• David García-Vega, Sergio Cinza-Sanjurjo, Sonia Eiras, and José Ramón González-Juanatey.
• University of Santiago de Compostela, Galicia, Spain; Cardiology Department, Clinical Hospital of Santiago de Compostela, Galicia, Spain; Centro de Investigación en Red en Enfermedades Cardiovasculares, Madrid, Spain. Electronic address: d.garcia.vega@secardiologia.es.
• Am. J. Med. 2024 Aug 1; 137 (8): 761769.e1761-769.e1.

BackgroundThe benefits of new glucose-lowering agents on cardiovascular disease have been demonstrated in randomized clinical trials. However, more evidence is required to assess the additive value of a combined therapy based on sodium-glucose transporter inhibitors (SGLT2i) and glucagon-like peptide receptor agonists (GLP1ra) in a real-world population.MethodsA nonconcurrent prospective study was conducted using integrated electronic medical records from primary care and hospitals obtained through "big data" technologies in a healthy area in Galicia. The study involved patients who were given SGLT2i, GLP1ra, or both treatments between January 2018 and June 2022 and were categorized as either mono- or combined therapy (SGLT2i, GLP1ra, or both). The cumulative risk for different events: hospitalization or mortality, or both, for 1) coronary artery disease, 2) heart failure, 3) cerebrovascular accident, and all-cause mortality were represented by Kaplan-Meier curves and multivariate Cox regression analysis to obtain the hazard ratio (HR) and (95% confidence interval [CI]). Validation was performed in a subpopulation with propensity score matching.ResultsThe patients (15,549) who were included were median (standard deviation) 68 (12) years old, with 41% of them being female and 46% experiencing obesity. The median (interquartile range) of follow-up was 19 (8-33) months. The Kaplan-Meier analysis determined that the cumulative risk for coronary artery disease and cerebrovascular accident events was similar among the 3 different therapy groups. However, the combined therapy vs SGLT2i reduced the risk of heart failure events (HR 0.69; 95% CI, 0.56-0.87) or all-cause mortality (HR 0.68; 95% CI, 0.54-0.86). Multivariate Cox regression analysis, after matching with a propensity score, confirmed the benefits of combined therapy regarding SGLT2i or GLP1ra monotherapy.ConclusionCompared with SGLT2i or GLP1ra alone, combined therapy SGLT2i + GLP1ra reduces heart failure risk and all-cause mortality in a real-world population.Copyright © 2024 Elsevier Inc. All rights reserved.

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