Association Between Oral Metformin Use and the Development of Age-Related Macular Degeneration in Diabetic Patients: A Systematic Review and Meta-Analysis

Abstract

Purpose Metformin is a biguanide derivative that is commonly used for the treatment of diabetes mellitus (DM). It demonstrates antioxidative, anti-inflammatory, and antiangiogenic activity within the ocular tissue and thus may be implicated in the treatment of age-related macular degeneration (AMD). However, epidemiological studies have shown conflicting results. Methods The Ovid MEDLINE/Embase, Cochrane Library, and Web of Science databases were systematically searched from inception through August 3, 2022. Studies reporting the association between metformin use and odds of AMD were enrolled. Adjusted odds ratios (ORs) of AMD were extracted and pooled with random-effects model meta-analysis. Subgroup analyses based on AMD subtypes, ethnicity, study design, sex, and confirmation of AMD diagnosis were conducted. Results A total of 9 observational studies with 1,446,284 participants were included in the analysis. The meta-analysis showed that metformin use was associated with a significant reduction in the odds of AMD (pooled ORs = 0.81, 95% confidence interval [CI] = 0.70–0.93). Subgroup analyses revealed that metformin use was not significantly associated with dry or wet AMD. Black (pooled ORs = 0.61, 95% CI = 0.58–0.64) and Hispanic populations (pooled ORs = 0.85, 95% CI = 0.81–0.89) demonstrated significantly lower odds of AMD. Conclusions This systematic review and meta-analysis found that patients with DM with metformin usage were at lower odds of developing AMD. Future prospective clinical trials are needed to confirm this association.

Shedding light on eye disease in obesity: A review

“…Laser photocoagulation can be used to treat fovea‐sparing CNV but may fail to adequately cover the entire lesion. In the setting of obesity, use of metformin for off‐label weight loss therapy and improved glycaemic control may prove particularly beneficial as several studies have associated metformin use with decreased odds of developing AMD (OR 0.81, 95% CI 0.70–0.93) 32 . Statin use has also been hypothesized to slow progression of AMD; however, recent large‐scale studies examining the relationship between statin use and AMD onset and progression have failed to generate reliable evidence to support this hypothesis 33 …”

Association of Metformin With the Development of Age-Related Macular Degeneration in the Diabetes Prevention Program Outcomes Study

“…We do have some questions regarding the results of this well-designed follow-up that led to some conclusions that were contrary to previous studies, suggesting that metformin may be useful as a preventive therapy for AMD . One limitation of this investigation was that the participants did not undergo a previous ophthalmological study.…”

Метформін — Препарат Першої Лінії Антигіперглікемічної Терапії: Від Механізмів Дії До Рекомендацій NICE

“…Відсутність негативного впливу метформіну на стан кісткової тканини та його здатність вірогідно знижувати ризик виникнення переломів (відносний ризик 0,91; 95% Ді 0,81-1,02) [16] дозволяє призначати метформін хворим із супутньою патологією опорно-рухового апарату та остеоартритом [17]. Зниження вірогідності виникнення вікової макулодегенерації (сукупне відношення шансів 0,81; 95% Ді 0,70-0,93) на тлі прийому метформіну у хворих на ЦД [18] підкреслює офтальмопротекторні властивості препарату. Завдяки хорошому профілю безпеки, мінімальної вірогідності виникнення гіпоглікемії метформін застосовують для лікування переддіабету [9], гестаційного діабету та синдрому полікістозних яєчників, при цьому особливо цінується його властивість знижувати вірогідність передчасних пологів [19].…”