GLP-1 receptor agonists lowered the risk of several obesity-associated cancers, a retrospective analysis of electronic health records suggested.

Compared with insulin, GLP-1s were associated with a lower risk for developing 10 of 13 cancers in people with type II diabetes, reported Nathan Berger, MD, of the Case Western Reserve University in Cleveland, and colleagues in JAMA Network Open.

The follow-up period spanned up to 15 years, and showed risk reductions for:

  • 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 0.37-0.74)
  • 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)
  • Kidney cancer: HR 0.76 (95% CI 0.64-0.91)

No decrease in cancer risk was associated with GLP-1 receptors compared with metformin.

“This study adds to the growing body of evidence supporting the pleiotropic effects of GLP-1 receptor agonists on cancer prevention, including obesity-associated cancers,” co-author and medical student Lindsey Wang, also of Case Western Reserve University School of Medicine, told MedPage Today. (Berger passed away before the study was published.)

“Given that obesity is a known risk factor for at least 13 cancer types, and considering the widespread use of GLP-1 receptor agonists for both type 2 diabetes management and weight loss, we saw an opportunity to investigate a potential link,” she said.

“The increasing popularity of newer GLP-1 receptor agonists like semaglutide [Ozempic, Wegovy] and tirzepatide [Mounjaro, Zepbound] further underscored the importance of this research,” Wang added.

The researchers identified a trend towards a reduced risk for stomach cancer with GLP-1s compared with insulin which did not reach statistical significance. GLP-1s were not associated with a reduced risk of postmenopausal breast cancer or thyroid cancer.

When GLP-1s were compared with metformin, the researchers found a nonsignificant trend toward a lower risk for colorectal and gallbladder cancer. Kidney cancers, however, showed an increased risk with GLP-1 treatment relative to metformin (HR 1.54, 95% CI 1.27-1.87).

The increase in kidney cancer risk suggests “the need for continued monitoring in patients being treated with GLP-1 receptor agonists,” the researchers noted. GLP-1s have direct effects on kidney function in renal vasculature but haven’t been tied with increased mitogenesis or previous reports of kidney cancers, they pointed out.

The analysis was conducted using electronic health records of 1,651,452 U.S. patients with type 2 diabetes who were prescribed GLP-1 receptor agonists, insulins, or metformin from 2005 to 2018. No patients had a prior diagnosis of obesity-associated cancers. The average age was about 59.8 years, 60.6% were white, and 50.1% were male.

Compared with insulin users, GLP-1 users tended to be younger; were more likely to be female and white; had a higher prevalence of family history of cancer, obesity or overweight, and medical encounters for cancer screening; and had prior prescriptions of other antidiabetic agents, including insulins, metformin, DPP-4 inhibitors, SGLT2 inhibitors, sulfonylureas, thiazolidinediones, and α-glucosidase inhibitors.

Patients in this study had medical encounters with a healthcare system and results may not be generalizable to other populations, the researchers said. The analysis did not control for healthcare utilization or insurance type.

  • author['full_name']

    Kristen Monaco is a senior staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.

Disclosures

The study was supported with grants and awards from the National Cancer Institute Case Comprehensive Cancer Center, American Cancer Society, The Landon Foundation-American Association for Cancer Research, National Institutes of Health (NIH) Director’s New Innovator Award Program, National Institute on Aging, and the National Institute on Alcohol Abuse and Alcoholism.

Berger and one co-author reported receiving grants from the NIH during the study. No other disclosures were reported.

Primary Source

JAMA Network Open

Source Reference: Wang L, et al “Glucagon-like peptide 1 receptor agonists and 13 obesity-associated cancers in patients with type 2 diabetes” JAMA Netw Open 2024; DOI: 10.1001/jamanetworkopen.2024.21305.



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