Use of GLP-1 drugs in type 2 diabetes tied to reduced risk of colorectal cancer: JAMA

"Colorectal risk reduction was more pronounced in obese/overweight patients taking GLP-1 agonists versus other antidiabetic agents, including metformin (HR 0.58) and insulin (HR 0.50)," researchers reported in JAMA Oncology.

GLP-1 receptor agonists are approved by the US Food and Drug Administration (FDA) for type 2 diabetes (T2D) treatment. GLP-1RAs have pleiotropic effects on inducing weight loss, lowering plasma glucose, and modulating immune functions. Because obesity/overweight is a major risk factor for colorectal cancer, Lindsey Wang, Case Western Reserve University School of Medicine, Cleveland, Ohio, and colleagues hypothesized that GLP-1RAs are associated with a reduced risk for CRC in T2D patients compared with non–GLP–1RA antidiabetics.

They conducted a nationwide, retrospective cohort study among drug-naive patients with type 2 diabetes comparing GLP-1RAs with 7 non–GLP–1RA antidiabetics, including insulin and metformin, which are suggested to impact the risk of colorectal cancer.

For this purpose, the researchers analyzed electronic medical record data for 1.2 million patients from 59 healthcare organizations across the U.S. using the TriNetX platform. It included individuals who received their first antidiabetic prescription (at an average age of 57 years) after medical encounters for T2D from 2005 to 2018, who had no prior CRC diagnosis and no such prior medication use.

Stratification of the patients was done according to overweight/obesity and sex, but limited sample sizes did not allow for stratification by race, age, and ethnicity.

Patients were assigned to exposure and comparison cohorts and propensity scores matched in the ratio of 1:1 for adverse socioeconomic determinants of health, demographics, family and personal history of cancers and colonic polyps, preexisting medical conditions, procedures such as colonoscopy, and lifestyle factors.

The research team analyzed the time between the first prescription of GLP-1 receptor agonists and other antidiabetics and the first diagnosis of CRC within the 15-year follow-up. Non-GLP-1 antidiabetics assessed included metformin, insulin, sulfonylureas, alpha-glucosidase inhibitors, and thiazolidinediones. For DPP-4 inhibitors and SGLT2 inhibitors, the researchers used data starting in 2013 and 2006, upon first approval of those drugs, respectively.

The study revealed the following findings:

• During a 15-year follow-up in 1 221 218 drug-naive patients with T2D, GLP-1RAs were associated with reduced risk for colorectal cancer compared with insulin (HR, 0.56), metformin (HR, 0.75), sulfonylureas, SGLT2 inhibitors, and thiazolidinediones, and with lower but not statistically significant risk compared with alpha-glucosidase or DPP-4 inhibitors. Consistent findings were observed in women and men.
• GLP-1RAs were associated with a lower risk for CRC in patients with obesity/overweight compared with metformin (HR, 0.58), insulin (HR, 0.50), or other antidiabetics.

The findings showed that GLP-1RAs were associated with a reduced risk of colorectal cancer in drug-naive patients with type 2 diabetes with and without overweight/obesity, with more profound effects in obese/overweight patients, suggesting a potential protective effect against CRC partially mediated by weight loss and other mechanisms not related to weight loss.

"Further studies are warranted to determine 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," they concluded.

Reference:

Wang L, Wang W, Kaelber DC, Xu R, Berger NA. 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 07, 2023. doi:10.1001/jamaoncol.2023.5573