Table 3.

Clinical Trials of GLP-1 Receptor Agonists in AD and PD

Disease	Drug	Treatment	Duration	Results and/or Effects	Reference
AD	Liraglutide	Increased from 0.6 mg/day to 1.8 mg/day.	26 weeks	Prevented the expected decline of cerebral Glucose Metabolism (CMRglc); No differences with respect to amyloid deposition or cognition	[222]
	Liraglutide	Increased from 0.6 mg/day to 1.8 mg/day	26 weeks	Restored blood-brain glucose transfer capacity (T max)	[223]
	Exenatide	Increased from 10 mcg/day to 20 mcg/day	18-month	No differences or trends compared to placebo for clinical and cognitive measures, MRI cortical thickness and volume, or biomarkers in cerebrospinal fluid, plasma, and plasma neuronal extracellular vesicles (EV) except for a reduction of Aβ42 in EVs	[194]
	Liraglutide	Increased from 0.6 mg/day to 1.8 mg/day	12 weeks	There were no cognitive differences	[195]
PD	Exenatide	5–10 µg twice daily	12 months	Mean improvement at 12 months on the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) of 2.7 points	[224]
	Exenatide	5–10 µg twice daily	Exenatide treatment for 12 months followed by 12 months of cessation (24 months)	Had an advantage of 5.6 points (95% CI, 2.2–9.0; p = 0.002) using blinded video rating of the MDS-UPDRS part 3 motor subscale, and an advantage of 5.3 points (95% CI, 9.3–1.4; p = 0.006) on the Mattis Dementia Rating scale	[225]
	Exenatide	2 mg once weekly	48 weeks followed by a 12-week washout period	Off-medication scores on part 3 of the MDS-UPDRS had improved by 1.0 points (95% CI −2.6 to 0.7)	[226]
	Exenatide	2mg once-weekly	48 weeks followed by a 12-week washout period	Have benefits in individual non-motor symptoms subdomains assessing mood dysfunction/depression	[227]
	Exenatide	2 mg once weekly	48 weeks followed by a 12-week washout period	Augmented tyrosine phosphorylation of insulin receptor substrate 1 at 48 weeks and 60 weeks; Elevated expression of downstream substrates, including total protein kinase B and phosphorylated mechanistic target of rapamycin (mTOR). Improvements in MDS-UPDRS part 3 off-medication scores were associated with levels of total mTOR and phosphorylated mTOR	[228]
	Exenatide	2 mg once weekly	48 weeks followed by a 12-week washout period	Tremor-dominant phenotype and lower MDS-UPDRS Part-2 scores predicted greatest motor response to exenatide. Patients with older age of onset and disease duration over 10 years responded less well	[229]