JAMA Intern Med

Glycemic control not drug class, tied to cognitive performance in T2DM

May 21, 2025

Study details: The GRADE study (NCT01794143), conducted at 36 U.S. clinical centers, randomized 3,721 patients with T2DM of less than 10 years’ duration to receive one of four second-line glucose-lowering medications—insulin glargine, glimepiride, liraglutide, or sitagliptin—in addition to metformin. Cognitive performance was assessed over a mean follow-up of 4.1 years.

Results: No significant differences in cognitive outcomes were observed among treatment groups. However, higher time-weighted hemoglobin A1c levels were associated with modest declines in measures of cognitive performance, including processing speed, verbal memory, and category fluency. Severe hypoglycemia was rare across all groups.

Clinical impact: The choice of second-line glucose-lowering therapy doesn't appear to affect cognitive performance in patients with early T2DM. However, worse glycemic control is linked to modest cognitive decline, reinforcing the importance of maintaining optimal blood glucose levels in diabetes management.

Source:

Luchsinger JA, et al; GRADE Research Group. (2025, May 19). JAMA Intern Med. Glucose-Lowering Medications, Glycemia, and Cognitive Outcomes: The GRADE Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/40388190/