Study: Liraglutide, Insulin More Effective Than Other Drugs in Maintaining Average Blood Glucose Levels


Patients with diabetes treated with liraglutide also saw more weight loss compared with patients in the other arms of the study.

New research from the GRADE study of adults with type 2 diabetes suggests that the use of liraglutide and insulin is more effective than other common diabetes drugs in maintaining average blood glucose levels, according to the American Diabetes Association (ADA).

Controlling blood glucose levels is a major challenge for individuals with type 2 diabetes. The GRADE study is the largest and longest study comparing the efficacy of common medications and was designed to compare the effectiveness of glucose-lowering medications in maintaining average blood glucose levels in the target range that has been identified to reduce the risk of long-term complications.

“The ultimate goal of GRADE is to help clinicians select the therapies that will work best for individual patients, as diabetes care is not a one-size-fits-all approach,” said David M. Nathan, MD, lead study chair and director of the Diabetes Center at Massachusetts General Hospital, in a press release. “We believe these results will provide value to both patients and their providers when deciding which medication is needed to meet their appropriate blood glucose target and we are encouraged that these findings can be applied to a very diverse range of patients.”

Type 2 diabetes disproportionately impacts Black and Hispanic individuals, who are 50% more likely to have diabetes than non-Hispanic White people, according to the press release. The GRADE study included a highly diverse patient population, including 20% Black and 18% Latinx patients.

The study enrolled more than 5000 patients with type 2 diabetes with an average age of 57 years and an average duration of diabetes of 4 years. Approximately 1250 patients were randomly assigned to each of the 4 medications being investigated and were followed for an average of 5 years and a maximum of more than 7 years.

Investigators performed a head-to-head comparison of the 4 most commonly used classes of medications used in conjunction with metformin and analyzed their ability to keep average blood glucose levels in the recommended target range, defined as an A1C level of less than 7%. The comparison included the 2 oral medications glimepiride and sitagliptin, and 2 injectable medications, insulin glargine and liraglutide.

The results demonstrated that liraglutide and insulin were the most effective of the 4 medications in keeping A1C levels below 7%. Glimepiride had a smaller effect and sitagliptin showed the lowest effect, according to the press release. Insulin glargine was the most effective in keeping A1C levels below 7.5%, which was a secondary outcome of the study. These findings were similar among both men and women an across the different races, ethnicities, and age groups.

In addition, the investigators found that participants treated with liraglutide and sitagliptin had more weight loss than those treated with glimepiride. The patients treated with insulin glargine had a stable weight over time.

Patients receiving liraglutide experienced more gastrointestinal adverse effects, including nausea, abdominal pain, and diarrhea, compared to patients in the other 3 research arms. Glimepiride was associated with a higher risk for hypoglycemia compared to the other medications.

Based on preliminary results, the researchers found that liraglutide had a relative benefit compared with the 3 other medications for reduction of a composite outcome of heart attacks, stroke, and other heart and vascular complications.

“Comparative effectiveness trials like GRADE are essential in helping people make decisions about how to best manage and treat chronic diseases like type 2 diabetes,” said Henry Burch, MD, National Institute of Diabetes and Digestive and Kidney Diseases project scientist for the study, in the press release. “[National Institutes of Health] supports GRADE and studies like it to help people with type 2 diabetes make informed choices between medications based on individual patient needs and the characteristics of the medications.”

The study results were presented during the 81st Scientific Sessions of the ADA. Future analyses of the results will help personalize the use of these glucose-lowering medications in patients with type 2 diabetes, according to the press release.


Liraglutide and Insulin More Effective in Maintaining Average Blood Glucose Levels Than Other Common Diabetes Drugs. News release. Presented at: American Diabetes Association 81st Scientific Sessions. June 28, 2021. Accessed July 6, 2021.

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