Two Popular Drugs for Type 2 Diabetes Have Achieved the Best Results in a Massive Clinical Trial

In a large clinical trial directly comparing four drugs commonly used to treat type 2 diabetes, researchers at the University of Minnesota Medical School helped find that insulin glargine and liraglutide were the most effective. The results were published in a pair of articles in The New England Journal of Medicine.

The GRADE study is the first to compare the effectiveness of four drugs commonly used to treat type 2 diabetes when added to metformin in people with short-term diabetes. It found that liraglutide was superior to glimepiride and sitagliptin in controlling blood sugar. This study provides evidence that clinicians can use to develop treatment plans with their patient.”

Elizabeth Seaquist, MD, chair of the Department of Medicine at the U of M School of Medicine and endocrinologist at M Health Fairview

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

Launched in 2013, the GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness) study was conducted at centers across the country, including the University of Minnesota. It was designed to compare four major drugs approved by the Food and Drug Administration (FDA) at the time GRADE began treating diabetes in combination with metformin. Although there is a general consensus among healthcare professionals that metformin plus diet and exercise is the best early approach in diabetes care, there is no consensus. on what to do next to better control high blood sugar.

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 the Advancement of Translational Sciences; the Centers for Disease Control and Prevention; and the American Diabetes Association. The Department of Veterans Affairs provided the resources and facilities. Material support in the form of drug and supply donations was provided by Becton, Dickinson and Company, Bristol-Myers Squibb, Merck & Co., Inc., Novo Nordisk, Roche Diagnostics and Sanofi. number: NCT01794143.


University of Minnesota School of Medicine

Journal reference:

The GRADE Study Research Group., (2022) Blood sugar reduction in type 2 diabetes – glycemic outcomes. New England Journal of Medicine.

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