Comparative Effectiveness and Safety of Four Second Line Pharmacological Strategies in Type 2 Diabetes Study
- Conditions
- Cardiovascular EventsType2 DiabetesRenal Disease
- Interventions
- Registration Number
- NCT05220917
- Lead Sponsor
- Brigham and Women's Hospital
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 781430
- 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
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description GLP-1 RA (Comparison 3) GLP-1RA For GLP-1 RA vs DPP-4i GLP-1 RA - exposure group DPP-4i - referent group SGLT-2i (Comparison 1) SGLT2 inhibitor For SGLT-2i vs. DPP4i SGLT-2i - exposure group DPP4i - referent group DPP-4i (Comparison 3) DPP-4 inhibitor For GLP-1 RA vs DPP-4i GLP-1 RA - exposure group DPP-4i - referent group GLP-1 RA (Comparison 5) GLP-1RA For GLP-1 RA vs SU GLP-1 RA - exposure group SU - referent group SGLT2i (Comparison 7) SGLT2 inhibitor 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 GLP-1 RA (Comparison 2) GLP-1RA For SGLT-2i vs GLP-1 RA SGLT-2i - exposure group GLP-1 RA - referent group SU (Comparison 5) 2nd generation SU For GLP-1 RA vs SU GLP-1 RA - exposure group SU - referent group DPP-4i (Comparison 6) DPP-4 inhibitor For DPP-4i vs SU DPP-4i - exposure group SU - referent group DPP-4i (Comparison 1) DPP-4 inhibitor For SGLT-2i vs. DPP4i SGLT-2i - exposure group DPP-4i - referent group SGLT-2i (Comparison 2) SGLT2 inhibitor For SGLT-2i vs GLP-1 RA SGLT-2i - exposure group GLP-1 RA - referent group SGLT-2i (Comparison 4) SGLT2 inhibitor For SGLT-2i vs SU SGLT-2i - exposure group SU - referent group SU (Comparison 4) 2nd generation SU For SGLT-2i vs SU SGLT-2i - exposure group SU - referent group SGLT2i (Comparison 8) SGLT2 inhibitor For SGLT2i vs. GLP-1RA vs. DPP-4i (3-way comparison) SGLT2i and GLP-1 RA - exposure groups DPP-4i - referent group DPP-4i (Comparison 7) DPP-4 inhibitor 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 SU (Comparison 7) 2nd generation SU 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 SU (Comparison 6) 2nd generation SU For DPP-4i vs SU DPP-4i - exposure group SU - referent group GLP-1 RA (Comparison 8) GLP-1RA For SGLT2i vs. GLP-1RA vs. DPP-4i (3-way comparison) SGLT2i and GLP-1 RA - exposure groups DPP-4i - referent group DPP-4i (Comparison 8) DPP-4 inhibitor For SGLT2i vs. GLP-1RA vs. DPP-4i (3-way comparison) SGLT2i and GLP-1 RA - exposure groups DPP-4i - referent group GLP-1 RA (Comparison 7) GLP-1RA 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
- Primary Outcome Measures
Name Time Method MACE through study completion, an average of 1 year Myocardial Infarction, Ischemic Stroke, Cardiovascular mortality
Modified MACE through study completion, an average of 1 year Myocardial Infarction, Ischemic Stroke, All-Cause mortality
Hospitalization for Heart Failure (HHF) Hospitalization for Heart Failure (HHF) through study completion, an average of 1 year
- Secondary Outcome Measures
Name Time Method Myocardial Infarction (MI) through study completion, an average of 1 year Stroke through study completion, an average of 1 year All-cause mortality through study completion, an average of 1 year Coronary revascularization through study completion, an average of 1 year Cardiovascular Mortality through study completion, an average of 1 year
Trial Locations
- Locations (1)
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States