential new chemotype with a better safety profile for the treatment of T2DM.

Keywords::

• adenosine-5-monophosphase-activated protein kinase
• adiponectin
• diabetes
• insulin secretagogue
• insulin sensitiser
• obesity
• topiramate

Acknowledgements

We gratefully acknowledge the support given by Pradip Kumar Bhatnagar, Senior Vice-President, NDDR, Ranbaxy Research Laboratories and Abhijit Ray, Director of Pharmacology for their support and encouragement. We also acknowledge the inputs given by Suchitra Sharma on AMPK.