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Enhancement of Impaired Olfactory Neural Activation and Cognitive Capacity by Liraglutide, but not Dapagliflozin or Acarbose, in Patients With Type 2 Diabetes: A 16-Week Randomized Parallel Comparative Study

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posted on 09.03.2022, 21:04 by Haiyan Cheng, Zhou Zhang, Bing Zhang, Wen Zhang, Jin Wang, Wenyu Ni, Yingwen Miao, Jiani Liu, Yan Bi
Objective: The comparative neuroprotective effects of different anti-diabetic drugs have not been characterized in randomized controlled trials. Here, we investigated the therapeutic effects of liraglutide, dapagliflozin, or acarbose treatment on brain functional alterations and cognitive changes in patients with type 2 diabetes.

Research design and methods: Thirty-six patients with type 2 diabetes inadequately controlled with metformin monotherapy were randomized to receive liraglutide, dapagliflozin, or acarbose treatment for 16 weeks. Brain functional magnetic resonance imaging (fMRI) scan and a battery of cognitive assessments were evaluated pre- and postintervention in all subjects.

Results: The 16-week treatment with liraglutide significantly enhanced the impaired odor-induced left hippocampal activation with GRF correction, and improved cognitive subdomains of delayed memory, attention, and executive function (all P < 0.05), whereas dapagliflozin or acarbose did not. Structural equation modeling analysis demonstrated that such improvements of brain health and cognitive function could be partly ascribed to a direct effect of liraglutide on left hippocampal activation (β = 0.330, P = 0.022) and delayed memory (β = 0.410, P = 0.004), as well as to the metabolic ameliorations of reduced waist circumference, decreased body fat ratio, and elevated fasting insulin (all P < 0.05).

Conclusions: Our head-to-head study demonstrated that liraglutide enhanced impaired brain activation and restored impaired cognitive domains in patients with type 2 diabetes, whereas dapagliflozin and acarbose did not. The results expand the clinical application of liraglutide and provide a novel treatment strategy for individuals with diabetes and a high risk of cognitive decline.


This work was supported by the National Natural Science Foundation of China Grant Awards (82030026, 81770819, 82000775, 81970689, 82070837, 81970704, 81800752, 81900787, 82000735, 82100868, and 81800719), the Key Project of Nanjing Clinical Medical Science, the Natural Science Foundation of Jiangsu Province of China (BK20200114, BK20201115, BK20200118, and BK20200136), the Six Talent Peaks Project of Jiangsu Province of China (YY-086), the China Postdoctoral Science Foundation (2020M671449), the Doctor of Entrepreneurship and Innovation Program of Jiangsu Province, and the Nanjing Health Science and Technology Development Project (JQX19004 and YKK18067).