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?

Type 2 diabetes is a long-term illness that causes high blood sugar levels, which can harm many parts of the body. Heart disease is the number one cause of death among people with type 2 diabetes. Different medicines can lower blood sugar levels and reduce the risk of heart disease. But past studies haven’t compared these treatments to each other to see how well each prevents heart disease. Also, past studies have included few patients with low or moderate risk of heart disease.

In this study, the research team is comparing four types of medicine to lower blood sugar in patients with type 2 diabetes who have a low or moderate risk of heart disease. The team wants to learn how well each type of medicine works to prevent heart disease and other outcomes, such as heart attack and stroke.

Who can this research help?

Results may help patients with type 2 diabetes and their doctors when considering treatments to lower blood sugar and manage risk for heart disease.

What is the research team doing?

The research team is reviewing health records and insurance claims for patients with type 2 diabetes who are taking one of four medicines to lower blood sugar. Patients received care at healthcare systems across the United States and the United Kingdom between 2013 and 2021.

The research team is looking at how well each medicine works to reduce the risk for heart attack, stroke, and heart-related death. The team also wants to learn about the side effects of each medicine, especially in older people and those who are less likely to take part in research studies. Finally, the team is looking to see if health outcomes differ based on patient traits, such as age and heart disease risk.

Patients with diabetes, caregivers, and clinicians are helping to plan and conduct this study.

Research methods at a glance

Design Element Description
Design Observational: cohort study
Population More than 2 million patients with type 2 diabetes
Interventions/
Comparators
  • Sodium-glucose Cotrasporter-2 inhibitors (e.g., dapagliflozin)
  • Glucagon-like peptide-1 receptor agonists (e.g., liraglutide)
  • Dipeptidyl peptidase-4 inhibitors (e.g., sitagliptin)
  • Sulfonylureas (e.g., glimepiride)
Outcomes

Primary: major cardiovascular events (e.g., myocardial infarction, stroke, heart failure hospitalization), mortality

Secondary: heart bypass surgery or stent placement, progression of kidney disease, blood sugar control, potential drug-related harms (e.g., severe hypoglycemia, diabetic ketoacidosis, non-traumatic lower limb amputation)

Timeframe Timeframe Length of follow-up for collecting data on primary outcomes. View Glossary 8.5-year follow-up for primary outcomes

Project Information

Elisabetta Patorno, MD, DrPH
Brigham and Women's Hospital
$4,443,087
The Comparative Effectiveness and Safety of Four Second-Line Pharmacological Strategies in a Type 2 Diabetes Study (The CER-4-T2D Study)

Key Dates

March 2021
July 2025
2021

Tags

Award Type
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
State State The state where the project originates, or where the primary institution or organization is located. View Glossary
Last updated: June 3, 2022