According to the PERISCOPE study, Takeda’s Actos (pioglitazone), but not Sanofi Aventis' Amaryl (glimepiride), stops continuing build-up of plaque in the arteries of patients with diabetes. Results of PERISCOPE were presented yesterday at the American College of Cardiology Annual Scientific Meeting in Chicago and published online in the Journal of the American Medical Association.

PERISCOPE randomised 543 patients with type-2 diabetes and coronary heart disease to 18 months treatment with either Actos or Amaryl, increased to maximum tolerated dosage. The primary endpoint was the rate of progression of plaque as measured by intravascular ultrasonography. At the end of the study, plaque had not progressed in patients treated with Actos, compared with a highly significant progression in those receiving Amaryl (-0.16% versus +0.73%).

There were also major differences in favour of Actos in important biochemical measures, including levels of HDL or ‘good’ cholesterol, triglycerides and C-reactive protein (both indicators of cardiovascular risk). Side-effects occurred in both groups: patients randomised to Amaryl were more likely to experience episodes of low blood sugar (hypoglycaemia) or angina, while more patients treated with Actos had oedema and fractures.

Both Actos and Amaryl help to control blood sugar, a key aim of diabetes treatment, but PERISCOPE is the first study to show that a diabetes treatment can prevent progression of atherosclerosis. This could have important implications for prescribing, because atherosclerosis is especially aggressive in people with diabetes, and until now there has been no reason to choose one anti-diabetic treatment to potentially reduce risk of coronary heart disease, the leading cause of death in people with diabetes.

Actos is a thiazolidinedione, a class of drug that acts by increasing the body's sensitivity to insulin, but PERISCOPE is unlikely to boost prescribing of the other available thiazolidinedione, GlaxoSmithKline's Avandia (rosiglitazone). PERISCOPE's lead investigator Dr Stephen Nissen of the Cleveland Clinic, USA, has played a major role in highlighting cardiovascular problems associated with Avandia, and in Chicago was keen to highlight important differences between the two drugs. “Rosiglitazone and pioglitazone are technically the same class and both lower blood glucose, but they otherwise have extraordinarily different effects. Pioglitazone seems to have a constellation of effects that produce benefit, while rosiglitazone clearly produces harm,” he concluded. By Sue Lyon in Chicago