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. 2023 Apr 6;45(3):1343–1381. doi: 10.1007/s11357-023-00782-w

Table 3.

Type II diabetes mellitus drugs tested in the 3xTg mouse model

Source Starting age Treatment period Age at analysis Treatment effects
Linagliptin
Kosaraju et al., 2017 9–10 months 8 weeks 11–12 months

Improved MWM and Y-maze performance

Decreased p-tau and Aβ

Decreased microglia activation/inflammation

No change in plasma glucose levels

Liraglutide
Chen et al., 2017 7 months 8 weeks 9 months

Improved MWM performance

Decreased neurodegeneration

No change in plasma glucose levels

Exenatide
Bomba et al., 2013 3 months 9 months 12 months

No change in MWM performance

No change in LDH activity or anaerobic glucose catabolism

Pioglitazone
Masciopinto et al., 2012 3 months 9 months 12 months

No change in NOR or MWM performance 

No changes in plasma glucose levels, GTT, or serum insulin levels

Searcy et al., 2012 10 months 14 weeks 14–15 months

Improved avoidance in AASB  

Decreased p-tau and Aβ

Increased synaptic plasticity

Yu et al., 2014 10 months 4 months 14 months

No change in spontaneous exploratory activity, locomotion, or anxiety

Improved MWM performance

Decreased p-tau

Decreased astrocyte levels

Rosiglitazone
Yu et al., 2014 10 months 4 months 14 months

No change in spontaneous exploratory activity, locomotion, or anxiety

No change in MWM performance

Decreased p-tau

Decreased astrocyte levels

GLP-1/GIP/Glucagon triagonist
Li et al., 2018 7 months 1 month 8 months

Improved MWM and Y-maze performance    

Increased Open Field activity

Decreased p-tau and Aβ

Increased synaptic plasticity

No changes in plasma glucose levels

Li et al., 2020 7 months 45 days 8 months

Improved radial arm maze performance  

Increased synaptophysin and PSD-95 in the hippocampus

Regulated altered neuron activity in the hippocampus

Insulin
Chen et al., 2014 9 months 7 days 9 months

Increased levels of synaptic proteins

Decreased microglia activation

Decreased Aβ levels

No change in p-tau levels

Sanguinetti et al., 2019 2 months 6 months 8 months

Improved Y-maze test performance

Normalized cytokine levels

No change in brain mass

Normalized thickness of brain layers

2 months 12 months 14 months

Improved Y-maze test performance

Decreased pro-inflammatory cytokine levels

No change in brain mass

Normalized thickness of brain layers

Vandal et al., 2014 6 months 9 months 15 months

Improved NOR performance

Decreased Aβ levels

LDH, lactate dehydrogenase; GTT, glucose tolerance test; AASB, active avoidance shuttle box