News Release

Research brief: Two popular diabetes drugs outperformed others in large clinical trial

Peer-Reviewed Publication

University of Minnesota Medical School

MINNEAPOLIS/ST. PAUL (10/07/2022) — In a large clinical trial that directly compared four drugs commonly used to treat type 2 diabetes, researchers from the University of Minnesota Medical School aided in the discovery that insulin glargine and liraglutide performed best. The results were published in a pair of papers in The New England Journal of Medicine.

“The GRADE study is the first to compare the efficacy of four drugs commonly used to treat type 2 diabetes when added to metformin in people with short-duration diabetes. It found that liraglutide was superior to glimepiride and sitagliptin in controlling blood sugars,” said Elizabeth Seaquist, MD, Department of Medicine Chair at the U of M Medical School and endocrinologist with M Health Fairview. “This study provides evidence that clinicians can use in developing treatment plans with their patient.”

The study found that participants taking metformin plus liraglutide or insulin glargine achieved and maintained their target blood levels for the longest time compared to sitagliptin or glimepiride. This translated into approximately six months more time with blood glucose levels in the target range compared with sitagliptin, which was the least effective in maintaining target levels. Treatment effects did not differ based on age, sex, race or ethnicity. However, none of the combinations overwhelmingly outperformed the others.

Launched in 2013, the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study was conducted at centers across the country, including the University of Minnesota. It was designed to compare four major medications approved by the Food and Drug Administration (FDA) at the time GRADE started to treat diabetes in combination with metformin. While there is general agreement among health care professionals that metformin combined with diet and exercise is the best early approach in diabetes care, there is no consensus on what to do next to best keep high blood glucose in check.

The GRADE Study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (U01DK098246). Additional support was provided by the National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences; National Center for Advancing Translational Sciences; the Centers for Disease Control and Prevention; and the American Diabetes Association. The Department of Veterans Affairs provided resources and facilities. Material support in the form of donated medications and supplies has been provided by Becton, Dickinson and Company, Bristol-Myers Squibb, Merck & Co., Inc., Novo Nordisk, Roche Diagnostics, and Sanofi. number: NCT01794143. 


About the University of Minnesota Medical School
The University of Minnesota Medical School is at the forefront of learning and discovery, transforming medical care and educating the next generation of physicians. Our graduates and faculty produce high-impact biomedical research and advance the practice of medicine. We acknowledge that the U of M Medical School, both the Twin Cities campus and Duluth campus, is located on traditional, ancestral and contemporary lands of the Dakota and the Ojibwe, and scores of other Indigenous people, and we affirm our commitment to tribal communities and their sovereignty as we seek to improve and strengthen our relations with tribal nations. For more information about the U of M Medical School, please visit

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.