Metformin and risk of age-related macular degeneration in individuals with type 2 diabetes: a retrospective cohort study

Abstract

BackgroundAge-related macular degeneration (AMD) in its late stages is a leading cause of sight loss in developed countries. Some previous studies have suggested that metformin may be associated with a reduced risk of developing AMD, but the evidence is inconclusive.AimsTo explore the relationship between metformin use and development of AMD among patients with type 2 diabetes in the UK.MethodsA large, population-based retrospective open cohort study with a time-dependent exposure design was carried out using IQVIA Medical Research Data, 1995–2019. Patients aged ≥40 with diagnosed type 2 diabetes were included.The exposed group was those prescribed metformin (with or without any other antidiabetic medications); the comparator (unexposed) group was those prescribed other antidiabetic medications only. The exposure status was treated as time varying, collected at 3-monthly time intervals.Extended Cox proportional hazards regression was used to calculate the adjusted HRs for development of the outcome, newly diagnosed AMD.ResultsA total of 173 689 patients, 57% men, mean (SD) age 62.8 (11.6) years, with incident type 2 diabetes and a record of one or more antidiabetic medications were included in the study. Median follow-up was 4.8 (IQR 2.3–8.3, range 0.5–23.8) years. 3111 (1.8%) patients developed AMD. The adjusted HR for diagnosis of AMD was 1.02 (95% CI 0.92 to 1.12) in patients prescribed metformin (with or without other antidiabetic medications) compared with those prescribed any other antidiabetic medication only.ConclusionWe found no evidence that metformin was associated with risk of AMD in primary care patients requiring treatment for type 2 diabetes.

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

“… 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. 20 Four studies exclusively enrolled patients with type 2 DM, 14 , 16 , 17 , 20 whereas 5 studies also recruited patients with type 1 DM.…”

Influence of metformin on age-related macular degeneration

“…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.…”

“…The retrospective design, the small sample size, and the missing data on some important confounders are the limitations of this study. Gokhale et al performed a further cohort study investigating the influence of metformin on the risk of AMD in patients with type 2 diabetes [42]. The group identified 173,689 patients with newly diagnosed type 2 diabetes from the United Kingdom IQVIA Medical Research Data.…”

“…Limitations of this study include the retrospective design, and the missing differentiation between AMD stages (early, late) that could for example mask findings if metformin was only protective for certain AMD stages [42].…”

“…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].…”