A large retrospective study using Medicare data has revealed that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may offer significant survival advantages for older patients managing both cancer and type 2 diabetes. The research, published in JAMA Network Open, provides new insights into the comparative effectiveness of diabetes medications in this vulnerable patient population.
Study Design and Patient Population
Researchers from the University of Florida analyzed Medicare data from 2013 to 2020, focusing on patients aged 66 years or older who had both type 2 diabetes and one of nine cancer types: thyroid, pancreatic, bladder, colorectal, lung, kidney, breast, endometrial, or prostate cancer. The study employed propensity score matching to reduce confounding factors and create comparable patient groups.
The analysis included two primary comparisons: 2,553 matched pairs comparing GLP-1 RAs to SGLT2 inhibitors, and 2,564 matched pairs comparing GLP-1 RAs to DPP4 inhibitors.
Mortality Outcomes and Risk Reduction
The study revealed striking differences in mortality outcomes between treatment groups. While no significant difference in mortality risk was observed between GLP-1 RA and SGLT2 inhibitor users, GLP-1 RA use was associated with significantly lower mortality compared to DPP4 inhibitor use, with a hazard ratio of 0.60.
This translates to a 40% reduction in mortality risk for patients using GLP-1 RAs compared to those using DPP4 inhibitors. The researchers calculated E-values of 1.21 for GLP-1 RA versus SGLT2i comparison and 2.73 for GLP-1 RA versus DPP4i comparison, indicating the robustness of the findings.
Consistent Benefits Across Cancer Types
Subgroup analyses demonstrated that the survival benefit of GLP-1 RAs over DPP4 inhibitors remained consistent across various patient characteristics and cancer types. The protective effect was observed regardless of age, sex, or race (specifically non-Hispanic White patients), and was particularly evident in patients with colorectal, lung, and breast cancers.
Clinical Implications and Mechanisms
Lead researcher Rotana M. Radwan, Ph.D., and colleagues suggest that the observed survival differences may reflect drug class-specific systemic effects of GLP-1 RAs. While the exact mechanisms remain unclear, the findings add to growing evidence of potential benefits of GLP-1 RAs beyond glucose control.
The researchers emphasize important limitations of their observational study. "While causality cannot be inferred, our study adds novel evidence on the comparative effectiveness of GLP-1 RAs," the authors write. "The observed survival differences may reflect drug class-specific systemic effects."
Study Limitations and Future Directions
As a retrospective observational study, the research cannot establish causality between GLP-1 RA use and improved survival outcomes. The findings represent associations that require validation through prospective clinical trials to confirm causal relationships and understand underlying mechanisms.
The study's focus on Medicare beneficiaries aged 66 and older also limits generalizability to younger patient populations. Additionally, the analysis was restricted to nine specific cancer types, leaving questions about potential benefits in other malignancies.
Despite these limitations, the research provides valuable real-world evidence for clinicians treating older patients with the dual burden of cancer and diabetes, potentially informing treatment decisions while awaiting more definitive clinical trial data.
