D-Glucose

證據等級: L5

預測適應症: 10 個

D-glucose: From Acute Hypoglycemia Management to Open-Angle Glaucoma

One-Sentence Summary

D-glucose (dextrose; DrugBank DB01914) is the body's principal energy substrate, administered clinically as intravenous dextrose for acute hypoglycaemia rescue and as a component of parenteral nutritional support. While non-syndromic esophageal malformation ranks first by TxGNN score (84.11%), the most evidence-supported prediction across all 10 candidates is Open-Angle Glaucoma (OAG) (rank 3, score 83.03%), underpinned by a bioenergetic neuroprotection hypothesis and validated by 1 double-blind randomised controlled trial alongside 20 publications.

Quick Overview

Item	Content
Original Indication	Acute hypoglycaemia; parenteral nutritional support (no formal Singapore registration)
Predicted New Indication	Open-Angle Glaucoma (highest-evidence prediction; TxGNN rank 3 of 10)
TxGNN Prediction Score	83.03%
Evidence Level	L2
Singapore Market Status	Not Marketed
Number of Registrations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

D-glucose is the principal energy substrate of mammalian cells, driving ATP synthesis via glycolysis and oxidative phosphorylation. While its recognised clinical application focuses on reversing hypoglycaemia, its role as the primary cellular fuel creates direct mechanistic relevance in tissues with exceptionally high metabolic demands.

Retinal ganglion cells (RGCs) rank among the most energetically demanding neurons in the central nervous system. In primary open-angle glaucoma (POAG), progressive RGC death and optic nerve degeneration are associated with mitochondrial dysfunction and energy failure at the optic nerve head. A 2008 review (PMID 18700928) formally proposed the "bioenergetic neuroprotection" hypothesis: that restoring adequate glucose supply to RGCs could rescue cellular function independent of intraocular pressure (IOP) reduction — currently the only proven treatment strategy for OAG. This is particularly significant because a substantial proportion of POAG patients continue losing vision despite well-controlled IOP, implying that additional non-pressure mechanisms, including metabolic failure, drive disease progression.

This hypothesis was directly tested by Casson et al. (PMID 24491639, Ophthalmology 2014), a double-blind, randomised study demonstrating that topical glucose application produced temporary, measurable improvement in visual contrast sensitivity in POAG patients. Complementing this, multiple Mendelian randomisation studies (PMIDs 35622353, 36162535, 38672220) and population-based cohorts (PMID 32966328) have established associations between systemic glucose metabolism indices and POAG risk, confirming that the glucose–energy axis is a biologically plausible and testable therapeutic target in glaucoma.

Clinical Trial Evidence

No registered clinical trials directly testing D-glucose as a therapeutic intervention for open-angle glaucoma have been identified. The trials below represent the most mechanistically relevant context in the OAG evidence landscape:

Trial Number	Phase	Status	Enrollment	Key Findings
NCT04118920	Phase 1	Active, not recruiting	18	Topical insulin eye drops for OAG safety — insulin promotes RGC glucose uptake via GLUT receptors, providing indirect mechanistic support for glucose-based neuroprotection; most directly relevant trial in this analysis
NCT05405868	Phase 3	Recruiting	496	Nicotinamide (NAM) to slow visual field loss in OAG — validates the broader metabolic/bioenergetic neuroprotection concept as a treatment approach
NCT03870230	Observational	Recruiting	120	Neurovascular coupling in glaucoma — investigates IOP-independent mechanisms including RGC energy supply and optic nerve head metabolism
NCT04645992	Observational	Unknown	80	Yoga + TENS in diabetic glaucoma — blood glucose measured as a secondary endpoint, confirming research interest in the glucose–IOP interaction
NCT07290244	Phase 1	Recruiting	18	ER-100 single-dose safety study in OAG and NAION — drug composition not publicly disclosed; included for background context only

Literature Evidence

PMID	Year	Type	Journal	Key Findings
24491639	2014	RCT (double-blind)	Ophthalmology	Core evidence: Topical glucose produced temporary improvement in visual contrast sensitivity in POAG patients — proof-of-concept for glucose-induced visual recovery
18700928	2008	Review	Clin Exp Ophthalmology	Bioenergetic neuroprotection hypothesis — energy failure at the optic nerve head as an IOP-independent POAG mechanism; proposes glucose supply restoration as a therapeutic strategy
35622353	2022	Meta-analysis	Invest Ophthalmol Vis Sci	Mendelian randomisation: causal associations between fasting glucose, HbA1c, and POAG risk evaluated across European and East Asian populations
36162535	2023	Mendelian Randomisation	Am J Ophthalmology	Causal association between genetically predicted glycaemic traits and POAG risk confirmed in the Japanese population
32966328	2020	Population-based Cohort	PloS One	Nationwide Korean cohort: fasting plasma glucose level independently and positively associated with OAG incidence
25283061	2015	Meta-analysis	Ophthalmology	Systematic review summarising the association of diabetes and blood glucose levels with glaucoma, IOP, and ocular hypertension
40263428	2025	Mendelian Randomisation	Scientific Reports	Drug-targeted MR: evaluated whether SGLT2 inhibition (which alters glucose homeostasis) has a causal effect on POAG risk
38672220	2024	Mendelian Randomisation	Biomedicines	Two-sample MR: causal relationship between T2D, fasting glucose, HbA1c and POAG in multi-ethnic populations
34303323	2022	RCT (yoga intervention)	J Complement Integr Med	Yoga concurrently reduced IOP and fasting blood glucose in T2DM patients with high-tension POAG
9111268	1997	Cohort	Ophthalmology	Blue Mountains Eye Study (Australia): foundational epidemiological evidence on the relationship between diabetes and OAG in older populations

Singapore Market Information

D-glucose has no standalone pharmaceutical product registered in Singapore. There are no product authorisations on record (total licences: 0).

Note: Dextrose infusion solutions are available as hospital formulary items but are typically not individually licensed under named drug authorisations for specific indications within the Health Sciences Authority (HSA) product database.

Safety Considerations

As a physiological molecule used clinically for decades, the primary safety considerations for a potential new ophthalmic indication are:

Hyperglycaemia risk: Any route that elevates systemic glucose requires glycaemic monitoring, particularly relevant given that diabetic patients represent a substantial OAG subgroup; inadvertent hyperglycaemia may exacerbate retinal vascular complications in this population
Topical ophthalmic use: The RCT evidence (PMID 24491639) used topical glucose; safety data for chronic topical ocular glucose application — including osmotic effects on the corneal epithelium, microbiological risk, and preservative requirements — have not been formally characterised

Please refer to product-specific prescribing information for the intended formulation for complete safety guidance.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: A double-blind RCT (PMID 24491639, Ophthalmology 2014) provided direct proof-of-concept that topical glucose produces temporary visual improvement in POAG patients, supported by a biologically coherent bioenergetic neuroprotection framework. However, the evidence base currently rests on a single small study with a temporary functional endpoint, and no registered clinical trials are actively testing D-glucose as an OAG therapeutic.

To proceed, the following is needed:

A formal Phase 2 randomised controlled trial to confirm and extend PMID 24491639 findings, incorporating structural endpoints (OCT retinal nerve fibre layer thickness, visual field progression rate) in addition to contrast sensitivity
Optimisation of formulation, route (topical vs. oral vs. IV), and dosing regimen for sustained RGC bioenergetic support
Safety characterisation of chronic topical glucose ophthalmic use, including corneal epithelial integrity, osmotic effects, and sterility requirements
Investigation of whether temporary functional improvement (contrast sensitivity) translates to durable disease modification — specifically, slowing of structural visual field loss
Glycaemic safety assessment in the target population, many of whom have concurrent diabetes or impaired glucose tolerance
Singapore HSA regulatory pathway consultation for pursuing a novel ophthalmic neuroprotection indication
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.