Two drugs, liraglutide and insulin, did better at keeping A1C (a measure of average blood sugar) below 7% in the latest GRADE study. The UNC Diabetes Care Center, led by Principal Investigator Sue Kirkman, MD, Professor of Medicine, Department of Endocrinology and Metabolism, was one of 37 sites that participated in this NIH-funded comparative efficacy study.
Sue Kirkman, MD, Study Director at the UNC site, GRADE study
Two drugs have been shown to be most effective at keeping blood sugar levels within target ranges while also treating type 2 diabetes, a disease that affects more than 32 million Americans. Of four drugs commonly used in conjunction with metformin, liraglutide and insulin were superior to glimepiride and sitagliptin for keeping A1C (a measure of average blood sugar) below 7%, according to the GRADE study.
Approximately 1,250 out of 5,000 patients with type 2 diabetes were randomly assigned to each of the four drugs in association with ongoing metformin therapy. The comparison included two oral drugs, the sulfonylurea glimepiride and the DPP-4 inhibitor sitagliptin, as well as two injectable drugs, insulin glargine and the GLP-1 receptor agonist liraglutide. The effects of each of the four drugs on diabetes complications and side effects were also studied. While the results showed that liraglutide and insulin were most effective (and similar) at keeping A1C levels below 7% (and similar), glimepiride had less effect and sitagliptin was the least effect, making A1C levels most likely to be persistently above 7%. developed. Insulin glargine was most effective at keeping A1C levels below 7.5%, a secondary finding of the study.
Presented at the American Diabetes Association’s (ADA) 81st virtual scientific sessions, the face-to-face comparison provided an informative guide for providers and their patients to assess individual treatment strategies for managing type 2 diabetes. Sue Kirkman, MD, lead investigator at the UNC site for the GRADE trial, said the results will help decide which secondary medication may be most beneficial once metformin stops keeping blood sugar levels within target ranges.
Injected liraglutide and once-a-day “basal” insulin controlled A1C / mean blood sugar significantly longer than either glimepiride or sitagliptin, with sitagliptin coming last in results. The differences were particularly noticeable when the baseline A1C was higher. This suggests that for glycemic control, especially if metformin control is not good, the two drugs that are injected are likely to work better, ”said Dr. Kirkman, who also co-chaired the Outcomes Adjudication Committee for the GRADE study.
Additional findings are:
Weight Loss: On average, participants treated with liraglutide and sitagliptin had more weight loss than participants treated with glimepiride, while participants treated with insulin glargine had stable weight over time.
Side effects and risk: Liraglutide had more gastrointestinal side effects such as nausea, abdominal pain, and diarrhea than the other three drugs.
Glimepiride was associated with a higher risk of severely low blood sugar than the other drugs, although this was rare.
Complication Benefits: Based on preliminary results, liraglutide had a relative advantage over the other three drugs in reducing the combined outcome of myocardial infarction, stroke, and other cardiovascular complications. However, Kirkman emphasized that these results could change as not all cardiovascular outcomes have been assessed. No differences in kidney disease or nerve damage were found between the four drugs.
In order to include a very heterogeneous population group, the GRADE study enrolled patients with a wide range of ages, races, and ethnic backgrounds. Because minorities and ethnic groups are disproportionately affected by diabetes, 20% blacks and 18% Hispanic / Latin American participated in the study. The UNC’s Diabetes Care Center played a prominent role in the study as it was one of only a few websites that enrolled people whose primary language was Spanish in addition to those whose primary language was English. Sponsored by the National Institutes of Health, GRADE accompanied the participants for an average of five years and a maximum of more than seven years.
“This study started in 2013 and ended in April 2021. This means that the last 15 months of the study took place during the COVID-19 pandemic. It is impressive how the study teams and participants were able to quickly deal with the disruptions of the pandemic, “said Dr. Kirkman.
“The visits have been switched from personal to virtual, blood draws in the research clinic have been replaced by the study participants taking blood samples from their fingertips and sending them to the laboratory for A1C measurements, etc. It’s amazing that we completed the study successfully and only very much few people dropped out or got lost on follow-up. It is a tribute in particular to the study coordinators and the study participants’ commitment to the study, ”she said.
Media contact: Brittany Phillips, UNC School of Medicine, 919-270-6212
