Adding one daily tablet of Servier’s Preterax to usual care of type-2 diabetes could save 1.5 million lives worldwide over five years.

This was the claim of investigators of ADVANCE, the largest-ever study of treatment diabetes complications, reported at the European Society of Cardiology congress in Vienna. Preterax is a fixed-dose combination of two blood-pressure lowering drugs—Servier’s ACE inhibitor Coversyl (perindopril) and the diuretic Natrilix (indapamide)—and is marketed in 97 countries worldwide, also under the brand names Predonium, Coversyl Plus, Biprel, Prelectal, Noriplex and Noliprel.

Investigator-led and funded by Servier and the National Health and Medical Research Council of Australia, ADVANCE randomised over 11,000 patients from 20 countries to Preterax plus usual treatment or usual treatment alone. After an average of 4.3 years, treatment with Preterax significantly reduced the relative risk of death from any cause by 14%, largely driven by an 18% fall in the relative risk of cardiovascular death. Coronary heart disease also fell by 14% and kidney disease by 21%.

Presenting the results, principal investigator Stephen MacMahon of the George Institute for International Health, Australia, said: “We saw similar benefits in patients with and without high blood pressure, and in those receiving a variety of treatments including ACE inhibitors, statins and aspirin. Finally, these benefits were achieved in a population with very good control of risk factors as recommended by many clinical guidelines. So benefits [from Preterax] were additional to all those provided by usual treatment.”

Previous clinical trials had highlighted the importance of treating high blood pressure in people with type-2 diabetes but until ADVANCE it was unclear that the benefits also applied to the many people with the disease who do not have high blood pressure.

Profe MacMahon stressed that, as in any clinical study, the balance between risk and benefit in ADVANCE relates solely to Preterax. Interviewed by PharmaTimes World News in Vienna, Prof MacMahon was also confident that, although final cost-effectiveness data are yet to be analysed, Preterax will be affordable not only in high-income countries, but also in middle-income areas that will bear the brunt of the global type-2 diabetes epidemic over the next 20 years.

So Servier has cause to celebrate results of ADVANCE, especially as it builds on positive results for Coversyl in previous studies such as PROGRESS, PREAMI and EUROPA. However, healthcare purchasers may well heed the views of sceptics such as noted clinical triallist Dr Norman Kaplan of the University of Texas Southwestern Medical Center, Dallas, USA.

In a comment that accompanied ADVANCE’s online publication in The Lancet, Dr Kaplan highlighted the price difference between Coversyl and generic ACE inhibitors, and reiterated the view shared by many experts: “in most circumstances, lowering blood pressure is what counts, not the way by which it is lowered”. By Sue Lyon in Vienna