Based on the results of a retrospective U.S. population–based cohort study, which were reported in JAMA Network Open by Wang et al, treatment with glucagon-like peptide 1 (GLP-1) receptor agonists vs insulins seemed to be associated with a decreased risk of developing specific obesity-associated malignant neoplasms in patients with type 2 diabetes who were cancer-free at baseline.

“Thirteen human malignant neoplasms have been identified as obesity-associated cancers,” the investigators commented. “The GLP-1 receptor agonist class of pharmaceuticals are effective agents for the treatment of type 2 diabetes and for achieving weight loss, but [prior to this study, their] association with the incident risk of the 13 obesity-associated cancers was unclear.”

Study Details

Using a nationwide multicenter database of electronic health records, the investigators identified 1,651,452 patients with type 2 diabetes (mean age = 59.8 years) who had no prior diagnosis of obesity-associated cancer and were prescribed GLP-1 receptor agonists, insulins, or metformin between March 2005 and November 2018. Data analysis was conducted in April 2024.

Obesity-Associated Cancer Risk

Treatment with GLP-1 receptor agonists vs insulins was found to be associated with a significantly decreased risk of developing 10 of the 13 identified obesity-associated cancers, namely gallbladder cancer (hazard ratio [HR] = 0.35), meningioma (HR = 0.37), pancreatic cancer (HR = 0.41), hepatocellular carcinoma (HR = 0.47), ovarian cancer (HR = 0.52), colorectal cancer (HR = 0.54), multiple myeloma (HR = 0.59), esophageal cancer (HR = 0.60), endometrial cancer (HR = 0.74), and kidney cancer (HR = 0.76). Although reportedly not statistically significant, a hazard ratio for stomach cancer of < 1 was documented in patients treated with GLP-1 receptor agonists compared with those who received insulins (HR = 0.73). Treatment with GLP-1 receptor agonists did not appear to be associated with a reduced risk of developing postmenopausal breast cancer or thyroid cancer.

Among the cancers with a demonstrated decreased incident risk in patients treated with GLP-1 receptor agonists vs insulins, hazard ratios for colorectal and gallbladder cancer relative to metformin were < 1; however, according to the investigators, the risk reduction was not statistically significant. Compared with metformin, treatment with GLP-1 receptor agonists was not found to correlate with a decreased risk of developing any cancers; rather, it showed an increased risk for kidney cancer (HR = 1.54).

“The potential cancer-preventative effects of obesity-associated cancers by GLP-1 receptor agonists warrant further long-term studies, as well as studies of individual newer and possibly more effective antidiabetic and weight loss agents and those with multihormone agonist activities,” the investigators concluded. “Studies are also warranted to evaluate the preventive effects of these agents on non-obesity–associated cancers.”

Nathan A. Berger, MD, and Rong Xu, PhD, of Case Western Reserve University School of Medicine, Cleveland, are the corresponding authors of the JAMA Network Open article.

Disclosure: The study was funded by National Cancer Institute Case Comprehensive Cancer Center, American Cancer Society, The Landon Foundation–American Association for Cancer Research, NIH Director’s New Innovator Award Program, National Institute on Aging, and the National Institute on Alcohol Abuse and Alcoholism. For full disclosures of the study authors, visit jamanetwork.com.