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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

Derek Connolly Orcid Logo, Edward Collins, Hongye Ren Orcid Logo, Simon Wan Yau Ming Orcid Logo, Jennifer Davidson Orcid Logo, Steve Bain Orcid Logo

Diabetes Therapy

Swansea University Author: Steve Bain Orcid Logo

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DOI (Published version): 10.1007/s13300-025-01715-w

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...

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Published in: Diabetes Therapy
ISSN: 1869-6953 1869-6961
Published: Springer Science and Business Media LLC 2025
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa68979
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.
Keywords: Cardiovascular; Cost; Diabetes; GLP-1RA; HCRU; MACE; T2D; DPP4 inhibitor; Basal insulin
College: Faculty of Medicine, Health and Life Sciences
Funders: Sponsorship for this study, support for statistical and editorial assistance, and the Rapid Service Fee were funded by Novo Nordisk A/S.

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