Diabetes and cancer – not again?

In 2010, the medical press was full of stories concerning a link between the long-acting insulin analogue, glargine, and various forms of cancer. A year later, the French authorities banned pioglitazone, on the basis that it might increase the risk of bladder cancer. Although neither of these links have been substantiated (and both agents remain part of NICE guidance in the UK), the spectre of increased cancer risk has now fallen on a novel diabetes pipeline agent, threatening to slow its launch.

Dapagliflozin is the first in class of specific sodium-glucose transporter (SGLT-2) inhibitors, a group of drugs which improve glycaemia by inhibiting glucose reabsorption in the kidney. As a result, there is increased glucose loss in the urine (glycosuria) and, via urinary enhanced calorie loss, weight reduction in the order of 2-3Kg. These effects, from a once daily oral medication, with the potential for use with insulin (and hence in type 1 diabetes) are an attractive therapeutic option.

Unfortunately, pooled data from early phase clinical trials show an ‘imbalance’ in risk for bladder and breast cancer. Although these differences are non-significant, have no plausible biological basis, were not seen in animal studies and did not result in an overall increase in trial cancer outcomes (which were identical), the FDA requires more data and licensing will be delayed, in the US at least.
Whilst safety vigilance is essential, there is a real possibility that all of the large on-going cardiovascular trials for new diabetes medications could show a statistical ‘imbalance’ in one of the many parameters being assessed. How to manage this is a major challenge for the licensing authorities…

Professor Steve Bain