Project Summary

What is the research about?

Type 2 diabetes is a long-term illness that causes blood sugar levels to rise. Diabetes can be hard to manage and can lead to many health problems, such as kidney disease. Many patients with diabetes take a medicine called metformin. Metformin helps the body better use the insulin it produces. But research studies done 50 years ago showed that medicines related to metformin were harmful for patients with kidney disease. As a result, many doctors don’t use metformin to treat patients with kidney disease. More recently, studies have shown metformin to be safe for patients with mild to moderate kidney disease. But researchers still don’t know if metformin is safe for people with serious kidney disease.

In this study, the research team is comparing metformin with other commonly used medicines to see how well each treats type 2 diabetes among patients with chronic kidney disease. The team is also looking to see if the effect of the medicines varies for different groups of people based on factors such as age and race.

Who can this research help?

Results may help patients with type 2 diabetes and chronic kidney disease and their doctors when considering how to treat type 2 diabetes.

What is the research team doing?

The research team is looking at health records and lab results from patients with type 2 diabetes and kidney disease. The team is comparing patients taking metformin and patients treated with other commonly used medicines to see how well each treatment reduces

  • Blood sugar levels
  • HbA1c, which measures average blood sugar levels over the past three months
  • Body mass index, or BMI, which estimates body fat based on height and weight
  • Hospital visits for buildup of acid in the bloodstream, high blood sugar, heart attack, stroke, and heart failure
  • Blood sugar and HbA1c for different groups of patients by age; sex; BMI; race; history of kidney disease, liver disease, and heart failure; renal function; and metformin dose

Patients are providing input on this study from start to finish, including helping to choose research questions and interpret results. 

Research methods at a glance

Design Elements Description
Design Observational: cohort study
Population 16,000 adults ages 18 and older with type 2 diabetes mellitus and chronic kidney disease who are starting metformin or one of the comparator drugs and have at least one prescription for metformin, sulfonylurea, or a DPP-4 inhibitor; at least 6 months preceding that prescription in which none of those drugs were used; and an eGFR within 1 month prior to the index date of <60 mL/min
  • Metformin
  • Sulfonylurea
  • DPP-4 inhibitor
  • SGLT2 inhibitor
  • GLP1 receptor agonist 

Primary: severe hypoglycemia defined as emergency room, observation, or inpatient visits where hypoglycemia is the primary diagnosis; change in HbA1c after 3–9 months; heterogeneity of treatment effect

Secondary: acidosis, hospitalization for hyperglycemia, acute myocardial infarction, stroke, hospitalization or emergency room visits for heart failure, change in HbA1c after 12–24 months, change in BMI, change in eGFR

Timeframe Up to 25-month follow-up for primary outcomes

Project Information

Alvin Mushlin, MD, ScM
Joan and Sanford I. Weill Medical College of Cornell University
Comparative Effectiveness of Metformin for Type 2 Diabetes with Chronic Kidney Disease

Key Dates

August 2018
April 2023

Study Registration Information

^James Flory, MD, was the original principal investigator on this project.


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
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Last updated: January 20, 2023