Comparative Effectiveness and Safety of Four Second Line Pharmacological Strategies in Type 2 Diabetes Study

Brigham and Women's Hospital1 site in 1 country781,430 target enrollmentStarted: August 1, 2021Last updated: August 13, 2026

Conditions

Interventions

Drugs

Trial Snapshot

Phase: Not Applicable
Status: Active, not recruiting
Sponsor: Brigham and Women's Hospital
Enrollment: 781,430
Locations: 1
Primary Endpoint: MACE

Study Overview Study Design Eligibility Criteria Arms & Interventions Outcomes Investigators Sites Records & Identifiers Similar Trials

Study Overview

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.

Study Design

Study Type: Observational
Observational Model: Cohort
Time Perspective: Retrospective

Eligibility Criteria

Ages: 18 Years to — (Adult, Older Adult)
Sex: All
Accepts Healthy Volunteers: No

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

Arms & Interventions

SU (Comparison 5)

For GLP-1 RA vs SU GLP-1 RA - exposure group SU - referent group

Intervention: 2nd generation SU (Drug)

SU (Comparison 6)

For DPP-4i vs SU DPP-4i - exposure group SU - referent group

Intervention: 2nd generation SU (Drug)

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

Intervention: GLP-1RA (Drug)

DPP-4i (Comparison 1)

For SGLT-2i vs. DPP4i SGLT-2i - exposure group DPP-4i - referent group

Intervention: DPP-4 inhibitor (Drug)

SU (Comparison 4)

For SGLT-2i vs SU SGLT-2i - exposure group SU - referent group

Intervention: 2nd generation SU (Drug)

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

Intervention: 2nd generation SU (Drug)