Cardiovascular EventsCER-4-T2DNCT05220917
Comparative Effectiveness and Safety of Four Second Line Pharmacological Strategies in Type 2 Diabetes Study
An observational study of Cardiovascular Events and Type2 Diabetes, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
To perform an observational analysis to emulate a target trial (i.e., a hypothetical pragmatic trial that would have answered the causal question of interest) comparing the effectiveness and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP-1RA), dipeptidyl… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiovascular Events, Type2 Diabetes, Renal Disease
- What is being tested?
- SGLT2 inhibitor, DPP-4 inhibitor and GLP-1RA
- How many people
- 781,430 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2021to 30 Sep 2027
- Phase
- Observational
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Optum and MarketScan databases are U.S. research claims databases that include adults with employer-based health plans, with nationwide coverage for over 60 million Americans, and meaningful numbers of patients ≥65 years from Medicare Advantage plans, employer-sponsored plans covering seniors, and Medicare supplemental insurance plans. Medicare FFS is a U.S. federal health insurance program providing coverage to individuals ≥65 years and to younger individuals with disabilities. The Partners RPDR captures longitudinal EHR data for all patients that receive care at 2 large health care provider networks in the Boston metro area. The VHA is the largest integrated national health system, serving over 12 million U.S. Veterans. The VHA database includes demographic, diagnostic and procedure information from inpatient/outpatient encounters. The CPRD is comprised of two large, computerized databases of longitudinal primary care records, GOLD and Aurum, for >50 million UK patients.
Who may be able to join
- Age ≥ 18 years for Optum Cliniformatics, IBM Marketscan, CPRD, and VHA, and ≥ 65 years for Medicare FFS at cohort entry
- At least 12 months of continuous health plan enrollment (only claims) or registration with a general practitioner (CPRD) before and including cohort entry
- Diagnosis of T2D within 12 months before (or ever before in CPRD) and including cohort entry
- Low or moderate cardiovascular (CV) risk (≤3% risk of CV events/year) at cohort entry *
- Metformin maintenance therapy, defined as 2 fills (or prescriptions in CPRD) of metformin monotherapy recorded within 6 months before and including cohort entry
Who cannot join
- Missing age or gender information
- Nursing care admission within 12 months before and including cohort entry (criteria ignored in CPRD)
- Diagnosis of type 1 diabetes within 12 months before and including cohort entry
- Diagnosis of secondary or gestational diabetes within 12 months before and including cohort entry
- Any insulin fill or prescription within 12 months before and including cohort entry
- Diagnosis of end stage renal disease (stage ≥ 5) within 12 months before and including cohort entry
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- Diagnosis of acute or chronic pancreatitis within 12 months before and including cohort entry
- Diagnosis of cirrhosis or acute hepatitis within 12 months before and including cohort entry
- Diagnosis of MEN-2 within 12 months before and including cohort entry
- Recorded solid organ transplant code within 12 months before and including cohort entry
- Patients with recorded initiation of more than one agent within a comparator class at cohort entry
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02120
About this study
To perform an observational analysis to emulate a target trial (i.e., a hypothetical pragmatic trial that would have answered the causal question of interest) comparing the effectiveness and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP-4i), and sulfonylureas (SU), at the class and individual agent level, in head-to-head comparisons in patients with type 2 diabetes (T2D).
Read the detailed description
Aim 1: (1a.) To evaluate the effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP-4i), and sulfonylureas (SU), at the class and individual agent level, in head-to-head comparisons with respect to cardiovascular (CV) events, mortality, renal events, and other patient-centered outcomes (e.g., time spent at home), in patients with T2D and moderate baseline CV risk (event rate ≤3%/year). (1b.) To examine heterogeneity in treatment effects by age, race/ethnicity, gender, levels of CV risk, including high (≥4%/year) and low risk (<2%/year), chronic kidney disease (CKD), frailty, and multimorbidity.
Aim 2: (2a.) To monitor and quantify the association of the initiation of SGLT2i, GLP-1RA, DPP-4i, or SU, at the class and individual agent level, with previously reported drug-related harms (e.g., diabetic ketoacidosis (DKA), fractures, amputations, pancreatitis, severe hypoglycemia). (2b.) To scan study data sources for signals of potential serious unanticipated drug-related adverse events, using a data-mining approach (tree-based scan statistics). (2c.) By using data generated in Aims 2a and 2b, to build treatment-specific outcome prediction models to identify individual patients' likelihood of drug-related harms, based on specific combinations of patient features.
- Conditions
- Cardiovascular Events, Type2 Diabetes, Renal Disease
- Being tested
- SGLT2 inhibitor, DPP-4 inhibitor, GLP-1RA, 2nd generation SU
- Medical subject headings
- Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SGLT2 inhibitorDrug
Also called CANAGLIFLOZIN, CANAGLIFLOZIN/METFORMIN HCL, DAPAGLIFLOZIN PROPANEDIOL/METFORMIN HCL, DAPAGLIFLOZIN PROPANEDIOL
Any SGLT2i dispensing claim
DPP-4 inhibitorDrug
Also called ALOGLIPTIN BENZOATE/METFORMIN HCL, ALOGLIPTIN BENZOATE, ALOGLIPTIN BENZOATE/PIOGLITAZONE HCL, SAXAGLIPTIN HCL
Any DPP-4 inhibitor claim
GLP-1RADrug
Also called INSULIN DEGLUDEC/LIRAGLUTIDE*, INSULIN GLARGINE, HUMAN RECOMBINANT ANALOG/LIXISENATIDE*, LIXISENATIDE, LIRAGLUTIDE
Any SGLT2i dispensing claim
2nd generation SUDrug
Also called PIOGLITAZONE HCL/GLIMEPIRIDE, ROSIGLITAZONE MALEATE/GLIMEPIRIDE, GLIPIZIDE/METFORMIN HCL, GLYBURIDE,MICRONIZED
Any 2nd generation SU claim
| Study group | Role | What they receive |
|---|---|---|
| SGLT-2i (Comparison 1) | For SGLT-2i vs. DPP4i SGLT-2i - exposure group DPP4i - referent group Receives: Drug: SGLT2 inhibitor | |
| DPP-4i (Comparison 1) | For SGLT-2i vs. DPP4i SGLT-2i - exposure group DPP-4i - referent group Receives: Drug: DPP-4 inhibitor | |
| SGLT-2i (Comparison 2) | For SGLT-2i vs GLP-1 RA SGLT-2i - exposure group GLP-1 RA - referent group Receives: Drug: SGLT2 inhibitor | |
| GLP-1 RA (Comparison 2) | For SGLT-2i vs GLP-1 RA SGLT-2i - exposure group GLP-1 RA - referent group Receives: Drug: GLP-1RA | |
| GLP-1 RA (Comparison 3) | For GLP-1 RA vs DPP-4i GLP-1 RA - exposure group DPP-4i - referent group Receives: Drug: GLP-1RA | |
| DPP-4i (Comparison 3) | For GLP-1 RA vs DPP-4i GLP-1 RA - exposure group DPP-4i - referent group Receives: Drug: DPP-4 inhibitor | |
| SGLT-2i (Comparison 4) | For SGLT-2i vs SU SGLT-2i - exposure group SU - referent group Receives: Drug: SGLT2 inhibitor | |
| SU (Comparison 4) | For SGLT-2i vs SU SGLT-2i - exposure group SU - referent group Receives: Drug: 2nd generation SU | |
| GLP-1 RA (Comparison 5) | For GLP-1 RA vs SU GLP-1 RA - exposure group SU - referent group Receives: Drug: GLP-1RA | |
| SU (Comparison 5) | For GLP-1 RA vs SU GLP-1 RA - exposure group SU - referent group Receives: Drug: 2nd generation SU | |
| DPP-4i (Comparison 6) | For DPP-4i vs SU DPP-4i - exposure group SU - referent group Receives: Drug: DPP-4 inhibitor | |
| SU (Comparison 6) | For DPP-4i vs SU DPP-4i - exposure group SU - referent group Receives: Drug: 2nd generation SU | |
| SGLT2i (Comparison 7) | For SGLT2i vs. GLP-1RA vs. DPP-4i vs. SU (4-way comparison) SGLT2i, GLP-1 RA, and SU - exposure groups DPP-4i - referent group Receives: Drug: SGLT2 inhibitor | |
| GLP-1 RA (Comparison 7) | For SGLT2i vs. GLP-1RA vs. DPP-4i vs. SU (4-way comparison) SGLT2i, GLP-1 RA, and SU - exposure groups DPP-4i - referent group Receives: Drug: GLP-1RA | |
| DPP-4i (Comparison 7) | For SGLT2i vs. GLP-1RA vs. DPP-4i vs. SU (4-way comparison) SGLT2i, GLP-1 RA, and SU - exposure groups DPP-4i - referent group Receives: Drug: DPP-4 inhibitor | |
| SU (Comparison 7) | For SGLT2i vs. GLP-1RA vs. DPP-4i vs. SU (4-way comparison) SGLT2i, GLP-1 RA, and SU - exposure groups DPP-4i - referent group Receives: Drug: 2nd generation SU | |
| SGLT2i (Comparison 8) | For SGLT2i vs. GLP-1RA vs. DPP-4i (3-way comparison) SGLT2i and GLP-1 RA - exposure groups DPP-4i - referent group Receives: Drug: SGLT2 inhibitor | |
| GLP-1 RA (Comparison 8) | For SGLT2i vs. GLP-1RA vs. DPP-4i (3-way comparison) SGLT2i and GLP-1 RA - exposure groups DPP-4i - referent group Receives: Drug: GLP-1RA | |
| DPP-4i (Comparison 8) | For SGLT2i vs. GLP-1RA vs. DPP-4i (3-way comparison) SGLT2i and GLP-1 RA - exposure groups DPP-4i - referent group Receives: Drug: DPP-4 inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
MACE
Myocardial Infarction, Ischemic Stroke, Cardiovascular mortality
Measured: through study completion, an average of 1 year
Modified MACE
Myocardial Infarction, Ischemic Stroke, All-Cause mortality
Measured: through study completion, an average of 1 year
Hospitalization for Heart Failure (HHF) Hospitalization for Heart Failure (HHF)
Measured: through study completion, an average of 1 year
Secondary outcomes (5)
Myocardial Infarction (MI)
Measured: through study completion, an average of 1 year
Stroke
Measured: through study completion, an average of 1 year
Cardiovascular Mortality
Measured: through study completion, an average of 1 year
All-cause mortality
Measured: through study completion, an average of 1 year
Coronary revascularization
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2022
- Study start1 Aug 2021
- Primary completion31 May 2026
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular EventsStudies 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
- 781,430 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute, VA Boston Healthcare System, McGill University
- Responsible party
- Principal investigator, Deborah Wexler, MD, Brigham and Women's Hospital
- Investigators
- Elisabetta Patorno, MD, DrPH, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05220917
- Sponsor's protocol ID
- 2021P001784
- Acronym
- CER-4-T2D
- Status last verified
- Aug 2026
- First submitted
- 22 Dec 2021
- Last updated
- 13 Aug 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No