We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

BESTMED: Observational Evaluation of Second Line Therapy Medications in Diabetes (BESTMED)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05161429
Recruitment Status : Recruiting
First Posted : December 17, 2021
Last Update Posted : December 23, 2021
Sponsor:
Collaborators:
Patient-Centered Outcomes Research Institute
Baylor College of Medicine
Baylor Scott and White Research Institute
The Cleveland Clinic
HealthCore, Inc.
Humana Inc.
Massachusetts General Hospital
Medical Outcomes Management
University of Iowa
Allina Health
Intermountain Health Care, Inc.
Marshfield Clinic
Medical College of Wisconsin
University of Missouri-Columbia
University of Utah
Information provided by (Responsible Party):
Alexander Turchin, Brigham and Women's Hospital

Study Description
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
An observational study of electronic patient data to compare diabetes medications and to determine which ones offer the best balance of risks and benefits.

Condition or disease Intervention/treatment
Diabetes Mellitus, Type 2 Drug: DPP4 Drug: GLP-1 receptor agonist Drug: Basal Insulin Drug: SLGT2 Drug: SU

Detailed Description:

Type 2 diabetes is an increasingly common disease that affects more than 10 percent of adults in the United States. Multiple medications are available to treat this condition. However, many of these medications have never been directly compared against one another, which makes it unclear which medication is the best to use.

Investigators will use a large database of electronic patient data to compare diabetes medications to determine which ones offer the best balance of risks and benefits. This database will draw from several large healthcare institutions and health insurance companies that collectively pull from a patient population of over 130 million across all major regions of the United States. Investigators will study adults aged 30 or older who have type 2 diabetes and are at moderate risk of heart attacks and strokes, and who are starting a second diabetes medication (after metformin). Investigators will use clinical trial emulation, a cutting-edge statistical technique, to compare the following classes of diabetes medications: (1) DPP4 inhibitors (alogliptin, linagliptin, sitagliptin, or saxagliptin); (2) GLP1 receptor agonists (dulaglutide, exenatide, liraglutide, or semaglutide); (3) basal insulin (degludec, detemir, glargine, or NPH); (4) SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin); and (5) sulfonylureas (glimepiride, glipizide, or glyburide).

To determine which diabetes medications provide the greatest benefit to patients, investigators will compare how much they reduce the risks of the following \conditions: (1) heart attack; (2) heart failure; (3) stroke; (4) kidney disease; (5) eye disease; and (6) liver disease. To allow patients with diabetes and their doctors to make fully informed decisions about which diabetes medication to take, investigators will also compare these medications' risks of the following possible side effects: (1) low blood sugar; (2) kidney infection; (3) severe skin infections in the genital area; (4) foot/leg amputations; (5) broken bones; (6) pancreatitis (i.e., severe inflammation of the pancreas); (7) pancreatic cancer; (8) thyroid cancer; and (9) death from causes other than heart attacks or strokes.

In order to minimize the risk of bias and confounding, the analysis will be conducted using causal inference techniques, by emulating a randomized clinical trial (including both intention-to-treat and per-protocol analyses), while incorporating rigorous data quality checks.

Study Design
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Observational
Estimated Enrollment : 550000 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: BESTMED: Observational Evaluation of Second Line Therapy Medications in Diabetes
Actual Study Start Date : July 1, 2021
Estimated Primary Completion Date : June 30, 2024
Estimated Study Completion Date : June 30, 2024
Groups and Cohorts
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort Intervention/treatment
DPP4
Patients receiving second line diabetes treatment with dipeptidyl peptidase-4 inhibitors (DPP4) following metformin
 Drug: DPP4
Dipeptidyl peptidase-4 inhibitors (DPP4) including alogliptin, linagliptin, sitagliptin, and saxagliptin
GLP1-RA
Patients receiving second line diabetes treatment with glucagon-like peptide-1 receptor agonists (GLP1-RA) following metformin
 Drug: GLP-1 receptor agonist
Glucagon-like peptide-1 receptor agonists (GLP1-RA) including dulaglutide, exenatide, liraglutide and semaglutide
Basal insulin
Patients receiving second line diabetes treatment with basal insulin following metformin
 Drug: Basal Insulin
degludec, detemir, glargine and NPH
SLGT2
Patients receiving second line diabetes treatment with sodium-glucose cotransporter-2 inhibitors (SLGT2) following metformin
 Drug: SLGT2
Sodium-glucose cotransporter-2 inhibitors (SLGT2) including canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin
SU
Patients receiving second line diabetes treatment with sulfonylureas (SU) following metformin
 Drug: SU
Sulfonylurea (SU) including glimepiride, glipizide, and glyburide


Outcome Measures
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 4-point major adverse cardiac events (MACE) [ Time Frame: Follow-up begins 30 days after enrollment and ends at the earliest of a) the first study outcome; b) study end or c) loss to follow-up. Maximum duration of follow-up will be 10.5 years. ]
    Includes: a) death from cardiovascular causes b) non-fatal myocardial infarction (MI) c) non-fatal stroke and d) hospitalization for heart failure (HF)

  2. 3-point major adverse cardiac events (MACE) [ Time Frame: Follow-up begins 30 days after enrollment and ends at the earliest of a) the first study outcome; b) study end or c) loss to follow-up. Maximum duration of follow-up will be 10.5 years. ]
    Includes: a) death from cardiovascular causes as reported in the National Death Index b) non-fatal MI and c) non-fatal stroke


Secondary Outcome Measures :
  1. Adverse outcomes [ Time Frame: Follow-up begins 30 days after enrollment and ends at the earliest of a) the first study outcome; b) study end or c) loss to follow-up. Maximum duration of follow-up will be 10.5 years. ]
    Includes a) severe hypoglycemia b) severe urinary tract infection (UTI) c) Fournier's gangrene d) lower extremity amputation e) bone fracture f) diabetic ketoacidosis (DKA) g) pancreatitis h) pancreatic cancer i) medullary thyroid cancer j) non-cardiovascular death

  2. Severe clinical outcomes [ Time Frame: Follow-up begins 30 days after enrollment and ends at the earliest of a) the first study outcome; b) study end or c) loss to follow-up. Maximum duration of follow-up will be 10.5 years. ]
    Includes: a) hospitalization for >= 30 days with any of the primary or secondary outcome endpoints as the primary or admitting diagnosis b) ICU admission with any of the primary or secondary outcome endpoints as the primary or admitting diagnosis or c) death from any cause

  3. Non-cardiovascular outcomes [ Time Frame: Follow-up begins 30 days after enrollment and ends at the earliest of a) the first study outcome; b) study end or c) loss to follow-up. Maximum duration of follow-up will be 10.5 years. ]
    Includes a) nephropathy b) diabetic retinopathy requiring treatment c) non-alcoholic fatty liver disease (NAFLD) with advanced fibrosis / nonalcoholic steatohepatitis (NASH)


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   30 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
The study population is adults aged 30 or older who have type 2 diabetes and are at moderate risk of Atherosclerotic Cardiovascular Disease (ASCVD), and who are starting a second diabetes medication (after metformin). Patients from collaborating institutions will be included in the analysis based on study population inclusion and exclusion criteria.
Criteria

Individuals meeting the following criteria between January 1, 2015 and December 31, 2021:

  • Diabetes mellitus (DM) type II
  • HbA1c of 7-11% within the past year
  • Monotherapy with metformin for at least 3 months
  • No prior non-metformin outpatient diabetes therapy
  • Aged ≥30y

  • At "moderate" risk of ASCVD

    • Men aged ≥35y and women aged ≥45y with no history* of stroke, myocardial infarction, revascularization, or heart failure hospitalization
    • Men aged 30-34 and women aged 30-44 with history* of hypertension, hyperlipidemia, retinopathy, kidney disease or neuropathy
  • estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73m2 within the past 3 years
  • Not pregnant at time 0
  • No history* of institutionalization with a diagnosis of dementia, metastatic cancer, end stage lung disease, end stage liver disease, pancreatitis, medullary thyroid cancer or severe UTIs
  • Engagement with the healthcare system: enrollment for at least 12 months and attendance of at least one outpatient encounter in the prior 12 months

(*) History will be derived from at least 12 months of EHR and claims prior to time zero and will use all available EHR and claims data between January 1, 2014 and time zero

Contacts and Locations
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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): NCT05161429


Contacts
Layout table for location contacts
Contact: Emma Hegermiller, MS 617-732-5661 emma@bestmed.org
Contact: Alexander Turchin, MD, MS 617-732-5661 aturchin@bwh.harvard.edu

Locations
Layout table for location information
United States, Delaware
HealthCore, Inc. Recruiting
Wilmington, Delaware, United States, 19801
Contact: Vincent Willey, PharmD         
United States, Kentucky
Humana Recruiting
Lexington, Kentucky, United States, 40512-4611
Contact: Vinit Nair, MS, RPh         
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Alexander Turchin, MD, MS         
United States, Ohio
Greater Plains Collaborative Recruiting
Beachwood, Ohio, United States, 44122
Contact: Ryan Carnahan, PhD         
United States, Texas
Baylor Scott & White Recruiting
Dallas, Texas, United States, 75246
Contact: Heather Kitzman Carmichael, PhD         
Sponsors and Collaborators
Brigham and Women's Hospital
Patient-Centered Outcomes Research Institute
Baylor College of Medicine
Baylor Scott and White Research Institute
The Cleveland Clinic
HealthCore, Inc.
Humana Inc.
Massachusetts General Hospital
Medical Outcomes Management
University of Iowa
Allina Health
Intermountain Health Care, Inc.
Marshfield Clinic
Medical College of Wisconsin
University of Missouri-Columbia
University of Utah
Investigators
Layout table for investigator information
Principal Investigator: Alexander Turchin, MD, MS Brigham and Women's Hospital
More Information
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications:

Layout table for additonal information
Responsible Party: Alexander Turchin, Associate Professor of Medicine, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT05161429    
Other Study ID Numbers: 2021P001171
First Posted: December 17, 2021    Key Record Dates
Last Update Posted: December 23, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
 Endocrine System Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs