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Subpopulation Differences in the Cardiovascular Efficacy of Long-Acting Glucagon-Like Peptide 1 Receptor Agonists in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

ABSTRACT: INTRODUCTION:The cardiovascular efficacy of glucagon-like peptide 1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) are well documented; however, the differences in cardiovascular efficacy among subpopulations remain unknown. This systematic review and meta-analysis aimed to explore the differences in cardiovascular efficacy of long-acting GLP-1RAs among subpopulations of patients with T2DM and to assess the drug safety. METHODS:Relevant studies up to March 31, 2020 were searched for in six electronic databases, namely PubMed, Cochrane Library, Embase, Clinical Trials, Science Direct, and Web of Science. The primary outcome was three-point major adverse cardiovascular events (including cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke). Subpopulations were defined using ten selected influential factors, and the differences in cardiovascular efficacy in subpopulations stratified by different influential factors were accessed by synthesizing studies with random-effects models one by one. RESULTS:A total of six cardiovascular outcome trials of long-acting GLP-1RAs, comprising 49,936 participants, were included. Among stratified subpopulations, no significant differences in the cardiovascular efficacy of long-acting GLP-1RAs were observed across the ten characteristics of subjects (all P for interaction?>?0.05). Favorable trends were observed in the subpopulation with established cardiovascular disease (CVD) compared to that without (P?=?0.171). With regards to safety, long-acting GLP-1RAs did not significantly increase the risk of retinopathy (OR 1.09; 95% CI 0.92-1.29; P?=?0.316), but increase the risk of serious gastrointestinal events (OR 1.37; 95% CI 1.02-1.83; P?=?0.037). Long-acting GLP-1RAs did not significantly increase the risk of serious adverse events (OR 0.92; 95% CI 0.85-1.00; P?=?0.039). CONCLUSIONS:Our analysis suggested no subpopulation differences in the cardiovascular efficacy of long-acting GLP-1RAs among stratified subpopulations, and favorable trends were only observed in the subpopulation with established CVD. These findings may have implications for the management of long-acting GLP-1RAs across subpopulations of patients with T2DM.

SUBMITTER: He L

PROVIDER: S-EPMC7434822 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Subpopulation Differences in the Cardiovascular Efficacy of Long-Acting Glucagon-Like Peptide 1 Receptor Agonists in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

He Liyun L Yang Na N Xu Lingling L Ping Fan F Li Wei W Li Yuxiu Y Zhang Huabing H

Diabetes therapy : research, treatment and education of diabetes and related disorders 20200730 9

<h4>Introduction</h4>The cardiovascular efficacy of glucagon-like peptide 1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) are well documented; however, the differences in cardiovascular efficacy among subpopulations remain unknown. This systematic review and meta-analysis aimed to explore the differences in cardiovascular efficacy of long-acting GLP-1RAs among subpopulations of patients with T2DM and to assess the drug safety.<h4>Methods</h4>Relevant studies up to March 31, 202 ...[more]

PMID: 32734559

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Project description:Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) have demonstrated efficacy in improving mortality and cardiovascular (CV) outcomes. However, the impact of GLP-1RAs therapy on cardiorenal outcomes of diabetic patients at the commencement of dialysis remains unexplored. This study aimed to investigate the long-term benefits of GLP-1RAs in type 2 diabetic patients at dialysis commencement. A cohort of type 2 diabetic patients initializing dialysis was identified from the TriNetX global database. Patients treated with GLP-1RAs and those treated with long-acting insulin (LAI) were matched by propensity score. We focused on all-cause mortality, four-point major adverse cardiovascular events (4p-MACE), and major adverse kidney events (MAKE). Among 82,041 type 2 diabetic patients initializing dialysis, 2.1% (n = 1685) patients were GLP-1RAs users (mean ages 59.3 years; 55.4% male). 1682 patients were included in the propensity-matched group, treated either with GLP-1RAs or LAI. The main causes of acute dialysis in this study were ischemic heart disease (17.2%), followed by heart failure (13.6%) and sepsis (6.5%). Following a median follow-up of 1.4 years, GLP-1RAs uses at dialysis commencement was associated with a reduced risk of mortality (hazard ratio [HR] = 0.63, p < 0.001), 4p-MACE (HR = 0.65, p < 0.001), and MAKE (HR = 0.75, p < 0.001). This association was particularly notable in long-acting GLP-1RAs users, with higher BMI, lower HbA1c, and those with eGFR > 15 ml/min/1.73m2. GLP-1RAs' new use at dialysis commencement was significantly associated with a lower risk of MACE (p = 0.047) and MAKE (p = 0.004). Additionally, GLP-1RAs use among those who could discontinue from acute dialysis or long-term RAs users was associated with a lower risk of mortality, 4p-MACE, and MAKE. Given to the limitations of this observational study, use of GLP-1RAs at the onset of dialysis was associated with a decreased risk of MACE, MAKE, and all-cause mortality. These findings show the lack of harm associated with the use of GLP-1RAs in diabetic patients at the initiation of acute dialysis.

Project description:IntroductionThis 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).MethodsThe 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.ResultsOn 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.ConclusionAmong the four GLP-1 RA CVOTs, the REWIND trial using once-weekly dulaglutide is most generalizable to Chinese patients with T2DM.Trial registrationTrial registration: NCT01128205 ( www.clinicaltrials.gov ).

Project description:BackgroundThe cardiovascular outcome trials (CVOTs) have shown that glucagon like peptide-1 receptor agonists (GLP1RAs) have varying degrees of cardiovascular (CV) safety in patients with type 2 diabetes mellitus (T2DM.) The lack of any head-to-head comparative trials among GLP1RAs urged the need for an indirect comparison of these agents. Therefore, this study was conducted to indirectly compare the CV safety and mortality effects among different GLP1RAs in patients with T2DM using network meta-analysis (NMA).MethodsMedline was searched to identify GLP1RA CVOTs to date. The outcomes of interest were CV death, myocardial infarction (IM), stroke, and death from any cause. An NMA with binomial likelihood logit link model was used for the binary outcomes. We conducted both fixed effects and random effects models for each outcome, and selected the best model based on the deviance information and the average posterior residual deviance. This NMA was reported in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA-NMA).ResultsA total of seven GLP1RA CVOTs were included having 56,004 patients. The NMA results showed that oral semaglutide was statistically better than exenatide (OR 0.47, 95% CI 0.21-0.99), dulaglutide (OR 0.46, 95% CI 0.20-0.97), albiglutide (OR 0.45, 95% CI 0.19-0.97), lixisenatide (OR 0.43, 95% CI 0.19-0.92) in reducing CV death events. No significant differences were detected between most of the treatments regarding reducing death from any cause, MI and stroke events. The ranking results showed that oral semaglutide had the highest probability to be ranked first (> 90%) in reducing CV death and death from any cause. Moreover, once weekly semaglutide had the highest probability to be ranked first in reducing MI and stroke events.ConclusionThe GLP1RAs have shown significant benefits in terms of CV safety. The indirect comparison and ranking probability results have shown that one weekly semaglutide and oral semaglutide seems to be the preferred option in patients with T2DM and established or at high risk of CVD. This result can aid health care providers, pharmacy and therapeutics committees in hospitals, and insurance companies when deciding which GLP1RA to start or add to their formulary.

Dataset Information

Subpopulation Differences in the Cardiovascular Efficacy of Long-Acting Glucagon-Like Peptide 1 Receptor Agonists in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

Publications

Subpopulation Differences in the Cardiovascular Efficacy of Long-Acting Glucagon-Like Peptide 1 Receptor Agonists in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

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