Safety of SGLT2-Inhibitors in Patients with Multiple Myeloma and Diabetes

Objective : An estimated 10-20% of patients with multiple myeloma (MM) have type 2 diabetes (T2DM). About half of patients with MM will experience renal insufficiency, the risk of which increases in the setting of T2DM. While sodium-glucose cotransporter 2 inhibitors (SGLT2i) are beneficial in patients with chronic kidney disease (CKD) due to diabetic or hypertensive nephropathy, the role of SGLT2i in MM-related CKD is unknown. MM therapies target the immune system and may increase the risk of infections associated with SGLT2i. The current work is the first to examine the potential benefit and safety of SGLT2i in patients with MM and T2DM.

Methods: A retrospective cohort study was performed on patients aged 18 years or older with MM who received SGLT2i therapy between March 2013 and December 2020 at a quaternary academic medical center. Electronic medical records were reviewed for the following data: demographics, comorbidities, MM parameters, medication and medical history, SGLT2i usage and duration, and hemoglobin A1c (HbA1c) and serum creatinine pre- and post-SGLT2i initiation. Data are presented as mean ± standard deviation, or counts and percentages. This study was approved by the Institutional Review Board.

Results: In total, 50 patients were identified. Patients who were diagnosed with MM after initiation of SGLT2i (n= 12), did not have any MM data available (n=1), or for whom SGLT2i usage could not be verified (n= 4) were excluded. Thirty-three patients were included in the final analysis. The mean age was 63 (±7.8) years, 63.6% were male, and 87.9% had active MM or MM in remission. Most had received stem-cell transplantation (55.0%) and multiple lines of chemotherapy (63.6%) prior to SGLT2i initiation. The average HbA1c was 7.4% (±1.2%) and 20% of patients had CKD prior to SGLT2i initiation. The overall SGLT2i discontinuation rate was 42.4%, and the mean duration of therapy was 2.2 (±1.5) years. Notably, 21.4% of discontinuation events were due to an increase in creatinine; however, there were no statistically significant changes in serum creatinine, total body weight, HbA1c, or 24-hour urine protein at 15 months follow-up. Other reasons for SLGT2i discontinuation included loss to follow-up, change of health insurance coverage for SGLT2i, and unrelated hospital admission. Genitourinary infection was not cited as a reason for SGLT2i discontinuation.

Discussion/Conclusion: SGLT2i therapy may be safe in patients with MM and T2DM, but no benefit was found with respect to serum creatinine, HbA1c, or 24-hour urine protein. Prospective research is required to further evaluate the potential benefit and safety of SGLT2i therapy in this population.