Popular diabetes drug cuts risk of 10 obesity-related cancers

A retrospective analysis of electronic health records suggests that GLP-1 receptor agonists reduce the risk of several obesity-related cancers.

Nathan Berger, MD, PhD, of Case Western Reserve University in Cleveland and colleagues reported that compared with insulin, GLP-1 was associated with a lower risk of developing 10 of 13 types of cancer in patients with type 2 diabetes. JAMA Network Open.

With follow-up up to 15 years, the study showed a reduction in risk of:

• 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)

Compared with metformin, no reduction in cancer risk was seen through the GLP-1 receptor.

“This study adds to the growing body of evidence supporting the pleiotropic effects of GLP-1 receptor agonists for cancer prevention, including obesity-related cancers,” said co-author Lindsay Wang, a medical student at Case Western Reserve University School of Medicine. Today's Medpage. (Burger passes away before the study is published.

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

“Newer GLP-1 receptor agonists such as semaglutide are becoming increasingly popular. [Ozempic, Wegovy] and tirzepatide [Mounjaro, Zepbound] “This further highlights the importance of this study,” Wang added.

The researchers found a trend toward a reduced risk of gastric cancer with GLP-1 compared with insulin, but this did not reach statistical significance. GLP-1 was not associated with a reduced risk of postmenopausal breast or thyroid cancer.

Comparing GLP-1 to metformin, the researchers found a non-significant trend toward a reduced risk for colorectal and gallbladder cancer, but for kidney cancer, there was an increased risk with GLP-1 treatment compared with metformin (HR 1.54, 95% CI 1.27-1.87).

The increased risk of kidney cancer suggests “the need for continued monitoring of patients treated with GLP-1 receptor agonists,” the researchers noted. Although GLP-1 directly influences renal function in the renal vasculature, this is not associated with increased mitogenesis or previous reports of kidney cancer, the researchers noted.

The analysis was conducted using electronic health records of 1,651,452 US patients with type 2 diabetes who were prescribed GLP-1 receptor agonists, insulin, or metformin between 2005 and 2018. No patients had been diagnosed with obesity-related cancer. The mean age was approximately 59.8 years, 60.6% were white, and 50.1% were male.

Compared with insulin users, GLP-1 users tended to be younger, more likely to be female and white, have a family history of cancer, be obese or overweight, have undergone cancer screening, and have been prescribed other diabetes medications, including insulin, metformin, DPP-4 inhibitors, SGLT2 inhibitors, sulfonylureas, thiazolidinediones, and α-glucosidase inhibitors.

The patients in this study were in the health care system, and the results may not be generalizable to other populations, the researchers said. The analysis did not account for health care utilization or type of insurance.