A new meta-analysis shows sodium glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of major adverse cardiovascular events in patients with either diabetes at high risk of atherosclerotic cardiovascular disease (ASCVD), heart failure, or chronic kidney disease (CKD). Findings were presented yesterday at the American College of Cardiology Annual Scientific Session & Expo and simultaneously published in Circulation.1
SGLT2 inhibitors, also called gliflozins, are a class of drug that lower blood glucose by increasing its excretion in the urine. While late-stage trials of these medicines have demonstrated reductions in heart failure and adverse kidney outcomes, the effects on major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and stroke, were less clear.
Researchers analysed data across 11 trials involving 78,607 patients with diabetes, heart failure, or CKD and found a 9% reduction in MACE and a 14% reduction in cardiovascular death with SGLT2 inhibitors versus placebo. The analysis showed a remarkably consistent effect across all three patient groups, as well as key subgroups (established ASCVD, prior myocardial infarction, diabetes, prior heart failure, and different levels of kidney function). The reduction in MACE was driven by a reduction in cardiovascular death, specifically heart failure death and sudden cardiac death. There were no significant effects on myocardial infarction or stroke.
Dr Brendon Neuen, Senior Research Fellow at The George Institute for Global Health and author on the paper said, “Individual SGLT2 inhibitor trials observed some benefit in reducing cardiovascular disease, but effects on different types of cardiovascular events across major patient subgroups were uncertain.
“By looking at the totality of the worldwide data from all large-scale, placebo-controlled outcome trials of SGLT2 inhibitors, we observed a conclusive reduction in cardiovascular death among patients with a broad range of clinical characteristics.”
Diabetes is a known risk factor for cardiovascular and kidney disease, with impaired glucose control causing damage to blood vessels in the heart and kidneys. Many patients with diabetes live with ASCVD, CKD, or heart failure, with prevalence increasing in the years following a diabetes diagnosis.2
Dr Neuen added, “Despite the various benefits of SGLT2 inhibitors on cardiovascular-kidney-metabolic diseases, this class of medicine remains under-prescribed.”
“We hope that our findings inform more tailored prescription of SGLT2 inhibitors, particularly in patients with comorbid presentation of diabetes and heart failure or chronic kidney disease, who may experience multiple treatment benefits.”
The SGLT2 Meta-Analysis Cardio-Renal Trialists' Consortium (SMART-C) is co-chaired by Dr Brendon Neuen and Prof Hiddo Heerspink of The George Institute for Global Health.
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References
- Patel S, et al. Sodium Glucose Co-transporter 2 Inhibitors and Major Adverse Cardiovascular Outcomes: A SMART-C Collaborative Meta-Analysis. Circulation. 2024. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.069568
- Pearson-Stuttard J, et al. Variations in comorbidity burden in people with type 2 diabetes over disease duration: A population-based analysis of real world evidence. EClinicalMedicine. 2022. https://doi.org/10.1016/j.eclinm.2022.101584
Journal
Circulation
Method of Research
Meta-analysis
Subject of Research
People
Article Title
Sodium Glucose Co-transporter 2 Inhibitors and Major Adverse Cardiovascular Outcomes: A SMART-C Collaborative Meta-Analysis
Article Publication Date
7-Apr-2024
COI Statement
Drs. Patel, Kang, Im, Sabatine and Wiviott are members of the TIMI Study Group, which has received institutional grant support through Brigham and Women’s Hospital from Abbott, Abiomed, Inc., Amgen, Anthos Therapeutics, ARCA Biopharma, Inc., AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Ionis Pharmaceuticals, Inc., Janssen Research and Development, LLC, MedImmune, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Saghmos Therapeutics, Inc., Softcell Medical Limited, The Medicines Company, Verve Therapeutics, Inc., Zora Biosciences. Dr. Patel reports consulting fees from Janssen. Dr. Neuen reports fees for travel support, advisory boards, scientific presentations, and steering committee roles from AstraZeneca, Alexion, Bayer, Boehringer and Ingelheim, Cambridge Healthcare Research, Cornerstone Medical Education, Janssen, the limbic, Medscape, and Travere Therapeutics with all honoraria paid to The George Institute for Global Health. Dr. Anker reports grants and personal fees from Vifor and Abbott Vascular, and personal fees for consultancies, trial committee work and/or lectures from Actimed, Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Brahms, Cardiac Dimensions, Cardior, Cordio, CVRx, Cytokinetics, Edwards, Farraday Pharmaceuticals, GSK, HeartKinetics, Impulse Dynamics, Occlutech, Pfizer, Regeneron, Repairon, Scirent, Sensible Medical, Servier, Vectorious, and V-Wave. Named co-inventor of two patent applications regarding MR-proANP (DE 102007010834 & DE 102007022367), but he does not benefit personally from the related issued patents. 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Dr. Butler reports consulting fees from Abbott, American Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardiocell, Cardior, CSL Bearing, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pharmacosmos, Pharmain, Pfizer, Prolaio, Regeneron, Renibus, Roche, Salamandra, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and Zoll. 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Dr. Herrington reports funding from the UK Medical Research Council, Kidney Research UK and Health Data Research UK; and grants to the University of Oxford from Boehringer Ingelheim and Eli Lilly for the EMPA-KIDNEY trial.Dr. Inzucchi reports serving as an advisor or consultant to Boehringer Ingelheim, AstraZen-eca, Bayer, Novo Nordisk, Merck, Pfizer, Lexicon, Abbott, VTV Therapeutics, and Esperion, and delivering lectures sponsored by Boehringer Ingelheim and AstraZeneca. Dr. Jardine is supported by an NHMRC Investigator Grant; is responsible for research projects that have received funding from Amgen, Baxter, CSL, Dimerix, Eli Lilly, Gambro, and MSD; has received fees for advisory, steering committee and/or scientific presentations from Akebia, Amgen, Astra Zeneca, Baxter, Bayer, Boehringer Ingelheim, Cesas Linx, Chinook, CSL, Janssen, Medscape, MSD, Occuryx, Roche and Vifor; with any consultancy, honoraria or travel support paid to her institution. 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Dr. Sabatine reports research grant support through Brigham and Women’s Hospital from Abbott; Amgen; Anthos Therapeutics, Inc.; AstraZeneca; Boehringer Ingelheim; Daiichi-Sankyo; Ionis; Merck; Novartis; Pfizer; Saghmos Therapeutics; Verve Therapeutics, and consulting for Amgen; Anthos Therapeutics, Inc.; AstraZeneca; Beren Therapeutics; Boehringer Ingelheim; Dr. Reddy’s Laboratories; Merck; Moderna; Novo Nordisk; Precision BioSciences; Silence Therapeutics.Dr. Wiviott reports research grants from Amgen, AstraZeneca, Janssen, Merck, and Pfizer, Consulting Fees or Honoraria from Icon Clinical and Novo Nordisk, Varian and Harvard Medical School. Dr. Wiviott’s spouse, Dr. Caroline Fox is an employee of Vertex, and former employee of Flagship Pioneering and Merck.