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

Abstract

<b>Objective:</b> <a></a><a>The comparative neuroprotective effects of different anti-diabetic drugs have not been characterized in randomized controlled trials. Here, </a><a>we investigated the therapeutic effects of liraglutide, dapagliflozin, or acarbose treatment on brain functional alterations and cognitive changes in patients with type 2 diabetes.</a> <p> </p> <p><b>Research design and methods: </b>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 <a>pre- and postintervention</a> in all subjects.</p> <p> </p> <p><b>Results: </b>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 <i>P</i> < 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 (<i>β</i> = 0.330, <i>P</i> = 0.022) and delayed memory (<i>β</i> = 0.410, <i>P</i> = 0.004), as well as to the metabolic ameliorations of reduced waist circumference, decreased body fat ratio, and elevated fasting insulin (all <i>P</i> < 0.05).</p> <p> </p> <p><b>Conclusions:</b> <a>Our head-to-head study demonstrated that liraglutide</a> 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>a novel treatment strategy for individuals with diabetes and a high risk of cognitive decline.</a><b></b></p>

Effects of dulaglutide combined with insulin degludec on glucose fluctuations and appetite in type 2 diabetes

“…Nauck, M (14) found that after the addition of sitagliptin to the treatment regimen of patients with diabetes with poor glucose control on oral antidiabetes drugs, it was found that the standard deviation of 24-h glucose, the 24-h mean glucose fluctuation range, and the glucose fluctuation range of patients decreased significantly.GLP-1 signaling in the central nervous system can control glucose uptake and production in peripheral tissues, and dulaglutide also plays a role through GLP-1 receptor signaling pathway (23), which may be similar to DPP4 inhibitors in keeping glucose stable. Recent studies suggest that GLP-1 acting can directly effect the brain's feeding center, affecting the perception of the reward value of food (24). The activation of GLP-1 receptors in the human brain helps to regulate appetite and food reward (25,26).…”