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      Sodium–glucose transporter-2 inhibitors for prevention and treatment of cardiorenal complications of type 2 diabetes

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          Abstract

          Hospitalization for major diabetes complications, including myocardial infarction, stroke, lower-extremity amputation, and end-stage kidney disease, is on the rise and represents a great health burden for patients with type 2 diabetes (T2D), in particular for older people. Newer glucose-lowering medications have generated some optimism on the possibility to influence the natural history of cardiorenal complications of T2D. This review summarizes work in the area of sodium–glucose cotransporter 2 inhibitors (SGLT-2i) treatment and prevention of cardiorenal complications in patients with T2D (major adverse cardiovascular events, hospitalization for heart failure, kidney outcomes), with a particular emphasis on the effect of age, the role of primary versus secondary prevention and the possible extension of their cardiorenal benefits to the entire class of SGLT-2i.

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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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            Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes

            Bruce Neal, Vlado Perkovic, Kenneth Mahaffey … (2017)
            Background Canagliflozin is a sodium-glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes. Methods The CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results The mean age of the participants was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease. The rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority). Although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant, the results showed a possible benefit of canagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal-replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77). Adverse reactions were consistent with the previously reported risks associated with canagliflozin except for an increased risk of amputation (6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal. Conclusions In two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease, patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal. (Funded by Janssen Research and Development; CANVAS and CANVAS-R ClinicalTrials.gov numbers, NCT01032629 and NCT01989754 , respectively.).
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              Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes

              Stephen Wiviott, Itamar Raz, Marc Bonaca … (2018)
              The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined.
              Article 0 comments Cited 1647 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Dario Giugliano:
                ORCID: http://orcid.org/0000-0002-9377-873X
                dario.giugliano@unicampania.it
                Journal
                Journal ID (nlm-ta): Cardiovasc Diabetol
                Journal ID (iso-abbrev): Cardiovasc Diabetol
                Title: Cardiovascular Diabetology
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1475-2840
                Publication date (Electronic): 11 January 2021
                Publication date PMC-release: 11 January 2021
                Publication date Collection: 2021
                Volume: 20
                Electronic Location Identifier: 17
                Affiliations
                [1 ]GRID grid.9841.4, ISNI 0000 0001 2200 8888, Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, , University of Campania Luigi Vanvitelli, ; Naples, Italy
                [2 ]GRID grid.9841.4, ISNI 0000 0001 2200 8888, Ph.D. of Translational Medicine, Chair of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, , University of Campania Luigi Vanvitelli, ; Naples, Italy
                [3 ]GRID grid.9841.4, ISNI 0000 0001 2200 8888, Diabetes Unit, Department of Advanced Medical and Surgical Sciences, , University of Campania Luigi Vanvitelli, ; Naples, Italy
                Author information
                http://orcid.org/0000-0002-9377-873X
                Article
                Publisher ID: 1213
                DOI: 10.1186/s12933-021-01213-w
                PMC ID: 7798345
                PubMed ID: 33430860
                SO-VID: aa4a81f0-c84c-4e4e-8771-2f68f30352a8
                Copyright © © The Author(s) 2021
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                Date received : 5 December 2020
                Date accepted : 5 January 2021
                Funding
                Funded by: Associazione Salute con Stile
                Categories
                Subject: Review
                Custom metadata
                issue-copyright-statement © The Author(s) 2021

                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: sglt-2 inhibitors,type 2 diabetes,mace,heart failure,diabetic kidney disease,age,primary and secondary prevention,class effect
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: sglt-2 inhibitors, type 2 diabetes, mace, heart failure, diabetic kidney disease, age, primary and secondary prevention, class effect

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