Safety and Tolerability of SGLT2 Inhibitors in 377 Patients with Amyloidosis

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have demonstrated efficacy in improving cardiac and kidney outcomes in patients with heart failure, type 2 diabetes mellitus, and chronic kidney disease. However, there is paucity of data on the safety and tolerability of SGLT-2i in amyloidosis pts. This study evaluated the safety, tolerability, and reasons for discontinuation during first six months after initiation of SGLT-2i in amyloidosis pts. Methods: We conducted a retrospective study of 377 amyloidosis pts who were prescribed SGLT-2i between 2014 and 2024. Data collected included demographics, type of amyloidosis, type of organ involved, reasons for discontinuation of SGLT-2i during first 6 months after starting SGLT-2i. Results: Among our cohort of 377 amyloidosis patients, 101 (26.8%) pts had light chain amyloidosis (AL-amyloidosis), 255 (67.6%) pts with transthyretin amyloidosis (ATTR), and 21 (5.6%) with other types of amyloidosis with mean age 74.3 yrs, 84.3% males, and 92% whites. Among AL amyloidosis pts, 73% had cardiac and 42.5% with kidney amyloidosis. 97.6% ATTR pts had cardiac amyloidosis. 41 pts (10.9%) discontinued SGLT-2i within 6 months of initiation (10.9% AL amyloidosis; 11.4% ATTR, 4.8% other). Among 41 pts who discontinued SGLT-2i, the reasons included decline in kidney function (n=8, 19.5%), cost of medication (n=7, 17%), electrolyte disturbance (n=4, 9.7%), urogenital infection (n=3, 7.3%), fatigue/lethargy ( n=3, 7.3%), ketoacidosis (n=2; 4.9%), hypotension (n=2, 4.9%), and other reasons (n= 12; 29.3%). The discontinuation reasons among AL and ATTR are outlined in Table. Conclusion: Our study suggests that SGLT-2i are well tolerated by approx. 90% of amyloidosis pts with only 10% discontinuation rate within first six months of SGLT-2i initiation. The reasons for discontinuation are similar to what has been described for non-amyloidosis pts. We suggest monitoring of renal function panel after SGLT-2i initiation. Future studies are warranted to assess efficacy of SGLT-2i in improving cardiac and kidney outcomes in amyloidosis. Funding: Clinical Revenue Support