Comparison of Type 2 Diabetes Pharmacotherapy Regimens

NCT05073692 | Completed Results FDA Drug

• 1 other identifier: 739857
• Study Type: observational
• Target: 241,981
• Locations: 1 country
• Sites: 6

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.

Conditions

Type 2 Diabetes Mellitus; Cardiovascular Diseases

Keywords

Type 2 Diabetes Mellitus; Cardiovascular Diseases; Medication; Treatment

Outcome Measures

Primary Outcomes (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.

  2.5 years

Interventions

SU DRUG

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

DPP4 DRUG

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

SGLT2i DRUG

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

GLP-1RA DRUG

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

SGLT2i or GLP-1RA DRUG

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)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Kaiser Permanente: lead
• Geisinger Clinic: collaborator
• Henry Ford Health System: collaborator
• HealthPartners Institute: collaborator
• Patient-Centered Outcomes Research Institute: collaborator

Study Sites (6)

Kaiser Permanente Southern California

Pasadena, California, 91101, United States

Location

Romain S. Neugebauer

Pleasanton, California, 94588, United States

Location

Kaiser Permanente Hawaii

Honolulu, Hawaii, 96817, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

HealthPartners Institute

Bloomington, Minnesota, 55425, United States

Location

Geisinger

Danville, Pennsylvania, 17821, United States

Location

Related Publications (4)

• 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.

  PMID: 38488777 BACKGROUND

• 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.

  PMID: 38745886 RESULT

• 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.

  PMID: 40734551 RESULT

• 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.

  PMID: 41091469 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Cardiovascular Diseases

Interventions

Linagliptin; Exenatide; Liraglutide; empagliflozin; glimepiride; Glipizide; alogliptin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinazolines; Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Sulfonylurea Compounds; Sulfones; Sulfur Compounds; Organic Chemicals

Results Point of Contact

• Title: Romain Neugebauer
• Organization: Kaiser Permanente Division of Research

Romain.S.Neugebauer@kp.org

510-891-3234

Study Officials

• Romain S. Neugebauer, PhD

  Kaiser Permanente

  PRINCIPAL INVESTIGATOR

• Patrick J O'Connor, MD, MA, MPH

  HealthPartners Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2021
• First Posted: October 11, 2021
• Study Start: July 1, 2021
• Primary Completion: December 31, 2024
• Study Completion: March 12, 2025
• Last Updated: November 21, 2025
• Results First Posted: November 21, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)