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Published on: December 11, 2016
Drug Development
Xin Li1, Bing Zhang1
1Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
Background:
The comparative neuroprotective effects of different hypoglycemic drugs have not been characterized in randomized controlled trials. Here, we investigated the effects of dapagliflozin, liraglutide, or acarbose treatment on the directed functional connectivity of primary olfactory cortex (POC) circuit and local activation under odor stimulation in patients with type 2 diabetes (T2D).
Method:
In the 16-week randomized parallel-group open-label trial, 36 patients with T2D, inadequately controlled with metformin, were randomized 1:1:1 to receive dapagliflozin, liraglutide or acarbose. Simultaneously, 36 normal controls were recruited. Olfactory task functional MRI and a battery of olfactory and cognitive tests were conducted in all subjects and postintervention. Generalized psychophysiological interaction analysis was used to identify directed functional connectivity of POC circuit under odor stimulation.
Result:
The 16-week treatment with dapagliflozin restored odor-induced functional integration of POC-sensorimotor cortex-middle temporal cortex circuit with Gaussian random field correction, but liraglutide and acarbose did not, and dapagliflozin tended to improve attention (P = 0.071). Liraglutide enhanced odor-induced activation in the left hippocampus, but dapagliflozin and acarbose did not. The decreased odor-induced directed functional connectivity was associated with improvements in lipid levels and changes in olfactory threshold, executive function, and memory performance (all P < 0.05).
Conclusion:
These results suggest that dapagliflozin and liraglutide have unique neuroprotective effects, respectively. Liraglutide may act on the activation of local olfactory-related regions, while dapagliflozin acts on the functional integration of neural circuits. These findings highlight the importance of targeting both metabolic and neural pathways in the management of T2D-related cognitive decline.
Insights
Dapagliflozin improved neural circuit connectivity in type 2 diabetes (T2D) patients, while liraglutide enhanced local brain activation. Both drugs show unique neuroprotective effects, suggesting combined metabolic and neural pathway targeting for T2D cognitive decline.
Area of Science:
- Neuroscience
- Endocrinology
- Pharmacology
Background:
- Comparative neuroprotective effects of hypoglycemic drugs are not well-established in randomized controlled trials.
- Type 2 diabetes (T2D) is associated with cognitive decline, potentially linked to altered brain function.
- Investigating the impact of dapagliflozin, liraglutide, and acarbose on neural circuits in T2D is crucial.
Purpose of the Study:
- To compare the neuroprotective effects of dapagliflozin, liraglutide, and acarbose in patients with type 2 diabetes (T2D).
- To assess the impact of these treatments on the directed functional connectivity of the primary olfactory cortex (POC) circuit and local brain activation during olfactory stimulation.
- To explore the relationship between treatment-induced changes in neural activity and cognitive/metabolic improvements.
Main Methods:
- A 16-week randomized, parallel-group, open-label trial involving 36 T2D patients inadequately controlled on metformin, randomized to dapagliflozin, liraglutide, or acarbose.
- 36 healthy normal controls were recruited for comparison.
- Olfactory task functional MRI and olfactory/cognitive tests were performed pre- and post-intervention. Generalized psychophysiological interaction analysis was used to determine directed functional connectivity.
Main Results:
- Dapagliflozin treatment restored odor-induced functional integration of the POC-sensorimotor cortex-middle temporal cortex circuit and tended to improve attention.
- Liraglutide enhanced odor-induced activation in the left hippocampus, while dapagliflozin and acarbose did not show these specific effects.
- Decreased odor-induced directed functional connectivity correlated with improvements in lipid levels, olfactory threshold, executive function, and memory.
Conclusions:
- Dapagliflozin and liraglutide exhibit distinct neuroprotective effects in T2D patients.
- Liraglutide appears to influence local olfactory-related region activation, whereas dapagliflozin impacts neural circuit functional integration.
- These findings underscore the significance of targeting both metabolic and neural pathways for managing T2D-related cognitive decline.
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