BESTMED: Observational Evaluation of Second Line Therapy Medications in Diabetes

NCT ID: NCT05161429

Last Updated: 2023-06-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

550000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-07-01

Study Completion Date

2024-06-30

Brief Summary

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An observational study of electronic patient data to compare diabetes medications and to determine which ones offer the best balance of risks and benefits.

Detailed Description

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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.

Conditions

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Diabetes Mellitus, Type 2

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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DPP4

Patients receiving second line diabetes treatment with dipeptidyl peptidase-4 inhibitors (DPP4) following metformin

DPP4

Intervention Type DRUG

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

GLP-1 receptor agonist

Intervention Type DRUG

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

Basal Insulin

Intervention Type DRUG

degludec, detemir, glargine and NPH

SLGT2

Patients receiving second line diabetes treatment with sodium-glucose cotransporter-2 inhibitors (SLGT2) following metformin

SLGT2

Intervention Type DRUG

Sodium-glucose cotransporter-2 inhibitors (SLGT2) including canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin

SU

Patients receiving second line diabetes treatment with sulfonylureas (SU) following metformin

SU

Intervention Type DRUG

Sulfonylurea (SU) including glimepiride, glipizide, and glyburide

Interventions

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DPP4

Dipeptidyl peptidase-4 inhibitors (DPP4) including alogliptin, linagliptin, sitagliptin, and saxagliptin

Intervention Type DRUG

GLP-1 receptor agonist

Glucagon-like peptide-1 receptor agonists (GLP1-RA) including dulaglutide, exenatide, liraglutide and semaglutide

Intervention Type DRUG

Basal Insulin

degludec, detemir, glargine and NPH

Intervention Type DRUG

SLGT2

Sodium-glucose cotransporter-2 inhibitors (SLGT2) including canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin

Intervention Type DRUG

SU

Sulfonylurea (SU) including glimepiride, glipizide, and glyburide

Intervention Type DRUG

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Patient-Centered Outcomes Research Institute

OTHER

Sponsor Role collaborator

Baylor College of Medicine

OTHER

Sponsor Role collaborator

Baylor Scott and White Research Institute

UNKNOWN

Sponsor Role collaborator

The Cleveland Clinic

OTHER

Sponsor Role collaborator

HealthCore, Inc.

INDUSTRY

Sponsor Role collaborator

Humana Inc.

INDUSTRY

Sponsor Role collaborator

Massachusetts General Hospital

OTHER

Sponsor Role collaborator

Medical Outcomes Management

UNKNOWN

Sponsor Role collaborator

University of Iowa

OTHER

Sponsor Role collaborator

Allina Health

UNKNOWN

Sponsor Role collaborator

Intermountain Health Care, Inc.

OTHER

Sponsor Role collaborator

Marshfield Clinic

UNKNOWN

Sponsor Role collaborator

Medical College of Wisconsin

OTHER

Sponsor Role collaborator

University of Missouri-Columbia

OTHER

Sponsor Role collaborator

University of Utah

OTHER

Sponsor Role collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Alexander Turchin

Associate Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Alexander Turchin, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

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HealthCore, Inc.

Wilmington, Delaware, United States

Site Status RECRUITING

Humana

Lexington, Kentucky, United States

Site Status RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Greater Plains Collaborative

Beachwood, Ohio, United States

Site Status RECRUITING

Baylor Scott & White

Dallas, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Emma Hegermiller, MS

Role: CONTACT

617-732-5661

Alexander Turchin, MD, MS

Role: CONTACT

617-732-5661

Facility Contacts

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Vincent Willey, PharmD

Role: primary

Vinit Nair, MS, RPh

Role: primary

Alexander Turchin, MD, MS

Role: primary

Ryan Carnahan, PhD

Role: primary

Heather Kitzman Carmichael, PhD

Role: primary

References

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Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998 May 12;97(18):1837-47. doi: 10.1161/01.cir.97.18.1837.

Reference Type BACKGROUND
PMID: 9603539 (View on PubMed)

D'Agostino RB, Wolf PA, Belanger AJ, Kannel WB. Stroke risk profile: adjustment for antihypertensive medication. The Framingham Study. Stroke. 1994 Jan;25(1):40-3. doi: 10.1161/01.str.25.1.40.

Reference Type BACKGROUND
PMID: 8266381 (View on PubMed)

Kannel WB, D'Agostino RB, Silbershatz H, Belanger AJ, Wilson PW, Levy D. Profile for estimating risk of heart failure. Arch Intern Med. 1999 Jun 14;159(11):1197-204. doi: 10.1001/archinte.159.11.1197.

Reference Type BACKGROUND
PMID: 10371227 (View on PubMed)

Other Identifiers

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2021P001171

Identifier Type: -

Identifier Source: org_study_id

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