Cardiovascular and mortality benefits of sodium–glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus: CVD-Real Catalonia – ScienceOpen
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      Cardiovascular and mortality benefits of sodium–glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus: CVD-Real Catalonia

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          Abstract

          Background

          Evidence from prospective cardiovascular (CV) outcome trials in type 2 diabetes (T2DM) patients supports the use of sodium–glucose co-transporter-2 inhibitors (SGLT2i) to reduce the risk of CV events. In this study, we compared the risk of several CV outcomes between new users of SGLT2i and other glucose-lowering drugs (oGLDs) in Catalonia, Spain.

          Methods

          CVD-REAL Catalonia was a retrospective cohort study using real-world data routinely collected between 2013 and 2016. The cohorts of new users of SGLT2i and oGLDs were matched by propensity score on a 1:1 ratio. We compared the incidence rates and hazard ratio (HR) for all-cause death, hospitalization for heart failure, chronic kidney disease, and modified major adverse CV event (MACE; all-cause mortality, myocardial infarction, or stroke).

          Results

          After propensity score matching, 12,917 new users were included in each group. About 27% of users had a previous history of CV disease. In the SGLT2i group, the exposure time was 60% for dapagliflozin, 26% for empagliflozin and 14% for canagliflozin. The use of SGLT2i was associated with a lower risk of heart failure (HR: 0.59; 95% confidence interval [CI] 0.47–0.74; p < 0.001), all-cause death (HR = 0.41; 95% CI 0.31–0.54; p < 0.001), all-cause death or heart failure (HR = 0.55; 95% CI 0.47–0.63; p < 0.001), modified MACE (HR = 0.62; 95% CI 0.52–0.74; p < 0.001), and chronic kidney disease (HR = 0.66; 95% CI 0.54–0.80; p < 0.001).

          Conclusions

          In this large, retrospective observational study of patients with T2DM from a Catalonia, initiation of SGLT-2i was associated with lower risk of mortality, as well as heart failure and CKD.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12933-021-01323-5.

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          Most cited references57

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          Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

          Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes.
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            Dapagliflozin in Patients with Chronic Kidney Disease

            Patients with chronic kidney disease have a high risk of adverse kidney and cardiovascular outcomes. The effect of dapagliflozin in patients with chronic kidney disease, with or without type 2 diabetes, is not known.
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              Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies

              Summary Background Uncertainties persist about the magnitude of associations of diabetes mellitus and fasting glucose concentration with risk of coronary heart disease and major stroke subtypes. We aimed to quantify these associations for a wide range of circumstances. Methods We undertook a meta-analysis of individual records of diabetes, fasting blood glucose concentration, and other risk factors in people without initial vascular disease from studies in the Emerging Risk Factors Collaboration. We combined within-study regressions that were adjusted for age, sex, smoking, systolic blood pressure, and body-mass index to calculate hazard ratios (HRs) for vascular disease. Findings Analyses included data for 698 782 people (52 765 non-fatal or fatal vascular outcomes; 8·49 million person-years at risk) from 102 prospective studies. Adjusted HRs with diabetes were: 2·00 (95% CI 1·83–2·19) for coronary heart disease; 2·27 (1·95–2·65) for ischaemic stroke; 1·56 (1·19–2·05) for haemorrhagic stroke; 1·84 (1·59–2·13) for unclassified stroke; and 1·73 (1·51–1·98) for the aggregate of other vascular deaths. HRs did not change appreciably after further adjustment for lipid, inflammatory, or renal markers. HRs for coronary heart disease were higher in women than in men, at 40–59 years than at 70 years and older, and with fatal than with non-fatal disease. At an adult population-wide prevalence of 10%, diabetes was estimated to account for 11% (10–12%) of vascular deaths. Fasting blood glucose concentration was non-linearly related to vascular risk, with no significant associations between 3·90 mmol/L and 5·59 mmol/L. Compared with fasting blood glucose concentrations of 3·90–5·59 mmol/L, HRs for coronary heart disease were: 1·07 (0·97–1·18) for lower than 3·90 mmol/L; 1·11 (1·04–1·18) for 5·60–6·09 mmol/L; and 1·17 (1·08–1·26) for 6·10–6·99 mmol/L. In people without a history of diabetes, information about fasting blood glucose concentration or impaired fasting glucose status did not significantly improve metrics of vascular disease prediction when added to information about several conventional risk factors. Interpretation Diabetes confers about a two-fold excess risk for a wide range of vascular diseases, independently from other conventional risk factors. In people without diabetes, fasting blood glucose concentration is modestly and non-linearly associated with risk of vascular disease. Funding British Heart Foundation, UK Medical Research Council, and Pfizer.
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                Author and article information

                Contributors
                didacmauricio@gmail.com
                josep.franch@gmail.com
                Journal
                Cardiovasc Diabetol
                Cardiovasc Diabetol
                Cardiovascular Diabetology
                BioMed Central (London )
                1475-2840
                9 July 2021
                9 July 2021
                2021
                : 20
                : 139
                Affiliations
                [1 ]GRID grid.482253.a, ISNI 0000 0004 0450 3932, DAP‑Cat Group, Unitat de Suport a la Recerca Barcelona, , Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), ; Barcelona, Spain
                [2 ]GRID grid.413448.e, ISNI 0000 0000 9314 1427, CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), , Instituto de Salud Carlos III (ISCIII), ; Madrid, Spain
                [3 ]GRID grid.410458.c, ISNI 0000 0000 9635 9413, Department of Endocrinology and Nutrition, , Institut d’Investigacions Biomèdiques August Pi i Suñer, Hospital Clinic, ; Barcelona, Spain
                [4 ]GRID grid.413448.e, ISNI 0000 0000 9314 1427, CIBER of Physiopathology of Obesity and Nutrition (CIBEROBN), , Instituto de Salud Carlos III (ISCIII), ; Madrid, Spain
                [5 ]GRID grid.22061.37, ISNI 0000 0000 9127 6969, Drug Area, Gerència d’Atenció Primaria, , Institut Català de la Salut, ; Barcelona, Spain
                [6 ]GRID grid.22061.37, ISNI 0000 0000 9127 6969, Primary Health Care Center La Mina, Gerència d’Àmbit d’Atenció Primària Barcelona Ciutat, , Institut Català de la Salut, ; Sant Adrià de Besòs, Spain
                [7 ]GRID grid.418152.b, AstraZeneca, ; Gaithersburg, MD USA
                [8 ]GRID grid.417815.e, ISNI 0000 0004 5929 4381, Cardiovascular Renal Metabolisms, BioPharmaceuticals Global Medical, , AstraZeneca, ; Cambridge, UK
                [9 ]GRID grid.419820.6, ISNI 0000 0004 0383 1037, Saint Luke’s Mid America Heart Institute and University of Missouri-Kansas City, ; Kansas City, MO USA
                [10 ]GRID grid.7080.f, Department of Endocrinology and Nutrition, , Hospital Universitari de la Santa Creu i Sant Pau, Autonomous Universtity of Barcelona, ; Sant Quintí, 89, 08041 Barcelona, Spain
                [11 ]GRID grid.440820.a, Departament of Medicine, , University of Vic-Central University of Catalonia, ; Vic, Barcelona, Spain
                [12 ]GRID grid.22061.37, ISNI 0000 0000 9127 6969, Primary Health Care Center Raval Sud, Gerència d’Atenció Primaria, , Institut Català de la Salut, ; Av. Drassanes, 17-21, 08001 Barcelona, Spain
                Author information
                http://orcid.org/0000-0002-5175-1555
                Article
                1323
                10.1186/s12933-021-01323-5
                8272340
                34243779
                78fa62b9-db9e-485a-9f24-166eaf17bebb
                © The Author(s) 2021

                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
                : 10 March 2021
                : 23 June 2021
                Funding
                Funded by: AstraZeneca Spain
                Award ID: 4R17/071-3
                Award Recipient :
                Categories
                Original Investigation
                Custom metadata
                © The Author(s) 2021

                Endocrinology & Diabetes
                sglt2i,heart failure,all-cause mortality,type 2 diabetes mellitus
                Endocrinology & Diabetes
                sglt2i, heart failure, all-cause mortality, type 2 diabetes mellitus

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