Project Summary

PCORI has identified second-line treatment of type 2 diabetes as an important research topic. Second-line treatment is given when the initial treatment does not work or stops working. Patients, caregivers, clinicians, and others want to learn: How do second-line medicines compare to each other for treating type 2 diabetes when metformin is no longer effective? To help answer this question, PCORI launched an initiative in 2020 on Observational Analyses of Second-Line Pharmacological Agents in Type 2 Diabetes. The initiative funded this research project.

This research project is in progress. PCORI will post the research findings on this page within 90 days after the results are final.

What is the research about?

Patients with type 2 diabetes are at increased risk of heart disease. Medicines that lower blood sugar in patients with diabetes may also help reduce the risk of complications of heart disease, such as stroke and heart attack. But questions remain about how these medicines compare with each other for preventing heart disease.

In this study, the research team is comparing how well different diabetes medicines work to lower heart disease risk.

Who can this research help?

Results may help patients with type 2 diabetes and their doctors when considering ways to reduce the risk of heart disease.

What is the research team doing?

The research team is looking at electronic health record and health insurance data from six healthcare systems in five U.S. states between 2014 and 2023. Data are for patients with type 2 diabetes who are taking one of four types of diabetes medicines that help lower blood sugar. The team is looking to see how outcomes related to heart health, such as stroke, heart attack, and death, differ between people taking the different types of medicines. The team is also looking to see if these outcomes differ based on when patients start taking medicines. Finally, the team is looking at whether outcomes differ by patient traits such as age, race, and weight.

Patients with type 2 diabetes, caregivers, clinicians, and health insurers are helping to design and conduct the study.

Research methods at a glance

Design Element Description
Design Observational: cohort study
Population Adults ages 18 and older with type 2 diabetes from 5 U.S. states
  • Sulfonylureas
  • DPP-4 inhibitors
  • SGLT2 inhibitors
  • GLP-1 receptor agonists

Time to first occurrence of (1) cardiovascular disease death, (2) nonfatal stroke, or (3) nonfatal heart attack

Timeframe Up to 7.5-year follow-up for study outcome

Project Information

Romain Neugebauer, PhD
Patrick O'Connor
Kaiser Foundation Research Institute, a Division of Kaiser Foundation Hospitals
Comparison of Type 2 Diabetes Pharmacotherapy Regimens Using Targeted Learning

Key Dates

March 2021
August 2025

Study Registration Information


Award Type
Health Conditions Health Conditions These are the broad terms we use to categorize our funded research studies; specific diseases or conditions are included within the appropriate larger category. Note: not all of our funded projects focus on a single disease or condition; some touch on multiple diseases or conditions, research methods, or broader health system interventions. Such projects won’t be listed by a primary disease/condition and so won’t appear if you use this filter tool to find them. View Glossary
Populations Populations PCORI is interested in research that seeks to better understand how different clinical and health system options work for different people. These populations are frequently studied in our portfolio or identified as being of interest by our stakeholders. View Glossary
Intervention Strategy Intervention Strategies PCORI funds comparative clinical effectiveness research (CER) studies that compare two or more options or approaches to health care, or that compare different ways of delivering or receiving care. View Glossary
State State The state where the project originates, or where the primary institution or organization is located. View Glossary
Last updated: March 14, 2024