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      Comparison of cardiovascular outcomes of new antihyperglycemic agents in Type 2 Diabetes Mellitus: a meta‐analysis

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          Abstract

          Aims

          The study aims to provide comprehensive evidence for the selection of agents in type 2 diabetes mellitus (T2DM) patients with cardiovascular risk and summarize the lasted evidence for the cardiovascular effects of sodium glucose cotransporter‐2 inhibitor (SGLT2i) in patients with heart failure (HF).

          Methods and results

          Several online databases were searched. All studies that explored the cardiovascular effects of SGLT2i or glucagon‐like peptide 1 receptor agonist (GLP1‐RA) were screened and reviewed. A total of 38 studies were included. Compared with GLP1‐RA, the use of SGLT2i significantly reduced the risk of cardiovascular death [risk ratio (RR) = 0.59; 95% confidence interval (CI), 0.44–0.58], hospitalization of heart failure (HHF) (RR = 0.77; 95% CI, 0.74–0.80), death from any cause (RR = 0.64; 95% CI, 0.60–0.68), and myocardial infarction (MI) (RR = 0.81; 95% CI, 0.76–0.87). However, SGLT2i significantly increased the risk of stroke (RR = 1.10; 95% CI, 1.04–1.17). Compared with the control group, SGLT2i treatment reduced the risk of cardiovascular death by 14% (RR = 0.86; 95% CI, 0.79–0.94), HHF by 25%, and death from any cause by 9% in patients with HF, regardless of diabetes status.

          Conclusions

          SGLT2i is associated with a lower risk of cardiovascular death, HHF, death from any cause, and MI in patients with T2DM compared with GLP1‐RA. In addition, SGLT2i brought more benefits with respect to the effects of cardiovascular death, HHF, and death from any cause in patients with HF, regardless of diabetes status.

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          Most cited references63

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

          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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            Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction

            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

              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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                Author and article information

                Contributors
                wuting127039@163.com
                Journal
                ESC Heart Fail
                ESC Heart Fail
                10.1002/(ISSN)2055-5822
                EHF2
                ESC Heart Failure
                John Wiley and Sons Inc. (Hoboken )
                2055-5822
                28 February 2024
                June 2024
                : 11
                : 3 ( doiID: 10.1002/ehf2.v11.3 )
                : 1647-1656
                Affiliations
                [ 1 ] Department of Cardiovascular Medicine Xiangya Hospital, Central South University Changsha Hunan China
                [ 2 ] Department of Critical Care Medicine Xiangya Hospital, Central South University Changsha Hunan China
                Author notes
                [*] [* ] Correspondence to: Ting Wu, Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, Hunan 410008, China. Email: wuting127039@ 123456163.com

                Article
                EHF214726 ESCHF-23-00889
                10.1002/ehf2.14726
                11098653
                38419382
                5e845d05-9c8d-4dce-840e-bb7550b7b172
                © 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 03 November 2023
                : 29 January 2024
                Page count
                Figures: 4, Tables: 0, Pages: 10, Words: 3054
                Funding
                Funded by: The China Postdoctoral Science Foundation
                Award ID: 2023M733963
                Funded by: Youth Science Foundation of Xiangya Hospital
                Award ID: 2022Q01
                Funded by: Natural Science Foundation of Changsha
                Award ID: kq2208369
                Funded by: Natural Science Foundation of Hunan Province , doi 10.13039/501100004735;
                Award ID: 2023JJ40996
                Funded by: National Nature Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 82300490
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                June 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.4.3 mode:remove_FC converted:16.05.2024

                cardiovascular outcomes,sodium glucose cotransporter‐2 inhibitor,glucagon‐like peptide 1 receptor agonist,type 2 diabetes,heart failure

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