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 blood sugar levels to rise. It affects more than 10 percent of adults in the United States and can lead to health problems such as heart disease, stroke, and kidney disease. To treat type 2 diabetes, doctors may first prescribe a medicine called metformin. Some patients may need to take medicines in addition to metformin, called second-line medicines. Questions remain about which second-line medicines work the best for treating type 2 diabetes.

This study is comparing five classes of second-line medicines for treating type 2 diabetes. The study is looking at the medicines’ side effects and their effects on heart health and other health outcomes.

Who can this research help?

Results may help patients and doctors when considering second-line medicines to treat type 2 diabetes.

What is the research team doing?

The research team is reviewing health records and insurance claims for more than 130 million patients across the United States. Patients have type 2 diabetes, take metformin, have moderate risk for heart disease, and are starting a second diabetes medicine. The team is looking at health record data up to nine years after patients start the second medicine.

The research team is dividing patients’ data into groups based on the second-line medicine they are taking. The team is comparing how many patients in each group had:

  • Side effects from the medicines.
  • Heart disease-related deaths.
  • Heart attacks.
  • Stroke.
  • Kidney, eye, or liver disease.

Patients with diabetes, caregivers, clinicians, patient advocates, and health insurers are helping to plan and conduct this study.

Research methods at a glance

Design Element Description
Design Observational: cohort study
Population Adults ages 30 and older with type 2 diabetes who are taking metformin and have a moderate risk of cardiovascular events and who are starting a second diabetes medicine
  • Sodium-glucose Cotransporter-2, or SGLT2, inhibitors
  • Glucagon-like peptide-1, or GLP1, receptor agonists
  • Dipeptidyl peptidase 4, or DPP4, inhibitors
  • Basal insulin
  • Sulfonylureas

Primary: death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure

Secondary: nephropathy, diabetic retinopathy requiring treatment, nonalcoholic fatty liver disease with advanced fibrosis, nonalcoholic steatohepatitis, severe hypoglycemia, severe urinary tract infection, Fournier’s gangrene, lower extremity amputation, bone fracture, diabetic ketoacidosis, pancreatitis, pancreatic cancer, medullary thyroid cancer, non-cardiovascular death

Timeframe Timeframe Length of follow-up for collecting data on primary outcomes. View Glossary Up to 9-year follow-up for primary outcomes

Project Information

Alexander Turchin, MD, MS
Alan F Kaul, PharmD, MS
Partners Healthcare Brigham and Women's Hospital
BESTMED: Observational Evaluation of Second-Line Therapy Medications in Diabetes

Key Dates

March 2021
July 2025


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: April 12, 2024