Could Results From The GRADE Study Lead To A More Personalized Approach To Diabetes Care?

Recently announced results from the Glycemia Reduction Approaches in Diabetes—A Comparative Effectiveness (GRADE) Study at the (virtual) 81st Scientific Sessions of the American Diabetes Association (ADA) revealed several key findings. GRADE, the largest and longest comparative effectiveness study to date for glucose-lowering medications in patients with type 2 diabetes, compared the four most common classes of medications used in this population, and assessed the ability of these medications, in conjunction with metformin, to keep Hemoglobin A1c (HbA1c) levels within the targeted range of less than 7%.¹    

Researchers divided and randomly assigned study subjects into one of the four medication categories, including two oral medications (sulfonylurea glimepiride and sitagliptin, a DPP-4 inhibitor) and two injectable medications (insulin glargine and liraglutide, the GLP-1 receptor agonist). Subjects used metformin in conjunction with each of the four other medications. GRADE followed the enrolled patients for an average of five years. The average age of participants in the study was 57 years, and the average duration of diabetes was four years.¹

Results from the study demonstrated that liraglutide and insulin were the most effective of the four medications at maintaining HbA1c levels less than 7%. In addition, as a secondary outcome of the study, insulin glargine was found to be the most effective at keeping A1C levels less than 7.5%. There were no significant differences noted between the groups based on gender, race, ethnicity and age. Furthermore, patients treated with liraglutide and sitagliptin demonstrated a greater weight loss over the course of the study than those treated with glimepiride, while subjects in the liraglutide group seemed to have more gastrointestinal side effects, i.e. nausea, abdominal pain, and diarrhea. An increased risk for hypoglycemia was associated with glimepiride, and liraglutide showed 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.”¹

Perhaps most notably, the study enrolled more than 5,000 subjects with type 2 diabetes and included an extremely diverse population consisting of 20% Black and 18% Latino patients.  And, as the authors note, this was critically important given the way diabetes “disproportionally impacts Black and Hispanic people, who are 50% more likely to have diabetes than non-Hispanic white people.”^1,2

In fact, racial and ethnic disparities exist not only in the incidence and risk of developing diabetes, but also in terms of lower extremity complications. Tan and colleagues recently reported that among Medicare beneficiaries, African Americans and Native Americans are far more likely (1.8–1.9 times higher risk) to undergo a major amputation, secondary to a diabetic foot ulcer or infection, than Caucasians.³ According to the GRADE authors, further analyses “will help personalize the use of glucose-lowering medications in type 2 diabetes.” This is due in large part to the highly diverse study population.¹ Indeed, more research is needed to understand the key differences between various groups in managing diabetes and its complications.

Dr. Isaac is a Diplomate of the American Board of Foot and Ankle Surgery (ABFAS) and serves as Co-Director of Research with Foot & Ankle Specialists of the Mid-Atlantic (FASMA).

References

1. American Diabetes Association. Liraglutide and insulin more effective in maintaining average blood glucose levels than other common diabetes drugs. Available at: https://www.diabetes.org/newsroom/press-releases/2021/liraglutide-insulin-more-effective-in-maintaining-average-blood-glucose-levels-than-other-common-diabetes-drugs . Published June 28, 2021. Accessed July 19, 2021.

2. Chow EA, Foster H, Gonzalez V, McIver L. The disparate impact of diabetes on racial/ethnic minority populations. Clin Diabetes. 2012;30(3):130-133.

3. Tan T-W, Armstrong DG, Concha-Moore KC, et al. Association between race/ethnicity and the risk of amputation of lower extremities among medicare beneficiaries with diabetic foot ulcers and diabetic foot infections. BMJ Open Diabetes Res Care. (2020;8(1):e001328.