Glucagon-Like Peptide 1 Receptor Agonists and Chronic Lower Respiratory
Disease among Type 2 Diabetes Patients: Replication and Reliability
Assessment Across a Research Network
Abstract
Introduction: Use observational methods to evaluate reliability
of evidence generated by a study of the effect of glucagon-like peptide
1 receptor agonists (GLP-1RA) on chronic lower respiratory disease
(CLRD) outcomes among type-2 diabetes mellites (T2DM) patients.
Research Design and Methods: We independently reproduced a
study comparing effects of GLP-1RA versus dipeptidyl peptidase-4
inhibitors (DPP4-i) on CLRD outcome among patients with T2DM and prior
CLRD. We reproduced inputs and outputs using the original study data
(national administrative claims) and evaluated robustness to alternate
design/analysis decisions. To evaluate generalizability, we applied the
protocol and meta-analyzed across a research network including diverse
array of populations and data sources. We also produced additional
analyses evaluating individual drugs within the GLP-1RA class.
Results: We confirmed alignment of study inputs and outputs and
closely reproduced effect estimates and sensitivity analyses. Adjusted
effect estimates were robust to empirical calibration. Network
meta-analysis confirmed original findings, but indicated weaker effects
than originally published. Meta-analyzing drugs within the GLP-1RA class
against DPP4-I provided some evidence that effects vary within the
GLP-1RA class, indicating stronger effects for exenatide and weaker
effects of dulaglutide. Conclusions: This study supports the
reliability of the original study by 1) confirming the findings in a
range of alternate databases and populations 2) demonstrating effects
for multiple drugs within the GLP-1RA class, and 3) independently
confirming the reproducibility original study and its findings. We
propose that clinicians treating patients with T2DM and a history of
CLRD consider GLP-1RA in absence of strong motivating reasons to select
another therapy.