Glucagon-Like Peptide-1 Receptor Agonist Treatment and Risk of Esophageal Cancer.

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) induce weight loss, and have been associated with an overall decreased risk of esophageal cancer. Obesity is strongly associated with esophageal adenocarcinoma and substantial weight loss may decrease the risk of this malignancy, whereas weight loss does not decrease the risk of esophageal squamous cell carcinoma. We examined the hypothesis that GLP-1RA treatment decreases the risk of esophageal adenocarcinoma. This multinational population-based case-control study included all cases of esophageal adenocarcinoma and esophageal squamous cell carcinoma in adults who had dispensed medication for type 2 diabetes in Denmark (2007-2020), Finland (2011-2018), Iceland (2009-2019), Norway (2007-2019), or Sweden (2007-2020). For each case participant, >10 control participants who had dispensed medication for type 2 diabetes were randomly sampled from the general populations. Data came from nationwide health-data registries. Multivariable logistic regression provided odds ratios (OR) with 95% confidence intervals (CI), adjusted for sex, age, calendar year, country, comorbidity, gastroesophageal reflux disease, obesity, alcohol overconsumption, and tobacco smoking. This study included 2,909 case participants with esophageal adenocarcinoma, 670 case participants with esophageal squamous cell carcinoma, and 55,408 control participants. The risk of esophageal adenocarcinoma was not decreased in GLP-1RA users compared with nonusers (adjusted OR 1.3, 95% CI 1.1-1.5). Instead, the risk of esophageal squamous cell carcinoma was decreased (adjusted OR 0.5, 95% CI 0.3-0.8). Standard GLP-1RA treatment in patients with type 2 diabetes might not decrease the risk of esophageal adenocarcinoma. The validity of the observed decreased risk of esophageal squamous cell carcinoma is uncertain.