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SGLT2 Inhibition in Type 1 Diabetes with Diabetic Kidney Disease: Potential Cardiorenal Benefits Can Outweigh Preventable Risk of Diabetic Ketoacidosis

  • Microvascular Complications—Nephropathy (B Roshanravan, Section Editor)
  • Published:
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Abstract

Purpose of Review

The aim of this review is to summarize existing research investigating the use of sodium glucose cotransporter-2 (SGLT2) inhibitors in patients with type 1 diabetes mellitus (T1DM) while highlighting potential strategies to mitigate the risk of diabetic ketoacidosis (DKA).

Recent Findings

SGLT2 inhibitors have been studied in patients with T1DM in phase 3 clinical trials such as the inTandem, DEPICT, and EASE trials, which demonstrated consistent reductions in HbA1c. Secondary analyses of these trials have also reported potential kidney protective effects that are independent of improved glycemic control. However, trials in patients with type 2 diabetes mellitus (T2DM) have found an increased risk of DKA with SGLT2 inhibitors, a serious concern in patients with T1DM.

Summary

SGLT2 inhibitors provide cardiovascular benefits and kidney protection in patients with T2DM and are a promising therapeutic option for patients with T1DM due to overlapping pathophysiological mechanisms. However, SGLT2 inhibitors increase the risk of DKA, and there is currently a lack of research investigating the beneficial effects of SGLT2 inhibitors in patients with T1DM. Preventative measure for DKA would have to be implemented and the risks would need to be carefully balanced with the benefits offered by SGLT2 inhibitors. Additional research will also be required to determine the kidney protective effects of SGLT2 inhibitors in patients with T1DM and diabetic kidney disease and to quantify the risk of DKA after the implementation of preventative measures, proper patient education, and ketone monitoring.

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Acknowledgements

D.Z.I.C. is supported by a Department of Medicine, University of Toronto Merit Award and receives support from the CIHR, the Heart and Stroke Richard Lewar Centre of Excellence, the Heart and Stroke Foundation and the Kidney Foundation of Canada. V.S.S. is supported by the Department of Medicine Eliot Phillipson Clinician Scientist Training Program, a Banting and Best Diabetes Centre Postdoctoral fellowship at the University of Toronto, and a CIHR Frederick Banting and Charles Best Canada Graduate Scholarships Doctoral Research Award. B.A.P. acknowledges support as the Sam and Judy Pencer Family Chair in Diabetes Clinical Research at the University of Toronto, from Diabetes Action Canada and its Innovations in Type 1 Diabetes Goal Group, Boehringer Ingelheim’s Beta Cell Preservation program, the Menkes Foundation, and contributions from David Wright.

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Authors and Affiliations

  1. Department of Medicine, Division of Nephrology, University Health Network, Toronto, ON, Canada

    Hongyan Liu, Vikas S. Sridhar & David Z. I. Cherney

  2. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada

    Hongyan Liu & David Z. I. Cherney

  3. Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada

    Vikas S. Sridhar & David Z. I. Cherney

  4. Department of Medicine, University of Toronto, Toronto, ON, Canada

    Vikas S. Sridhar & David Z. I. Cherney

  5. Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada

    Bruce A. Perkins

  6. Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Toronto, ON, Canada

    Bruce A. Perkins

  7. Dallas Diabetes Research Center at Medical City, Dallas, TX, USA

    Julio Rosenstock

  8. Toronto General Hospital, 585 University Ave, Toronto, ON, 8N-845M5G 2N2, Canada

    David Z. I. Cherney

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Correspondence to David Z. I. Cherney.

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Conflicts of Interest

D.Z.I.C. has received consulting fees or speaking honorarium or both from Janssen, Bayer, Boehringer Ingelheim-Eli, Lilly, AstraZeneca, Merck & Co Inc, Prometic and Sanofi, and has received operating funds from Janssen, Boehringer Ingelheim-Eli, Lilly, Sanofi, AstraZeneca and Merck & Co Inc. B.A.P. has received speaker honoraria from Abbott, Medtronic, Insulet, and Novo-Nordisk; research support to his research institute from Boehringer Ingelheim, Novo Nordisk, and the Bank of Montreal (BMO), and has served as a consultant to Boehringer Ingelheim, Abbott, Insulet, and Novo-Nordisk. J.R. has served on advisory boards for Applied Therapeutics, Boehringer Ingelheim, Eli Lilly, Intarcia, Janssen, Novo Nordisk, Oramed, Sanofi, and Zealand; and has received research support from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Genentech, GlaxoSmithKline, Intarcia, Janssen, Lexicon, Merck, Novo Nordisk, Oramed, Pfizer and Sanofi. No potential conflicts of interest relevant to this article were reported for H.L. and V.S.S.

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This article is part of the Topical Collection on Microvascular Complications—Nephropathy

Hongyan Liu and Vikas S. Sridhar are Co-primary authors

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Liu, H., Sridhar, V.S., Perkins, B.A. et al. SGLT2 Inhibition in Type 1 Diabetes with Diabetic Kidney Disease: Potential Cardiorenal Benefits Can Outweigh Preventable Risk of Diabetic Ketoacidosis. Curr Diab Rep 22, 317–332 (2022). https://doi.org/10.1007/s11892-022-01471-2

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