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Common treatment for type 2 diabetes associated with rare, aggressive cance
A large-scale population based cohort study has revealed an association between incretin-based drugs used to treat type 2 diabetes and cholangiocarcinoma, an extremely rare, but highly fatal cancer of the bile duct. The study was led by Dr. Laurent Azoulay, senior investigator with the Lady Davis Institute at the Jewish General Hospital, and published in The BMJ.

“This study was conducted in part because of imbalances of this cancer observed in some of the previous large trials of incretin-base drugs, and the potential effect of glucagon-like peptide-1 (GLP-1) on cholangiocytes, the cells that line the bile duct,” reports Dr. Azoulay, an Associate Professor in the Department of Epidemiology, Biostatistics, and Occupational Health and Gerald Bronfman Department of Oncology at McGill University. “Our study provides important information that can be useful when assessing the risk-benefit profile of these drugs.”

There are two types of incretin-based drugs: dipeptidyl peptidase-4 (DPP-4) inhibitors and GLP-1 receptor agonists. These drugs have proven to be highly effective in treating type 2 diabetes. Large trials have shown that these drugs can be cardio-protective and help with weight loss, both of which are important for individuals with type 2 diabetes. However, their long-term association with important potential adverse events such as cancer requires further study.

Using the UK Clinical Practice Research Datalink, one of the world’s most extensive sources of health care data, Dr. Azoulay and his team observed 105 cases of cholangiocarcinoma among more than 154,000 adults treated with anti-diabetic drugs over the ten-year period since the incretin-based drugs were first introduced. Dr. Azoulay’s study reveals that DPP-4 inhibitors are significantly associated with a 77% increased risk of this cancer. An association of similar magnitude was observed with GLP-1 receptor agonists, but this analysis did not achieve statistical significance.

“All incretin-based drugs are associated with an increase in GLP-1 levels, which we believe is the main mechanism responsible for this association. Normally GLP-1 is in the system for a matter of minutes during digestion. However, for those taking these drugs, GLP-1 remains active for hours,” reports Devin Abrahami, lead author and doctoral student working with Dr. Azoulay. “Fortunately cholangiocarcinoma is a rare cancer, but studies such as this one provide important insight on the effects of these drugs on various tissues.”

As this is the first study of its kind, the authors assert that further research is needed to replicate their findings. This would include a more thorough analysis of previous large incretin-based drug trials and additional observational studies.

For further information or to arrange interviews with Dr. Azoulay, contact:
Tod Hoffman
Research Communications Officer
Lady Davis Institute at the Jewish General Hospital
Office: 514-340-8222, ext. 28661
tod.hoffman@ladydavis.ca

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