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JAMA Ophthalmol. 2015 Aug;133(8):915-23. doi: 10.1001/jamaophthalmol.2015.1440.

Association of Geroprotective Effects of Metformin and Risk of Open-Angle Glaucoma in Persons With Diabetes Mellitus.

Author information

1
Department of Applied Health Science, Indiana University, Bloomington.
2
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor3Institute for Health Care Policy and Innovation, University of Michigan, Ann Arbor.
3
Department of Biostatistics, University of Michigan, Ann Arbor.
4
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor5Center for Statistical Consultation and Research, University of Michigan, Ann Arbor.
5
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor6Department of Biological Chemistry, University of Michigan, Ann Arbor.
6
Department of Epidemiology, University of Michigan, Ann Arbor.

Abstract

IMPORTANCE:

Caloric restriction mimetic drugs have geroprotective effects that delay or reduce risks for a variety of age-associated systemic diseases, suggesting that such drugs might also have the potential to reduce risks of blinding ophthalmologic conditions for which age is a major risk factor.

OBJECTIVE:

To determine whether the caloric restriction mimetic drug metformin hydrochloride is associated with reduced risk of open-angle glaucoma (OAG) in persons with diabetes mellitus.

DESIGN, SETTING, AND PATIENTS:

Retrospective cohort study of patients aged 40 years or older with diabetes mellitus and no preexisting record of OAG in a large US managed care network from January 1, 2001, through December 31, 2010.

EXPOSURES:

Quantity of metformin and other prescribed diabetes medications as captured from outpatient pharmacy records.

MAIN OUTCOMES AND MEASURES:

Risk of developing OAG.

RESULTS:

Of 150 016 patients with diabetes mellitus, 5893 (3.9%) developed OAG. After adjusting for confounding factors, those prescribed the highest quartile of metformin hydrochloride (>1110 g in 2 years) had a 25% reduced OAG risk relative to those who took no metformin (hazard ratio = 0.75; 95% CI, 0.59-0.95; P = .02). Every 1-g increase in metformin hydrochloride use was associated with a 0.16% reduction in OAG risk (adjusted hazard ratio = 0.99984; 95% CI, 0.99969-0.99999; P = .04), which predicts that taking a standard dose of 2 g of metformin hydrochloride per day for 2 years would result in a 20.8% reduction in risk of OAG. After accounting for potential confounders, including metformin and diabetic medications, the risk of developing OAG was increased by 8% (hazard ratio = 1.08; 95% CI, 1.03-1.13; P = .003) for each unit of increase in glycated hemoglobin level.

CONCLUSIONS AND RELEVANCE:

Metformin use is associated with reduction in risk of developing OAG, and risk is reduced even when accounting for glycemic control in the form of glycated hemoglobin level. Other diabetes medications did not confer a similar OAG risk reduction. This study suggests that metformin may be affecting OAG risk on multiple levels, some involving improved glycemic control and some involving mechanisms outside glycemic control such as neurogenesis, inflammatory systems, or longevity pathways targeted by caloric restriction mimetic drugs. If confirmed by prospective clinical trials, these findings could lead to novel treatments for this sight-threatening disease.

PMID:
26022641
PMCID:
PMC4537372
DOI:
10.1001/jamaophthalmol.2015.1440
[Indexed for MEDLINE]
Free PMC Article

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