A retrospective cohort study found that glucagon-like peptide-1 receptor agonists could be associated with a significantly lower risk of hematologic malignancies in patients with type 2 diabetes compared with insulin therapy, including an 81% lower risk of myelodysplastic syndromes.

The study, led by Omer S. Ashruf, BS, and colleagues from the Cleveland Clinic and Northeast Ohio Medical University, analyzed data from TriNetX, an aggregated electronic health record repository covering approximately 25% of the U.S. population. The investigators identified 1.6 million patients with type 2 diabetes (T2D) who were prescribed glucagon-like peptide-1 receptor agonists (GLP-1 RA), insulin, or metformin between April 2005 and October 2023.

After propensity matching, the investigators compared the outcomes of 50,590 patients who took only GLP-1 RAs with 50,590 who took metformin alone as well as 47,716 who took only GLP-1 RAs with 47,716 who took insulin alone. The mean duration of GLP-1 RA prescription was 485.4 days.

When compared with metformin, GLP-1 RA use was associated with a statistically significant lower risk of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). No statistically significant difference in the risk of other hematologic malignancies was observed between these two groups.

When compared with insulin, GLP-1 RA use was associated with significantly lower risks across all categories of hematologic malignancies:

• Myeloid leukemia

• Lymphoid leukemia 

• Non-Hodgkin lymphoma 

• MDS

• MPN

• Monoclonal gammopathy 

• Multiple myeloma 

• Primary amyloidosis 

Across all hematologic malignancies, GLP-1 RA use was associated with a 54% lower risk compared with insulin.

In the comparison between GLP-1 RAs and metformin, the overall incidence of hematologic malignancies was similar, indicating that significant differences were limited to MDS and MPN.

"The findings of this cohort study suggest that GLP-1 RAs are associated with reduced risk of developing several hematologic [malignancies], particularly MDS and MPN, in patients with T2D," the study authors stated. They noted that the protective effects of GLP-1 RAs appear to be independent of glycemic control, potentially operating "through the reduction of proinflammatory cytokines implicated in hematopoiesis dysregulation and the development of MDS and MPN," they added.

The study’s limitations included reliance on encounter codes, potential residual confounding by indication, limited adjustment for multiple testing, lack of age stratification, and inability to assess dose-response relationships.

For insights into another potential complication associated with GLP-1 receptor agonists—diabetic retinopathy—see Sherrol A. Reynolds, OD, FAAO’s recent article in Optometric Management, “Diabetic Retinopathy and Glucagon-Like Peptide-1 Agonists: What’s the latest, and what are the implications for practice?”

The study authors concluded that GLP-1 RAs represent "a promising novel strategy for reducing cancer risk" but emphasized that further prospective studies are needed to explore the biological mechanisms by which these medications might prevent hematologic malignancies.

Source: JAMA Network Open