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Comparison of Type 2 Diabetes Pharmacotherapy Regimens (ON TARGET DM)

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ClinicalTrials.gov Identifier: NCT05073692
Recruitment Status : Recruiting
First Posted : October 11, 2021
Last Update Posted : October 11, 2021
Sponsor:
Collaborators:
Geisinger Clinic
Henry Ford Health System
HealthPartners Institute
Patient-Centered Outcomes Research Institute
Information provided by (Responsible Party):
Kaiser Permanente

Brief Summary:
This study is designed to help patients with type 2 diabetes and their clinicians: (a) identify which glucose lowering medications have the most favorable effects on heart health and other patient-important outcomes, (b) inform the timing of medication initiation, and (c) identify whether medication benefits apply equally to all adults with type 2 diabetes, or may be different based on age, sex, race/ethnicity, baseline heart health status, baseline renal function, or other factors.

Condition or disease Intervention/treatment
Type 2 Diabetes Mellitus Cardiovascular Diseases Drug: SU Drug: DPP4 Drug: SGLT2i Drug: GLP-1RA Drug: SGLT2i or GLP-1RA Drug: Linagliptin (DPP4) Drug: Exenatide (GLP-1RA) Drug: Liraglutide (GLP-1RA) Drug: Empagliflozin (SGLT2i) Drug: Glimepiride (SU) Drug: Glipizide (SU) Drug: Glimepiride (SU) or Glipizide (SU) Drug: SU or DPP4 (excluding saxagliptin and alogliptin) Drug: Exenatide (GLP-1RA) or Liraglutide (GLP-1RA)

Detailed Description:

The study will conduct head-to-head comparisons of type 2 diabetes mellitus (T2DM) treatment strategies using observational data from real-world clinical settings to assess cardiovascular disease (CVD) outcomes and other patient-centered outcomes in T2DM patients with moderate baseline CVD risk who are treated with each of these four classes of glucose-lowering medications known as SGLT2, GLP-1RA, DPP4, and SU. To mitigate bias concerns related to confounding and informative loss to follow-up, analyses will be based on modern causal inference methods combined with machine learning that emulate intention-to-treat (ITT) and per-protocol (PP) analyses of pragmatic randomized trials with active comparators to provide the most robust and precise estimates of relative and absolute effects we would expect in usual care settings.

Specific Aims and Hypotheses:

Aim 1. Compare the effect off SGLT21, GLP-1RA, DPP4, and SU on each study outcome in adults with T2DM when each type of medication is (a) initiated as second-line therapy after metformin, and (b) initiated as first-, second-, or third-line therapy, or after any history of glucose-lowering therapy independent of prior metformin use.

Aim 2. Compare the effect on each study outcome of earlier versus later initiation of SGLT2i, GLP-1RA, DPP4, SU as first-, or second-, or third-line therapy, or after any history of glucose-lowering therapy triggered by various changes in A1C, or CVD risk, or other patient characteristics.

Aim 3. Assess in each of the prior analyses whether the treatment effects on study outcomes vary across categories of baseline CVD risk and CVD event history, renal function, congestive heart failure status, age, sex and race/ethnicity, or other patient characteristics.

Glucose-lowering medications will be compared at both the class and agent level. The key outcomes that will be considered are MACE 3-point, Myocardial Infarction, Stroke, Heart Failure, Hospitalization, Coronary or Carotid Artery Stent or Bypass Procedure, CVD Mortality, Overall Mortality. Additional patient-centered outcomes will be specified based on insights from stakeholder members of the research team.

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Study Type : Observational
Estimated Enrollment : 270000 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Comparison of Type 2 Diabetes Pharmacotherapy Regimens Using Targeted Learning
Actual Study Start Date : July 1, 2021
Estimated Primary Completion Date : June 30, 2024
Estimated Study Completion Date : August 30, 2025

Resource links provided by the National Library of Medicine



Intervention Details:
  • Drug: SU
    Exposure to the class of drugs known as Sulfonylureas (SU)
  • Drug: DPP4
    Exposure to the class of drugs known as Dipeptidyl peptidase-4 inhibitors (DPP4)
  • Drug: SGLT2i
    Exposure to the class of drugs known as Sodium-glucose cotransporter-2 inhibitors (SGLT2i)
  • Drug: GLP-1RA
    Exposure to the class of drugs known as Glucagon-like peptide-1 receptor agonists (GLP-1RA)
  • Drug: SGLT2i or GLP-1RA
    Exposure to either SGLT2i or GLP-1RA
  • Drug: Linagliptin (DPP4)
    Exposure to agent Linagliptin (DPP4)
  • Drug: Exenatide (GLP-1RA)
    Exposure to agent Exenatide (GLP1-RA)
  • Drug: Liraglutide (GLP-1RA)
    Exposure to agent Liraglutide (GLP-1RA)
  • Drug: Empagliflozin (SGLT2i)
    Exposure to agent Empagliflozin (SGLT2i)
  • Drug: Glimepiride (SU)
    Exposure to agent Glimepiride (SU)
  • Drug: Glipizide (SU)
    Exposure to Glimepiride (SU)
  • Drug: Glimepiride (SU) or Glipizide (SU)
    Exposure to agent Glimepiride (SU) or Glipizide (SU)
  • Drug: SU or DPP4 (excluding saxagliptin and alogliptin)
    Exposure to either SU or DPP4 excluding Saxagliptin and Alogliptin
  • Drug: Exenatide (GLP-1RA) or Liraglutide (GLP-1RA)
    Exposure to either Exenatide (GLP-1RA) or Liraglutide (GLP-1RA)


Primary Outcome Measures :
  1. Incidence of 3-point Major Adverse Cardiovascular Events (MACE) [ Time Frame: 1/1/2014 to 6/30/2021 ]
    3-point MACE is defined as a single outcome measure, which is a composite measure of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular disease death.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients from six large care delivery systems with integrated administrative and EHR clinical data sources (Geisinger in Pennsylvania, Henry Ford Health System in Michigan, HealthPartners Institute in Minnesota and Wisconsin, and Kaiser Permanente of Northern California, Southern California, and Hawaii) who were new users of glucose-lowering medications between 01/01/2014 and 06/30/2023.
Criteria
  • Dispensing of either of the set of drugs being compared
  • No prior dispensing of any of the drugs compared
  • Evidence of Type 2 Diabetes Mellitus diagnosis
  • Age 18-85
  • Not currently pregnant
  • No evidence of dementia or short-term life expectancy from prior cancer diagnoses
  • History of ≥2 years of continuous health plan membership
  • ≥1 A1c test in the past 18 months

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 ClinicalTrials.gov identifier (NCT number): NCT05073692


Contacts
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Contact: Romain S. Neugebauer, PhD 510-891-3234 Romain.S.Neugebauer@kp.org
Contact: Rosa M. Hippler, MA 5108913721 Rosa.M.Hippler@kp.org

Locations
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United States, California
Romain S. Neugebauer Recruiting
Oakland, California, United States, 94612
Contact: Romain S Neugebauer, PhD    510-891-3234    Romain.S.Neugebauer@kp.org   
Contact: Rosa M Hippler    510-891-3721    Rosa.M.Hippler@kp.org   
Kaiser Permanente Southern California Recruiting
Pasadena, California, United States, 91101
Contact: Jaejin An, PhD    626-807-4298    Jaejin.X.An@kp.org   
Contact: Cecilia Portugal    626-710-6777    Cecilia.X.Portugal@kp.org   
United States, Hawaii
Kaiser Permanente Hawaii Recruiting
Honolulu, Hawaii, United States, 96817
Contact: Caryn Oshiro, PhD    808-432-5555 ext 1486    Caryn.ES.Oshiro@kp.org   
Contact: Yannica Martinez    808-432-5555 ext 1571    Yannica-theda.s.martinez@kp.org   
United States, Michigan
Henry Ford Health System Recruiting
Detroit, Michigan, United States, 48202
Contact: Andrea Cassidy-Bushrow, PhD    313-874-6097    acassid1@hfhs.org   
Contact: Lisa King    313-874-6223    Lking2@hfhs.org   
United States, Minnesota
HealthPartners Institute Recruiting
Bloomington, Minnesota, United States, 55425
Contact: Patrick O'Connor, MD, MA, MPH    952-967-5080    patrick.j.oconnor@healthpartners.com   
Contact: Kris Ohnsorg, RN, MPH, PMP       Kris.A.Ohnsorg@HealthPartners.Com   
United States, Pennsylvania
Geisinger Recruiting
Danville, Pennsylvania, United States, 17821
Contact: Jove Graham, PhD    570-214-9578    jhgraham1@geisinger.edu   
Contact: Vanessa Duboski    570-714-6682    vduboski1@geisinger.edu   
Sponsors and Collaborators
Kaiser Permanente
Geisinger Clinic
Henry Ford Health System
HealthPartners Institute
Patient-Centered Outcomes Research Institute
Investigators
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Principal Investigator: Romain S. Neugebauer, PhD Kaiser Permanente
Principal Investigator: Patrick J O'Connor, MD, MA, MPH HealthPartners Institute
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Responsible Party: Kaiser Permanente
ClinicalTrials.gov Identifier: NCT05073692    
Other Study ID Numbers: 739857
First Posted: October 11, 2021    Key Record Dates
Last Update Posted: October 11, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kaiser Permanente:
Type 2 Diabetes Mellitus
Cardiovascular Diseases
Medication
Treatment
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Cardiovascular Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Liraglutide
Exenatide
Empagliflozin
Glimepiride
Linagliptin
Saxagliptin
Alogliptin
Glipizide
Glucagon
Glucagon-Like Peptide 1
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Obesity Agents
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Immunosuppressive Agents
Immunologic Factors
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors