TOPLINE:

In patients with type 2 diabetes (T2D), dual therapy with metformin and GLP-1 receptor agonists (RAs) was associated with a 39% lower risk for adiposity-related cancers and a 67% lower risk for mortality over 5 years than DPP-4 inhibitor therapy.

METHODOLOGY:

• Previous studies have suggested that T2D drugs such as metformin and GLP-1 RAs may lower the risk for cancer, but their combined effects on the incidence of cancer remain unclear.
• Researchers conducted a cohort study using the TriNetX database to evaluate the individual and combined effects of metformin and GLP-1 RA use on the risk for adiposity-related cancers and incidence of mortality in patients with T2D aged over 18 years.
• They compared outcomes in three treatment cohorts — metformin, GLP-1 RAs, and metformin plus GLP-1 RA — with those in a reference cohort receiving DPP-4 inhibitor intervention; after propensity score matching, the matched sample sizes in each group were 88,786 (for metformin vs DPP-4), 112,735 (for GLP-1 RA vs DPP-4), and 36,347 (for metformin plus GLP-1 RA vs DPP-4).
• The primary outcome was time to incident composite adiposity-related cancer.
• Patients were followed for 5 years from the initiation of treatment.

TAKEAWAY:

• In patients with T2D, the use of metformin was associated with a 4% lower risk for adiposity-related cancers (hazard ratio [HR], 0.96; 95% CI, 0.92-0.99) and a 22% lower incidence of mortality (HR, 0.78; 95% CI, 0.76-0.80) than DPP-4 inhibitor therapy.
• GLP-1 RA therapy alone was associated with a 14% reduction in the incidence of all adiposity-related cancers (HR, 0.86; 95% CI, 0.82-0.89) and a 39% reduction in the incidence of mortality (HR, 0.61; 95% CI, 0.59-0.63).
• Dual therapy with metformin and GLP-1 RAs was associated with a 39% reduced risk for all adiposity-related cancers (HR, 0.61; 95% CI, 0.57-0.65) and a 67% reduction in the incidence of mortality (HR, 0.33; 95% CI, 0.32-0.35).
• Specifically, dual therapy was associated with reduced risks for hepatocellular, colorectal, pancreatic, esophageal, stomach, uterine, breast, kidney, and brain cancers, as well as multiple myeloma, head and neck cancers, and melanoma.

IN PRACTICE:

“Crucially, for the first time, we highlight a novel synergistic association of dual metformin and GLP-1 RA treatment with (reduced) cancer incidence in patients with T2D, both with and without obesity,” the authors of the study wrote.

“Considering the worldwide pandemics of obesity, T2D and these higher rates of cancer incidence, particularly in younger people, explorations of effective cancer prevention strategies are of great clinical and public health importance,” they added.

SOURCE:

This study was led by Alex E. Henney, MBChB, University of Liverpool, Liverpool, England. It was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The study could not establish causation. The researchers extracted data from electronic health records, which may have contained missing data, and residual bias could have existed due to coding limitations for potential confounding variables. Additionally, the 5-year follow-up may have been too short to capture the full effects of metformin and GLP-1 RA on incidence of cancer.

DISCLOSURES:

Some authors reported receiving research support, grants, fellowships, honoraria; serving as consultants; and/or holding other ties with various pharmaceutical companies and organizations. One author declared being an employee of TriNetX, LLC.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.