Incretin-based therapy and risk of cholangiocarcinoma: a nested case–control study in a population of subjects with type 2 diabetes
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Background and aims
One cohort and several basic science studies have raised suspicion about an association between incretin therapies and cholangiocarcinoma. Our aim was to verify the occurrence of CC in relation to incretin-based medication use versus any antidiabetic treatment in an unselected population of diabetic patients.
A population-based matched case–control study was conducted using administrative data from the Region of Piedmont (4,400,000 inhabitants), Italy. From a database of 312,323 patients treated with antidiabetic drugs, we identified 744 cases hospitalized for cholangiocarcinoma from 2010 to 2016 and 2976 controls matched for gender, age and initiation of antidiabetic therapy; cases and controls were compared for exposure to incretin-based medications. All analyses were adjusted for risk factors for CC, as ascertained by hospital discharge records. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by fitting a conditional logistic model.
The mean age of the sampled population (cases and controls, 75 years) was very high, with no gender prevalence. Five per cent was treated with incretin-based medications. After adjusting for possible confounders, we found no increased risk of cholangiocarcinoma associated with the use of either DPP4i (OR 0.98, 95% CI 0.75–1.29: p = 0.89) or GLP-1-RA (OR 1.09, 95% CI 0.63–1.89; p = 0.76) in the 24 months before hospital admission. Neither the duration of the therapy nor the dose modified the risk of cholangiocarcinoma.
Our findings suggest that, in an unselected population, the use of both classes of incretin-based medications is not associated with an increased risk of cholangiocarcinoma.
KeywordsIncretin-based medications Cholangiocarcinoma Safety in diabetes treatment Case–control study Administrative data
CBG and RG performed literature search, study design, data collection, data interpretation and writing; RP was involved in data collection and data analysis; EN and BT carried out literature search and data collection; LM contributed to literature search, study design and data interpretation; GC performed data interpretation and writing; and CBG, RP, GC and RG had access to the raw data. CBG had full access to all the data in the study and the final responsibility for the decision to submit for publication.
Compliance with ethical standards
Conflict of interest
All authors have nothing to disclose.
Ethical Standard Statement
This is an observational study and data were collected retrospectively. The Local Health was responsible for collecting and processing these data. The study was performed in accordance with Local Health Authority. No ethical approval was required according to Italian Law 211/2003, which explains that no ethics committee permission is required for this kind of study.
According to Italian Privacy Law, no patient’s or relative’s consent is required for large retrospective population-based studies if data are published only in aggregated form.
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