Mike Cawthorne proposes radical rethink of diabetes treatment

23 January 2009

Mike Cawthorne, Director of Metabolic Research at the Clore Laboratory, gave a talk entitled ‘Glitazones revisited’ to diabetes healthcare professionals at the 10th National Diabetes Conference: The Diabetes Epidemic held in London on 22-23 January 2009.

Quoting from a talk presented by FDA staff member Karen Mahoney at the American Diabetes Association annual meeting in 2008, he concluded that there was an increased risk of heart failure with thiazolidinediones, which was universally acknowledged. However, the early report based on small-scale trials and relatively short-term studies of increased myocardial ischaemic events was not borne out in larger longer-term studies, although it was not possible to exclude an increased risk.

Mike agreed with the proposal put forward by Ralph De Fronzo in his Banting Lecture that there was a need for a radical review of diabetes treatment paradigms focusing on pathophysiological events of which the most important was prevention of pancreatic β-cell failure. Glitazones were the only proven treatment to reduce β-cell failure probably via a sparing action through improved insulin sensitivity. GLP-1 analogues potentially have a more direct effect to stimulate islet cell neogenesis, but this is not yet proven in man. Thus, the likely most effective treatment to reduce β-cell failure at present was a combination of a glitazone insulin sensitiser, such as rosiglitazone or pioglitazone, and GLP-1 analogue such as exendin-4. The further addition of metformin could have additional benefits.