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Replication of the LEADER Diabetes Trial in Healthcare Claims

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03936049
Recruitment Status : Active, not recruiting
First Posted : May 3, 2019
Last Update Posted : January 2, 2020
Information provided by (Responsible Party):
Jessica Franklin, 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.

Condition or disease Intervention/treatment
Diabetes Drug: Liraglutide Drug: DPP-4 inhibitor

Detailed Description:
This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative ( of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as is 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 according to 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.

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Study Type : Observational
Actual Enrollment : 168690 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Replication of the LEADER Diabetes Trial in Healthcare Claims
Actual Study Start Date : September 22, 2017
Estimated Primary Completion Date : September 22, 2020
Estimated Study Completion Date : September 22, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Liraglutide

Group/Cohort Intervention/treatment
DPP-4 inhibitor
Reference group
Drug: DPP-4 inhibitor
DPP-4 inhibitor dispensing claim is used as the reference group

Exposure group
Drug: Liraglutide
Liraglutide dispensing claim is used as the exposure group

Primary Outcome Measures :
  1. Relative hazard of composite outcome of Stroke, MI, and Mortality [ Time Frame: Through study completion (a median of 154-188 days) ]
    Relative hazard of composite outcome of MI, stroke, and mortality - Please refer to uploaded protocol for full definition due to size limitations.

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
This study will involve a new user, parallel group, cohort study design comparing liraglutide to the DPP4 inhibitor (DPP4i) antidiabetic class as a proxy for placebo. Both 2nd generation sulfonylureas (SUs) and DPP4is are not known to have an impact on the outcome of interest. The comparison against DPP4i is the primary comparison. Initiators of 2nd generation SUs are used as a secondary comparator group. The patients will be required to have continuous enrollment during the baseline period of 180 days before initiation of liraglutide or a comparator drug (cohort entry date). Follow-up for the outcome (3P-MACE), begins the day after drug initiation. As in the trial, patients are allowed to take other antidiabetic medications during the study.

Please see: for full code and algorithm definitions.

Eligible cohort entry dates Market availability of liraglutide in the U.S. started on January 20, 2010. For Marketscan and Medicare: January 20, 2010-Dec 31, 2016 (end of data availability).

For Optum: January 20, 2010-Sep 30, 2017 (end of data availability).

Inclusion Criteria:

  • Men or women with type 2 diabetes
  • Either of the following:

    • Prior cardiovascular disease cohort: Age ≥ 50 years at screening, AND at least one of the following:

      • Prior MI
      • Prior stroke or TIA
      • Prior coronary, carotid or peripheral arterial revascularization
    • >50% stenosis of coronary, carotid, or lower extremity arteries coded by Peripheral vascular disease
    • Chronic heart failure NYHA class II-III
    • CKD stage 3-6 as Chronic renal failure:
  • No Prior cardiovascular disease group: Age ≥ 60 years at screening, AND at least one of the following:

    • Microalbuminuria or proteinuria
    • Hypertension and left ventricular hypertrophy by ECG or imaging
    • Ankle-brachial index <0.9

Exclusion Criteria:

  • Type 1 diabetes
  • Use of a GLP-1 receptor agonist (exenatide, liraglutide or other) or pramlintide or any (dipeptidyl peptidase 4 (DPP-4) inhibitor within the 3 months prior to screening
  • Use of long-term insulin in 90 days prior
  • Diabetic ketoacidosis in 3 months prior to index date as Acute decompensation of glycaemic control requiring immediate intensification of treatment to prevent acute complications of diabetes (e.g., diabetic ketoacidosis) in the previous 3 months
  • Inpatient (hospitalization) code for MI, stroke, revascularization, PTCA, CABG IN PRIOR 14 DAYS as An acute coronary or cerebrovascular event in the previous 14 days
  • inpatient Heart failure (CHF) as Chronic heart failure NYHA class IV
  • ESRD codes as Current continuous renal replacement therapy
  • Liver disease as "End stage liver disease, defined as the presence of acute or chronic liver disease and recent history of one or more of the following: ascites, encephalopathy, variceal bleeding, bilirubin ≥ 2.0 mg/dL, albumin level ≤ 3.5 g/dL, prothrombin time ≥ 4 seconds prolonged, international normalised ratio (INR) ≥1.7 or prior liver transplant"
  • Organ transplant codes as A prior solid organ transplant or awaiting solid organ transplant
  • History of malignant neoplasm in previous 5 years 140.xx-208.xx (except 173.xx, non-melanoma skin cancer)
  • Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (FMTC)
  • Personal history of non-familial medullary thyroid carcinoma
  • Drug abuse or dependence as Known use of non prescribed narcotics or illicit drugs
  • Encounter for contraceptive management, Oral contraceptives, and pregnancy as "Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures as required by local law or practice)"

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03936049

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United States, Massachusetts
Brigham And Women's Hospital
Boston, Massachusetts, United States, 02120
Sponsors and Collaborators
Brigham and Women's Hospital
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Principal Investigator: Jessie Franklin, PhD
  Study Documents (Full-Text)

Documents provided by Jessica Franklin, Brigham and Women's Hospital:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Jessica Franklin, Assistant Professor of Medicine, Brigham and Women's Hospital Identifier: NCT03936049    
Other Study ID Numbers: DUPLICATE-LEADER
First Posted: May 3, 2019    Key Record Dates
Last Update Posted: January 2, 2020
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action