New Data Suggest GLP-1s May Improve Survival in Patients With Cancer and Diabetes

New research suggests that using glucagon-like peptide-1 receptor agonists (GLP-1 1RAs) may be associated with improved survival in older patients with both cancer and type 2 diabetes.¹ The retrospective cohort study, published in JAMA Network Open, found that patients taking a GLP-1 RA had a significantly lower risk of all-cause mortality compared to those taking dipeptidyl peptidase-4 inhibitors (DPP4is), another class of glucose-lowering drugs.

Study Design and Key Findings

The study, led by researchers from the University of Florida, analyzed Medicare data from 2013 to 2020. The cohort included more than 5100 patients aged 66 or older with type 2 diabetes and 1 of 9 different cancer types, including endometrial, colorectal, lung, and breast cancers. The researchers compared the survival outcomes of patients who initiated treatment with a GLP-1 RA (such as semaglutide [Ozempic]) to those who started taking an SGLT2i or a DPP4i. To minimize confounding factors, the study used a 1:1 propensity score matching approach.

The primary finding was a significant association between GLP-1 RA use and reduced mortality when compared to DPP4i use. The hazard ratio (HR) for all-cause mortality was 0.60 (95% CI, 0.51–0.70), indicating a 40% reduction in mortality risk.

“The survival benefit over DPP4i persisted across age, sex, non-Hispanic White race, obesity status, and several cancer types (colorectal, lung, and breast),” study authors wrote.

Interestingly, the study found no significant difference in mortality risk between GLP-1RA users and SGLT2i users (HR, 1.03; 95% CI, 0.85–1.23). This finding suggests that while GLP-1 RAs may offer a survival advantage over some glucose-lowering drugs, they may be comparable to SGLT2is in this specific patient population.

Potential Mechanisms and Clinical Implications

While the study is not designed to establish causality, the authors propose several potential mechanisms for the observed survival difference. Although both GLP-1 RAs and DPP4is target the incretin pathway, GLP-1 RAs have been shown to provide more robust metabolic benefits. These include greater reductions in hemoglobin A1c levels and body weight, as well as improvements in beta-cell and cardiac function, and reduced albuminuria. These systemic effects could potentially slow cancer progression by mitigating factors like hyperinsulinemia and inflammation, which are often linked to tumor growth.

The study's findings add to a growing body of evidence exploring the complex relationship between metabolic health and cancer outcomes. Previous research on other glucose-lowering drugs like metformin has shown mixed results, highlighting the need for more targeted studies. The potential for GLP-1 RAs to improve survival in a high-risk population with cancer and diabetes warrants further investigation.

Limitations and Future Research

The authors acknowledge several limitations of this retrospective study. The potential for unmeasured confounding factors, despite the use of propensity score matching, remains a concern. The study's E-value of 2.73 for the GLP-1 RA vs DPP4i comparison suggests that a confounder would need to have a strong association with both drug use and mortality to negate the observed effect.

Additionally, some subgroup analyses were underpowered due to small sample sizes, which limited the ability to detect meaningful differences in certain patient groups. The study also focused on an older Medicare population, and the findings may not be generalizable to younger patients with cancer and diabetes.

Previous data, including a 2024 study published in JAMA Network Open, provided supporting evidence that GLP-1 RAs may reduce the risk of specific obesity-related cancers when compared with insulin.²

REFERENCES:

1. Radwan RM, Lu Y, Dai H, et al. GLP-1 RA Use and Survival Among Older Adults With Cancer and Type 2 Diabetes. JAMA Netw Open. 2025 Jul 1;8(7):e2521887. doi: 10.1001/jamanetworkopen.2025.21887.

2. Wang L, Xu R, Kaelber DC, et al. Glucagon-Like Peptide 1 Receptor Agonists and 13 Obesity-Associated Cancers in Patients With Type 2 Diabetes. JAMA Netw Open. 2024 Jul 1;7(7):e2421305. doi: 10.1001/jamanetworkopen.2024.21305.