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
Connolly, Derek Collins, Edward Ren, Hongye Wan Yau Ming, Simon Davidson, Jennifer Bain, Steve
Connolly, Derek
Collins, Edward
Ren, Hongye
Wan Yau Ming, Simon
Davidson, Jennifer
Bain, Steve
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Sandwell and West Birmingham NHS Trust; Aston University; Birmingham University; Novo Nordisk; et al.
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2025-03-21
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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.
Citation
Connolly D, Collins E, Ren H, Wan Yau Ming S, Davidson J, Bain S. 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. Diabetes Ther. 2025 May;16(5):955-975. doi: 10.1007/s13300-025-01715-w. Epub 2025 Mar 21
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