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From Skepticism to Hope: The Evolving Concept of the Initiation and Use of Sodium-Glucose Cotransporter 2 Inhibitors in Hospitalized Patients

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Abstract

The management of hyperglycemia in patients admitted to hospital is mainly based on insulin therapy. However, the positive and rapid effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on cardiorenal outcomes raises the possibility that they might confer benefits to hospitalized patients. In recent, well designed, randomized trials (SOLOIST-WHF and EMPULSE) recruiting inpatients with heart failure (HF), SGLT2i demonstrated the potential to improve survival and quality of life and reduce the number of HF events, time to first HF event, hospitalizations, and urgent visits for HF compared with placebo. They were also well tolerated, whereas incidence of diabetic ketoacidosis was low. In EMBODY, empagliflozin was shown to be protective against the deleterious effects of cardiac injury in patients with acute myocardial infarction. In DARE-19, the administration of dapagliflozin to inpatients with cardiometabolic risk factors and COVID-19 was based on the hypothesis that the anti-inflammatory properties of SGLT2i could alleviate organ damage. Although the findings did not reach statistical significance, the efficacy and safety profiles of the drug were encouraging. These promising findings in the field of cardiometabolic medicine set the stage for future research to explore whether the benefits of gliflozins can expand to inpatients with non-cardiometabolic disorders, including sepsis, cirrhotic ascites, and malignancies. The concept of inpatient use of SGLT2i has evolved greatly over the past few years. The latest evidence suggests that SGLT2i may be effective and safe in the hospital setting, provided patients are carefully selected and closely monitored. Real-world data will prove whether present hope about inpatient use of gliflozins will transform into future confidence.

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Authors and Affiliations

  1. Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 1 St. Kiriakidi Street, 54636, Thessaloniki, Greece

    Theocharis Koufakis, Pantelis Zebekakis & Kalliopi Kotsa

  2. Department of Diabetes, King’s College Hospital, London, UK

    Omar G. Mustafa

  3. Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds Ringgold Standard Institution, Leeds, UK

    Ramzi A. Ajjan

  4. Cardiology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma, 91 Mas Casanova, 08041, Barcelona, Spain

    Xavier Garcia-Moll

  5. Medical School, National and Kapodistrian University of Athens, Athens, Greece

    George Dimitriadis

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Conflict of interest

TK has received honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Pharmaserve Lilly, and Novo Nordisk, for advisory boards from Novo Nordisk, and has participated in sponsored studies by Eli-Lilly and Novo Nordisk; OGM has received speaker honoraria and educational grants from Sanofi, Eli Lilly, Boehringer Ingelheim and Novo Nordisk; RAA has received institutional research grants from Abbott, Bayer, Eli Lilly, NovoNordisk and Roche, and honoraria/education support/consultant from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Menarini Pharmaceuticals, Merck Sharp & Dohme, NovoNordisk, and Takeda; XG-M has received honoraria for lectures/advisory boards from Astra-Zeneca, Boehringer-Ingelheim, Esteve, Lilly, Merck, Novo-Nordisk, and Sanofi; GD has received honoraria for lectures and financial support for research (through the University of Athens Medical School) from Abbott, Astra Zeneca, VIANEX, Pharmaserve Lilly, ELPEN, Galenica, MSD, Novartis, Novo Nordisk, and Sanofi; KK has received honoraria for lectures/advisory boards and research support from Astra Zeneca, Boehringer Ingelheim, Pharmaserve Lilly, Sanofi-Aventis, ELPEN, MSD, and Novo Nordisk; PZ declares no potential conflicts of interest that might be relevant to this work.

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TK reviewed the literature and drafted the first version of the manuscript. OGM, RAA, XG-M, PZ, GD, and KK reviewed the literature and edited the manuscript. All authors have read and approved the final version of the manuscript.

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Koufakis, T., Mustafa, O.G., Ajjan, R.A. et al. From Skepticism to Hope: The Evolving Concept of the Initiation and Use of Sodium-Glucose Cotransporter 2 Inhibitors in Hospitalized Patients. Drugs 82, 949–955 (2022). https://doi.org/10.1007/s40265-022-01730-2

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