GLP-1RAs may reduce the risk of blood cancers in T2D patients

Blood cancers

By Siobhan Calafiore

10 Jul 2024

GLP-1 receptor agonists may lower the risk of specific obesity-associated cancers including multiple myeloma in patients with type 2 diabetes, US researchers have found.

Writing in JAMA Network Open [link here], US-based researchers say their findings provide preliminary evidence of the potential benefit of GLP-1RAs for cancer prevention in high-risk patients and support further preclinical and clinical research on the topic.

The team drew from a nationwide multicentre database of electronic health records of 113 million US patients, with 1.7 million patients diagnosed with T2D and with no prior diagnosis of obesity-associated cancers included in the study.

Patients (mean age 60, 50% male) had been prescribed GLP-1RAs, insulins or metformin between March 2005 and November 2018.

Findings revealed that compared with insulins, patients treated with GLP-1RAs had a significant risk reduction in 10 of 13 obesity-associated cancers.

These included lower risks for multiple myeloma (HR 0.59), as well as gallbladder cancer (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), oesophageal cancer (HR 0.60), endometrial cancer (HR 0.74),and kidney cancer (HR 0.76).

Although not statistically significant, there was also a risk reduction observed for stomach cancer among patients taking GLP-1RAs versus insulin (HR 0.73).

But the researchers said they did not find any associations for a risk reduction between GLP-1RAs and postmenopausal breast cancer or thyroid cancer.

When compared with metformin, GLP-1RAs were not associated with a reduced risk of any cancers, but were associated with an increased risk of kidney cancer (HR 1.54).

The researchers remarked on their unexpected finding that kidney cancers showed an increased risk with GLP-1RA treatment relative to that with metformin, which they said required further evaluation.

“GLP-1RAs have direct effects on kidney function mediated by GLP-1 [receptors] in renal vasculature; however, these are not associated with increased mitogenesis, and to our knowledge, there have been no previous reports of kidney cancers with the use of GLP1-RAs,” they said.

“These divergent risks require further clinical and mechanistic studies for full evaluation. Nonetheless, they suggest the need for continued monitoring in patients being treated with GLP-1RAs.”

For thyroid cancer, the researchers said their findings, together with previous reports of insulins promoting cancer growth, suggested that GLP-1RAs might be associated with increased risk of thyroid cancer.

“These studies support the package warnings included with GLP-1RAs that these agents are contraindicated in patients with multiple endocrine neoplasia syndrome type 2 and that patients should be counselled regarding the potential risk of medullary thyroid carcinoma and symptoms of thyroid tumours.”

They also said the lack of effect of GLP-1RAs on breast cancer risk required further investigation to determine the impact of longer duration of therapy as well as to more fully understand the relation between the agents and oestrogen metabolism.

“The lack of breast cancer risk reduction by GLP-1RAs and the similar lack of protection by bariatric surgery [as seen in other studies] may also suggest the possibility that factors determining the incidence of breast cancer in patients with overweight or obesity may have been initiated long before intervention with GLP-1RAs and/or bariatric surgery and therefore require earlier intervention to affect risk reduction,” they said.

“The concept that early intervention might reduce breast cancer incidence is supported by the observation that both pregnancy and breastfeeding reduce the incidence of breast cancer.”

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