Replication of the LEAD-2 Diabetes Trial in Healthcare Claims Data

Completed

• Conditions: Diabetes
• Interventions: Drug: Glimepiride; Drug: Liraglutide

• Registration Number: NCT05162183
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

Investigators are building an empirical evidence base for real world data through large-scale replication of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.

Detailed Description

This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not replicable in healthcare claims data but was proxied through a statistical balancing of measured covariates through standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for replication for a range of possible reasons and does not provide information on the validity of the original RCT finding.

Study Timeline

• Study Start: 2019-09-01
• Primary Completion: 2021-09-01
• Study Completion: 2021-09-01
• Study First Submitted: 2021-09-20
• Study First Submitted QC: 2021-12-16
• Study First Posted: 2021-12-17
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-25
• Last Update Posted: 2023-07-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 3474

Inclusion Criteria

• Diagnosis of Type 2 Diabetes mellitus [0,0] days
• 3 or more recorded HbA1c values [-365, 0] days
• At least two dispensing claims for metformin [-180,0] days
• 1 or more recorded HbA1c values [-90,0] days
• Age between 18-80 [0,0] days

Exclusion Criteria

• Cancer, malignant neoplasm, or MEN2 [-1,825,0] days
• Use of other anti-diabetic medications [-180,0] days
• Cirrhosis or Hepatic decompensation [-180,0] days
• Viral hepatitis B or C [-180,0] days
• Stage 5 CKD, ESRD, dialysis or renal transplant [-180,0] days
• MI or HF [-180,0] days
• Treatment with Anti-VEGFi or Photocoagulation [-180,0] days
• Hypertensive crisis or uncontrolled hypertension [-180,0] days
• Two diagnoses of hypoglycemia [-180,0] days
• Alcohol/drug abuse/dependence [-180,0] days
• Dementia and brain damages or non-compliance [-180,0] days
• Pregnancy [-180,0] days
• Type 1 DM, DKA, or other metabolic acidosis [-180,0] days
• Systemic corticosteroids [-90,0] days

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Glimepiride	Glimepiride	Reference Group
Liraglutide	Liraglutide	Exposure group

Primary Outcome Measures

Name	Time	Method
Relative Hazard of change in HbA1c from baseline to 26 weeks of treatment (end of follow-up)	26-week follow-up window with a median follow-up time of 99 [84, 148] days	Claims-based algorithm: relative hazard of change in HbA1c from baseline to 26 weeks of treatment (end of follow-up)

Trial Locations

Locations (1)

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States