ON TARGET DM: Comparison of Type 2 Diabetes Pharmacotherapy Regimens

Sponsor

Kaiser Permanente (Other)

Overall Status

Recruiting

CT.gov ID

NCT05073692

Collaborator

Geisinger Clinic (Other), Henry Ford Health System (Other), HealthPartners Institute (Other), Patient-Centered Outcomes Research Institute (Other)

270,000

Enrollment

Locations

Anticipated Duration (Months)

45000

Patients Per Site

900.5

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus Cardiovascular Diseases	Drug: SU Drug: DPP4 Drug: SGLT2i Drug: GLP-1RA Drug: SGLT2i or GLP-1RA Drug: Linagliptin (DPP4) Drug: Exenatide (GLP-1RA) Drug: Liraglutide (GLP-1RA) Drug: Empagliflozin (SGLT2i) Drug: Glimepiride (SU) Drug: Glipizide (SU) Drug: Glimepiride (SU) or Glipizide (SU) Drug: SU or DPP4 (excluding saxagliptin and alogliptin) Drug: Exenatide (GLP-1RA) or Liraglutide (GLP-1RA)

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

270000 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

Official Title:

Comparison of Type 2 Diabetes Pharmacotherapy Regimens Using Targeted Learning

Actual Study Start Date :

Jul 1, 2021

Anticipated Primary Completion Date :

Jun 30, 2024

Anticipated Study Completion Date :

Aug 30, 2025

Outcome Measures

Primary Outcome Measures

Incidence of 3-point Major Adverse Cardiovascular Events (MACE) [1/1/2014 to 6/30/2021]
3-point MACE is defined as a single outcome measure, which is a composite measure of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular disease death.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Dispensing of either of the set of drugs being compared
No prior dispensing of any of the drugs compared
Evidence of Type 2 Diabetes Mellitus diagnosis
Age 18-85
Not currently pregnant
No evidence of dementia or short-term life expectancy from prior cancer diagnoses
History of ≥2 years of continuous health plan membership
≥1 A1c test in the past 18 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Romain S. Neugebauer	Oakland	California	United States	94612
2	Kaiser Permanente Southern California	Pasadena	California	United States	91101
3	Kaiser Permanente Hawaii	Honolulu	Hawaii	United States	96817
4	Henry Ford Health System	Detroit	Michigan	United States	48202
5	HealthPartners Institute	Bloomington	Minnesota	United States	55425
6	Geisinger	Danville	Pennsylvania	United States	17821