BESTMED: Observational Evaluation of Second Line Therapy Medications in Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

— BESTMED  

Official title:

BESTMED: Observational Evaluation of Second Line Therapy Medications in Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05161429
• Other study ID #: 2021P001171
• Status: Recruiting
• Start date: July 1, 2021
• Est. completion date: June 30, 2024

Study information

• Verified date: June 2023
• Source: Brigham and Women's Hospital
• Contact: Emma Hegermiller, MS
• Phone: 617-732-5661
• Email: emma[@]bestmed.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 550000
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• DPP4
Dipeptidyl peptidase-4 inhibitors (DPP4) including alogliptin, linagliptin, sitagliptin, and saxagliptin
• GLP-1 receptor agonist
Glucagon-like peptide-1 receptor agonists (GLP1-RA) including dulaglutide, exenatide, liraglutide and semaglutide
• Basal Insulin
degludec, detemir, glargine and NPH
• SLGT2
Sodium-glucose cotransporter-2 inhibitors (SLGT2) including canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin
• SU
Sulfonylurea (SU) including glimepiride, glipizide, and glyburide

Locations

Country	Name	City	State
United States	Greater Plains Collaborative	Beachwood	Ohio
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Baylor Scott & White	Dallas	Texas
United States	Humana	Lexington	Kentucky
United States	HealthCore, Inc.	Wilmington	Delaware

Sponsors (16)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	Allina Health, Baylor College of Medicine, Baylor Scott and White Research Institute, HealthCore, Inc., Humana Inc., Intermountain Health Care, Inc., Marshfield Clinic, Massachusetts General Hospital, Medical College of Wisconsin, Medical Outcomes Management, Patient-Centered Outcomes Research Institute, The Cleveland Clinic, University of Iowa, University of Missouri-Columbia, University of Utah

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	4-point major adverse cardiac events (MACE)	Includes: a) death from cardiovascular causes b) non-fatal myocardial infarction (MI) c) non-fatal stroke and d) hospitalization for heart failure (HF)	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.
Primary	3-point major adverse cardiac events (MACE)	Includes: a) death from cardiovascular causes as reported in the National Death Index b) non-fatal MI and c) non-fatal stroke	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.
Secondary	Adverse outcomes	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	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.
Secondary	Severe clinical outcomes	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	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.
Secondary	Non-cardiovascular outcomes	Includes a) nephropathy b) diabetic retinopathy requiring treatment c) non-alcoholic fatty liver disease (NAFLD) with advanced fibrosis / nonalcoholic steatohepatitis (NASH)	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.