medwireNews: A nationwide study has revealed a reduced risk for colorectal cancer (CRC) in people with type 2 diabetes taking glucagon-like peptide (GLP)-1 receptor agonists versus other antidiabetic medications.
Moreover, the risk reduction was “more profound” in those with obesity or overweight, note Nathan Berger (Case Comprehensive Cancer Center, Cleveland, Ohio, USA) and colleagues in a research letter published in JAMA Oncology.
The findings suggest “a potential protective effect against CRC partially mediated by weight loss and other mechanisms not related to weight loss,” they continue.
The study authors explain that as “overweight/obesity is a major risk factor” for CRC, GLP-1 receptor agonists – which “have pleiotropic effects on lowering plasma glucose, inducing weight loss, and modulating immune functions” – could potentially impact this risk.
Drawing on the TriNetX platform that includes electronic health record data from 59 healthcare organizations across all 50 US states, the team identified 1,221,218 drug-naïve patients with type 2 diabetes who were prescribed antidiabetic medications between 2005 and 2019, and who did not have a prior CRC diagnosis.
Over a follow-up of 15 years, starting from the first prescription of antidiabetic medication, use of GLP-1 receptor agonists was associated with a significantly reduced risk for CRC relative to receipt of insulin, metformin, sodium-glucose cotransporter (SGLT)2 inhibitors, sulfonylureas, and thiazolidinediones. The respective hazard ratios (HRs) in propensity score-matched cohorts were 0.56, 0.75, 0.77, 0.82, and 0.82.
GLP-1 receptor agonist use also correlated with a lower CRC risk versus use of alpha-glucosidase inhibitors and dipeptidyl peptidase (DPP)-4 inhibitors, but the corresponding HRs of 0.59 and 0.93 did not reach statistical significance.
The findings were consistent, albeit more pronounced, in patients with obesity or overweight. Specifically, use of GLP-1 receptor agonists significantly reduced the CRC risk compared with insulin, metformin, SGLT2 inhibitors, sulfonylureas, and thiazolidinediones, with HRs of 0.50, 0.58, 0.68, 0.63, and 0.73, respectively.
And in this subgroup, the risk reduction relative to DPP-4 inhibitors was borderline significant (HR=0.77), say Berger et al.
They draw attention to some limitations of the analysis, such as “potential unmeasured or uncontrolled confounders, self-selection, reverse causality, and other biases inherent in observational studies.”
And the team concludes: “Further research is warranted to investigate the effects in patients with prior antidiabetic treatments, underlying mechanisms, potential differential effects within GLP-1 [receptor agonists], and effects of GLP-1 [receptor agonists] on other obesity-associated cancers.”
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