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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.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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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
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
Are there results?
Not yet: the study is under way

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
Show all 11Show fewer
  • 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

Other trials in United States

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.

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 groups in NCT05220917
Study groupRoleWhat 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.

  1. MACE

    Myocardial Infarction, Ischemic Stroke, Cardiovascular mortality

    Measured: through study completion, an average of 1 year

  2. Modified MACE

    Myocardial Infarction, Ischemic Stroke, All-Cause mortality

    Measured: through study completion, an average of 1 year

  3. Hospitalization for Heart Failure (HHF) Hospitalization for Heart Failure (HHF)

    Measured: through study completion, an average of 1 year

Secondary outcomes (5)

  1. Myocardial Infarction (MI)

    Measured: through study completion, an average of 1 year

  2. Stroke

    Measured: through study completion, an average of 1 year

  3. Cardiovascular Mortality

    Measured: through study completion, an average of 1 year

  4. All-cause mortality

    Measured: through study completion, an average of 1 year

  5. 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.

  1. First posted2 Feb 2022
  2. Study start1 Aug 2021
  3. Primary completion31 May 2026
  4. Study completion30 Sep 2027 (estimated)

Resources

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)
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

Questions about this trial

What is this clinical trial studying?

An observational study of Cardiovascular Events and Type2 Diabetes, run by Brigham and Women's Hospital at 1 site 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?

The sponsor lists 5 inclusion and 11 exclusion criteria. 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: under way, not looking for participants, as of the sponsor's last update on 13 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MACE (time frame: through study completion, an average of 1 year). The study lists 3 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 NCT05220917.

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 13 Aug 2026.

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