In ohdsi-studies/LegendT2dm: Large-Scale Evidence Generation and Evaluation in a Network of Databases

Strengths and Limitations of This Study

• The proposal seeks to determine real-world comparative effectiveness and safety of traditionally second-line T2DM agents using health information encompassing millions of patients with T2DM, with a focus on individuals at moderate cardiovascular risk and other key subgroups.
• We will conduct three large-scale, systematic, observational studies to make pairwise comparisons of all SGLT2 inhibitor, GLP1 receptor agonist, DPP4 inhibitor and sulfonylurea agents at the drug-, class- and population subgroup-level within our proposed Large-Scale Evidence Generations Across a Network of Databases for T2DM (LEGEND-T2DM) initiative.
• LEGEND-T2DM will leverage the Observational Health Data Science and Informatics (OHDSI) community that provides access to a standing global network of administrative claims and electronic health record (EHR) data sources, representing the 13 data sources already committed to LEGEND-T2DM cover over 190 million patients in the US and about 50 million internationally, and include two academic medical centers, IBM MarketScan and Optum databases, and the US Department of Veterans Affairs. All adults with type 2 diabetes across data sources are included. The outcomes of interest include a composite of major adverse cardiovascular events, and secondary effectiveness and safety outcomes, guided by stakeholders.
• The studies represent an observational, active-comparator, new-user cohort design with a systematic framework to address residual confounding, publication bias, and p-hacking using data-driven, large-scale propensity adjustment for measured confounding, a large set of negative control outcome experiments to address unmeasured and systematic bias, prespecification and full disclosure of hypotheses tested and their results. These approaches capitalize on mature OHDSI open-source resources and a large body of clinical and quantitative research that the LEGEND-T2DM investigators originated and continue to drive.
• LEGEND-T2DM is dedicated to open science and transparency and will publicly share all our analytic code from reproducible cohort definitions through turn-key software, enabling other research groups to leverage our methods, data, and results in order to verify and extend our findings.

ohdsi-studies/LegendT2dm documentation built on July 4, 2025, 8:25 p.m.