More evidence suggests that medications such as Ozempic and Mounjaro, originally developed for diabetes and then approved for obesity, have benefits that go beyond these conditions. Those include lower risk of 10 cancers, protection against heart and kidney diseases, and reduction in systemic inflammation, according to recently published research.
This drug class, known as GLP-1 agonists, includes semaglutide—approved as Ozempic for type 2 diabetes and Wegovy for obesity—and tirzepatide—approved as Mounjaro for diabetes and Zepbound for obesity. Some of these protective effects likely result from patients’ weight loss when taking these medications, but the drugs appear to have other effects that improve health independent of the weight loss.
“The cardioprotective effect of semaglutide observed in people with obesity developed within months of drug initiation, well before meaningful weight loss had been achieved in most trial participants” in one 2022 trial, Daniel Drucker, a physician-scientist at the Lunenfield-Tanenbaum Research Institute at Mt. Sinai Hospital in Toronto, states in a commentary published Thursday in Science. “The initial chapter of GLP-1 innovation focused on glucose control, and later, weight loss,” he writes. “Subsequent waves seem likely to improve health outcomes in people with a range of chronic disorders.”
Indeed, a recent study in JAMA Network Open is the first to suggest that even protection from certain cancers could be among the ways these drugs can help improve health. People with obesity have a higher risk of developing 13 cancers, and the new research found a reduced risk for 10 of these cancers in patients with type 2 diabetes who were prescribed a GLP-1 agonist drug, compared to just insulin.
While the study was large, with more than 1.6 million patients from the United States, it has multiple limitations that warrant “cautious optimism,” says William Murphy, a cancer immunologist at the University of California Davis School of Medicine who studies obesity’s impact.
Lower cancer rates
The JAMA study analyzed electronic health records for 113 million people from all 50 states and compared cancer risk over 15 years in 1.65 million patients who had type 2 diabetes. The researchers focused only on patients with type 2 diabetes because their prescriptions were tracked through 2018, when GLP-1 drugs were still approved only for diabetes, explained Lindsey Wang, the lead author and a sophomore at Case Western Reserve University who has been studying under the senior author, the late Nathan Berger, for the past five years. Semaglutide was first approved for obesity in 2021.
(Ozempic and Mounjaro have another benefit: treating inflammation)
“This study mainly adds to the growing body of evidence that supports all these different beneficial effects of GLP-1 receptor agonists,” Wang says. “For patients and clinicians, we want to encourage them both to consider this potential added benefit of cancer prevention when they’re selecting treatments for type 2 diabetes management, especially for patients who are at a higher risk for developing these cancers.”
Compared to patients prescribed insulin, patients prescribed a GLP-1 agonist had a 65 percent lower risk of gallbladder cancer and 62 percent lower risk of a central nervous system tumor called meningioma.
They also had a 59 percent lower risk of pancreatic cancer, 53 percent lower risk of liver cancer, 48 percent lower risk of ovarian cancer, 46 percent lower risk of colorectal cancer, 41 percent lower risk of multiple myeloma, 40 percent lower risk of esophageal cancer, 26 percent lower risk of endometrial cancer and 24 percent lower risk of kidney cancer.
A reduced risk for stomach cancer was also seen but was not statistically significant. The results did not show any difference in risk for thyroid cancer or for post-menopause breast cancer.
When the researchers compared patients prescribed GLP-1 drugs to those prescribed metformin, another common type 2 diabetes drug, they saw some reduction in risk for gallbladder and colorectal cancer, though, again, the findings were not statistically significant. They also found a 1.5 times greater risk of kidney cancer that was statistically significant, a finding that requires more research to understand, the authors write.
Caveats to consider
Because the JAMA Network Open study only looked at who was prescribed certain medications, it was not possible to determine whether patients filled those prescriptions or how long they took the medication. The dataset does not reveal whether the patients lost weight.
Murphy highlighted other study limitations that make it difficult to fully understand the relationship between GLP-1 drugs and reduced cancer risk. Many patients were prescribed both GLP-1 agonists and metformin, but the GLP-1 agonists did not show a risk reduction when compared to metformin alone. Murphy would therefore like to have seen comparisons between patients receiving insulin and patients receiving GLP-1s without metformin.
In addition, only 37 percent of the patients were overweight or had obesity, so it would be helpful to see comparisons in cancer risk only in those patients, he says. “You have to be very careful before you highlight that this is another benefit,” Murphy adds.
(New obesity drugs are coming. Here’s how they could change everything.)
He remains cautiously optimistic, however, because the “bottom line is that you do see a reduction in cancer incidence with the GLP-1 agonists,” he says, and it’s possible that reduction would be even greater if the researchers had only focused on patients with obesity or overweight.
Human studies are messy in terms of all the possible variables that can interfere with identifying effects in observational studies, but more animal studies could help “tease out some of these different factors and control for them,” Murphy says.
Megha Poddar, an endocrinologist and obesity medicine specialist at LMC Endocrinology and Diabetes Group in Toronto, was unsurprised by the findings but pointed out that the study did not necessarily compare “apples to apples.” That is, patients receiving insulin tend to be sicker than those receiving GLP-1 agonists and may be at higher risk for obesity-related cancers, especially since insulin can contribute to weight gain.
But given the length of the study and concerns some patients have regarding the long-term effects of GLP-1 drugs, these findings are reassuring in showing no increased risk of cancer, she adds.
“It makes us feel a little bit more comfortable in terms of the safety of GLP-1 class because it’s looking at such a wide population over a really long time,” Poddar says. “There is a lot of stigma around these medications and staying on them for a long time,” especially among patients with obesity, she says, “so it’s very reassuring that the numbers aren’t going the opposite direction.”
Sonali Thosani, an endocrinologist at MD Anderson, agreed that it’s reassuring to see reduced cancer risks with long-term use of these drugs. “When GLP-1s first came out, there was some concern about them causing an increased risk of pancreatic cancer,” she says, and studies have shown mixed results on risk of thyroid cancer with these medications, but these findings are encouraging.
Though the study cannot show that GLP-1 drugs directly lower cancer risk, there are a couple of ways they might induce a protective effect.
One way that obesity is thought to increase the risk of cancer is because adipose (fat) tissue releases inflammatory hormones that can then cause uncontrolled cell growth, Thosani says. With less fat there is less inflammation.
Insulin resistance—when the body struggles to take up sugar from the blood, leading to the development of type 2 diabetes—drives cancer-causing dysfunctional fat tissue, and GLP-1 drugs also help reduce insulin resistance, says Laura Montour, an obesity medicine specialist at the University of Washington in Seattle.
Other pathways for reducing cancer
Another way GLP-1 drugs may help reduce cancer risk is in the way they can change patients’ eating behaviors, Montour says. Many people taking GLP-1 drugs feel unwell after eating more highly processed foods or higher carbohydrate foods. They tend to crave more protein-rich foods, so a shift toward higher quality foods may contribute not only to their weight loss but to a lower risk in cancer, she says.
Finally, a reduction in inflammation from GLP-1 drugs may help lower cancer risk since cancer is a “pro-inflammatory state,” Poddar says.
Karen M. Basen-Engquist, a professor at The University of Texas MD Anderson Cancer Center in Houston who studies health behavior and cancer risk, says these findings complement previous research that showed reduced cancer risk in patients who lose weight through bariatric surgery, even though this study did not include data on whether patients lost weight.
The main takeaway is that GLP-1 drugs may be a better option than insulin for people with type 2 diabetes at risk of obesity-related cancers if the GLP-1 drug sufficiently treats the diabetes, she says.
“Obviously there are other factors that doctors and patients consider when choosing drugs for treating diabetes,” Basen-Engquist says, but patients taking insulin may want to discuss with their physician whether they might gain additional benefit from a GLP-1 medication.
Thosani notes that some patients have added a GLP-1 drug to taking insulin and then lost enough weight that they no longer require insulin therapy. She says it makes sense that a medication which treats obesity could result in weight loss that could then decrease the risk of obesity-associated cancers, but it’s hard to determine whether GLP-1s are causing the lower cancer risk without more trials.
“There’s a good chance that, as we have more patients who get GLP-1 agonists for obesity, we might find similar results,” Thosani says.
Montour agrees that GLP-1s are great tools.
“These medicines are exciting adjuncts,” she says, “but the lifestyle piece is also really important in terms of getting good sleep and getting 150 minutes of exercise each week for overall health and likely cancer protection as well.”
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