Generalizability of glucagon-like peptide-1 receptor agonist cardiovascular outcome trials enrollment criteria to the US type 2 diabetes population

Abstract

Objectives: Cardiovascular outcomes trials (CVOTs) for evaluating the safety of novel antidiabetic agents are required by the FDA. CVOTs vary in their design and inclusion criteria, making it difficult to evaluate their applicability to the general population. This study examined the proportion of adults eligible for 7 ongoing or completed glucagon-like peptide-1 receptor agonist (GLP-1 RA) CVOTs.

Study design: This cross-sectional, retrospective, cohort study compared data from the National Health and Nutrition Examination Survey (NHANES) with published eligibility criteria from GLP-1 RA CVOTs.

Methods: Patient information on T2D status and other relevant characteristics were extracted from the 2009 to 2010 and the 2011 to 2012 NHANES. Weighted analyses of these data were used to calculate the numbers of adults with T2D in the US population who would have met eligibility criteria for enrollment in the following published or ongoing CVOTs: ELIXA (lixisenatide; NCT01147250), EXSCEL (Exenatide Study of Cardiovascular Event Lowering) (exenatide once weekly; NCT01144338), FREEDOM-CVO (exenatide via ITCA 650 miniature osmotic pump; NCT01455896), HARMONY Outcomes (albiglutide; NCT02465515), LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results) (liraglutide; NCT01179048), REWIND (Researching Cardiovascular Events With a Weekly INcretin in Diabetes) (dulaglutide; NCT01394952), and SUSTAIN-6 (semaglutide; NCT01720446).

Results: The proportion of adults with T2D eligible for enrollment varied substantially among CVOTs (6.4%-47.2%); EXSCEL, which had a pragmatic study design, had the most generalizable inclusion criteria. More than 60% of patients with T2D would have qualified for enrollment into at least 1 GLP-1 RA CVOT.

Conclusions: Most adults with T2D in the United States would have qualified for enrollment into at least 1 of the GLP-1 RA CVOTs evaluated. EXSCEL had the most generalizable eligibility criteria of these trials and ELIXA the least.