NCT05426044

Metformin as a Neuroprotective Therapy for Glaucoma

Recruiting now Phase 2 Last updated 20 November 2025

What this trial tests

Phase 2 trial testing Metformin in Glaucoma in 125 participants. Currently enrolling.

Timeline

1 June 2025

Primary endpoint
31 December 2027

31 December 2027

Quick facts

Lead sponsor	Christopher Kai Shun Leung
Phase	Phase 2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	125
Start date	1 June 2025
Primary completion	31 December 2027
Estimated completion	31 December 2027
Sites	1 location across Hong Kong

Drugs / interventions tested

• Metformin (metformin) — full drug profile →
• Placebo

Conditions studied

• Glaucoma — all drugs for Glaucoma →

Sponsor

Christopher Kai Shun Leung

Who can join

18 and older, any sex, with Glaucoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Glaucoma, a chronic degenerative disease of the optic nerve, is the leading cause of irreversible blindness worldwide. Although lowering the intraocular pressure (IOP) has been shown to be effective to slow optic nerve degeneration, a significant portion of glaucoma patients continue to develop progressive loss in vision despite adequate control of IOP. Development of neuroprotective therapy to prevent optic nerve degeneration by mechanisms other than IOP- lowering is critical to reduce the burden of glaucoma blindness. With 76 million glaucoma patients in 2020 worldwide, the need to investigate neuroprotection for glaucoma is pressing. While metformin is a widely adopted oral hypoglycemic medication for treatment of type 2 diabetes mellitus (DM), increasing evidence from clinical studies has shown that metformin can decrease the risk of many age-related diseases including neurodegenerative diseases. In a retrospective study of 150,016 patients with DM, those taking metformin at \>1500mg/day had a 25% reduced risk of development of open-angle glaucoma than those who took no metformin. Metformin has a high safety profile. The investigators aim to investigate whether metformin can be repurposed to a neuroprotective therapy for glaucoma patients in a randomized controlled trial.

The investigators propose to conduct a 24-month, double-blind, placebo-controlled, parallel group, randomizing 125 primary open angle glaucoma patients who have progressive retinal nerve fiber layer (RNFL) and/or ganglion cell inner plexiform layer (GCIPL) thinning in at least one eye, as determined by optical coherence tomography Trend-based Progression Analysis (TPA) or Guided Progression Analysis (GPA), to receive metformin 1500mg/day or placebo. All patients will be followed up at 2-month intervals for IOP, RNFL thickness, and visual field (VF) measurements. The objectives are to compare (1) the rates of change of average RNFL thickness (primary outcome measure), and (2) the rates of change of VF mean deviation (MD) (secondary outcome measure) between treatment groups. The investigators hypothesize that patients treated with metformin have a slower rate of RNFL thinning, and a slower rate of VF MD decline compared with those treated with placebo at similar levels of IOP over the 24-month follow-up. The proposed study has the potential to mark a paradigm shift in the management of glaucoma patients by demonstrating that neuroprotection is attainable with metformin, which will alleviate the increasing burden of glaucoma blindness in China and other Asian countries where glaucoma patients with normal levels of IOP are prevalent. Furthermore, it will inform and impact the study design in future neuroprotection trials which can expedite the development of neuroprotective therapy for glaucoma.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Association of Metformin and Other Diabetes Medication Use and the Development of New-Onset Dry Age-Related Macular Degeneration: A Case-Control Study.
   Kaufmann GT, Hyman MJ, Gonnah R, Hariprasad S, et al · · 2023 · cited 10× · PMID 37589984 · DOI 10.1167/iovs.64.11.22
2. Pharmaceutical Agents for Targeting Autophagy and Their Applications in Clinics.
   Kench U, Sologova S, Smolyarchuk E, Prassolov V, et al · · 2024 · cited 6× · PMID 39458996 · DOI 10.3390/ph17101355