The success and popularity of GLP-1 receptor agonists (RAs) for the treatment of patients with diabetes and obesity has led to intense interest in other potential effects of treatment, including whether using them has any association with getting cancer.

Study outcomes to date have been conflicting. Results from a new systematic review and meta-analysis of 48 trials involving 94,245 participants provide some reassurance related to cancer risk and these drugs but suggest the jury is still out.

The analysis showed “little or no effect [of GLP-1 RA] on risk for obesity-related cancers,” Albert Ko, MD, of the Harvard T.H. Chan School of Public Health, Boston, and colleagues reported.

The findings were published online on December 8, 2025, in Annals of Internal Medicine.

What Is Known About the Association Between GLP-1s and Cancer?

A target trial emulation using a database of records for more than 86,600 treated adults and matched controls showed a lower cumulative cancer incidence among GLP-1 RA users vs nonusers during follow-up (13.6 vs 16.4 incidents per 1000 person-years, respectively; hazard ratio [HR], 0.83).

In that study, published in August in JAMA Oncology, GLP-1 RAs were associated with a significantly lower risk for endometrial cancer, ovarian cancer, and meningioma (HRs, 0.75, 0.53, and 0.69, respectively), and with trends for a lower risk for pancreatic, bladder, and breast cancers. However, there was also a trend toward increased kidney cancer risk among GLP-1 RA users vs nonusers (HR, 1.38), as reported by Medscape Medical News.

A study presented in September at the American Thyroid Association (ATA) 2025 Meeting in Scottsdale, Arizona, found no association between GLP-1 RA treatment and risk for recurrence of progression of differentiated thyroid cancer. The investigators highlighted the findings against a backdrop of conflicting data, noting that prior research related to GLP-1 RAs and thyroid cancer focused mainly on the potential to trigger new cancer.

As reported at the time, findings have ranged from “one recent meta-analysis showing an odds ratio [OR] of 1.55 for an increased thyroid cancer risk, to another study suggesting the potential to lower cancer incidence with GLP-1s, to still another study showing an increased risk — but only in the first year.”

Raphael Cuomo, PhD, of the University of California, San Diego (UCSD), recently found a strong association between GLP-1 RA use and reduced risk for colon cancer mortality. In a study published online on November 11, 2025, in Cancer Investigation, the 5-year mortality rate among 6800 patients with colon cancer was 15.5% vs 37.1% in GLP-1 RA-treated vs nontreated patients.

“Taken together, the message [of the UCSD colon cancer study and new meta-analysis] is that GLP-1 drugs do not appear to meaningfully increase cancer risk and may, in some settings, be linked to better survival once cancer is present,” Cuomo, associate adjunct professor at UCSD and member of the UCSD Moores Cancer Center, said in an interview.

“More work is needed to be definitive,” he added, noting that “the field currently views GLP-1s primarily as cardiometabolic drugs with a reassuring cancer safety profile and a plausible, but as yet unconfirmed, upside for some cancer outcomes.”

What Did the New Study Show?

Ko and his colleagues reviewed 48 trials involving 94,245 participants and found, with moderate certainty, that GLP-1 RAs appear to have little or no effect on the risk for thyroid cancer (OR, 1.37), pancreatic cancer (OR, 0.84), breast cancer (OR, 0.95), or kidney cancer (OR, 1.12).

The investigators also found, with low certainty, that GLP-1 RAs may have little or no effect on colorectal, esophageal, liver, gallbladder, ovarian, or endometrial cancer, and on multiple myeloma and meningioma, whereas the effect of GLP-1 RAs on gastric cancer is “very uncertain.”

No significant differences were seen based on specific agent used or drug class, follow-up duration, patient population, weight-loss profile, dose, and duration of action, they noted.

Though limited by short follow-up and the fact that the trials included in the review were not designed to evaluate cancer outcomes, the findings suggest that GLP-1 RA treatment has little or no effect on the risk for obesity-related cancers, the investigators concluded. They noted, however, longer-term studies are needed to confirm the findings.

Do the Findings Have Implications for Research and Practice?

Ko and his colleagues concluded that “evidence from [randomized controlled trials] does not suggest increased risk for site-specific cancers with GLP-1 RAs or dual agonists, including thyroid, pancreatic, and other obesity-related cancers. However, for many site-specific cancers, the certainty of evidence was low or very low, largely due to sparse events and short follow-up, limiting our ability to detect long-latency outcomes.”

“These findings offer important insights into the safety of GLP-1 RAs but highlight the need for longer-term studies with cancer-specific endpoints to clarify potential risks or protective effects,” they wrote.

Cuomo said the findings to date are “reassuring for clinicians and patients who need these drugs for diabetes, obesity, or cardiovascular risk reduction.”

“Observational studies, including our own, that point toward improved survival in patients with established colon cancer and severe obesity are encouraging, but they do not yet justify prescribing GLP-1s as anticancer therapy,” he said. “In practice, I would suggest GLP-1s when patients meet standard metabolic indications, including in those with a history of cancer or high cancer risk.

“What this new meta-analysis does very well is to lower the temperature on fears that GLP-1s might be associated with developing cancer. If you pair that with our previous published study showing cancer survival benefits for people with high BMI [who took GLP-1s], we see the potential anticancer benefits of improved metabolic health.”

A “coordinated research agenda” to provide risk and benefit data that will help oncologists and patients make evidence-based treatment decisions should be the next step, Cuomo said, stressing a need for randomized trials with cancer outcomes, further observational analyses, and mechanistic studies.

Cancer immunologist Erika J. Crosby, PhD, is doing her part toward achieving that goal.

“The drugs that have really made an impact on weight loss…have only been around and widely used for a few years. For cancer, that is just not enough time to truly know what the impact will be,” she said in an interview. “The number of events is very low in this time frame. The studies that will really address the question of risk will come out in 10 or 15 years.”

Crosby’s lab at the Duke Cancer Institute, Durham, North Carolina, is gathering data to help answer that question.

“Mechanistically, we don’t have a great understanding of exactly which elements of dysfunction/risk are reversed by weight loss,” said Crosby, who is an assistant professor in the surgery and integrative immunobiology at Duke University Medical School, Durham, North Carolina. “Some things, like cardiovascular risk, seem to go down dramatically if even a small percentage of weight is lost, but others, like immune system dysfunction and chronic inflammation, may not return to baseline so quickly, or at all, after weight loss. This is one of the ways we are hoping to leverage preclinical models to measure these things directly.”

Ko reported consulting and other relationships with multiple pharmaceutical companies, as well as support from the Brazilian Ministry of Health, the World Health Organization, and the National Institutes of Health for education, research, and training purposes. Cuomo and Crosby reported having no disclosures.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape Medical News, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on X @SW_MedReporter.