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Research develops new treatment for type 2 diabetes



New drugs to treat type 2 diabetes may soon become available which are safer and more effective, with reduced side effects and the need for insulin injections, research has revealed.

New drugs to treat type 2 diabetes may soon become available which are safer and more effective, with reduced side effects and the need for insulin injections, research has revealed.

Two studies led by the University of Adelaide, published in the Journal of Medicinal Chemistry and BBA-General Subjects, have shown for the first time how the new potential anti-diabetic drugs interact with patients.

Type 2 diabetes is currently treated with Metformin, insulin injections, improved diet and exercise, and monitoring blood glucose levels.

These new drugs have a completely different action than Metformin, the most commonly prescribed anti-diabetic, which acts on the liver to reduce glucose production.

They target a protein receptor known as PPARgamma found in fat tissue throughout the body, and either fully or partially activate it in order to lower blood sugar by increasing sensitivity to insulin and changing the metabolism of fat and sugar. This tactic is thought to be more effective.

‘People with severe diabetes need to take insulin but having to inject this can be problematic, and it’s difficult to get insulin levels just right. It’s highly desirable for people to come off insulin injections and instead use oral therapeutics,’ said lead researcher Dr John Bruning.

‘A major finding of this study was being able to show which regions of the drug are most important for interacting with the PPARgamma receptor,’ he said.

‘This means we now have the information to design modified drugs which will work even more efficiently.’

The first study, in collaboration with The Scripps Research Institute in Florida, examined 14 different versions of a drug which partially activates PPARgamma. Partial activation can have the benefit of fewer side-effects than full activation.The original drug, INT131, is currently being tested in clinical trials in the US.

The second study, in collaboration with Flinders University, also in Adelaide, used x-ray crystallography to demonstrate for the first time exactly how another potential new drug, rivoglitazone, binds with the PPARgamma receptor. Rivoglitazone fully activates PPARgamma but has less side effects than others with this mode of action.

‘Showing how this compound interacts with its target is a key step towards being able to design new therapeutics with higher efficiencies and less side-effects,’ said lead author Dr Rajapaksha.

‘Lack of structural information was hampering determination of the precise mechanisms involved.’