Dataset Information

Generalizability of glucagon-like peptide-1 receptor agonist cardiovascular outcome trials to the overall type 2 diabetes population in the United States.

ABSTRACT:

Aim

To examine the generalizability of results from glucagon-like peptide-1 receptor agonist (GLP-1 RA) cardiovascular outcome trials (CVOTs) in the US type 2 diabetes (T2D) population.

Materials and methods

Patients enrolled or eligible for inclusion in four CVOTs (EXSCEL, LEADER, REWIND, and SUSTAIN-6) were examined in reference to a retrospective clinical database weighted to match the age and sex distribution of the US adult T2D population. We descriptively compared key baseline characteristics of the populations enrolled in each trial to those of the reference population and estimated the proportions of individuals in the reference population represented by those in the trials for each characteristic. We also estimated the proportions of individuals in the reference population that might have been enrolled in each trial based upon meeting the trial inclusion and exclusion (I/E) criteria.

Results

No trial's enrolled population perfectly matched the reference population in key characteristics. The EXSCEL population most closely matched in mean age (62.7 vs. 60.5?years) and percentage with estimated glomerular filtration rate <60 (18.6 vs. 17.3%), while REWIND most closely matched in HbA1c, sex distribution, and proportion with a prior myocardial infarction. Based on I/E criteria, 42.6% of the reference population were eligible for enrolment in REWIND, versus 15.9% in EXSCEL, 13.0% in SUSTAIN-6, and 12.9% in LEADER.

Conclusions

Although none of the trials are fully representative of the general population, among the four trials examined, results from baseline REWIND were found to be more generalizable to the US adult T2D population than those of other GLP-1 RA CVOTs.

SUBMITTER: Boye KS

PROVIDER: S-EPMC6593714 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

Generalizability of glucagon-like peptide-1 receptor agonist cardiovascular outcome trials to the overall type 2 diabetes population in the United States.

Boye Kristina S KS Riddle Matthew C MC Gerstein Hertzel C HC Mody Reema R Garcia-Perez Luis-Emilio LE Karanikas Chrisanthi A CA Lage Maureen J MJ Riesmeyer Jeffrey S JS Lakshmanan Mark C MC

Diabetes, obesity & metabolism 20190312 6

<h4>Aim</h4>To examine the generalizability of results from glucagon-like peptide-1 receptor agonist (GLP-1 RA) cardiovascular outcome trials (CVOTs) in the US type 2 diabetes (T2D) population.<h4>Materials and methods</h4>Patients enrolled or eligible for inclusion in four CVOTs (EXSCEL, LEADER, REWIND, and SUSTAIN-6) were examined in reference to a retrospective clinical database weighted to match the age and sex distribution of the US adult T2D population. We descriptively compared key baseli ...[more]

PMID: 30714309

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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:Rationale & objectiveInformation regarding disparities in initiating sodium/glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) in patients with chronic kidney disease (CKD) is limited. We examined sociodemographic and clinical factors associated with the initiation of SGLT2i, GLP-1RA, or second-generation sulfonylureas in a Medicare Fee-For-Service patient population with CKD and type 2 diabetes.Study designRetrospective cohort study.Setting & participantsThe 20% random sample of Medicare Fee-For-Service claims, 2012-2018.ExposuresPatients' sociodemographic and clinical factors.OutcomesUse of SGLT2i, GLP-1RA, or sulfonylureas.Analytical approachPatients with a newly initiated prescription of SGLT2i, GLP-1RA, or second-generation sulfonylureas from January 1, 2013, to December 31, 2018, were identified. Multinomial logistic regression model was used to evaluate demographic and clinical factors associated with the initiation of SGLT2i, GLP-1RA, or second-generation sulfonylureas.ResultsThe study cohort comprised 53,029 adults (aged greater than or equal to 18 years) with CKD and type 2 diabetes, of whom 10.0%, 17.4%, and 72.6% had a first prescription for SGLT2i, GLP-1RA, and sulfonylurea, respectively. Patients aged greater than or equal to 75 years versus those aged 65-74 years had lower odds to start SGLT2i or GLP-1RA compared with sulfonylureas. Black patients were associated with lower odds of initiation of SGLT2i (OR, 0.67; 95% CI, 0.61-0.74) and GLP-1RA (OR, 0.73; 95% CI, 0.68-0.79), compared with White patients. Hispanic and Asian patients had lower odds of initiation of GLP-1RA. Patients with cardiovascular disease or hyperlipidemia had higher odds to start SGLT2i or GLP-1RA.LimitationsCKD and type 2 diabetes diagnosis; CKD stage; and patient clinical status were identified with diagnosis or procedure codes. There is potential for residual confounding with the use of retrospective data.ConclusionsThe results of this study identified disparities in the use of SGLT2i and GLP-1RA in patients with CKD. Black and older patients were significantly less likely to be initiated on SGLT2i or GLP-1RA than on second-generation sulfonylureas.

Project description:BackgroundEfficacy trials showed that glucagon-like peptide-1 receptor (GLP1R) agonists reduced metabolic risk factors in addition to glucose lowering, but the cardiovascular and microvascular efficacy of this drug class remains to be determined. We aimed to evaluate the overall cardiovascular and microvascular efficacy of GLP1R agonists by performing a meta-analysis with trial sequential analysis.MethodsRandomized controlled, cardiovascular outcomes trials including at least 2000 patient-years' follow-up and 100 composite cardiovascular events were included. Trial sequential analysis (TSA) was performed and the quality of evidence was graded.ResultsThirty-three thousand four hundred fifty-seven patients and 4105 cardiovascular events from 4 large trials were included. GLP1R agonists were associated with a statistically significant reduction in risks for all-cause mortality (hazard ratio [HR]: 0.88, 95% CI: 0.81 to 0.95; number needed to treat [NNT]: 286 person-years), cardiovascular mortality (HR: 0.87, 95% CI: 0.79 to 0.96; NNT: 412 person-years), stroke (HR: 0.87, 95% CI: 0.76 to 0.98; NNT: 209 person-years) and the composite adverse cardiovascular outcome (MACE; HR: 0.91, 95% CI: 0.85 to 0.96; NNT: 241 person-years). The magnitude of benefit on MACE was attenuated in patients with a history of congestive heart failure (HR: 0.96, 95% CI: 0.85 to 1.08 with; HR: 0.87, 95% CI: 0.77 to 1.00 without). The risks for hospitalization for heart failure and myocardial infarction were not significantly different. The quality of the evidence was deemed as moderate to high based on GRADE approach. TSA provided firm evidence for a 10% reduction in all-cause mortality, a 15% reduction in MACE, and lack of a 15% reduction in hospitalization for heart failure, but evidence remains inconclusive for cardiovascular mortality and myocardial infarction. GLP1R agonists numerically reduced the rates for nephropathy but the risk for retinopathy was similar.ConclusionsMeta-analysis with trial sequential analysis suggested that GLP1R agonists significantly reduced the risk for all-cause mortality and composite cardiovascular outcomes, but the reduction of cardiovascular mortality remains to be confirmed.

Dataset Information

Generalizability of glucagon-like peptide-1 receptor agonist cardiovascular outcome trials to the overall type 2 diabetes population in the United States.

Aim

Materials and methods

Results

Conclusions

Publications

Generalizability of glucagon-like peptide-1 receptor agonist cardiovascular outcome trials to the overall type 2 diabetes population in the United States.

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