Metformin as a Neuroprotective Therapy for Glaucoma - A Randomized Controlled Trial
Status:
Not yet recruiting
Trial end date:
2025-12-31
Target enrollment:
Participant gender:
Summary
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. We aim to investigate whether metformin can be
repurposed to a neuroprotective therapy for glaucoma patients in a randomized controlled
trial.
We propose to conduct a 24-month, double-blind, placebo-controlled, parallel group, multi-
center trial, randomizing 240 primary open angle glaucoma patients who have progressive
retinal nerve fiber layer ganglion cell inner plexiform layer (RNFL-GCIPL) thinning in at
least one eye, as determined by wide-field optical coherence tomography Trend-based
Progression Analysis, to receive metformin 1500mg/day or placebo. All patients will be
followed up at 2- month intervals for IOP, RNFL-GCIPL thickness, and visual field (VF)
measurements. The objectives are to compare (1) the rates of change of average RNFL-GCIPL
thickness (primary outcome measure), and (2) the rates of change of VF mean deviation (MD)
(secondary outcome measure) between treatment groups. We hypothesize that patients treated
with metformin have a slower rate of RNFL-GCIPL 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.