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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
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URI: https://cronfa.swan.ac.uk/Record/cronfa68979
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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&#x2013;40%) and 23% (13&#x2013;23%) lower versus DPP4 inhibitor and basal insulin cohorts, respectively. The adjusted total cardiovascular-related cost among very-high-risk individuals was &#xA3;208.14 (&#xA3;155.81&#x2013;&#xA3;260.47) and &#xA3;151.74 (&#xA3;110.69&#x2013;&#xA3;192.79) lower in the GLP-1RA versus DPP4 inhibitor or basal insulin cohorts, respectively. 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spelling 2025-04-11T14:53:17.6129553 v2 68979 2025-02-27 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 5399f4c6e6a70f3608a084ddb938511a 0000-0001-8519-4964 Steve Bain Steve Bain true false 2025-02-27 MEDS 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. Journal Article Diabetes Therapy 0 Springer Science and Business Media LLC 1869-6953 1869-6961 Cardiovascular; Cost; Diabetes; GLP-1RA; HCRU; MACE; T2D; DPP4 inhibitor; Basal insulin 21 3 2025 2025-03-21 10.1007/s13300-025-01715-w COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University Another institution paid the OA fee Sponsorship for this study, support for statistical and editorial assistance, and the Rapid Service Fee were funded by Novo Nordisk A/S. 2025-04-11T14:53:17.6129553 2025-02-27T12:50:57.0034253 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Derek Connolly 0000-0002-5471-133x 1 Edward Collins 2 Hongye Ren 0000-0003-0080-4765 3 Simon Wan Yau Ming 0000-0002-0146-0151 4 Jennifer Davidson 0000-0003-1599-7504 5 Steve Bain 0000-0001-8519-4964 6 68979__34020__7cedc34de6394d66a2958023791a732d.pdf 68979.VOR.pdf 2025-04-11T14:51:46.1850525 Output 1152237 application/pdf Version of Record true © The Author(s) 2025. This article is licensed under a Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0). true eng http://creativecommons.org/licenses/by-nc/4.0/
title 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
spellingShingle 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
Steve Bain
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
author_id_str_mv 5399f4c6e6a70f3608a084ddb938511a
author_id_fullname_str_mv 5399f4c6e6a70f3608a084ddb938511a_***_Steve Bain
author Steve Bain
author2 Derek Connolly
Edward Collins
Hongye Ren
Simon Wan Yau Ming
Jennifer Davidson
Steve Bain
format Journal article
container_title Diabetes Therapy
container_volume 0
publishDate 2025
institution Swansea University
issn 1869-6953
1869-6961
doi_str_mv 10.1007/s13300-025-01715-w
publisher Springer Science and Business Media LLC
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
document_store_str 1
active_str 0
description 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.
published_date 2025-03-21T11:34:51Z
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