SGLT-2 Inhibitors are Associated With a Lower Risk of Multiple Myeloma

Area of Science:

• Oncology
• Pharmacology
• Genetics

Background:

• Multiple myeloma (MM) is a hematologic malignancy with complex underlying mechanisms.
• Sodium-glucose transport protein-2 inhibitors (SGLT2i) are used for diabetes management and may influence MM-related conditions.
• Dipeptidyl peptidase-4 inhibitors (DPP4i) serve as a comparator drug class in this study.

Purpose of the Study:

• To investigate the association between SGLT2i use and the risk of developing multiple myeloma (MM).
• To explore the potential mechanisms underlying SGLT2i's effects on MM through gene expression analysis.
• To compare the risk of MM in patients exposed to SGLT2i versus DPP4i.

Main Methods:

• A pharmacoepidemiologic study using US nationwide health insurance claims data.
• Cox proportional hazards models were employed to assess the comparative risk of MM.
• Differential gene expression analysis was performed on cell lines treated with SGLT2i and DPP4i.

Main Results:

• SGLT2i exposure was associated with a significantly reduced risk of MM compared to DPP4i exposure (HR ≤ 0.37, p < 0.001).
• This reduced risk was consistent across various subpopulations, including those with anemia, renal failure, and monoclonal gammopathy of undetermined significance.
• Gene expression analysis revealed unique differentially expressed genes for SGLT2i and DPP4i, with MM-associated genes enriched in SGLT2i-related genes, suggesting tumor-suppressing activities.

Conclusions:

• SGLT2i use is linked to a lower incidence of multiple myeloma in patients, particularly those with diabetes.
• The findings suggest SGLT2i may possess tumor-suppressing properties relevant to MM.
• Further research into SGLT2-mediated pathways could offer novel therapeutic strategies for MM prevention and treatment.