Can GLP-1s Protect Against Obesity-Related Cancers?
New data suggest that glucagon-like peptide 1 (GLP-1) receptor agonists, used to treat diabetes and obesity, may also help guard against obesity-related cancers.
In a large observational study, new GLP-1 agonist users with obesity and diabetes had a significantly lower risk for 14 obesity-related cancers than similar individuals who received dipeptidyl peptidase-4 (DPP-4) inhibitors, which are weight-neutral.
This study provides a 'reassuring safety signal' showing that GLP-1 drugs are linked to a modest drop in obesity-related cancer risk, and not a higher risk for these cancers, said lead investigator Lucas Mavromatis, medical student at NYU Grossman School of Medicine in New York City, during a press conference at American Society of Clinical Oncology (ASCO) 2025 annual meeting.
However, there were some nuances to the findings. The protective effect of GLP-1 agonists was only significant for colon and rectal cancers and for women, Mavromatis reported. And although GLP-1 users had an 8% lower risk of dying from any cause, the survival benefit was also only significant for women.
Still, the overall 'message to patients is GLP-1 receptor treatments remain a strong option for patients with diabetes and obesity and may have an additional, small favorable benefit in cancer,' Mavromatis explained at the press briefing.
'Intriguing Hypothesis'
Obesity is linked to an increased risk of developing more than a dozen cancer types, including esophageal, colon, rectal, stomach, liver, gallbladder, pancreatic, kidney, postmenopausal breast, ovarian, endometrial and thyroid, as well as multiple myeloma and meningiomas.
About 12% of Americans have been prescribed a GLP-1 medication to treat diabetes and/or obesity. However, little is known about how these drugs affect cancer risk.
To investigate, Mavromatis and colleagues used the Optum healthcare database to identify 170,030 adults with obesity and type 2 diabetes from 43 health systems in the United States.
Between 2013 and 2023, half started a GLP-1 agonist and half started a DPP-4 inhibitor, with propensity score matching used to balance characteristics of the two cohorts.
Participants were a mean age of 56.8 years, with an average body mass index of 38.5; more than 70% were White individuals and more than 14% were Black individuals.
During a mean follow-up of 3.9 years, 2501 new obesity-related cancers were identified in the GLP-1 group and 2671 in the DPP-4 group — representing a 7% overall reduced risk for any obesity-related cancer in the GLP-1 group (hazard ratio [HR], 0.93).
When analyzing each of the 14 obesity-related cancers separately, the protective link between GLP-1 use and cancer was primarily driven by colon and rectal cancers. GLP-1 users had a 16% lower risk for colon cancer (HR, 0.84) and a 28% lower risk for rectal cancer (HR, 0.72).
'No other cancers had statistically significant associations with GLP-1 use,' Mavromatis told briefing attendees. But 'importantly, no cancers had statistically significant adverse associations with GLP-1 use,' he added.
Experts have expressed some concern about a possible link between GLP-1 use and pancreatic cancer given that pancreatitis is a known side effect of GLP-1 use. However, 'this is not borne out by epidemiological data,' Mavromatis said.
'Additionally, we were not able to specifically assess medullary thyroid cancer, which is on the warning label for several GLP-1 medications, but we did see a reassuring lack of association between GLP-1 use and thyroid cancer as a whole,' he added.
During follow-up, there were 2783 deaths in the GLP-1 group and 2961 deaths in the DPP-4 group — translating to an 8% lower risk for death due to any cause among GLP-1 users (HR, 0.92; P = .001).
Mavromatis and colleagues observed sex differences as well. Women taking a GLP-1 had an 8% lower risk for obesity-related cancers (HR, 0.92; P = .01) and a 20% lower risk for death from any cause (HR, 0.80; P < .001) compared with women taking a DPP-4 inhibitor.
Among men, researchers found no statistically significant difference between GLP-1 and DPP-4 use for obesity-related cancer risk (HR, 0.95; P = .29) or all-cause mortality (HR, 1.04; P = .34).
Overall, Mavromatis said, it's important to note that the absolute risk reduction seen in the study is 'small and the number of patients that would need to be given one of these medications to prevent an obesity-related cancer, based on our data, would be very large.'
Mavromatis also noted that the length of follow-up was short, and the study assessed primarily older and weaker GLP-1 agonists compared with newer agents on the market. Therefore, longer-term studies with newer GLP-1s are needed to confirm the effects seen as well as safety.
In a statement, ASCO President Robin Zon, MD, said this trial raises the 'intriguing hypothesis' that the increasingly popular GLP-1 medications might offer some benefit in reducing the risk of developing cancer.
Zon said she sees many patients with obesity, and given the clear link between cancer and obesity, defining the clinical role of GLP-1 medications in cancer prevention is 'important.'
This study 'leads us in the direction' of a potential protective effect of GLP-1s on cancer, but 'there are a lot of questions that are generated by this particular study, especially as we move forward and we think about prevention of cancers,' Zon told the briefing.
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