Diabetes Mellitus, Type 2BESTMEDNCT05161429
BESTMED: Observational Evaluation of Second Line Therapy Medications in Diabetes
An observational study of Diabetes Mellitus, Type 2, run by Brigham and Women's Hospital at 5 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- DPP4, GLP-1 receptor agonist and Basal Insulin
- How many people
- 550,000 participants
- Where
- 5 sitesUnited States
- Study dates
- 1 Jul 2021to 30 Jun 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
Greater Plains Collaborative
Beachwood, Ohio, 44122
Ryan Carnahan, PhD
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Alexander Turchin, MD, MS
- Recruiting
Baylor Scott & White
Dallas, Texas, 75246
Heather Kitzman Carmichael, PhD
- Recruiting
Humana
Lexington, Kentucky, 40512-4611
Vinit Nair, MS, RPh
- Recruiting
HealthCore, Inc.
Wilmington, Delaware, 19801
Vincent Willey, PharmD
About this study
An observational study of electronic patient data to compare diabetes medications and to determine which ones offer the best balance of risks and benefits.
Read the 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.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- DPP4, GLP-1 receptor agonist, Basal Insulin, SLGT2, SU
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DPP4Drug
Dipeptidyl peptidase-4 inhibitors (DPP4) including alogliptin, linagliptin, sitagliptin, and saxagliptin
GLP-1 receptor agonistDrug
Glucagon-like peptide-1 receptor agonists (GLP1-RA) including dulaglutide, exenatide, liraglutide and semaglutide
Basal InsulinDrug
degludec, detemir, glargine and NPH
SLGT2Drug
Sodium-glucose cotransporter-2 inhibitors (SLGT2) including canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin
SUDrug
Sulfonylurea (SU) including glimepiride, glipizide, and glyburide
| Study group | Role | What they receive |
|---|---|---|
| DPP4 | Patients receiving second line diabetes treatment with dipeptidyl peptidase-4 inhibitors (DPP4) following metformin Receives: Drug: DPP4 | |
| GLP1-RA | Patients receiving second line diabetes treatment with glucagon-like peptide-1 receptor agonists (GLP1-RA) following metformin Receives: Drug: GLP-1 receptor agonist | |
| Basal insulin | Patients receiving second line diabetes treatment with basal insulin following metformin Receives: Drug: Basal Insulin | |
| SLGT2 | Patients receiving second line diabetes treatment with sodium-glucose cotransporter-2 inhibitors (SLGT2) following metformin Receives: Drug: SLGT2 | |
| SU | Patients receiving second line diabetes treatment with sulfonylureas (SU) following metformin Receives: Drug: SU |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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.
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
Measured: 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 outcomes (3)
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
Measured: 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.
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
Measured: 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.
Non-cardiovascular outcomes
Includes a) nephropathy b) diabetic retinopathy requiring treatment c) non-alcoholic fatty liver disease (NAFLD) with advanced fibrosis / nonalcoholic steatohepatitis (NASH)
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2021
- Study start1 Jul 2021
- Primary completion30 Jun 2024 (estimated)
- Study completion30 Jun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 550,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute, Baylor College of Medicine, Baylor Scott & White The Heart Hospital, The Cleveland Clinic, HealthCore, Inc., Humana Inc., Massachusetts General Hospital, Medical Outcomes Management, University of Iowa, Allina Health System, Intermountain Health Care, Inc., Marshfield Clinic, Medical College of Wisconsin, University of Missouri-Columbia, University of Utah
- Responsible party
- Principal investigator, Alexander Turchin, Brigham and Women's Hospital
- Investigators
- Alexander Turchin, MD, MS, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05161429
- Sponsor's protocol ID
- 2021P001171
- Acronym
- BESTMED
- Status last verified
- Jun 2023
- First submitted
- 23 Nov 2021
- Last updated
- 22 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 9603539D'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.
PubMed 8266381Kannel 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.
PubMed 10371227
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BESTMED: Observational Evaluation of Second Line Therapy Medications in Diabetes
- ClinicalTrials.gov ID
- NCT05161429
- Acronym / sponsor ID
- BESTMED / 2021P001171
- Conditions
- Diabetes Mellitus, Type 2
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 550,000 participants (estimated)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute, Baylor College of Medicine, Baylor Scott & White The Heart Hospital, The Cleveland Clinic, HealthCore, Inc., Humana Inc., Massachusetts General Hospital, Medical Outcomes Management, University of Iowa, Allina Health System, Intermountain Health Care, Inc., Marshfield Clinic, Medical College of Wisconsin, University of Missouri-Columbia, University of Utah
- Study start
- 1 Jul 2021 (actual)
- Primary completion
- 30 Jun 2024 (estimated)
- Study completion
- 30 Jun 2024 (estimated)
- First posted
- 17 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| DPP4 | – | Drug: DPP4Patients receiving second line diabetes treatment with dipeptidyl peptidase-4 inhibitors (DPP4) following metformin |
| GLP1-RA | – | Drug: GLP-1 receptor agonistPatients receiving second line diabetes treatment with glucagon-like peptide-1 receptor agonists (GLP1-RA) following metformin |
| Basal insulin | – | Drug: Basal InsulinPatients receiving second line diabetes treatment with basal insulin following metformin |
| SLGT2 | – | Drug: SLGT2Patients receiving second line diabetes treatment with sodium-glucose cotransporter-2 inhibitors (SLGT2) following metformin |
| SU | – | Drug: SUPatients receiving second line diabetes treatment with sulfonylureas (SU) following metformin |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DPP4Dipeptidyl peptidase-4 inhibitors (DPP4) including alogliptin, linagliptin, sitagliptin, and saxagliptin | Drug | DPP4 |
| GLP-1 receptor agonistGlucagon-like peptide-1 receptor agonists (GLP1-RA) including dulaglutide, exenatide, liraglutide and semaglutide | Drug | GLP1-RA |
| Basal Insulindegludec, detemir, glargine and NPH | Drug | Basal insulin |
| SLGT2Sodium-glucose cotransporter-2 inhibitors (SLGT2) including canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin | Drug | SLGT2 |
| SUSulfonylurea (SU) including glimepiride, glipizide, and glyburide | Drug | SU |
Primary outcome
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)
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
3 secondary outcomes
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.
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.
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2023.
- Background: PubMed 9603539Wilson 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.
- Background: PubMed 8266381D'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.
- Background: PubMed 10371227Kannel 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexander Turchin, MD, MS principal investigator
Brigham and Women's Hospital
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetes Mellitus, Type 2, run by Brigham and Women's Hospital at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Emma Hegermiller, MS (617-732-5661, emma@bestmed.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05161429, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2023.