NCT05220917

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

• Status: Active Not Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 781,430 (estimated)
• Sponsor: Brigham and Women's Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Cardiovascular Events
• Type2 Diabetes
• Renal Disease

Interventions

Type	Name	Description
DRUG	SGLT2 inhibitor	Any SGLT2i dispensing claim
DRUG	DPP-4 inhibitor	Any DPP-4 inhibitor claim
DRUG	GLP-1RA	Any SGLT2i dispensing claim
DRUG	2nd generation SU	Any 2nd generation SU claim

Timeline

• Start date: 2021-08-01
• Primary completion: 2026-01-31
• Completion: 2026-07-01
• First posted: 2022-02-02
• Last updated: 2025-12-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study