Real-world comparisons between Glucagon-like peptide-1 receptor agonists and other glucose-lowering agents in type 2 Diabetes : retrospective analyses of cardiovascular and economic outcomes in England

Abstract

Introduction: Clinical trials have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes (T2D) who have established cardiovascular disease (CVD) or a high risk of CVD. Nevertheless, GLP-1RAs remain underutilized. This real-world, retrospective study compared cardiovascular and economic outcomes between individuals treated with GLP-1RAs and other glucose-lowering agents in England. Methods: Clinical Practice Research Datalink-registered people indexed on GLP-1RAs, dipeptidyl peptidase-4 (DPP4) inhibitors, or basal insulin between January 1, 2014 and December 31, 2018 for their fourth line of T2D treatment were stratified into six cohorts based on their: (1) cardiovascular risk (high or very high risk) and (2) indexed therapy. Cox proportional hazards regression was used to compare the risk of MACE and all-cause death between GLP-1RA and other treatment cohorts. Generalized linear regression was used to quantify differences in healthcare resource use (HCRU) and costs between groups. Results: Of 63,237 subjects, 10,607 were at high cardiovascular risk (GLP-1RA: 2709; DPP4 inhibitor: 2673; basal insulin: 5225) and 52,630 at very high cardiovascular risk (GLP-1RA: 14,692; DPP4 inhibitor: 18,461; basal insulin: 19,477). The crude incidence of all outcomes was lower in the GLP-1RA versus other treatment cohorts, regardless of cardiovascular risk. Among very-high-risk individuals treated with GLP-1RA, the adjusted risk of MACE was 33% (24-40%) and 23% (13-23%) lower versus DPP4 inhibitor and basal insulin cohorts, respectively. The adjusted total cardiovascular-related cost among very-high-risk individuals was £208.14 (£155.81-£260.47) and £151.74 (£110.69-£192.79) lower in the GLP-1RA versus DPP4 inhibitor or basal insulin cohorts, respectively. Conclusions: In a real-world setting, GLP-1RAs may be associated with a lower risk of MACE and reduced HCRU and costs than DPP4 inhibitors or basal insulin in individuals with T2D, particularly among those at very high cardiovascular risk.