These antidiabetic drugs may lead to bile duct cancer

Canada: DPP-4 inhibitors and GLP-1 receptor agonists, used for the treatment of type 2 diabetes (T2D), are associated with an increased risk of cholangiocarcinoma (also called bile duct cancer), compared with other second or third line antidiabetic drugs, finds a new study published in The BMJ.

DPP-4 inhibitors and GLP-1 receptor agonists are second or third line drugs commonly used for the management of T2D. These incretin-based drugs work through the effects of GLP-1 hormone that stimulates the secretion of insulin.

Although incretin-based drugs have favorable clinical effects, some biological evidence suggests that the incretin system might be involved in the development of cholangiocarcinoma (bile duct cancer), a rare but highly fatal cancer

Devin Abrahami, doctoral student, Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada, and colleagues conducted this population-based cohort study to determine whether the use of DPP-4 inhibitors and GLP-1 receptor agonists is associated with an increased risk of cholangiocarcinoma in type 2 diabetes patients.

For the purpose, the researchers followed 154 162 adults newly treated with antidiabetic drugs for 10 years. Use of DPP-4 inhibitors and GLP-1 receptor agonists was modeled as a time-varying variable and compared with the use of other second or third line antidiabetic drugs. All exposures were lagged by one year to account for cancer latency and to minimize reverse causality.

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Key Findings:

• Use of DPP-4 inhibitors was associated with a 77% increased hazard of cholangiocarcinoma.


• Use of GLP-1 receptor agonists was associated with an increased hazard with a wide confidence interval.


• In the pharmacovigilance analysis, the use of DPP-4 inhibitors and GLP-1 receptor agonists were both associated with increased reporting odds ratios for cholangiocarcinoma, compared with the use of sulfonylureas or thiazolidinediones.

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"Compared with use of other second or third line antidiabetic drugs, use of DPP-4 inhibitors, and possibly GLP-1 receptor agonists, might be associated with an increased risk of cholangiocarcinoma in adults with type 2 diabetes," concluded the authors.

For further reference follow the link: https://doi.org/10.1136/bmj.k4880