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      An exploration of the experience of dapagliflozin in clinical practice

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          Abstract

          Despite the availability of established treatments, heart failure (HF) is associated with a poor prognosis and suboptimal management, highlighting the need for new treatment and prevention options. It is suggested that sodium-glucose cotransporters 2 inhibitors can provide a beneficial therapeutic approach to significantly lower the disease burden associated with cardiovascular illness in both patients with and without Type 2 diabetes mellitus. This review focuses on the therapeutic aspects of dapagliflozin in clinical practice. Future studies may intend to confirm the significant clinical benefits of sodium-glucose cotransporter-2 inhibitors.

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          Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction

          John J.V. McMurray, Scott D. Solomon, Silvio E Inzucchi … (2020)
          In patients with type 2 diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-independent mechanisms. More data are needed regarding the effects of SGLT2 inhibitors in patients with established heart failure and a reduced ejection fraction, regardless of the presence or absence of type 2 diabetes.
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            SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review

            Subodh Verma, John J V McMurray (2018)
            Sodium-glucose cotransporter (SGLT)2 inhibitors have been demonstrated to reduce cardiovascular events, particularly heart failure, in cardiovascular outcome trials. Here, we review the proposed mechanistic underpinnings of this benefit. Specifically, we focus on the role of SGLT2 inhibitors in optimising ventricular loading conditions through their effect on diuresis and natriuresis, in addition to reducing afterload and improving vascular structure and function. Further insights into the role of SGLT2 inhibition in myocardial metabolism and substrate utilisation are outlined. Finally, we discuss two emerging themes: how SGLT2 inhibitors may regulate Na+/H+ exchange at the level of the heart and kidney and how they may modulate adipokine production. The mechanistic discussion is placed in the context of completed and ongoing trials of SGLT2 inhibitors in the prevention and treatment of heart failure in individuals with and without diabetes.
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              The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial

              Michael E Nassif, Sheryl Windsor, Barry Borlaug … (2021)
              Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3–9.2, P = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0–9.6, P = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7–10.0, P = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6–34.7, P = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1–7.8, P = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05–2.85, P = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01–1.42, P = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Future Sci OA
                Journal ID (iso-abbrev): Future Sci OA
                Journal ID (publisher-id): FSOA
                Title: Future Science OA
                Publisher: Future Science Ltd (London, UK )
                ISSN (Electronic): 2056-5623
                Publication date (Electronic, pub): 01 November 2022
                Publication date (Electronic, collection): September 2022
                Publication date PMC-release: 01 November 2022
                Volume: 8
                Issue: 8
                Electronic Location Identifier: FSO816
                Affiliations
                [1 ]Department of Pharmacy Practice, SRM College of Pharmacy, SRM IST, Kattankulathur, Kancheepuram, Tamil Nadu, 603203, India
                [2 ]Drug Testing Laboratory, Interdisciplinary Institute of Indian System of Medicine (IIISM), SRM Institute of Science & Technology, Kattankulathur, Tamil Nadu, 603203, India
                Author notes
                [* ]Author for correspondence: sarveshtvg@ 123456gmail.com
                Author information
                https://orcid.org/0000-0002-0792-392X
                Article
                DOI: 10.2144/fsoa-2022-0038
                PMC ID: 9704035
                PubMed ID: 36457541
                SO-VID: 9b815a00-8654-4b25-a542-fd9108112d8e
                Copyright © © 2022 The Authors
                License:

                This work is licensed under the Creative Commons Attribution 4.0 License

                History
                Date received : 19 June 2022
                Date accepted : 13 October 2022
                Date: 01 November 2022
                Page count
                Pages: 6
                Categories
                Subject: Commentary

                Keywords: clinical pharmacist,clinical research,cyp3a4,dapagliflozin,diabetes,drug interaction,hyperglycemic,metabolism,pharmacokinetics,sodium-glucose cotransporters-2
                Data availability:
                Keywords: clinical pharmacist, clinical research, cyp3a4, dapagliflozin, diabetes, drug interaction, hyperglycemic, metabolism, pharmacokinetics, sodium-glucose cotransporters-2

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