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Review
. 2022 Oct 13;11(20):6051.
doi: 10.3390/jcm11206051.

Physicians' Considerations and Practice Recommendations Regarding the Use of Sodium-Glucose Cotransporter-2 Inhibitors

Serge A Jabbour  1 , Nasrien E Ibrahim  2 , Christos P Argyropoulos  3
Affiliations
Review

Physicians' Considerations and Practice Recommendations Regarding the Use of Sodium-Glucose Cotransporter-2 Inhibitors

Serge A Jabbour et al. J Clin Med. .

Abstract

Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) (canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), although initially developed as glucose-lowering drugs, provide significant beneficial effects on cardiorenal outcomes, including heart failure, regardless of type 2 diabetes status. Integration of SGLT-2is into clinical practice requires practical guidance for physicians about their use. To overcome physicians' clinical inertia for SGLT-2i use, including addressing safety, potentially a barrier to their use, a roundtable discussion with physicians from three specialties (cardiology, endocrinology, and nephrology) was conducted. This review summarizes the physicians' clinical experience and recommendations about SGLT-2i use across different patient populations, taking into consideration the beneficial effects of SGLT-2is and their safety. The key aspects discussed regarding SGLT-2i safety include acute effects on kidney function (estimated glomerular filtration rate acute dip upon SGLT-2i initiation and acute kidney injury), volume depletion, diabetic ketoacidosis, genitourinary infections, hyperkalemia, and hypoglycemia. To mitigate any potential risks related to SGLT-2i safety, physicians can make minor adjustments to an individual patient's treatment plan, while retaining the SGLT-2i cardiorenal benefits for effective disease management. Recognition by physicians that the benefits of SGLT-2i use on clinical outcomes outweigh the risks will result in the integration of SGLT-2is into clinical practice and lead to improved patient care and outcomes.

Keywords: cardiovascular; renal; safety; sodium-glucose cotransporter-2 inhibitors; type 2 diabetes.

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Conflict of interest statement

S.A.J. has received honoraria from AstraZeneca, Novo Nordisk, and Eli Lilly. N.E.I. has received honoraria from Medtronic, Novartis, and Roche and is a consultant for Cytokinetics. C.P.A. has had consultant agreements with Momenta Pharma and Alkahest, has served as an advisor to Baxter Healthcare, Bayer, and the Health Services Advisory Group, and received research support from Dialysis Clinic Inc.

Figures

Figure 1
Figure 1
Timeline summarizing the development and approval of SGLT-2is. CKD, chronic kidney disease; CV, cardiovascular; CVD, cardiovascular disease; FDA, US Food and Drug Administration; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HHF, hospitalization for heart failure; SGLT-2i, sodium-glucose cotransporter-2 inhibitor; T2D, type 2 diabetes.
Figure 2
Figure 2
Mechanisms of action of sodium-glucose cotransporter-2 inhibitors. ATP, adenosine triphosphate; GLUT, glucose transporter; K+, potassium; Na+, sodium; PCT, proximal convoluted tubule; SGLT-2, sodium-glucose cotransporter-2. ©2020 S. Joshi. [19] Re-use permitted under CC BY 4.0. Published by BMJ. The original figure published in Joshi et al., was created using Servier Medical Art (http://smart.servier.com).
Figure 3
Figure 3
Adverse events associated with SGLT-2is and proposed preventative measures [36,37,40]. a Occurs only in patients with type 2 diabetes. AKI, acute kidney injury; DKA, diabetic ketoacidosis; eGFR, estimated glomerular filtration rate; HbA1c, glycated hemoglobin; SBP, systolic blood pressure; SGLT-2i, sodium-glucose cotransporter-2 inhibitor; SU, sulfonylurea.
See this image and copyright information in PMC

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