New Weight Loss Drugs May Fight Obesity-Related Cancer, Too

The latest glucagon-like peptide 1 (GLP-1) receptor agonists have been heralded for their potential to not only boost weight loss and glucose control but also improve cardiovascular, gastric, hepatic, and renal values.

Throughout 2024, research has also indicated GLP-1 drugs may reduce risks for obesity-related cancer as well.

In a US study of more than 1.6 million patients with type 2 diabetes, cancer researchers found that patients who took a GLP-1 drug had significant risk reductions for 10 of 13 obesity-associated cancers, as compared with patients who only took insulin.

The research team found a reduction in esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma. They also saw a declining risk for stomach cancer, though it wasn’t considered statistically significant, but not a reduced risk for postmenopausal breast cancer or thyroid cancer.

The associations make sense, particularly because GLP-1 drugs have unexpected effects on modulating immune functions linked to obesity-associated cancers.

“The protective effects of GLP-1s against obesity-associated cancers likely stem from multiple mechanisms,” said lead author Lindsey Wang, a medical student and research scholar at Case Western Reserve University in Cleveland.

“These drugs promote substantial weight loss, reducing obesity-related cancer risks,” she said. “They also enhance insulin sensitivity and lower insulin levels, decreasing cancer cell growth signals.”

Additional GLP-1 Studies

The Case Western team also published a study in December 2023 that found people with type 2 diabetes who took GLP-1s had a 44% lower risk for colorectal cancer than those who took insulin and a 25% lower risk than those who took metformin. The research suggested even greater risk reductions among those with overweight or obesity, with GLP-1 users having a 50% lower risk than those who took insulin and a 42% lower risk than those who took metformin.

In another recent Case Western study, both bariatric surgery and GLP-1 drugs reduced the risk for obesity-related cancers. While those who had bariatric surgery had a 22% risk reduction over 10 years, as compared with those who received no treatment, those taking GLP-1 had a 39% risk reduction.

Other studies worldwide have looked at GLP-1 drugs and tumor effects among various cancer cell lines. In a study using pancreatic cancer cell lines, GLP-1 liraglutide suppressed cancer cell growth and led to cell death. Similarly, a study using breast cancer cells found liraglutide reduced cancer cell viability and the ability for cells to migrate.

As researchers identify additional links between GLP-1s and improvements across organ systems, the knock-on effects could lead to lower cancer risks as well. For example, studies presented at The Liver Meeting in San Diego in November pointed to GLP-1s reducing fatty liver disease, which can slow the progression to liver cancer.

“Separate from obesity, having higher levels of body fat is associated with an increased risk of several forms of cancer,” said Neil Iyengar, MD, an oncologist at Memorial Sloan Kettering Cancer Center in New York City. Iyengar researches the relationship between obesity and cancer.

“I foresee that this class of drugs will revolutionize obesity and the cancer burden that comes with it, if people can get access,” he said. “This really is an exciting development.”

Ongoing GLP-1 Research

On the other hand, cancer researchers have also expressed concerns about potential associations between GLP-1s and increased cancer risks. In the obesity-associated cancer study by Case Western researchers, patients with type 2 diabetes taking a GLP-1 drug appeared to have a slightly higher risk for kidney cancer than those taking metformin.

In addition, GLP-1 studies in animals have indicated that the drugs may increase the risks for medullary thyroid cancer and pancreatic cancer. However, the data on increased risks in humans remain inconclusive, and more recent studies refute these findings.

For instance, cancer researchers in India conducted a systematic review and meta-analysis of semaglutide and cancer risks, finding that 37 randomized controlled trials and 19 real-world studies didn’t find increased risks for any cancer, including pancreatic and thyroid cancers.

In another systematic review by Brazilian researchers, 50 trials found GLP-1s didn’t increase the risk for breast cancer or benign breast neoplasms.

In 2025, new retrospective studies will show more nuanced data, especially as more patients — both with and without type 2 diabetes — take semaglutide, tirzepatide, and new GLP-1 drugs in the research pipeline.

“The holy grail has always been getting a medication to treat obesity,” said Anne McTiernan, MD, PhD, an epidemiologist and obesity researcher at the Fred Hutchinson Cancer Center in Seattle.

“There have been trials focused on these medications’ effects on diabetes and cardiovascular disease treatment, but no trials have tested their effects on cancer risk,” she said. “Usually, many years of follow-up of large numbers of patients are needed to see cancer effects of a carcinogen or cancer-preventing intervention.”

Those clinical trials are likely coming soon, she said. Researchers will need to conduct prospective clinical trials to examine the direct relationship between GLP-1 drugs and cancer risks, as well as the underlying mechanisms linked to cancer cell growth, activation of immune cells, and anti-inflammatory properties.

Because GLP-1 medications aren’t intended to be taken forever, researchers will also need to consider the associations with long-term cancer risks. Even so, weight loss and other obesity-related improvements could contribute to overall lower cancer risks in the end.

“If taking these drugs for a limited amount of time can help people lose weight and get on an exercise plan, then that’s helping lower cancer risk long-term,” said Sonali Thosani, MD, associate professor of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston.

“But it all comes back to someone making lifestyle changes and sticking to them, even after they stop taking the drugs,” she said. “If they can do that, then you’ll probably see a net positive for long-term cancer risks and other long-term health risks.”