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Type 2 Diabetes MellitusON TARGET DMNCT05073692

Comparison of Type 2 Diabetes Pharmacotherapy Regimens

An observational study of Type 2 Diabetes Mellitus and Cardiovascular Diseases, run by Kaiser Permanente at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 85 years
What is being tested?
SU, DPP4 and SGLT2i
How many people
241,981 participants
Where
6 sitesUnited States
Study dates
1 Jul 2021to 12 Mar 2025
Phase
Observational
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Patients from six large care delivery systems with integrated administrative and EHR clinical data sources (Geisinger in Pennsylvania, Henry Ford Health System in Michigan, HealthPartners Institute in Minnesota and Wisconsin, and Kaiser Permanente of Northern California, Southern California, and Hawaii) who were new users of glucose-lowering medications between 01/01/2014 and 12/31/2021.

  • Dispensing of either of the set of drugs being compared
  • No prior dispensing of nor contraindication for any of the drugs compared
  • Evidence of Type 2 Diabetes Mellitus diagnosis
  • Age 18 or older
  • 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

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • HealthPartners Institute

    Bloomington, Minnesota, 55425

  • Geisinger

    Danville, Pennsylvania, 17821

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • Kaiser Permanente Hawaii

    Honolulu, Hawaii, 96817

  • Kaiser Permanente Southern California

    Pasadena, California, 91101

  • Romain S. Neugebauer

    Pleasanton, California, 94588

Other trials in United States

About this study

Official title: Comparison of Type 2 Diabetes Pharmacotherapy Regimens Using Targeted Learning

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.

Read the 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.

Being tested
SU, DPP4, SGLT2i, GLP-1RA, SGLT2i or GLP-1RA
Keywords
Type 2 Diabetes Mellitus, Cardiovascular Diseases, Medication, Treatment
Medical subject headings
Diabetes Mellitus, Type 2, Cardiovascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SUDrug

    Exposure to the class of drugs known as Sulfonylureas (SU)

  • DPP4Drug

    Exposure to the class of drugs known as Dipeptidyl peptidase-4 inhibitors (DPP4)

  • SGLT2iDrug

    Exposure to the class of drugs known as Sodium-glucose cotransporter-2 inhibitors (SGLT2i)

  • GLP-1RADrug

    Exposure to the class of drugs known as Glucagon-like peptide-1 receptor agonists (GLP-1RA)

  • SGLT2i or GLP-1RADrug

    Exposure to either SGLT2i or GLP-1RA

  • Linagliptin (DPP4)Drug

    Exposure to agent Linagliptin (DPP4)

  • Exenatide (GLP-1RA)Drug

    Exposure to agent Exenatide (GLP1-RA)

  • Liraglutide (GLP-1RA)Drug

    Exposure to agent Liraglutide (GLP-1RA)

  • Empagliflozin (SGLT2i)Drug

    Exposure to agent Empagliflozin (SGLT2i)

  • Glimepiride (SU)Drug

    Exposure to agent Glimepiride (SU)

  • Glipizide (SU)Drug

    Exposure to Glimepiride (SU)

  • Glimepiride (SU) or Glipizide (SU)Drug

    Exposure to agent Glimepiride (SU) or Glipizide (SU)

  • SU or DPP4 (excluding saxagliptin and alogliptin)Drug

    Exposure to either SU or DPP4 excluding Saxagliptin and Alogliptin

  • Exenatide (GLP-1RA) or Liraglutide (GLP-1RA)Drug

    Exposure to either Exenatide (GLP-1RA) or Liraglutide (GLP-1RA)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of 3-point Major Adverse Cardiovascular Events (MACE)

    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.

    Measured: 2.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Oct 2021
  2. Study start1 Jul 2021
  3. Primary completion31 Dec 2024
  4. Study completion12 Mar 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Retrospective
Enrolment
241,981 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05073692
Sponsor's protocol ID
739857
Acronym
ON TARGET DM
Status last verified
Nov 2025
First submitted
14 Sep 2021
Last updated
21 Nov 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Thomas TW, Hooker SA, Schmittdiel JA. Principles for Stakeholder Engagement in Observational Health Research. JAMA Health Forum. 2024 Mar 1;5(3):e240114. doi: 10.1001/jamahealthforum.2024.0114.

    PubMed 38488777

  • Rodriguez LA, Finertie H, Neugebauer RS, Gosiker B, Thomas TW, Karter AJ, Gilliam LK, Oshiro C, An J, Simonson G, Cassidy-Bushrow AE, Dombrowski S, Nolan M, O'Connor PJ, Schmittdiel JA. Race and ethnicity and pharmacy dispensing of SGLT2 inhibitors and GLP-1 receptor agonists in type 2 diabetes. Lancet Reg Health Am. 2024 May 7;34:100759. doi: 10.1016/j.lana.2024.100759. eCollection 2024 Jun.

    PubMed 38745886

  • Thapa B, Schmittdiel JA, Arterburn D, Neugebauer R, Dyer W, O'Connor PJ, An J, Cassidy-Bushrow AE, Gilliam LK, Hooker SA, Nolan MB, Oshiro CES, Thomas T, Simonson G, Dombrowski SK, Rodriguez LA. Clinical and Demographic Characteristics Associated With Diabetes Remission in Six Integrated Health Care Systems: A Retrospective Cohort Study. Diabetes Care. 2025 Oct 1;48(10):1737-1743. doi: 10.2337/dc25-0530.

    PubMed 40734551

  • Neugebauer R, An J, Dombrowski SK, Oshiro C, Cassidy-Bushrow A, Gilliam L, Simonson G, Karter AJ, Bergenstal R, Finertie H, Yassin MM, Knowlton G, Lin SR, Dyer W, Pimentel N, Izadian K, Schmittdiel J, Thomas TW, Hooker SA, Nolan MB, Wright E, Aurora L, Rodriguez LA, Kaur J, Adams AS, van der Laan MJ, O'Connor PJ. Glucose-Lowering Medication Classes and Cardiovascular Outcomes in Patients With Type 2 Diabetes. JAMA Netw Open. 2025 Oct 1;8(10):e2536100. doi: 10.1001/jamanetworkopen.2025.36100.

    PubMed 41091469

Questions about this trial

What is this clinical trial studying?

An observational study of Type 2 Diabetes Mellitus and Cardiovascular Diseases, run by Kaiser Permanente at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of 3-point Major Adverse Cardiovascular Events (MACE) (time frame: 2.5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05073692, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2025.

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