Cardiovascular risk profiles: A cross‐sectional study evaluating the generalizability of the glucagon‐like peptide‐1 receptor agonist cardiovascular outcome trials REWIND, LEADER and SUSTAIN‐6 to the real‐world type 2 diabetes population in the United Kingdom

Abstract

Aims: To determine the proportion of UK patients with type 2 diabetes (T2D) who meet the cardiovascular (CV) or combined CV/core eligibility criteria used for the CV outcome trials (CVOTs) of UK-marketed glucagon-like peptide-1 receptor agonists showing CV benefit (dulaglutide in REWIND, liraglutide in LEADER and injectable semaglutide in SUSTAIN-6).Materials and Methods: Adults with T2D on/before June 2018 were identified from the UK Clinical Practice Research Datalink GOLD primary care database and linked to Hospital Episode Statistics data (Protocol 19_262). Patient CV and clinical data were evaluated against the CVOT eligibility criteria. Data were analysed descriptively. Results:The study cohort (N = 33 118 patients with T2D) had a mean (standard deviation) age of 66.0 (13.3) years and 56.6% were male. Almost two-thirds (64.5%) of the study cohort met the CV criteria for REWIND, versus 43.0% for both LEADER and SUSTAIN-6. The proportions of the study cohort who met the CVOT criteria of "established CV disease" and "CV risk factors only" for REWIND were 22.4% and 42.1%, respectively, versus 38.7% and 4.3%, respectively, for both LEADER and SUSTAIN-6. The proportions of patients satisfying both CV and core criteria were 44.4% for REWIND, 13.3% for LEADER and 13.5% for SUSTAIN-6. Study findings remained consistent when restricted to GLP-1RA users.Conclusions: REWIND captured a trial population more representative of the realworld T2D population in the United Kingdom than LEADER or SUSTAIN-6 with regard to both CV and combined CV/core eligibility criteria.

Therapeutic inertia related to the injectable glucagon‐like peptide‐1 receptor agonists dulaglutide and semaglutide in patients with type 2 diabetes in UK primary care

“…All the variables used in this study are presented in Supporting Information Table S1. Code lists compiled for the purposes of variable definitions were taken from a recent study 17 and supplemented with additional product codes for T2D medications where appropriate.…”

Glucagon-like peptide-1 receptor agonists: new strategies and therapeutic targets to treat atherosclerotic cardiovascular disease

“…The REWIND study of dulaglutide, published in 2019, stood out from previous CVOTs as the longest-follow-up CVOTs in the lowest CVD-risk and baseline glycated hemoglobin A 1c (HbA 1c ) population ( Webb et al, 2022 ). The research enrolled 9,901 T2DM patients aged 50 years or older with confirmed CVD or risk factors for CVD, with a baseline HbA 1c of 7.2%.…”

Incretins and cardiovascular disease: to the heart of type 2 diabetes?

“…Because of such strict methodology, the populations included in CVOTs may not be representative of the general diabetes population. When the clinical characteristics of participants in the LEADER, REWIND and SUSTAIN-6 trials were compared with the typical diabetes population in Spain [ 30 ], the UK [ 31 ] and the USA [ 32 ], even the most representative of these CVOTs (REWIND) captured only a fraction (42.6–53.6%) of the real-world type 2 diabetes population (Fig. 3 ).…”