Lower Cancer Risk Noted in GLP-1RAs for Diabetes Vs Insulin

Results from a retrospective cohort study display evidence of potential benefit from GLP-1RAs for the reduction of 13 obesity-associated cancers for those with type 2 diabetes.

Glucagon-like peptide receptor agonists (GLP-1RAs) used to treat diabetes may have a lower risk of obesity-associated cancers (OACs) compared with insulin or metformin in patients with type 2 diabetes, according to a retrospective cohort study published in JAMA Network Open.

Of 13 OACs, GLP-1RA use was associated with a significantly lower risk of 10 than insulin use, including gallbladder cancer (HR, 0.35; 95% CI, 0.15-0.83), meningioma (HR, 0.37; 95% CI, 0.18-0.74), pancreatic cancer (HR, 0.41; 95% CI, 0.33-0.50), hepatocellular carcinoma (HR, 0.47; 95% CI, 0.36-0.61), ovarian cancer (HR, 0.52; 95% CI, 0.03-0.74), colorectal cancer (HR, 0.54; 95% CI, 0.46-0.64), multiple myeloma (HR, 0.59; 95% CI, 0.44-0.77), esophageal cancer (HR, 0.60; 95% CI, 0.42-0.86), endometrial cancer (HR, 0.74; 95% CI, 0.60-0.91), and kidney cancer (HR, 0.76; 95% CI, 0.64-0.91).

Additionally, the authors of the study announced that the potential cancer-preventative effects of OACs by GLP-1RAs warrant long-term studies and studies of newer antidiabetic and weight loss agents.

Results found for GLP-1RA use compared to metformin use showed no statistically significant reduction in any OACs but was associated with an increased risk of kidney cancer (HR, 1.54; 95% CI, 1.27-1.87). Although lower risk of colorectal cancer, gallbladder cancer, and meningioma were observed, they were not statistically significant.

The TriNetX platform was utilized to access deidentified electronic health records of 113 million patients from 64 United States-based health organizations. The study population of 1,651,452 patients complied from the platform had diagnoses of type 2 diabetes and were prescribed GLP-1RAs vs insulin or metformin and no history of 13 OACs between March 2005 and November 2018.

When comparing GLP-1RAs with insulins, the study population was divided into two groups; 48,983 patients prescribed a GLP-1RA without insulin and 1,044,745 patients prescribed insulin but not GLP-1RAs. Similarly, 32,365 patients were prescribed GLP-1RA but not metformin, and 856,160 were prescribed metformin but not GLP-1RAs.

The mean follow-up time for a colorectal cancer outcome was 2074.7 days for the GLP-1RA with no insulin group and 1981.8 days for the insulin without GLP-1RA group.Additionally, the mean follow-up time for a liver cancer outcome was 2023.1 days for the GLP-1RA/no insulin group and 2037.9 days for the insulin/no GLP-1RA group.

Similarly, the mean follow-up time for a colorectal cancer outcome was 1967.2 days for the GLP-1RA with no metformin group and 2101.6 days for the metformin without GLP-1RA group.Additionally, the mean follow-up time for a liver cancer outcome was 1970.9 days for the GLP-1RA/no metformin group and 2129.8 days for the metformin/no GLP-1RA group.

A decreased non-significant risk reduction in stomach cancer was observed in GLP-1RAs compared with insulin (HR, 0.73; 95% CI, 0.51-1.03). No signs of an increase or decrease in the risk for breast cancer in postmenopausal women with type 2 diabetes were observed in patients treated with GLP-1RAs compared with insulin or metformin.

Furthermore, although kidney cancers showed an increased risk with GLP-1RA compared with metformin, it was associated with a non-significant decreased risk compared to insulin (HR, 0.76; 95% CI 0.64-0.91). Thyroid cancer showed no statistically different risk in patients treated with GLP-1RAs when compared with both insulin and metformin.

The median patient age was 59.8 years, 50.1% of patients were male, and 60.6% were White.

Findings from this study match the OAC-reducing effects of intensive lifestyle interventions observed in the Look AHEAD trial and of metabolic-bariatric surgery as reported in the SPLENDID trial. The trials observed a 16% (HR, 0.84; 95% CI, 0.68-1.04) and 32% (HR, 0.68; 95% CI, 0.53-0.87), respectively.

Reference

Wang L, Xu R, Kaelber DC, et al. Glucagon-like peptide 1 receptor agonists and 13 obesity-associated cancers in patients with type 2 diabetes. JAMA Netw Open. 2024;7(7):e2421305. doi:0.1001/jamanetworkopen.2024.21305