Metformin Has Multiple Therapeutic Effects on Diabetic Complications, Including Macular Edema

Author: Edward Shahady, MD
Clinical Professor, Family and Community Medicine, University of Florida.

Medical Director, Diabetes Master Clinician Program, Parkland, Florida.

Citation: Shahady E. Metformin has multiple therapeutic effects on diabetic complications, including macular edema [Published online November 12, 2018]. Consultant360.


Metformin is the most widely prescribed drug to treat hyperglycemia in type 2 diabetes. The American Diabetes Association recommends metformin as the first-line therapy for type 2 diabetes, along with lifestyle modifications.1

This recommendation is based on the UK Prospective Diabetes Study (UKPDS),2 a randomized controlled trial of different therapies for type 2 diabetes. This landmark study reported that intensive glucose control with metformin appears to decrease the risk of diabetes-related endpoints and death in overweight patients with diabetes.

The reduction of cardiovascular mortality by metformin compared with any other oral diabetes agent or placebo was confirmed by a meta-analysis that included 30 clinical trials.3,4

Metformin also demonstrates associated efficacy in treating diabetic nephropathy, retinopathy, neuropathy, polycystic ovary disease and prevention or treatment of cancer.5It treats hyperglycemia by decreasing hepatic glucose production (thus, inhibiting gluconeogenesis).6

This explains some of the associated efficacy of metformin, but other mechanisms like a decrease in inflammation and oxidative stress are responsible for additional effects of metformin.7 Reduction of inflammation and oxidative stress may play a role in decreasing the rate of age-related macular degeneration (AMD) in diabetes, as recently reported in a study presented at the annual meeting of the American Academy of Ophthalmology.8

For the study, Yu-Yen Chen, MD, and colleagues identified 73,118 patients with new diagnoses of diabetes between 2001 and 2013. Patients with type 1 diabetes and a diagnosis of AMD at the time of enrollment were excluded.8

Of 68,205 eligible patients, 45,524 had 1 or more prescriptions for metformin. At baseline, those receiving metformin had a higher prevalence of systemic comorbidities compared with controls.8

Following adjustment for age, gender, and comorbidities, results of the study indicated that participants who were treated with metformin had a significantly lower risk of AMD compared with controls (hazard ratio 0.53), leading Dr Chen and colleagues to conclude that metformin use was associated with a significantly lower risk of AMD in patients with type 2 diabetes.8


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3. Selvin E, Bolen S, Yeh HC, et al. Cardiovascular outcomes in trials of oral diabetes medications: a systematic review. Arch Intern Med. 2008;168:2070–2080.

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5. Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli F. Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond). 2012;122(6):253-70.

6. Cusi K, Consoli A, DeFronzo RA. Metabolic effects of metformin on glucose and lactate metabolism in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1996;81:4059–4067.

7. Abolfazl A et al. Metformin; a mini-review to its antioxidative and anti-inflammatory properties. J Renal Inj Prev. 2018; 7(1):7-10

8. Chen Y. Metformin reduces the risk of AMD in type 2 diabetic patients: a nationwide cohort study. Presented at: American Academy of Ophthalmology 2018 Annual Meeting; October 28, 2018; Chicago, Illinois.