Combined sodium-glucose-transporters inhibitors and glucagon-like-peptide receptor agonist compared with monotherapy improves long-term survival: A Real-World Registry

David Garcia-Vega; Sergio Cinza-Sanjurjo; Sonia Eiras; José Ramón González-Juanatey

doi:10.1016/j.amjmed.2024.04.032

Combined sodium-glucose-transporters inhibitors and glucagon-like-peptide receptor agonist compared with monotherapy improves long-term survival: A Real-World Registry

Am J Med. 2024 May 8:S0002-9343(24)00276-6. doi: 10.1016/j.amjmed.2024.04.032. Online ahead of print.

Authors

David Garcia-Vega¹, Sergio Cinza-Sanjurjo², Sonia Eiras³, José Ramón González-Juanatey⁴

Affiliations

¹ University of Santiago de Compostela, Spain; Cardiology department, Clinical Hospital of Santiago de Compostela, Spain; Centro de Investigación en Red en Enfermedades Cardiovasculares, Spain. Electronic address: d.garcia.vega@secardiologia.es.
² Centro de Investigación en Red en Enfermedades Cardiovasculares, Spain; Centro de Salud de Milladoiro-Ames, Área Sanitaria de Santiago de Compostela, Spain.
³ Centro de Investigación en Red en Enfermedades Cardiovasculares, Spain; Traslational cardiology group, Health Research Institute of Santiago de Compostela, Spain.
⁴ University of Santiago de Compostela, Spain; Cardiology department, Clinical Hospital of Santiago de Compostela, Spain; Centro de Investigación en Red en Enfermedades Cardiovasculares, Spain.

PMID: 38729592
DOI: 10.1016/j.amjmed.2024.04.032

Abstract

Background: The 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.

Methods: A non-concurrent 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 and/or mortality for a) coronary artery disease, b) heart failure, c) cerebrovascular accident, and all-cause mortality were represented by Kaplan Meier curves and multivariate Cox regression analysis to obtain the hazard rate (HR) and (95% confidence interval (CI)). Validation was performed in a subpopulation with a propensity score matching.

Results: The patients (15,549) who were included were 68 (12) years old, with 41% of them being females 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.

Conclusion: Compared to SGLT2i or GLP1ra alone, combined therapy SGLT2i + GLP1ra reduces heart failure risk and all-cause mortality in a real-world population.

Keywords: GLP1ra; SGLT2i; cardiovascular disease; diabetes; heart failure.