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      Mortality and cardiovascular events in diabetes mellitus patients at dialysis initiation treated with glucagon-like peptide-1 receptor agonists

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          Abstract

          Background

          Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) have demonstrated efficacy in improving mortality and cardiovascular (CV) outcomes. However, the impact of GLP-1RAs therapy on cardiorenal outcomes of diabetic patients at the commencement of dialysis remains unexplored.

          Purpose

          This study aimed to investigate the long-term benefits of GLP-1RAs in type 2 diabetic patients at dialysis commencement.

          Methods

          A cohort of type 2 diabetic patients initializing dialysis was identified from the TriNetX global database. Patients treated with GLP-1RAs and those treated with long-acting insulin (LAI) were matched by propensity score. We focused on all-cause mortality, four-point major adverse cardiovascular events (4p-MACE), and major adverse kidney events (MAKE).

          Results

          Among 82,041 type 2 diabetic patients initializing dialysis, 2.1% ( n = 1685) patients were GLP-1RAs users (mean ages 59.3 years; 55.4% male). 1682 patients were included in the propensity-matched group, treated either with GLP-1RAs or LAI. The main causes of acute dialysis in this study were ischemic heart disease (17.2%), followed by heart failure (13.6%) and sepsis (6.5%). Following a median follow-up of 1.4 years, GLP-1RAs uses at dialysis commencement was associated with a reduced risk of mortality (hazard ratio [HR] = 0.63, p < 0.001), 4p-MACE (HR = 0.65, p < 0.001), and MAKE (HR = 0.75, p < 0.001). This association was particularly notable in long-acting GLP-1RAs users, with higher BMI, lower HbA1c, and those with eGFR > 15 ml/min/1.73m 2. GLP-1RAs’ new use at dialysis commencement was significantly associated with a lower risk of MACE ( p = 0.047) and MAKE ( p = 0.004). Additionally, GLP-1RAs use among those who could discontinue from acute dialysis or long-term RAs users was associated with a lower risk of mortality, 4p-MACE, and MAKE.

          Conclusion

          Given to the limitations of this observational study, use of GLP-1RAs at the onset of dialysis was associated with a decreased risk of MACE, MAKE, and all-cause mortality. These findings show the lack of harm associated with the use of GLP-1RAs in diabetic patients at the initiation of acute dialysis.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12933-024-02364-2.

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          Most cited references35

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          Sensitivity Analysis in Observational Research: Introducing the E-Value.

          Sensitivity analysis is useful in assessing how robust an association is to potential unmeasured or uncontrolled confounding. This article introduces a new measure called the "E-value," which is related to the evidence for causality in observational studies that are potentially subject to confounding. The E-value is defined as the minimum strength of association, on the risk ratio scale, that an unmeasured confounder would need to have with both the treatment and the outcome to fully explain away a specific treatment-outcome association, conditional on the measured covariates. A large E-value implies that considerable unmeasured confounding would be needed to explain away an effect estimate. A small E-value implies little unmeasured confounding would be needed to explain away an effect estimate. The authors propose that in all observational studies intended to produce evidence for causality, the E-value be reported or some other sensitivity analysis be used. They suggest calculating the E-value for both the observed association estimate (after adjustments for measured confounders) and the limit of the confidence interval closest to the null. If this were to become standard practice, the ability of the scientific community to assess evidence from observational studies would improve considerably, and ultimately, science would be strengthened.
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            Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes

            The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown.
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              Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes

              Regulatory guidance specifies the need to establish cardiovascular safety of new diabetes therapies in patients with type 2 diabetes in order to rule out excess cardiovascular risk. The cardiovascular effects of semaglutide, a glucagon-like peptide 1 analogue with an extended half-life of approximately 1 week, in type 2 diabetes are unknown.
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                Author and article information

                Contributors
                q91421028@ntu.edu.tw
                Journal
                Cardiovasc Diabetol
                Cardiovasc Diabetol
                Cardiovascular Diabetology
                BioMed Central (London )
                1475-2840
                29 July 2024
                29 July 2024
                2024
                : 23
                : 277
                Affiliations
                [1 ]Taipei Medical University, ( https://ror.org/05031qk94) Taipei, Taiwan
                [2 ]GRID grid.412040.3, ISNI 0000 0004 0639 0054, Division of Nephrology, Department of Internal Medicine, College of Medicine, , National Cheng Kung University Hospital, National Cheng Kung University, ; Tainan, Taiwan
                [3 ]Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, ( https://ror.org/05bqach95) Taipei, 100 Taiwan
                [4 ]Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Centre, ( https://ror.org/02y2htg06) Tainan, Taiwan
                [5 ]Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, ( https://ror.org/02834m470) Tainan, Taiwan
                [6 ]Division of Nephrology, Primary Aldosteronism Centre of Internal Medicine, National Taiwan University Hospital, ( https://ror.org/03nteze27) Taipei, Taiwan
                [7 ]NSARF (National Taiwan University Hospital Study Group of ARF), Consortium for Acute Kidney Injury and Renal Diseases), ( https://ror.org/03nteze27) Taipei, Taiwan
                [8 ]Department of Internal Medicine, National Taiwan University Hospital, ( https://ror.org/03nteze27) 7 Chung-Shan South Road, Taipei, 100 Taiwan
                Article
                2364
                10.1186/s12933-024-02364-2
                11287940
                39080745
                8c3c68dd-9e49-4adc-b8fc-7d5adefe7d15
                © The Author(s) 2024

                Open Access This 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
                : 26 April 2024
                : 15 July 2024
                Categories
                Research
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2024

                Endocrinology & Diabetes
                renal replacement therapy,acute kidney injury,glp-1,mortality,major adverse kidney events,major adverse cardiac events

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