SGLT-2 Inhibitors: New Horizons for Rheumatologists

Overview

Journal Curr Opin Rheumatol

Specialty Rheumatology

Date 2024 Jul 15

PMID 39007236

Authors

Katherine Chakrabarti

W Joseph McCune

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: Sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of medications initially developed for the treatment of diabetes, although their cardiac and renal protective benefits are far reaching. There has been marked interest in the rheumatology community to adopt these medications into our clinical practice, particularly for chronic kidney disease with persistent proteinuria.

Recent Findings: SGLT2 inhibitors have been approved for patients with type 2 diabetes mellitus, heart failure with reduced or preserved ejection fraction, atherosclerotic cardiovascular disease in the setting of type 2 diabetes mellitus, as well as chronic kidney disease with proteinuria. Large studies on SGLT2 inhibitors have largely excluded patients with proteinuric chronic kidney disease due to autoimmune glomerulonephritis due to concerns for confounding from immunosuppression. The Dapagliflozin and Prevention of Adverse Outcomes in CKD Trial (DAPA-CKD) showed that SGLT2 inhibition decreased progression of renal disease in patients with IgA nephropathy. Expanding this to other autoimmune glomerulonephropathies, several small studies have shown improvements in proteinuria in patients with lupus nephritis treated with SGLT2 inhibitors. A study evaluating safety of SGLT2 inhibitors in patients with lupus identified no specific concerns even with concomitant use of immunosuppression.

Summary: Small studies have shown that SGLT2 inhibitors can been utilized safely and efficaciously in patients with lupus nephritis. Additional research is needed to identify where these medications fit into the rheumatology treatment armamentarium.

References

Burke K, Schumacher C, Harpe S . SGLT2 Inhibitors: A Systematic Review of Diabetic Ketoacidosis and Related Risk Factors in the Primary Literature. Pharmacotherapy. 2016; 37(2):187-194. DOI: 10.1002/phar.1881. View

Taylor S, Blau J, Rother K, Beitelshees A . SGLT2 inhibitors as adjunctive therapy for type 1 diabetes: balancing benefits and risks. Lancet Diabetes Endocrinol. 2019; 7(12):949-958. PMC: 6872914. DOI: 10.1016/S2213-8587(19)30154-8. View

Lytvyn Y, Kimura K, Peter N, Lai V, Tse J, Cham L . Renal and Vascular Effects of Combined SGLT2 and Angiotensin-Converting Enzyme Inhibition. Circulation. 2022; 146(6):450-462. PMC: 9354594. DOI: 10.1161/CIRCULATIONAHA.122.059150. View

Neuen B, Young T, Heerspink H, Neal B, Perkovic V, Billot L . SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2019; 7(11):845-854. DOI: 10.1016/S2213-8587(19)30256-6. View

Nyirjesy P, Zhao Y, Ways K, Usiskin K . Evaluation of vulvovaginal symptoms and Candida colonization in women with type 2 diabetes mellitus treated with canagliflozin, a sodium glucose co-transporter 2 inhibitor. Curr Med Res Opin. 2012; 28(7):1173-8. DOI: 10.1185/03007995.2012.697053. View

Saemann M, Kronbichler A . Call for action in ANCA-associated vasculitis and lupus nephritis: promises and challenges of SGLT-2 inhibitors. Ann Rheum Dis. 2021; 81(5):614-617. DOI: 10.1136/annrheumdis-2021-221474. View

McQuarrie E, Gillis K, Mark P . Seven suggestions for successful SGLT2i use in glomerular disease - a standalone CKD therapy?. Curr Opin Nephrol Hypertens. 2022; 31(3):272-277. DOI: 10.1097/MNH.0000000000000786. View

Certo M, Niven J, Mauro C . Repurposing SGLT2 inhibitors for autoimmune diseases? YES, WE MAY!. Cell Chem Biol. 2023; 30(9):1009-1011. DOI: 10.1016/j.chembiol.2023.07.020. View

Zhao X, Li S, He Y, Yan L, Lv F, Liang Q . SGLT2 inhibitors alleviated podocyte damage in lupus nephritis by decreasing inflammation and enhancing autophagy. Ann Rheum Dis. 2023; 82(10):1328-1340. DOI: 10.1136/ard-2023-224242. View

10.

Wang H, Li T, Sun F, Liu Z, Zhang D, Teng X . Safety and efficacy of the SGLT2 inhibitor dapagliflozin in patients with systemic lupus erythematosus: a phase I/II trial. RMD Open. 2022; 8(2). PMC: 9615980. DOI: 10.1136/rmdopen-2022-002686. View

11.

Morales E, Galindo M . SGLT2 inhibitors in lupus nephropathy, a new therapeutic strategy for nephroprotection. Ann Rheum Dis. 2022; 81(9):1337-1338. DOI: 10.1136/annrheumdis-2022-222512. View

12.

Musso G, Gambino R, Cassader M, Pagano G . A novel approach to control hyperglycemia in type 2 diabetes: sodium glucose co-transport (SGLT) inhibitors: systematic review and meta-analysis of randomized trials. Ann Med. 2011; 44(4):375-93. DOI: 10.3109/07853890.2011.560181. View

13.

Wanner C, Inzucchi S, Lachin J, Fitchett D, von Eynatten M, Mattheus M . Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016; 375(4):323-34. DOI: 10.1056/NEJMoa1515920. View

14.

Heerspink H, Stefansson B, Correa-Rotter R, Chertow G, Greene T, Hou F . Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020; 383(15):1436-1446. DOI: 10.1056/NEJMoa2024816. View

15.

Khouri C, Cracowski J, Roustit M . SGLT-2 inhibitors and the risk of lower-limb amputation: Is this a class effect?. Diabetes Obes Metab. 2018; 20(6):1531-1534. DOI: 10.1111/dom.13255. View

16.

Zelniker T, Bonaca M, Furtado R, Mosenzon O, Kuder J, Murphy S . Effect of Dapagliflozin on Atrial Fibrillation in Patients With Type 2 Diabetes Mellitus: Insights From the DECLARE-TIMI 58 Trial. Circulation. 2020; 141(15):1227-1234. DOI: 10.1161/CIRCULATIONAHA.119.044183. View

17.

Packer M, Anker S, Butler J, Filippatos G, Pocock S, Carson P . Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020; 383(15):1413-1424. DOI: 10.1056/NEJMoa2022190. View

18.

Neal B, Perkovic V, Mahaffey K, de Zeeuw D, Fulcher G, Erondu N . Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017; 377(7):644-657. DOI: 10.1056/NEJMoa1611925. View

19.

Spertus J, Birmingham M, Nassif M, Damaraju C, Abbate A, Butler J . The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial. Nat Med. 2022; 28(4):809-813. PMC: 9018422. DOI: 10.1038/s41591-022-01703-8. View

20.

Qiu M, Ding L, Zhang M, Zhou H . Safety of four SGLT2 inhibitors in three chronic diseases: A meta-analysis of large randomized trials of SGLT2 inhibitors. Diab Vasc Dis Res. 2021; 18(2):14791641211011016. PMC: 8481734. DOI: 10.1177/14791641211011016. View