GLP-1 receptor agonists show potential in reducing obesity-associated cancers among type 2 diabetes patients: JAMA

Patients with T2D treated with GLP-1 receptor agonists versus insulin had a significant risk reduction in 10 of 13 OACs, including colorectal, esophageal, gallbladder, endometrial, liver, kidney, ovarian, and pancreatic cancer as well as meningioma and multiple myeloma, the researchers report in JAMA Network Open. Compared with metformin, no decrease in cancer risk was associated with GLP-1RAs.

Thirteen human malignant neoplasms have been identified as OACs, i.e., excess body fat is associated with an increased risk of cancer development and a worse prognosis in patients with these specific tumors. The glucagon-like peptide receptor agonist class of pharmaceuticals are effective agents for type 2 diabetes treatment and achieving weight loss, however, there is no clarity on the association of GLP-1RAs with the incident risk of 13 OACs. Therefore, Lindsey Wang, Case Western Reserve University School of Medicine, Cleveland, Ohio, and colleagues aimed to compare the incident risk of each of the 13 obesity-associated cancers in patients with T2D who were prescribed GLP-1RAs versus insulins or metformin.

The retrospective cohort study utilized a nationwide multicenter database comprising electronic health records (EHRs) from 113 million US patients. The study cohort comprised 1,651,452 patients diagnosed with T2D with no prior history of OACs and were prescribed GLP-1 receptor agonists, insulins, or metformin between March 2005 and November 2018. Data analysis was performed on April 26, 2024.

The researchers examined incident (first-time) diagnosis of each of the 13 OACs occurring during a 15-year follow-up after the exposure using Cox proportional hazard and Kaplan-Meier survival analyses with censoring applied.

The study led to the following findings:

• In the study population of 1 651 452 patients with T2D (mean age, 59.8 years; 50.1% male), GLP-1RAs compared with insulin were associated with a significant risk reduction in 10 of 13 OACs, including in gallbladder cancer (HR, 0.35), meningioma (HR, 0.37), hepatocellular carcinoma (HR, 0.47), pancreatic cancer (HR, 0.41), ovarian cancer (HR, 0.52), multiple myeloma (HR, 0.59), colorectal cancer (HR, 0.54), esophageal cancer (HR, 0.60), kidney cancer (HR, 0.76), and endometrial cancer (HR, 0.74).
• Although not statistically significant, the HR for stomach cancer was less than one among patients who took GLP-1RAs compared with those who took insulin (HR, 0.73).
• GLP-1RAs were not associated with a reduced risk of postmenopausal breast cancer or thyroid cancer.
• Of those cancers that showed a decreased risk among patients taking GLP-1RAs compared with those taking insulin, HRs for patients taking GLP-1RAs vs those taking metformin for colorectal and gallbladder cancer were less than 1, but the risk reduction was not statistically significant.
• Compared with metformin, GLP-1RAs were not associated with a decreased risk of any cancers but were associated with an increased risk of kidney cancer (HR, 1.54).

In the study, GLP-1RAs were associated with lower risks of specific types of OACs compared with metformin or insulins in patients with T2D.

"These findings offer initial evidence suggesting that GLP-1 receptor agonists may have potential benefits in preventing cancer among populations at heightened risk," the researchers concluded. "They underscore the need for additional preclinical and clinical investigations aimed at preventing specific obesity-associated cancers."

Reference:

Wang L, Xu R, Kaelber DC, Berger NA. 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:10.1001/jamanetworkopen.2024.21305