GLP-1 Treatment Associated With Lower CRC Risk

A cohort study of more than 1.2 million drug-naive patients with Type 2 diabetes (T2D) found that glucagon-like peptide 1 receptor agonists (GLP-1RA s) were associated with reduced risk of developing colorectal cancer (CRC), according to a research letter published in JAMA Oncology.

“Because overweight/obesity is a major risk factor for colorectal cancer (CRC), we hypothesize that GLP-1RAs are associated with a decreased risk for CRC in patients with T2D compared with non–GLP-1RA antidiabetics,” the authors wrote. “We conducted a nationwide, retrospective cohort study among drug-naive patients with T2D comparing GLP-1RAs with 7 non–GLP-1RA antidiabetics, including metformin and insulin, which are suggested to influence CRC risk.”

The study population comprised 1,221,218 patients with and without obesity/overweight who received medical care for T2D from 2005 to 2019. These patients had no prior antidiabetic medication use and no prior CRC diagnosis.

Approved by the US Food and Drug Administration for treating T2D, GLP-1RAs have pleiotropic effects on lowering plasma glucose, inducing weight loss, and modulating immune functions. The risk of CRC among patients prescribed GLP-1RAs was compared to the risks of CRC among patients using insulin, metformin, alpha-glucosidase inhibitors, dipeptidyl-peptidase 4 (DPP-4) inhibitors, sodium-glucose cotransporter-2 (SGLT2) inhibitors, sulfonylureas, and thiazolidinediones.

“Cohorts were propensity score matched (1:1, using nearest neighbor greedy matching) for demographics, adverse socioeconomic determinants of health, pre-existing medical conditions, family and personal history of cancers and colonic polyps, lifestyle factors (exercise, diet, smoking, and alcohol drinking), and procedures such as colonoscopy. The outcome was the first diagnosis of CRC that occurred within 15 years starting from the index event (first prescription of GLP-1RAs vs non–GLP-1RA antidiabetics),” the researchers reported.

During the 15-year follow-up, GLP-1RAs were associated with decreased risk for CRC compared with insulin (HR, 0.56; 95% CI, 0.44-0.72), metformin (HR, 0.75; 95% CI, 0.58-0.97), SGLT2 inhibitors, sulfonylureas, and thiazolidinediones, and with lower, but not statistically significant, risk compared with alpha-glucosidase or DPP-4 inhibitors. These findings were consistent in women and men. Furthermore, GLP-1RAs were associated with a lower risk for CRC in patients with obesity/overweight compared with insulin (HR, 0.50; 95% CI, 0.33-0.75), metformin (HR, 0.58; 95% CI, 0.38-0.89), or other antidiabetics.

“In this cohort study, GLP-1RAs were associated with reduced CRC risk in drug-naive patients with T2D with and without obesity/overweight, with more profound effects in patients with obesity/overweight, suggesting a potential protective effect against CRC partially mediated by weight loss and other mechanisms not related to weight loss,” the investigators stated. “Further research is warranted to investigate the effects in patients with prior antidiabetic treatments, underlying mechanisms, potential differential effects within GLP-1RAs, and effects of GLP-1RAs on other obesity-associated cancers.”

Reference:

Wang L, Wang W, Kaelber DC, et al. GLP-1 receptor agonists and colorectal cancer risk in drug-naive patients with type 2 diabetes, with and without overweight/obesity. JAMA Oncol. Published online December 7, 2023. doi:10.1001/jamaoncol.2023.5573