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Mitch Conover

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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.