Myocardial deformation links combined liraglutide–empagliflozin therapy with improved cardiovascular and economic outcomes in type 2 diabetes: a 6-year study

Abstract Aims We investigated whether the early favorable effects of combined GLP-1 receptor agonist (GLP-1RA) and SGLT2 inhibitor (SGLT2i) therapy in left ventricular deformation is associated with long-term cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM). We also addressed the healthcare costs. Methods We enrolled 336 consecutive participants with T2DM, aged 60±10 years old, 252/336 (75%) were males and were categorized into four groups: insulin, liraglutide, empagliflozin and liraglutide+empagliflozin. We measured at baseline and at 6 months Left Ventricular Global Longitudinal Strain (LVGLS) via echocardiography. Patients were followed for 6 years and we recorded the incidence of composite endpoint of non-fatal cardiovascular events (myocardial infarction, heart failure hospitalization, ischemic stroke and coronary revascularization). Multivariable Cox regression models were built to assess associations between treatment groups, LVGLS changes and outcomes. A cost analysis was also conducted. Results At 6 months LVGLS increased significantly (p=0.020), with the greatest improvement observed in the combination group compared with insulin, GLP-1RA, and SGLT2i groups (p<0.05). At 6-year follow-up, 92 events were recorded. Combination therapy was associated with the lowest risk of events (Insulin vs Combination: HR=4.36,95%CI:2.04-9.33,p<0.001; GLP1-RA vs Combination: HR=2.45, 95%CI:1.06-5.64, p=0.035; SGLT2i vs Combination: HR=3.07, 95%CI:1.38-6.81, p=0.006). In combination group, improvement of LVGLS independently predicted reduced event risk (HR=0.89, 95%CI:0.79-0.98,p=0.040). Combination group demonstrated the lowest mean cost per patient per month (Insulin:691€, 95%CI:472-911; GLP1-RA:224€, 95%CI:44-404; SGLT2i:528€,95%CI:305-751;Combination:175€, 95%CI: 30-321). Conclusion Combined GLP-1RA and SGLT2i therapy is associated with early improvement in myocardial deformation, which translates into reduced long-term cardiovascular risk and favorable economic outcomes.