Association between metformin use and the risk of age-related macular degeneration in patients with type 2 diabetes: a retrospective study

Abstract

ObjectivesTo investigate the effect of metformin on the decreased risk of developing age-related macular degeneration (AMD) in patients with type 2 diabetes mellitus (T2DM) for ≥10 years.DesignA retrospective study.ParticipantsPatients aged ≥50 with a diagnosis of T2DM no less than 10 years were included.MethodsVariables predisposing to AMD were reviewed; the potential confounders related to T2DM or AMD were selected from literature records; AMD and diabetic retinopathy (DR) were diagnosed by funduscopy, optical coherence tomography and/or fluorescein angiography. The subgroup analysis was performed in early and late AMD. The protective effect of metformin was evaluated in duration-response and dose-response patterns.ResultsA total of 324 patients (115 metformin non-users and 209 users) were included in the final analysis. AMD was observed in 15.8% of metformin users and 45.2% of metformin non-users (p<0.0001). The ORs for any AMD, early AMD and late AMD present in patients with DR were 0.06 (0.02–0.20), 0.03 (0.00–0.20) and 0.17 (0.04–0.75). The serum high-density lipoprotein level was positively associated with the late AMD risk (p=0.0054). When analysed by the tertiles of cumulative duration, a similarly reduced risk was observed for the second (5–9 years) (OR: 0.24, 95% CI: 0.08 to 0.75) and third tertiles (≥10 years) (OR: 0.22, 95% CI: 0.09 to 0.52) compared with the first tertile (≤4 years).ConclusionAmong patients with T2DM for ≥10 years, metformin users were less likely to develop any AMD and early AMD than non-users; however, the late AMD was not significantly associated with the use of metformin. Also, AMD was less prevalent in patients with DR. The prolonged metformin treatment with a high cumulative dose enhanced the protective effect against AMD. Metformin significantly reduces the AMD risk when the cumulative duration is >5 years.

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

“…The included studies consisted of one cross-sectional, 19 three case‒control, 12 , 13 , 18 and five cohort studies. 14 – 17 , 20 Eight studies were retrospective in design, 12 – 19 and one was conducted prospectively. 20 Four studies were performed in the United States, 12 , 13 , 15 , 19 three in Asia, 14 , 17 , 18 and the other two in Europe.…”

“… 14 – 17 , 20 Eight studies were retrospective in design, 12 – 19 and one was conducted prospectively. 20 Four studies were performed in the United States, 12 , 13 , 15 , 19 three in Asia, 14 , 17 , 18 and the other two in Europe. 16 , 20 Seven studies obtained a diagnosis of DM with International Classification of Diseases (ICD) codes, 12 – 15 , 17 – 19 one with database read codes, 16 and one with medical records.…”

Influence of metformin on age-related macular degeneration

“…Additionally, prospective trials should not only concentrate on late-stage dry AMD but consider all AMD stages. Jiang et al [41] found for example, that especially the early stage of AMD was associated with a beneficial effect of metformin. Finally, prospective trials should consider patients with and without a diagnosis of diabetes to rule out possible confounding effects of the diabetic disease.…”

“…Eight retrospective studies have analyzed the association of metformin use with AMD, of which one was a crosssectional study [39], four were cohort studies [40][41][42][43], two were case-control studies [44,45], and one was a nested case-control study [46]. Five studies exclusively determined the association between metformin use and the risk of developing AMD in diabetic patients [39][40][41][42][43], whereas three studies included broader patient groups according to their cohort definition [44][45][46]. One study examined the association of metformin use with dry AMD only [43], while the remaining studies considered all forms of AMD or did not further specify.…”

“…In summary, five out of eight retrospective studies found associations of metformin with decreased odds of developing AMD [39-41, 44, 45], one study found conflicting associations [43], and two studies report no association of metformin use with the development of AMD [42,46]. Three studies found positive associations with either the duration of metformin use or dose-dependent effects [40,41,44], while one study did not detect an association with longer metformin use [46]. In addition, a meta-analysis by Romdhoniyyah et al over five of the above-reported retrospective trials did not find a significant association between metformin use and the risk to develop AMD [3].…”