DRUG

metformin

Type 2 diabetes (FDA 1995)

38 hypotheses across 9 therapeutic domains

CROSS-DOMAIN PATTERN

Same drug, multiple disease domains

metformin appears in hypotheses across 9 disease domains: ALS, Alzheimer, Depression, Epilepsy, Glioblastoma, Inflammatory bowel disease, Multiple sclerosis, Pancreatic cancer, Type 2 diabetes. Shared mediators that recur across at least two of those domains: AMPK, α-synuclein, IL-17, Stat3, Hsp70.

Aggregated from the catalog. Biological interpretation of any multi-indication mechanism would require independent validation — this is a structural observation only.

ALL HYPOTHESES

Repurposing candidates for metformin

ALS 5

Mediator	Outcome	Score	Tier	Lit. status	Trial
AMPK	amyotrophic lateral sclerosis	0.449	High	reproduces known	active
α-synuclein	multiple system atrophy	0.269	Mid	novel signal	none
α-synuclein	neurodegenerative diseases	0.269	Mid	reproduces known	active
caspase-3	neuronal apoptosis	0.208	Mid	reproduces known	none
nitric oxide	sporadic amyotrophic lateral sclerosis	0.208	Mid	novel signal	none

Alzheimer 6

Mediator	Outcome	Score	Tier	Lit. status	Trial
α-synuclein	Parkinson's disease	0.416	High	reproduces known	active
Caspase-3	dendritic spine loss	0.208	Mid	novel signal	none
α-synuclein	cognitive symptom onset	0.208	Mid	novel signal	none
α-synuclein	clinical impairment exceeding biological stage	0.208	Mid	novel signal	none
α-synuclein	progression from MCI to AD	0.208	Mid	novel signal	none
mTORC1	early endosomal enlargement	0.208	Mid	novel signal	none

Depression 1

Mediator	Outcome	Score	Tier	Lit. status	Trial
α-synuclein	major depressive disorder	0.208	Mid	reproduces known	completed

Epilepsy 5

Mediator	Outcome	Score	Tier	Lit. status	Trial
AMPK	epileptiform network activity	0.449	High	partial evidence	none
IL-17	suspected autoimmune epilepsy	0.269	Mid	novel signal	none
IL-17	idiopathic epilepsy	0.269	Mid	novel signal	none
Stat3	seizure frequency	0.208	Mid	partial evidence	none
Stat3	seizure progression	0.208	Mid	novel signal	none

Glioblastoma 6

Mediator	Outcome	Score	Tier	Lit. status	Trial
mTOR	glioblastoma	0.312	High	reproduces known	active
Hsp70	necrosis	0.208	Mid	reproduces known	active
mTORC1 signaling	therapy resistance	0.208	Mid	reproduces known	completed
Stat3	GBM progression	0.208	Mid	partial evidence	none
Hsp70	GBM	0.208	Mid	reproduces known	active
DR5	apoptosis	0.208	Mid	reproduces known	none

Inflammatory bowel disease 4

Mediator	Outcome	Score	Tier	Lit. status	Trial
AMPK	intestinal inflammation	0.449	High	reproduces known	completed
AMPK	intestinal epithelial repair	0.449	High	partial evidence	none
c-myc	IBD-associated intestinal adenocarcinoma	0.208	Mid	novel signal	none
Per2	intestinal inflammation	0.208	Mid	reproduces known	completed

Multiple sclerosis 5

Mediator	Outcome	Score	Tier	Lit. status	Trial
IL-17	new enhancing MRI lesions	0.269	Mid	novel signal	none
IL-17	social-cognitive functioning	0.269	Mid	novel signal	none
IL-17	disease activity	0.269	Mid	reproduces known	completed
IL-17	cGVHD severity	0.269	Mid	novel signal	none
IL-17	MS relapse	0.269	Mid	novel signal	completed

Pancreatic cancer 5

Mediator	Outcome	Score	Tier	Lit. status	Trial
AMPK	pancreatic cancer progression	0.449	High	partial evidence	active
c-Myc	DNA damage	0.208	Mid	reproduces known	none
c-Myc	gemcitabine resistance	0.208	Mid	partial evidence	none
GSK-3β	PanIN progression	0.208	Mid	novel signal	none
Hsp70	pancreatic cancer growth	0.208	Mid	partial evidence	completed

Type 2 diabetes 1

Mediator	Outcome	Score	Tier	Lit. status	Trial
AMPK pathway	memory dysfunction	0.269	Mid	reproduces known	active

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