Study Links GLP-1 Drugs to Lower Cancer Risk

CHICAGO — In patients with type 2 diabetes and obesity, use of GLP-1 receptor agonists was associated with a lower risk of obesity-related cancers and death from any cause, a target trial emulation study found.

In a matched group of more than 170,000 adults, those treated with GLP-1 agonists had a lower risk of developing an obesity-related cancer over a median follow-up of about 4 years when compared with DPP-4 inhibitor treatment (HR 0.93, 95% CI 0.88-0.98), reported Lucas Mavromatis, BSc, a medical student at NYU Grossman School of Medicine.

And GLP-1 agonists were associated with an 8% lower mortality risk as well (HR 0.92, 95% CI 0.87-0.97), according to findings presented during a press briefing ahead of the American Society of Clinical Oncology (ASCO) annual meeting.

“This large cohort study represents a reassuring safety signal showing that GLP-1 drugs are not linked to a higher incidence of cancers, and rather are linked to a modest 7% drop in obesity-related cancers,” said Mavromatis, adding that the effect was primarily driven by cancers of the colon (HR 0.84, 95% CI 0.72-0.98) and rectum (HR 0.72, 95% CI 0.56-0.93).

No cancers had statistically significant adverse associations with GLP-1 use, he noted, including pancreatic cancer (HR 1.00, 95% CI 0.83-1.20) and thyroid cancer (HR 1.02, 95% CI 0.83-1.25).

“Because of GLP-1s’ known side effect of pancreatitis, there’s been some concern about links between GLP-1 use and pancreatic cancer. And this just shows, as have other human studies, that that is sort of not borne out by epidemiological data,” said Mavromatis. “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.”

The findings add to other research showing a lower risk of obesity-related cancers in patients taking GLP-1 drugs, a class of drugs initially approved for type 2 diabetes and obesity but now with expanding indications that include cardiovascular disease, chronic kidney disease, and sleep apnea.

Mavromatis explained that obesity is a known driver of 13 major cancers, including cancers of the gastrointestinal tract — such as colorectal and pancreatic cancers — and cancers that affect women, including postmenopausal breast cancer and endometrial cancer.

In a statement, ASCO President Robin Zon, MD, said the trial raises an intriguing hypothesis — that the increasingly popular GLP-1 medications — including the blockbuster injectables semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound) — might offer some benefit in reducing cancer risk.

“I see 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,” she said. “Though this trial does not establish causation, it hints that these drugs might have a preventative effect. Future research is needed to validate these findings, including in patients who do not have diabetes.”

Discussing the GLP-1 agonists’ possible role as a cancer preventive agent, Mavromatis noted the study suggested a large number needed to treat to prevent one obesity-related cancer.

The target trial emulation study included two propensity score-matched cohorts from 43 health systems in the U.S.: 85,015 patients who started on a GLP-1 agonist from 2013 to 2023 and 85,015 who started on a DPP-4 inhibitor. For inclusion, these individuals had to have a diabetes diagnosis and a body mass index (BMI) of 30 or above.

Average participant age was 57 years, about half were women, over 70% were white, and more than 14% were Black. Mean BMI was 38.5. The most commonly used GLP-1 receptor agonist in the study was liraglutide (Victoza, Saxenda), said Mavromatis, an older-generation drug with a weaker effect on weight loss compared with the newer injectables. DPP-4 inhibitors have not been shown to have an effect on weight.

Over a median follow-up of 3.9 years, 2,501 newly diagnosed obesity-related cancers occurred in the GLP-1 group as compared with 2,671 in the DPP-4 inhibitor group. Deaths occurred in 2,783 and 2,961, respectively.

When looking at sex, only women on GLP-1 drugs had a significantly lower risk of both obesity-related cancers and death from any cause:

Women: HR 0.92 (95% CI 0.86-0.98) for cancers and HR 0.80 (95% CI 0.74-0.86) for mortalityMen: HR 0.95 (95% CI 0.86-1.05) for cancers and HR 1.04 (95% CI 0.96-1.11) for mortality
Limitations included the short follow-up time and that patients largely were taking older-generation GLP-1 drugs.

Disclosures

No study funding was reported.

Mavromatis had no relationships to disclose.

Zon reported a relationship with Cincinnati Cancer Advisors and stock and other ownership interests in AstraZeneca, Berkshire Hathaway, CRISPR Therapeutics, McKesson, Moderna Therapeutics, Oncolytics, Select Sector SPDR Health Care, and TG Therapeutics.

Primary Source

American Society of Clinical Oncology

Source Reference: Mavromatis LA “Glucagon-like peptide-1 receptor agonists and incidence of obesity-related cancer in adults with diabetes: a target-trial emulation study” ASCO 2025; Abstract 10507.