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Metformin and risk of age-related macular degeneration in individuals with type 2 diabetes: a retrospective cohort study
  1. Krishna M Gokhale1,
  2. Nicola J Adderley1,
  3. Anuradhaa Subramanian1,
  4. Wen Hwa Lee2,
  5. Diana Han1,
  6. Jesse Coker2,
  7. Tasanee Braithwaite1,3,4,
  8. Alastair K Denniston5,6,7,8,
  9. Pearse A Keane6,
  10. Krishnarajah Nirantharakumar1,8
  1. 1 Institute of Applied Health Research, University of Birmingham, Birmingham, UK
  2. 2 Action Against Age-Related Macular Degeneration, London, UK
  3. 3 The School of Immunology and Microbial Sciences and The School of Life Course Sciences, King's College London, London, UK
  4. 4 The Medical Eye Unit, Guy's and St Thomas' NHS Foundation Trust, London, UK
  5. 5 Department of Ophthalmology, University Hospitals Birmingham NHSFT, Birmingham, UK
  6. 6 NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and Institute of Ophthalmology, University College London, London, UK
  7. 7 Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
  8. 8 Health Data Research UK, London, UK
  1. Correspondence to Dr Nicola J Adderley, Institute of Applied Health Research, University of Birmingham, Birmingham, Birmingham, UK; n.j.adderley{at}; Dr Pearse A Keane, NIHR Biomedical Research Centre, Moorfields Eye Hospital and Institute of Ophthalmology, University College London, London, UK; pearse.keane1{at}


Background Age-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.

Aims To explore the relationship between metformin use and development of AMD among patients with type 2 diabetes in the UK.

Methods A 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.

Results A 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.

Conclusion We found no evidence that metformin was associated with risk of AMD in primary care patients requiring treatment for type 2 diabetes.

  • degeneration
  • epidemiology
  • macula

Data availability statement

Data may be obtained from a third party and are not publicly available.

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Data availability statement

Data may be obtained from a third party and are not publicly available.

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  • KMG and NJA are joint first authors.

  • PAK and KN are joint senior authors.

  • Twitter @againstAMD

  • Contributors PAK, KN and AKD conceived the research question. KN, KMG and NJA designed the analysis. KMG performed the analysis, with supervision and contributions by KN and NJA. NJA and KMG drafted the manuscript. All authors (KMG, NJA, AS, WHL, DH, JC, TB, AKD, PAK, KN) reviewed and revised the manuscript, provided critical feedback and agreed to its publication. NJA and KN act as guarantors; the guarantors accept full responsibility for the work and the conduct of the study, had access to the data, and controlled the decision to publish.

  • Funding This research was funded by Action Against Age-related Macular Degeneration, Charity numbers 1 170 224 and SC048549 (award number: none).

  • Competing interests Drs Adderley, Nirantharakumar and Denniston reported a grant from Action Against Age-related Macular Degeneration during the conduct of the study. Dr Adderley reported receiving grants from MRC UKRI and NIHR RfPB outside the submitted work. Dr Nirantharakumar reported receiving grants from Medical Research Council, National Institute for Health Research, AstraZeneca, MSD, Boehringer Ingelheim, Vifor, and Health Data Research UK and personal fees from Sanofi outside the submitted work. Dr Denniston reported receiving grant support from Health Data Research UK outside the submitted work. Dr Braithwaite reported receiving salary support from the patient charity Olivia’s Vision. No other disclosures were reported.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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