Large-scale evidence generation and evaluation across a network of databases for type 2 diabetes mellitus (LEGEND-T2DM)

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Effectiveness study (incl. comparative)

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (A10) DRUGS USED IN DIABETES

  DRUGS USED IN DIABETES
• Medical condition to be studied:
  Type 2 diabetes mellitus

Population studied

• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Renal impaired
• Estimated number of subjects:
  1000000

Study design details

• Main study objective:
  To determine, through systematic evaluation, the comparative effectiveness and safety of traditionally second-line T2DM agents, SGLT2 inhibitors and GLP1 receptor agonists, with each other and with DPP4 inhibitors and sulfonylureas, for cardiovascular and safety outcomes.
• Outcomes:
  3- and 4-point major cardiovascular events, Acute myocardial infarction, acute renal failure, glycemic control, hospitalization for heart failure, measured renal dysfunction, stroke, sudden cardiac death, and 22 other patient-centered safety outcomes
• Data analysis plan:
  LEGEND-T2DM will execute all pairwise class-vs-class and drug-vs-drug comparisons in each data source that meet a minimum patient count of 1,000 per arm and extensive study diagnostics that assess reliability and generalizability through cohort balance and equipoise to examine the relative risk of cardiovascular and safety outcomes. Our systematic framework will 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. 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.