Clinical trial NCT05220917: Comparative Effectiveness and Safety of Four Second Line Pharmacological Strategies in Type 2 Diabetes Study
Official title: Comparative Effectiveness and Safety of Four Second Line Pharmacological Strategies in Type 2 Diabetes Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cardiovascular Events
Type2 Diabetes
Renal Disease
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
name: VA Boston Healthcare System
name: McGill University
First posted: 2022-02-02
Enrollment: 781430
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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 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).

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: MACE
timeFrame: through study completion, an average of 1 year
measure: Modified MACE
timeFrame: through study completion, an average of 1 year
measure: Hospitalization for Heart Failure (HHF) Hospitalization for Heart Failure (HHF)
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: Myocardial Infarction (MI)
timeFrame: through study completion, an average of 1 year
measure: Stroke
timeFrame: through study completion, an average of 1 year
measure: Cardiovascular Mortality
timeFrame: through study completion, an average of 1 year
measure: All-cause mortality
timeFrame: through study completion, an average of 1 year
measure: Coronary revascularization
timeFrame: through study completion, an average of 1 year
Other outcomes:
measure: CKD progression
timeFrame: through study completion, an average of 1 year
measure: Sustained decrease in eGFR
timeFrame: through study completion, an average of 1 year
measure: Kidney replacement therapy (KRT)
timeFrame: through study completion, an average of 1 year
measure: Kidney death
timeFrame: through study completion, an average of 1 year
measure: Kidney failure
timeFrame: through study completion, an average of 1 year
measure: Early kidney disease
timeFrame: through study completion, an average of 1 year
measure: Glycemic control
timeFrame: through study completion, an average of 1 year
measure: Insulin initiation
timeFrame: through study completion, an average of 1 year
measure: Weight loss or gain
timeFrame: through study completion, an average of 1 year
measure: Diabetic ketoacidosis
timeFrame: through study completion, an average of 1 year
measure: Bone fractures
timeFrame: through study completion, an average of 1 year
measure: Lower-limb amputations
timeFrame: through study completion, an average of 1 year
measure: Acute kidney injury
timeFrame: through study completion, an average of 1 year
measure: Urinary infections
timeFrame: through study completion, an average of 1 year
measure: Genital infections
timeFrame: through study completion, an average of 1 year
measure: Acute pancreatitis
timeFrame: through study completion, an average of 1 year
measure: Biliary events
timeFrame: through study completion, an average of 1 year
measure: Severe hypoglycemia
timeFrame: through study completion, an average of 1 year
measure: Short-term retinopathy progression
timeFrame: through study completion, an average of 1 year
measure: Home time
timeFrame: through study completion, an average of 1 year
measure: Medication persistence
timeFrame: through study completion, an average of 1 year
measure: Switching patterns
timeFrame: through study completion, an average of 1 year
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Elisabetta Patorno, MD, DrPH
role: PRINCIPAL_INVESTIGATOR
References: