Incretins and cancer of the bile duct in type 2 diabetes

Is this issue of The BMJ, Abrahami and colleagues (doi:10.1136/bmj.k4880) report that use of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists (collectively called incretins) “might be associated with an increased risk of cholangiocarcinoma in adults with type 2 diabetes.”1 If incretins are associated only indirectly with cholangiocarcinoma, people with diabetes would not have a problem. The issue for patients, doctors, and regulators is establishing for certain whether these drugs cause cholangiocarcinoma, a conclusion that this single observational study cannot support.

Abrahami and colleagues’ well executed pharmacoepidemiological study shows that people who take incretins have higher rates of cholangiocarcinoma than people who do not take incretins. One possibility is that non-incretin treatments prevent cholangiocarcinoma—an interpretation the authors discount. Another possibility is that incretins cause cholangiocarcinoma. Concluding this from an observational study (even a good one) might be like concluding that hospitals cause people to die—while knowing …