Incretin-based diabetes drugs don't increase cholangiocarcinoma risk: Study
Sweden: A recent study using nationwide data from three countries found the use of DPP4 inhibitors and GLP-1-receptor agonists to be not associated with a significant increase in cholangiocarcinoma risk compared with sulfonylureas use. The study appears in the journal Diabetologia.
Dipeptidyl peptidase 4 (DPP4) inhibitors and glucagon-like peptide-1 (GLP-1)-receptor agonists are incretin-based drugs that are commonly used for the treatment of type 2 diabetes. Recently, concerns have been raised regarding a potential association between incretin-based drugs and cholangiocarcinoma. Considering this, Peter Ueda, Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden, and colleagues examined this association in nationwide data from three countries.
For this purpose, the researchers used data from nationwide registers in Sweden, Denmark, and Norway, 2007–2018, and conducted two cohort studies, one for DPP4 inhibitors and one for GLP-1-receptor agonists, to investigate the risk of incident cholangiocarcinoma compared with an active-comparator drug class (sulfonylureas).
The cohorts included patients initiating treatment episodes with DPP4 inhibitors vs sulfonylureas, and GLP-1-receptor agonists vs sulfonylureas. Hazard ratios were estimated from day 366 after treatment initiation to account for cancer latency.
The main analyses of DPP4 inhibitors included 1,414,144 person-years of follow-up from 222,577 patients receiving DPP4 inhibitors (median follow-up time, 4.5 years) and 123,908 patients receiving sulfonylureas (median follow-up time, 5.1 years) during which 350 cholangiocarcinoma events occurred.
The research yielded the following findings:
- Use of DPP4 inhibitors, compared with sulfonylureas, was not associated with a statistically significant increase in the risk of cholangiocarcinoma (incidence rate 26 vs 23 per 100,000 person-years; adjusted HR, 1.15; absolute rate difference 3 events per 100,000 person-years).
- The main analyses of GLP-1-receptor agonists included 1,036,587 person-years of follow-up from 96,813 patients receiving GLP-1-receptor agonists (median [IQR] follow-up time, 4.4 years) and 142,578 patients receiving sulfonylureas (median follow-up time, 5.5 years) during which 249 cholangiocarcinoma events occurred.
- Use of GLP-1-receptor agonists was not associated with a statistically significant increase in the risk of cholangiocarcinoma (incidence rate 26 vs 23 per 100,000 person-years; adjusted HR, 1.25; absolute rate difference 3 events per 100,000 patient-years).
The researchers concluded that in this study using nationwide data from three Scandinavian countries and sulfonylureas as the comparator, neither the use of DPP4 inhibitors nor the use of GLP-1-receptor agonists was associated with a significantly increased risk of cholangiocarcinoma.
Ueda, P., Wintzell, V., Melbye, M. et al. Use of incretin-based drugs and risk of cholangiocarcinoma: Scandinavian cohort study. Diabetologia 64, 2204–2214 (2021). https://doi.org/10.1007/s00125-021-05508-1