Medical Researchers Finding This Rare But Highly Fatal Cancer Call For More Investigation Into New Possible Drug Side Effect
A recent medical study shows that the use of diabetes medicines in the dipeptidyl peptidase-4 (DPP-4) inhibitor drug class was associated with a near doubling of the risk of cholangiocarcinoma.
Diabetes drugs in the DPP-4 inhibitors class include the following:
- Januvia (sitagliptin)
- Janumet (sitagliptin / metformin HCl)
- Onglyza (saxagliptin)
- Kombiglyze XR (saxagliptin and metformin)
- Qtern (dapagliflozin and saxagliptin)
- Nesina (alogliptin)
- Kazano (alogliptin and metformin)
- Oseni (alogliptin and pioglitazone)
- Tradjenta (linagliptin)
- Jentadueto (linagliptin and metformin HCl)
- Glyxambi (empagliflozin / linagliptin)
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From this BMJ article, "Incretin based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: population based cohort study", published in December 2018 we get the following:
In this study, use of dipeptidyl peptidase-4 (DPP-4) inhibitors was associated with a near doubling of the risk for cholangiocarcinoma. The use of glucagon-like peptide-1 (GLP-1) receptor agonists was also associated with an increased hazard ratio of similar magnitude but generated a wide confidence interval that included the null value....
An association between incretin based drugs and incidence of cholangiocarcinoma is biologically plausible. One mechanism could involve the increased GLP-1 levels associated with use of both DPP-4 inhibitors and GLP-1 receptor agonists; GLP-1 might promote the development of cholangiocarcinoma through its proliferative and anti-apoptotic effects on cholangiocytes. Another mechanism could involve chronic inflammation of the biliary epithelium, bile stasis, and bacterial infections, which might be a particular concern with GLP-1 receptor agonists. These drugs have been associated with an increased risk of gallbladder related events (such as cholelithiasis, cholecystitis, cholangitis) in an observational study and in the LEADER trial. Finally, we observed increased hazard ratios in secondary analyses assessing possible duration-response relations with DPP-4 inhibitors. Specifically, the hazard ratio was particularly increased with cumulative durations ranging between one and two years of use and with more than two years since treatment initiation. Although these relatively rapid effects suggest that these drugs might act as tumour promoters among susceptible people, these secondary analyses were based on few events that generated wide confidence intervals and should thus be interpreted with caution. [footnotes omitted]
The medical researcher who were the authors concluded this December 2018 BMJ medical journal article with an important call-to-action:
Given the high fatality rate of this cancer, post hoc analyses of randomised controlled trials and additional observational studies are needed to corroborate our findings.
We will continue to monitor the medical literature for more about cholangiocarcinoma being a possible side effect of DPP-4 inhibitor diabetes drugs.
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