Generalizability of the Results of Cardiovascular Outcome Trials of Glucagon-Like Peptide 1 Receptor Agonists in Chinese Patients with Type 2 Diabetes Mellitus

Abstract

Introduction: This study aimed to investigate the generalizability of the results of cardiovascular outcome trials (CVOTs) of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) to Chinese patients with type 2 diabetes mellitus (T2DM). Methods: The 3B (Blood Glucose, Blood Pressure, and Blood Lipid) population, a nationally representative population of patients with T2DM in China (n = 25,411), was examined for eligibility of enrollment in four GLP-1 RAs CVOTs (Dulaglutide-REWIND, Exenatide-EXSCEL, Liraglutide-LEADER, and Semaglutide-SUSTAIN-6). We first estimated the proportion of 3B population who would meet the six inclusion and exclusion (I/E) criteria, namely age, hemoglobin A1c (HbA1c), body mass index (BMI), estimated glomerular filtration rate (eGFR), history of cardiovascular disease (CVD), and antidiabetic medication, in each CVOT. Then we compared 11 baseline characteristics, namely age, gender, duration of diabetes, HbA1c, BMI, eGFR, history of CVD, prior myocardial infarction (MI), low-density lipoprotein cholesterol (LDL-c), diastolic blood pressure (DBP), and systolic blood pressure, between the population in each CVOT and the 3B population. Lastly, we estimated the proportion of 3B population that matched the characteristics in each CVOT population. Results: On the basis of the I/E criteria, 31.1% of the 3B population would have been eligible for enrollment in REWIND, 15.0% for SUSTAIN-6, 12.9% for LEADER, and 11.3% for EXSCEL. On the basis of the baseline characteristics, REWIND most closely matched the 3B population on gender, duration of diabetes, HbA1c, DBP, LDL-c, history of CVD, and prior MI. The proportion of 3B population matching on at least eight or at least ten baseline characteristics with CVOT populations was highest for REWIND compared to other CVOTs. Conclusion: Among the four GLP-1 RA CVOTs, the REWIND trial using once-weekly dulaglutide is most generalizable to Chinese patients with T2DM. TrialRegistration: Trial registration: NCT01128205 (www.clinicaltrials.gov).

Liraglutide on type 2 diabetes mellitus with nonalcoholic fatty liver disease: A systematic review and meta-analysis of 16 RCTs

“…It may also lead to heart, brain, kidney, eye, liver, vascular and other organ injuries. [ 54 ] The prolonged and sustained hyperglycemic state will aggravate or accelerate the liver damage. It causes a gradual development of fatty liver, liver fibrosis and even liver failure.…”

Does race/ethnicity influence the impact of new glucose-lowering agents on cardiovascular outcomes? a comparison between Asian versus White patients

“…Asian Indians are more susceptible to develop T2DM than Chinese and Malays and when diabetes mellitus occurs, the risk of ischaemic heart disease is higher than for their Chinese and Malays counterparts ( 28 ). Of note, a study reported that ≤15% of a nationally representative population of patients with T2DM in China would have been eligible for enrolment in three CVOTs with GLP-1RAs considered in a previous meta-analysis ( 22 ), thus questioning about the generalizability of CVOTs results to Chinese patients with T2DM ( 29 ).…”

Safety and effectiveness of dulaglutide in Chinese adults with type 2 diabetes mellitus in a real‐world setting: A prospective, observational post‐marketing study

“…5 In addition, among four GLP-1 RA CV outcome trials, the REWIND trial of once-weekly dulaglutide is the most generalizable to Chinese patients with T2DM. 6 Once-weekly dulaglutide is an optimal treatment for Chinese patients with T2DM inadequately controlled by 1-2 oral antidiabetes treatments according to the primary findings and post-hoc analyses of AWARD-CHN2. [2][3][4] However, patients participating in randomized, controlled trials are highly selected, based on the inclusion/exclusion criteria, and these studies are performed under controlled conditions.…”

“…In contrast, evidence to support primary prevention of CVD events is not available for other GLP‐1 RAs 5 . In addition, among four GLP‐1 RA CV outcome trials, the REWIND trial of once‐weekly dulaglutide is the most generalizable to Chinese patients with T2DM 6 . Once‐weekly dulaglutide is an optimal treatment for Chinese patients with T2DM inadequately controlled by 1‐2 oral antidiabetes treatments according to the primary findings and post‐hoc analyses of AWARD‐CHN2 2–4 .…”