It’s hard to miss all the ads for the diabetes medications called incretin drugs (you probably know them better as Januvia, Trulicity and Victoza, among others). They promise better blood sugar control, but they may come at a potentially steep price—cancer.
Incretins are naturally occurring hormones produced in the gut in response to food. They help stimulate the production of insulin and lower blood sugar. For people with type 2 diabetes, incretin diabetes medications enhance the action of these hormones. One type of incretin drug, glucagon-like peptide-1 (GLP-1) receptor agonists such as liraglutide (Victoza) and dulaglutide (Trulicity), directly stimulate the production of these hormones. Another type, dipeptidyl peptidase-4 (DPP-4) inhibitors including sitagliptin (Januvia) and saxagliptin (Onglyza), prolong the hormones’ effects.
Although these drugs benefit many people with type 2 diabetes, two early studies have suggested that they may increase the risk for a serious bile duct cancer called cholangiocarcinoma. An international team of researchers collaborated on a new, larger study to learn more about this risk—how common the bile duct cancers are among people on diabetes drugs and whether patients on incretin drugs were at higher risk for them than patients on other types of diabetes medications.
They used the Clinical Practice Research Datalink from the UK to follow more than 150,000 type 2 diabetes patients, ages 40 and over, for five years on average. Patients in the study were being treated with a DPP-4 inhibitor (21%), a GLP-1 agonist (4%) or one of seven other drugs, including insulin. (Patients with existing risk factors for bile duct cancer, such as HIV/AIDS or any gall bladder or liver disease, were excluded.)
Over the course of the study, 105 cases of bile duct cancer were diagnosed. Patients taking either a DPP-4 or a GLP-1 had double the risk for bile duct cancer compared with patients taking other drugs. However, because so few patients were taking a GLP-1 drug, the findings are not considered as significant as those for the DPP-4 drug. The overall risk for bile duct cancer was still very low—well under 1%, but because bile duct cancer is a disease with a high fatality rate, the researchers concluded that alerting the public and the medical community to the risk is important, along with urging more research.
Two possible causes are suspected for the increased cancer risk. Incretin drugs may stimulate overproduction of bile duct cells, which may start to grow out of control. Incretins also increase the risk for gallstones and inflammation, which may, in turn, increase the cancer risk.
If you’re on an incretin drug or your doctor suggests starting one, have a discussion about all the risks and benefits. Along with lifestyle changes, there are many other treatment options for type 2 diabetes. Especially if you’re already at higher risk for bile duct cancer because of a history of gall bladder or liver disease, an alternative to these drugs may be better for you.