The question has been, “Which one?”
A presentation at the virtual 81st Scientific Sessions of the American Diabetes Association (ADA) offers the clearest answer yet to the question. Researchers in the GRADE study advise that liraglutide and insulin were the most effective of the four medications in keeping hemoglobin A1C levels lower than 7%.
“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 lead study chair David M. Nathan, MD, director, Diabetes Center, Massachusetts General Hospital and professor of medicine, Harvard Medical School, both in Boston. “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.”
The study points out that glimepiride had a smaller effect, while sitagliptin appeared to have the least effect, with the highest frequency of developing A1C levels greater than 7%. On the other hand, in a secondary finding, insulin glargine was most effective in keeping A1C levels less than 7.5%.
The authors say the findings of the National Institutes of Health–sponsored study hold true despite gender, race, ethnicity, or age groups.
Because Black and Hispanic people are 50% more likely to have diabetes than non-Hispanic white people, the GRADE investigators made sure to include a highly diverse population of 20% Black and 18% Latino patients. The purpose was to compare the effectiveness of glucose-lowering medications in maintaining average blood glucose levels in the target range shown to reduce the risk of long-term complications.
To do that, the GRADE study team did a head-to-head comparison of the four most commonly used classes of medications added on to metformin; the goal was to keep patients’ hemoglobin A1C under 7%.
Included in the comparison were two oral medications—the sulfonylurea glimepiride and the DPP-4 inhibitor sitagliptin—and two injectable medications—insulin glargine and the GLP-1 receptor agonist liraglutide.
Participants were more than 5,000 type 2 diabetes patients with an average age of 57 years and an average duration of diabetes of 4 years. About 1,250 were randomly assigned to each of the four medications, with the study lasting an average of 5 years and a maximum of more than 7 years.
The study also determined the following:
• On average, use of liraglutide and sitagliptin was associated with more weight loss than glimepiride, with participants on insulin glargine therapy maintaining stable weight over time.
• More gastrointestinal side effects, including nausea, abdominal pain, and diarrhea, were reported with liraglutide than the other three medications.
• Hypoglycemia was more of a risk with glimepiride than the other medications.
• Liraglutide appeared to have a relative benefit compared with the three 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,” explained Henry Burch, MD, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) project scientist for the study. “NIH 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.”
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