Studies have shown that having overweight or obesity increases the risk of developing more than a dozen cancers, including meningioma; multiple myeloma; and esophageal, thyroid, breast, gallbladder, stomach, liver, pancreatic, kidney, ovarian, uterine, and colorectal cancers. The presence of excess body fat is also linked to worse prognosis in patients with these specific tumors.
A large observational study aimed to evaluate whether glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or dipeptidyl peptidase–4 (DPP-4) inhibitors, a weight-neutral class of diabetes medication, may reduce the risk of obesity-related cancers more effectively in adults with diabetes and obesity. Mavromatis et al reported ahead of the 2025 ASCO Annual Meeting that GLP-1 RAs were associated with a lower risk of obesity-related cancers in this population (Abstract 10507).
Study Methodology
The researchers collected data on 170,030 adults from 43 health systems nationwide. Patients with a body mass index (BMI) of ≥ 30 kg/m2 and a diagnosis of diabetes who newly initiated a GLP-1 RA or DPP-4 inhibitor between 2013 and 2023 were included in the study. Half of the participants—85,015—were included in the GLP-1 RA group, and half, 85,015 were included in the DDP-4 inhibitor group.
Patients prescribed GLP-1 RAs (mean age = 56.8 years) were matched 1:1 on propensity score for GLP-1 RA prescription and prescription year with patients prescribed DPP-4 inhibitors (mean age = 56.8 years). About half of the participants were women, more than 70% were White, and more than 14% were Black. The average BMI was 38.5 kg/m2.
The researchers then compared obesity-related cancer incidence between the two groups. Adjusted hazard ratios (HRs) were calculated using Cox regression, representing ratios of the incidence of composite obesity-related cancer and all-cause death in matched pairs of patients prescribed GLP-1 RAs vs DPP-4 inhibitors over an average follow-up duration of 3.8 years for GLP-1 RAs and 3.9 years for DPP-4 inhibitors.
Key Results
The researchers found that over a mean follow-up of 3.9 years, there was a lower risk of obesity-related cancers (adjusted HR = 0.93; 95% confidence interval [CI] = 0.88–0.98, P = .005) and all-cause death (adjusted HR = 0.92; 95% CI = 0.87–0.97, P = .001) associated with GLP-1 RA use vs DPP-4 inhibitor use.
When the researchers looked at the difference between the risk of obesity-related cancer in men and women, for men, there was not a statistically significant difference between the two treatment arms for either obesity-related cancers or all causes of death. Women treated with GLP-1 RAs were found to have an 8% lower risk of obesity-related cancer and a 20% lower risk of all causes of death compared with women treated with DDP-4 inhibitors. In addition, assessments of cancer subtypes showed protective associations between GLP-1 RA use and colon and rectal cancers.
“GLP-1 RAs were associated with a lower risk of obesity-related cancer compared with DPP-4 inhibitors in a large, real-world cohort of patients with diabetes and obesity. Future studies should prospectively assess the role of GLP-1 RAs in cancer prevention,” concluded the study authors.
Clinical Significance
“Although obesity is now recognized as an increasingly important cause of cancer in the United States and worldwide, no medications have been proven to lower the cancer risk associated with obesity,” said Lucas A. Mavromatis, ScB, lead author of this study and a medical student at the NYU Grossman School of Medicine in New York City. “Our study begins to fill that gap by evaluating GLP-1 RAs, a relatively new but widely prescribed medication [class] that treats diabetes, obesity, and related conditions. Our results suggest they may modestly cut the chance of developing certain cancers—especially cancers of the colon and rectum—and reduce rates of death due to all causes. These data are reassuring, but more studies are required to prove causation.”
ASCO Perspective
“This trial raises an intriguing hypothesis that the increasingly popular GLP-1 medications used to treat diabetes and obesity might offer some benefit in reducing the risk of developing cancer,” said ASCO President Robin T. Zon, MD, FACP, FASCO. “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. 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.”
Disclosure: Funding for this study was provided by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. For full disclosures of the study authors, visit coi.asco.org.
