NCT05073692

Comparison of Type 2 Diabetes Pharmacotherapy Regimens

Comparison of Type 2 Diabetes Pharmacotherapy Regimens Using Targeted Learning

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 241,981 (actual)
• Sponsor: Kaiser Permanente · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

This study is designed to help patients with type 2 diabetes and their clinicians: (a) identify which glucose lowering medications have the most favorable effects on heart health and other patient-important outcomes, (b) inform the timing of medication initiation, and (c) identify whether medication benefits apply equally to all adults with type 2 diabetes, or may be different based on age, sex, race/ethnicity, baseline heart health status, baseline renal function, or other factors.

Detailed description

The study will conduct head-to-head comparisons of type 2 diabetes mellitus (T2DM) treatment strategies using observational data from real-world clinical settings to assess cardiovascular disease (CVD) outcomes and other patient-centered outcomes in T2DM patients with moderate baseline CVD risk who are treated with each of these four classes of glucose-lowering medications known as SGLT2, GLP-1RA, DPP4, and SU. To mitigate bias concerns related to confounding and informative loss to follow-up, analyses will be based on modern causal inference methods combined with machine learning that emulate intention-to-treat (ITT) and per-protocol (PP) analyses of pragmatic randomized trials with active comparators to provide the most robust and precise estimates of relative and absolute effects we would expect in usual care settings. Specific Aims and Hypotheses: Aim 1. Compare the effect off SGLT21, GLP-1RA, DPP4, and SU on each study outcome in adults with T2DM when each type of medication is (a) initiated as second-line therapy after metformin, and (b) initiated as first-, second-, or third-line therapy, or after any history of glucose-lowering therapy independent of prior metformin use. Aim 2. Compare the effect on each study outcome of earlier versus later initiation of SGLT2i, GLP-1RA, DPP4, SU as first-, or second-, or third-line therapy, or after any history of glucose-lowering therapy triggered by various changes in A1C, or CVD risk, or other patient characteristics. Aim 3. Assess in each of the prior analyses whether the treatment effects on study outcomes vary across categories of baseline CVD risk and CVD event history, renal function, congestive heart failure status, age, sex and race/ethnicity, or other patient characteristics. Glucose-lowering medications will be compared at both the class and agent level. The key outcomes that will be considered are MACE 3-point, Myocardial Infarction, Stroke, Heart Failure, Hospitalization, Coronary or Carotid Artery Stent or Bypass Procedure, CVD Mortality, Overall Mortality. Additional patient-centered outcomes will be specified based on insights from stakeholder members of the research team.

Conditions

• Type 2 Diabetes Mellitus
• Cardiovascular Diseases

Interventions

Type	Name	Description
DRUG	SU	Exposure to the class of drugs known as Sulfonylureas (SU)
DRUG	DPP4	Exposure to the class of drugs known as Dipeptidyl peptidase-4 inhibitors (DPP4)
DRUG	SGLT2i	Exposure to the class of drugs known as Sodium-glucose cotransporter-2 inhibitors (SGLT2i)
DRUG	GLP-1RA	Exposure to the class of drugs known as Glucagon-like peptide-1 receptor agonists (GLP-1RA)
DRUG	SGLT2i or GLP-1RA	Exposure to either SGLT2i or GLP-1RA
DRUG	Linagliptin (DPP4)	Exposure to agent Linagliptin (DPP4)
DRUG	Exenatide (GLP-1RA)	Exposure to agent Exenatide (GLP1-RA)
DRUG	Liraglutide (GLP-1RA)	Exposure to agent Liraglutide (GLP-1RA)
DRUG	Empagliflozin (SGLT2i)	Exposure to agent Empagliflozin (SGLT2i)
DRUG	Glimepiride (SU)	Exposure to agent Glimepiride (SU)
DRUG	Glipizide (SU)	Exposure to Glimepiride (SU)
DRUG	Glimepiride (SU) or Glipizide (SU)	Exposure to agent Glimepiride (SU) or Glipizide (SU)
DRUG	SU or DPP4 (excluding saxagliptin and alogliptin)	Exposure to either SU or DPP4 excluding Saxagliptin and Alogliptin
DRUG	Exenatide (GLP-1RA) or Liraglutide (GLP-1RA)	Exposure to either Exenatide (GLP-1RA) or Liraglutide (GLP-1RA)

Timeline

• Start date: 2021-07-01
• Primary completion: 2024-12-31
• Completion: 2025-03-12
• First posted: 2021-10-11
• Last updated: 2025-11-21
• Results posted: 2025-11-21

Locations

6 sites across 1 country: United States

Regulatory

• FDA-regulated drug study