BMJ Finds No Link Between Incretins and Pancreatic Cancer, but Debate Likely to Continue

If patients with type 2 diabetes (T2D) are confused, it’s no wonder.

This week, BMJ published a study involving more than 970,000 patients, who were followed for an average of 1.3 to 2.8 years, which found those taking incretin-based drugs had no greater risk of pancreatic cancer than those taking sulfonylureas. But the authors included a catch:

While the findings should offer “some reassurance on the safety” of incretins, “this potential adverse drug reaction will need to be monitored long term owing to the latency of the cancer.”

In other words, this study says it’s fine to take incretins to control diabetes, but we’re going to keep watching anyway.

The drugs, which include dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists, have been among the top selling therapies in recent years to control T2D without insulin. Many offer the added benefit of modest weight loss.

However, as the BMJ authors noted, FDA’s adverse events database has found that reporting rates of pancreatic cancer were 2.9 times higher with exenatide and 2.7 times higher with sitagliptin compared with other oral antidiabetic medications.

Meanwhile, concern about incretin mimetics and pancreatic cancer has spilled into the mainstream press. This week, philly.com featured the story of a Philadelphia police officer, now deceased, who was among 744 plaintiffs who saw their failure-to-warn cases against Merck & Co., Eli Lilly & Co., and Novo Nordisk thrown out by a federal judge in California. According to the report, the case is on appeal.

Cardiovascular outcomes trials ordered by the FDA on all new diabetes and obesity drugs routinely check for adverse effects on the pancreas and for pancreatic cancer. So far, these trials have not found increased cancer risks. As noted by the BMJ authors, however, prior to these current findings, 6 observational studies designed to assess any association offered conflicting results, which prompted regulators to keep a watchful eye for safety problems.

This is what prompted the Canadian Network for Observational Drug Effect (CNODES) to set up the study published in BMJ.

The authors, led by Laurent Azoulay, assistant professor of oncology at the Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital and McGill University, Montreal; started with a giant cohort of patients who started taking antidiabetic drugs between June 2007 and June 2013. The patients were followed through June 2014. Some were followed as long as 8 years, but most were followed for shorter periods.

Patients were matched for up to 20 controls—sex, age, cohort entry date, how long they’d been treated for diabetes, how long they were followed. Researchers also studied effect by class and duration of use.

Compared with sulfonylureas, incretin-based drugs were “not associated with an increased risk of pancreatic cancer,” the authors found. The pooled adjusted hazard ratio was 1.02, 95% confidence interval 0.84 to 1.23. The researchers also found that the risk did not vary by class and that “evidence of a duration-response relation was lacking.”

Reference

Azoulay L, Filion KB, Platt RW, et al. Incretin based drugs and the risk of pancreatic cancer: international multicenter cohort study [published February 17, 2016]. BMJ 2016;352 doi http://dx.doi.org/10.1136.bmj.i581.