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. 2024 Jan 4;13(1):283.
doi: 10.3390/jcm13010283.

Safety and Tolerability of SGLT2 Inhibitors in Cardiac Amyloidosis-A Clinical Feasibility Study

Maximilian J Steinhardt  1   2 , Vladimir Cejka  1   3 , Mengmeng Chen  3 , Sabrina Bäuerlein  3 , Julia Schäfer  3 , Ali Adrah  3 , Sandra M Ihne-Schubert  1   2   4   5 , Aikaterini Papagianni  1   6 , K Martin Kortüm  1   2 , Caroline Morbach  1   3   7 , Stefan Störk  1   3   7
Affiliations

Safety and Tolerability of SGLT2 Inhibitors in Cardiac Amyloidosis-A Clinical Feasibility Study

Maximilian J Steinhardt et al. J Clin Med. .

Abstract

Sodium-glucose transport protein 2 inhibitors (SGLT2i) slow the progression of renal dysfunction and improve the prognosis of patients with heart failure. Amyloidosis constitutes an important subgroup for which evidence is lacking. Amyloidotic fibrils originating from misfolded transthyretin and light chains are the causal agents in ATTR and AL amyloidosis. In these most frequent subtypes, cardiac involvement is the most common organ manifestation. Because cardiac and renal function frequently deteriorate over time, even under best available treatment, SGLT2i emerge as a promising treatment option due to their reno- and cardioprotective properties. We retrospectively analyzed patients with cardiac amyloidosis, who received either dapagliflozin or empagliflozin. Out of 79 patients, 5.1% had urinary tract infections; 2 stopped SGLT2i therapy; and 2.5% died unrelated to the intake of SGLT2i. No genital mycotic infections were observed. As expected, a slight drop in the glomerular filtration rate was noted, while the NYHA functional status, cardiac and hepatic function, as well as the 6 min walk distance remained stable over time. These data provide a rationale for the use of SGLT2i in patients with amyloidosis and concomitant cardiac or renal dysfunction. Prospective randomized data are desired to confirm safety and to prove efficacy in this increasingly important group of patients.

Keywords: SGLT2 inhibitors; amyloidosis; chronic kidney disease; heart failure.

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Conflict of interest statement

C.M. reports research cooperation with the University of Würzburg and Tomtec Imaging Systems funded by a research grant from the Bavarian Ministry of Economic Affairs, Regional Development and Energy, Germany; advisory and speakers honoraria as well as travel grants from Amgen, Tomtec, Alnylam, Sobi, Alexion, Janssen, Pfizer, Boehringer Ingelheim, AstraZeneca, Bayer, and EBR Systems. He was also principal investigator in trials sponsored by Alnylam, AstraZeneca, NovoNordisk, and Bayer. S.S. is supported by the CHFC Würzburg, and by the German Federal Ministry of Education and Research (BMBF). He has received consultancy and lecture fees as well as the reimbursement of travel costs from Alnylam, AstraZeneca, Bayer, Boehringer Ingelheim, IONIS, MSD, Novartis, Pfizer, and Servier. S.M. Ihne-Schubert received financial reimbursement for consulting, advisory board activities, speaker honoraria, and/or travel support to attend scientific meetings by Akcea Therapeutics, Alnylam, Pfizer, Janssen-Cilag, and Takeda, and further research funding from Pfizer and Akcea Therapeutics. Her internship was supported by ONLUS. She was a fellow of the local clinician scientist program of the IZKF Würzburg during the period 2018–2021. AP received financial reimbursement for consulting, advisory board activities, speaker honoraria, and/or travel support to attend scientific meetings by AKCEA, Alnylam, Pfizer, SOBI, AstraZeneca. She was also principal investigator in trial sponsored by Ionis and received research funding from Pfizer (ASPIRE 2019) and IZKF Würzburg, The other authors reported no conflicts of interest.

Figures

Figure 1
Figure 1
Significant alterations in laboratory markers (absolute changes) in 79 amyloidosis patients after initiation of treatment with SGLT2i. eGFR = estimated glomerular filtration rate. Hs-TropT = high-sensitivity troponin T. PTT = partial thromboplastin time. Hs-TropT was log-transformed (natural logarithm) to approximate for normal distribution. Median follow-up was 8.2 months.
Figure 2
Figure 2
(A) Visualization of (B) numeric changes in the NYHA functional class from primary presentation to follow-up. Change in the NYHA functional status (p < 0.001) at primary presentation and follow-up. Median follow-up was 8.2 months. Patients at risk: n = 79. NYHA: New York Heart Association functional class.
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