Hormone-linked tumours benefit the most – although kidney cancer may be an outlier.
Yet another unexpected benefit to GLP-1 drugs is a lower risk of cancer, new US research suggests.
The retrospective cohort study compared more than 43,000 US adults with obesity who were taking GLP-1 receptor agonists with another 43,000 adults with obesity who weren’t taking the medication.
Researchers found that patients taking the medicine had lower rates of 13 in 14 cancers: specifically, a 17% reduction in overall cancer risk, 25% reduction in endometrial cancer, 47% reduction in ovarian cancer and 31% reduction in meningioma.
There were also non-significant reductions in myeloma, colorectal, thyroid, prostate, breast, lung, pancreatic, liver, bladder and upper GI cancers.
However, there was a non-significant increase in kidney cancer, especially in under-65s and those who were overweight.
Overall cancer rates were 13.6 vs 16.4 in 1000 person-years among the GLP-1 users compared with non-users.
“Obesity significantly increases the risk of developing several serious conditions, including type 2 diabetes,” the authors wrote in JAMA Oncology.
“More critically, obesity is associated with at least 13 types of cancer, which account for approximately 40% of all cancer diagnoses each year in the US. As obesity rates continue to rise, identifying effective interventions to mitigate cancer risk among individuals with obesity is a critical public health priority.”
Laureate Professor Clare Collins AO, professor of nutrition and dietetics at the University of Newcastle, said the findings were “astounding”.
While this observational study could not definitively pin the lower cancer rates on GLP-1 medication use, Professor Collins said it would trigger more research and could eventually lead to an expansion of their use in people at high risk of some of these cancers.
But the trend toward more renal cancer was a red flag, particularly because many taking the medication already have chronic kidney disease, said Professor Collins, co-director of the food and nutrition research program at Hunter Medical Research Institute.
New research suggested a diet with a high diversity of plant foods helped slow the progression of chronic kidney disease, she said.
This could be a problem for people taking these appetite-suppressing drugs, however.
“Nobody wants to go out of the frying pan and jump into the fire,” Professor Collins said.
“I think now is the time to say, ‘Hey, we want you to get the best response out of these medications. You’re going to really lose your appetite, but it’s important now to focus on nutritional quality’.”
Studies into GLP-1 receptor agonists usually paired the medication with nutritional support, highlighting the importance of considering a referral to a dietician when initiating the drugs, she added.
And Professor Collins said the uptake of GLP-1 receptor agonists had been a “really positive” development in how people interacted with dieticians.
“Now is a really good time in which people can actually look at their diet quality, separate from all of the food noise was that was getting in the way of their best intentions,” she said.
It is still unclear exactly why GLP-1 receptor agonists may reduce cancer risk – but it may not simply be down to weight loss.
While previous research had investigated the link between these drugs and cancer, studies focused on participants with diabetes rather than obesity alone.
The researchers said their findings aligned with this previous research, which found significant drops endometrial, ovarian and meningioma cancer rates in people taking the medication.
“These patterns raise the hypothesis that GLP-1RAs may be associated with a lower risk of hormone-sensitive malignant neoplasms,” the researchers wrote.
They pointed to preclinical research linking endometrial cancer development to metabolic and hormonal pathways.
“Given that obesity and hyperinsulinemia are major risk factors for endometrial cancer, the metabolic effects of GLP-1RAs, particularly their role in weight loss and insulin sensitivity improvement, likely contribute to this association with reduced cancer risk,” they wrote.
In ovarian cancer, GLP-1 receptor agonists can downregulate metalloproteinases and upregulating their inhibitors, hindering ovarian cancer cells.
“Given ovarian cancer is closely associated with obesity, hyperinsulinemia and chronic inflammation, it is also plausible that the metabolic improvements induced by GLP-1RAs contribute to reduced risk,” the researchers wrote.
“In a survey of human tumours, approximately 35% of meningiomas were found to express measurable levels of GLP-1 receptors, suggesting that meningioma cells may directly respond to GLP-1 or its analogues.
“GLP-1RAs significantly improve metabolic profiles, and given that meningiomas are known to exhibit hormone sensitivity, these metabolic changes could plausibly influence tumour biology.”
But more research was needed to understand the potential mechanisms underpinning the reduction in meningiomas, as well as the marginally increased risk of kidney cancer, the authors said.
