GSK's Avandia (rosiglitazone) reduces the risk of developing type 2 diabetes by 62% compared to placebo in patients with pre-diabetes, according to the largest-ever diabetes prevention trial, DREAM. Furthermore, patients taking Avandia were around 70% more likely than those taking placebo to return to normal blood sugar levels. The results of DREAM were announced on 15 September at the 42nd Annual Meeting of the European Association for the Study of Diabetes in Copenhagen, and were published online in The Lancet and the New England Journal of Medicine.
DREAM also compared placebo with Sanofi-Aventis and King Pharmaceuticals' Altace (ramipril). The results for Altace were disappointing compared to the impressive results outcomes with Avandia, since there was no significant difference between Altace and placebo in the incidence of diabetes or death. However, Altace did significantly increase the chance of regression to normal blood sugars - an important consolation prize as doctors will be more likely to choose the drug when treating high blood pressure in patients at risk of developing diabetes.
Both Merck's Glucophage (metformin) and Bayer's Glucobay (acarbose) have also been shown to reduce the risk of diabetes in patients with impaired glucose regulation. The results for Avandia in DREAM were, however, more impressive and equivalent to those in trials involving intensive diet and exercise. Despite this, some important questions remain for GSK.
Compared to placebo, Avandia was more likely to cause weight gain - an important consideration in pre-diabetes patients, who are already likely to be overweight or obese. Furthermore, while both drugs were well tolerated compared to placebo, there were significantly more cases of heart failure in patients taking Avandia (14 versus 2 for placebo). Given the known adverse events of the 'glitazones' and the risk of heart failure demonstrated with Eli Lilly and Takeda's Actos (pioglitazone) in the ProActive trial, this was not unexpected, but will certainly cause concern among regulators as well as potential prescribers.
Finally, while the benefits of diet and exercise are sustained long-term, it is possible that Avandia's effects on diabetes risk may not persist when the patient stops taking the drug. In light of the increased risk of heart failure shown in DREAM and the proven benefits of intensive lifestyle intervention, providers may well be reluctant to reimburse long-term use of Avandia for diabetes prevention.
The Avandia portfolio of drugs is already a significant earner for the firm as GSK's second most-important drug by sales, pulling in £1.3 billion ($2.5 billion) in 2005. And the UK giant is clearly hoping these new data from the DREAM study could open a door to a massive new market in patients with a family history of the disease who are at high risk of developing diabetes. by Sue Lyon