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      Cardiovascular effects and mechanisms of sodium-glucose cotransporter-2 inhibitors

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          Abstract

          Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) are a new type of drug for the treatment of diabetes, and they have been proven to have a good hypoglycemic effect. Several lines of clinical evidence have shown that SGLT2 inhibitors can significantly reduce the risks of atherosclerosis, hospitalization for heart failure, cardiovascular death, and all-cause mortality and delay the progression of chronic kidney disease. Because of the protective effects of SGLT2 inhibitors on the heart and kidney, they are being studied for the treatment of heart failure and chronic kidney disease in patients without diabetes. Therefore, it is necessary for cardiologists, patients with diabetes, and nephrologists to fully understand this type of drug. In this review, we summarize the following three aspects of SGLT2 inhibitors: the recent clinical evidence of their cardiovascular benefits, their mechanisms of action, and their safety.

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          Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.

          Bernard Zinman, Christoph Wanner, John M. Lachin … (2015)
          The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known.
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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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              SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials

              Thomas Zelniker, Stephen Wiviott, Itamar Raz … (2019)
              The Lancet, 393(10166), 31-39
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                Author and article information

                Contributors
                Da-Long Zhu
                Journal
                Journal ID (nlm-ta): Chronic Dis Transl Med
                Journal ID (iso-abbrev): Chronic Dis Transl Med
                Title: Chronic Diseases and Translational Medicine
                Publisher: Chinese Medical Association
                ISSN (Print): 2095-882X
                ISSN (Electronic): 2589-0514
                Publication date PMC-release: 15 August 2020
                Publication date Collection: December 2020
                Publication date (Electronic): 15 August 2020
                Volume: 6
                Issue: 4
                Pages: 239-245
                Affiliations
                [1]Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, Jiangsu 210008, China
                Author notes
                [∗ ]Corresponding author. Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, Jiangsu 210008, China. zhudalong@ 123456nju.edu.cn
                [a]

                Fan Yang and Ran Meng contributed equally to this work.

                Article
                Publisher Item ID: S2095-882X(20)30064-5
                DOI: 10.1016/j.cdtm.2020.07.002
                PMC ID: 7729105
                PubMed ID: 33336169
                SO-VID: 7f51c119-2cea-491d-be89-9189fa3f8a90
                Copyright © © 2020 Chinese Medical Association. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 21 May 2020
                Categories
                Subject: Review

                Keywords: sodium-glucose cotransporter-2 inhibitors,type 2 diabetes,cardiovascular outcomes,mechanisms of cardiovascular benefits
                Data availability:
                Keywords: sodium-glucose cotransporter-2 inhibitors, type 2 diabetes, cardiovascular outcomes, mechanisms of cardiovascular benefits

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