Combined sodium-glucose-transporters inhibitors (SGLT2i) and glucagon-like-peptide receptor agonist (GLP1ra) compared with SGLT2i or GLP1ra alone improves survival: a Real-World Registry

Abstract Background Prior clinical trials found diabetic patients, after being treated with SGLT2i (sodium-glucose-transporters inhibitors) and/or GLP1ra (glucagon-like-peptide receptor agonist), had lower rates of cardiovascular (CV) complications. But there is poor evidence of the additive benefits of combined therapy in the general population. Purpose This study sought to determine if the combined therapy reduced the major CV complications or all-cause of death in comparison with SGLT2i or GLP1ra alone in a health area. Methods This is a retrospective observational study of patients who were prescribed with an SGLT2i, GLP1ra or both between January 1st 2018 and 30th June 2022 from one healthcare area that includes primary care centres and hospitals. They were followed up until 31st October 2022. The primary outcomes were the combined incidence of hospitalisation or/and death for heart failure (HF), coronary artery disease (CAD), cerebrovascular accident (CVA) and all-cause mortality. Sex, age, glucose lowering drugs (GLD) (and duration), diabetes (and duration), arterial hypertension (HBP), dyslipidemia (DLP), CAD, HF, atrial fibrillation (AF) and CVA were included on a Cox regression analysis for determining the main predictors for each outcome. Results We have included 15.549 patients with/out CVD who were prescribed GLD from 2018. The population was represented by 97% with T2DM, 46% with obesity, 71% with HBP, 59% with DLP, 15% CAD, 10% with HF, 12% with AF and 6% with CVA (Figure 1). The mean follow-up was 33 (19) months. The Kaplan Meier analysis determined that the cumulative risk for CAD and CVA events was similar among the 3 different therapy groups. However, the combined therapy reduced the risk for HF events (HR: 0,771 [95% CI: 0,612-0,970]) or all-cause mortality (HR: 0,255 [95% CI: 0,325-0,414]) (Figure 2a, 2c). The multivariate Cox regression analysis showed that combined therapy, treatment duration and DLP were associated with a significant reduction in HF and all-cause mortality events; while age, sex (male), CAD, HF and AF increased them (Figure 2b, 2d). Conclusions Compared with SGLT2i or GLP1ra alone, combined therapy SGLT2i + GLP1ra reduces HF risk and all-cause mortality in a real-world population.Figure 1Figure 2