Dataset Information

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

ABSTRACT:

Objectives

To 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.

Design

A retrospective study.

Participants

Patients aged ≥50 with a diagnosis of T2DM no less than 10 years were included.

Methods

Variables 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.

Results

A 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).

Conclusion

Among 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.

SUBMITTER: Jiang J

PROVIDER: S-EPMC9045056 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Jiang Jingjing J Chen Yi Y Zhang Hongsong H Yuan Wei W Zhao Tong T Wang Na N Fan Guohui G Zheng Dongxing D Wang Zhijun Z

BMJ open 20220426 4

<h4>Objectives</h4>To 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.<h4>Design</h4>A retrospective study.<h4>Participants</h4>Patients aged ≥50 with a diagnosis of T2DM no less than 10 years were included.<h4>Methods</h4>Variables predisposing to AMD were reviewed; the potential confounders related to T2DM or AMD were selected from literature records; AMD and diabetic r ...[more]

PMID: 35473747

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Project description:ImportanceMetformin use may protect against the development of age-related macular degeneration (AMD) based on results from observational studies. However, its potential effectiveness among patients without diabetes remains unclear.ObjectiveTo assess the association between metformin use and the development of AMD in patients without diabetes.Design, setting, and participantsThis case-control study used data from 2006 to 2017 in the Merative MarketScan Research Database, a nationwide insurance claims database that includes between 27 and 57 million patients in the US with primary or Medicare supplemental health insurance. Cases with AMD and controls without AMD aged 55 years or older were matched 1:1 by year, age, anemia, hypertension, region, and Charlson Comorbidity Index score. Then, cases and matched controls without a diagnosis of diabetes were selected. In subgroup analyses, cases with dry AMD and their matched controls were identified to explore the association between metformin use and AMD staging in patients without diabetes. Data were analyzed between March and September 2023.ExposuresExposure to metformin in the 2 years prior to the index date (ie, date of AMD diagnosis in cases and date of a randomly selected eye examination for controls) was assessed from the claims database and categorized into quartiles based on cumulative dose (1-270, 271-600, 601-1080, and >1080 g/2 y). Exposure to other antidiabetic medications was also noted.Main outcomes and measuresOdds of new-onset AMD development as assessed by multivariable conditional logistic regression after adjusting for known risk factors for AMD, including female sex, hyperlipidemia, smoking, and exposures to other antidiabetic medications. Asymptotic Cochran-Armitage tests for trend were also performed.ResultsWe identified 231 142 patients with any AMD (mean [SD] age, 75.1 [10.4] years; 140 172 females [60.6%]) and 232 879 matched controls without AMD (mean [SD] age, 74.9 [10.5] years; 133 670 females [57.4%]), none of whom had a diagnosis of diabetes. The sample included 144 147 cases with dry AMD that were matched to 144 530 controls. In all, 2268 (1.0%) cases and 3087 controls (1.3%) were exposed to metformin in the 2 years before their index visit. After data adjustment, exposure to any metformin was associated with reduced odds of any AMD development (adjusted odds ratio [AOR], 0.83; 95% CI, 0.74-0.87), specifically in the dosing quartiles of 1 to 270, 271 to 600, and 601 to 1080 g/2 y. Any metformin use was also associated with a reduced odds of developing dry AMD (AOR, 0.85; 95% CI, 0.79-0.92), specifically in the dosing quartiles of 1 to 270 and 271 to 600 g/2 y. Adjusted odds ratios for any AMD and dry AMD development did not differ across the dosing quartiles. Asymptotic Cochran-Armitage tests for trend revealed 2-sided P = .51 and P = .66 for the any and dry AMD samples, respectively.Conclusions and relevanceIn this case-control study of a population without a diagnosis of diabetes, metformin use was associated with reduced odds of developing AMD. This association does not appear to be dose dependent. These findings provide further impetus to study metformin's usefulness in protecting against AMD in prospective clinical trials.

Project description:BackgroundWhether metformin may reduce the risk of age-related macular degeneration (AMD) requires confirmation. This study compared the risk of AMD between ever users and never users of metformin matched on propensity score (PS) in Taiwanese patients with type 2 diabetes mellitus.MethodsWe enrolled study subjects from Taiwan's National Health Insurance. A total of 423,949 patients with new onset diabetes from 1999 to 2005 were identified. After excluding ineligible patients and enrolling only patients aged between 50 and 79 years, we created 13,303 pairs of ever users and never users of metformin matched on PS. The patients were followed from 1 January 2006 to 31 December 2011. We estimated hazard ratios by Cox regression.ResultsAMD was newly diagnosed in 506 ever users and 639 never users. The respective incidence rates (per 100,000 person-years) were 778.72 and 1016.62. The hazard ratio (HR) and 95% confidence interval (CI) for ever versus never users was 0.756 (0.673-0.850). While ever users were categorized by tertiles of cumulative duration (<31.8, 31.8-63.9 and >63.9 months) and cumulative dose (<947.1, 947.1-2193.5 and >2193.5 g) of metformin, a dose-response pattern was observed. For the respective tertiles of cumulative duration, the HRs (95% CIs) were 1.131 (0.961-1.330), 0.821 (0.697-0.967) and 0.464 (0.384-0.561), while compared to never users. For the respective tertiles of cumulative dose, the HRs (95% CIs) were 1.131 (0.962-1.329), 0.739 (0.624-0.876) and 0.525 (0.438-0.629). A risk reduction among ever users was observed for all tertiles of defined daily dose but was most remarkable for the third tertile with a defined daily dose of >0.64. Subgroup analyses suggested that the benefit of metformin could be similarly observed among men and women and for age subgroups of 50-64 and 65-79 years. However, patients with diabetic retinopathy would not be significantly benefited and metformin did not seem to be preventive for exudative AMD.ConclusionIn general, metformin significantly reduces the risk of AMD.

Project description:ImportanceAge-related macular degeneration (AMD), the leading cause of irreversible blindness in older adults, appears to have no effective preventive measures. The common antidiabetic drug metformin has been shown to have protective outcomes in multiple age-associated diseases and may have the potential to protect against the development of AMD.ObjectiveTo determine whether metformin use is associated with reduced odds of developing AMD.Design, setting, and participantsThis case-control study of patients from a nationwide health insurance claims database included a population-based sample of patients. Those aged 55 years and older with newly diagnosed AMD from January 2008 to December 2017 were defined as cases and matched with control participants. Data analyses were completed from June 2019 to February 2020.ExposuresDosage of metformin and exposure to other prescribed medications, as identified from outpatient drug claims.Main outcomes and measuresRisk of developing AMD.ResultsA total of 312 404 affected individuals were included (181 817 women [58.2%]). After matching, 312 376 control participants were included (172 459 women [55.2%]; age range, 55 to 107 years). The case group had a slightly higher percentage of participants with diabetes (81 262 participants [26.0%]) compared with the control group (79 497 participants [25.5%]). Metformin use was associated with reduced odds of developing AMD (odds ratio [OR], 0.94 [95% CI, 0.92-0.96]). This association was dose dependent, with low to moderate doses of metformin showing the greatest potential benefit (dosages over 2 years: 1-270 g, OR, 0.91 [95% CI, 0.88-0.94]; 271-600 g, OR, 0.90 [95% CI, 0.87-0.93]; 601-1080 g, OR, 0.95 [95% CI, 0.92-0.98]). Doses of more than 1080 g of metformin over 2 years did not have reduced odds of developing AMD. Both the reduction in odds ratio and the dose-dependent response were preserved in a cohort consisting only of patients with diabetes. Metformin use was associated with a decreased OR of AMD in patients with diabetes without coexisting diabetic retinopathy (OR, 0.93 [95% CI, 0.91-0.95]) but was a risk factor in patients with diabetic retinopathy (OR, 1.07 [95% CI, 1.01-1.15]).Conclusion and relevanceIn this study, metformin use was associated with reduced odds of developing AMD. This association was dose dependent, with the greatest benefit at low to moderate doses. When looking only at patients with diabetes, we saw a preservation of the dose-dependent decrease in the odds of patients developing AMD. Metformin does not appear to be protective in patients with diabetes and coexisting diabetic retinopathy. This study suggests that metformin may be useful as a preventive therapy for AMD and provides the basis for potential prospective clinical trials.

Project description:ImportanceAge-related macular degeneration (AMD) is a leading cause of blindness with no treatment available for early stages. Retrospective studies have shown an association between metformin and reduced risk of AMD.ObjectiveTo investigate the association between metformin use and age-related macular degeneration (AMD).Design, setting, and participantsThe Diabetes Prevention Program Outcomes Study is a cross-sectional follow-up phase of a large multicenter randomized clinical trial, Diabetes Prevention Program (1996-2001), to investigate the association of treatment with metformin or an intensive lifestyle modification vs placebo with preventing the onset of type 2 diabetes in a population at high risk for developing diabetes. Participants with retinal imaging at a follow-up visit 16 years posttrial (2017-2019) were included. Analysis took place between October 2019 and May 2022.InterventionsParticipants were randomly distributed between 3 interventional arms: lifestyle, metformin, and placebo.Main outcomes and measuresPrevalence of AMD in the treatment arms.ResultsOf 1592 participants, 514 (32.3%) were in the lifestyle arm, 549 (34.5%) were in the metformin arm, and 529 (33.2%) were in the placebo arm. All 3 arms were balanced for baseline characteristics including age (mean [SD] age at randomization, 49 [9] years), sex (1128 [71%] male), race and ethnicity (784 [49%] White), smoking habits, body mass index, and education level. AMD was identified in 479 participants (30.1%); 229 (14.4%) had early AMD, 218 (13.7%) had intermediate AMD, and 32 (2.0%) had advanced AMD. There was no significant difference in the presence of AMD between the 3 groups: 152 (29.6%) in the lifestyle arm, 165 (30.2%) in the metformin arm, and 162 (30.7%) in the placebo arm. There was also no difference in the distribution of early, intermediate, and advanced AMD between the intervention groups. Mean duration of metformin use was similar for those with and without AMD (mean [SD], 8.0 [9.3] vs 8.5 [9.3] years; P = .69). In the multivariate models, history of smoking was associated with increased risks of AMD (odds ratio, 1.30; 95% CI, 1.05-1.61; P = .02).Conclusions and relevanceThese data suggest neither metformin nor lifestyle changes initiated for diabetes prevention were associated with the risk of any AMD, with similar results for AMD severity. Duration of metformin use was also not associated with AMD. This analysis does not address the association of metformin with incidence or progression of AMD.

Project description:Importance:Amyloid-β is a major component of retinal drusen, the primary lesions of age-related macular degeneration (AMD), and autopsy and animal models suggested that anticholinergic drug (ACD) use increased brain amyloid-β deposition. Objective:To investigate the association between exposure to ACDs and late AMD (features of neovascular AMD or geographic atrophy of the retinal pigment epithelium in at least 1 eye). Design, Setting and Participants:A multicenter case-control study in 4 French ophthalmologic centers comprising 200 cases with late AMD and 200 controls enrolled from July 2016 to June 2017. Exposures:Exposure to at least 3 months of ACDs started before AMD diagnosis was recorded during a specific interview. A dose-effect association with cumulative exposure duration and Anticholinergic Burden Score was explored. The association between ACD exposure and AMD was assessed by multivariate logistic regression analysis adjusted for age, sex, smoking status, family history of AMD, alcohol consumption, and use of anticoagulant and anti-inflammatory drugs. Odds ratios (ORs) and 95% confidence intervals were estimated. Main Outcomes and Measures:Association between exposure to ACDs and late AMD. Results:Among case participants, the mean (SD) age was 74.8 (9.2) years, 129 (64.5%) were women, 192 (96%) were white, 65 (32.5%) had geographic atrophy, 135 (67.5%) had neovascular AMD, 116 (58%) had unilateral AMD, and 84 (42%) had bilateral AMD. Among control participants, the mean (SD) age was 75.5 (7.2) years, with 116 (58%) women and 187 (93.5%) white participants. Twenty-six cases (13%) and 10 controls (5%) were exposed to ACDs throughout life for at least 3 months before AMD onset. Risk of AMD was increased with ever exposure to ACDs (adjusted OR [aOR], 2.84; 95% CI, 1.33-6.06; P = .007), high Anticholinergic Burden Score (≥3) (aOR, 6.42; 95% CI, 1.38-29.92; P = .02), and longest cumulative exposure to ACD (≥15 years) (aOR, 5.88; 95% CI, 1.22-28.31; P = .03). Conclusions and Relevance:Risk of late AMD may be increased with at least 3 months' use of ACDs. A dose-effect association was suggested by a greater association with prolonged use and high Anticholinergic Burden Score. Further studies, in particular those with longitudinal design, are needed to confirm this association.

Dataset Information

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

Objectives

Design

Participants

Methods

Results

Conclusion

Publications

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

Similar Datasets

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