Aims/hypothesis <p>Although benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been demonstrated in treatment of type 2 diabetes and weight management, their potential role in cancer prevention remains inadequately explored.</p> Methods <p>Using the TriNetX Research Network, we conducted a retrospective cohort study comparing new users of GLP-1RAs with users of other glucose-lowering medications. Propensity score matching was performed for demographic factors, socioeconomic factors, family history, lifestyle factors and cancer risk factors. The primary outcome was the incidence of obesity-related gastrointestinal cancers, and secondary outcomes were the incidence of individual cancer types.</p> Results <p>Using adjusted HRs (aHRs), GLP-1RA use was found to be associated with a significantly lower risk of overall gastrointestinal cancer compared with all other glucose-lowering medications (insulin: aHR 0.29; 95% CI 0.23, 0.37; metformin: aHR 0.84; 95% CI 0.71, 0.99; sulfonylureas: aHR 0.71; 95% CI 0.62, 0.80; thiazolidinediones: aHR 0.86; 95% CI 0.74, 0.99; dipeptidyl peptidase-4 inhibitors: aHR 0.80; 95% CI 0.70, 0.91; sodium–glucose cotransporter-2 inhibitors: aHR 0.80; 95% CI 0.68, 0.96). The protective effect was most pronounced compared with insulin therapy, with significant risk reductions across all individual cancers.</p> Conclusions/interpretation <p>GLP-1RA use is associated with a reduced risk of gastrointestinal cancers in individuals with type 2 diabetes. These findings suggest potential cancer-protective benefits of GLP-1RAs beyond their established roles in glycaemic management and weight reduction.</p> Graphical Abstract <p></p>

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Glucagon-like peptide-1 receptor agonists and gastrointestinal cancer risk in individuals with type 2 diabetes

  • Chia-Chih Kuo,
  • Min-Hsiang Chuang,
  • Chun-Hsien Li,
  • Ya-Wen Tsai,
  • Po-Yu Huang,
  • Hsing-Tao Kuo,
  • Chih-Cheng Lai

摘要

Aims/hypothesis

Although benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been demonstrated in treatment of type 2 diabetes and weight management, their potential role in cancer prevention remains inadequately explored.

Methods

Using the TriNetX Research Network, we conducted a retrospective cohort study comparing new users of GLP-1RAs with users of other glucose-lowering medications. Propensity score matching was performed for demographic factors, socioeconomic factors, family history, lifestyle factors and cancer risk factors. The primary outcome was the incidence of obesity-related gastrointestinal cancers, and secondary outcomes were the incidence of individual cancer types.

Results

Using adjusted HRs (aHRs), GLP-1RA use was found to be associated with a significantly lower risk of overall gastrointestinal cancer compared with all other glucose-lowering medications (insulin: aHR 0.29; 95% CI 0.23, 0.37; metformin: aHR 0.84; 95% CI 0.71, 0.99; sulfonylureas: aHR 0.71; 95% CI 0.62, 0.80; thiazolidinediones: aHR 0.86; 95% CI 0.74, 0.99; dipeptidyl peptidase-4 inhibitors: aHR 0.80; 95% CI 0.70, 0.91; sodium–glucose cotransporter-2 inhibitors: aHR 0.80; 95% CI 0.68, 0.96). The protective effect was most pronounced compared with insulin therapy, with significant risk reductions across all individual cancers.

Conclusions/interpretation

GLP-1RA use is associated with a reduced risk of gastrointestinal cancers in individuals with type 2 diabetes. These findings suggest potential cancer-protective benefits of GLP-1RAs beyond their established roles in glycaemic management and weight reduction.

Graphical Abstract