METformin for the MINimization of Geographic Atrophy Progression (METforMIN): A Randomized Trial

Liangbo Linus Shen, MD; Jeremy D. Keenan, MD, MPH; Noor Chahal, BS; Abu Tahir Taha, BS; Jasmeet Saroya, BS; Chu Jian Ma, MD; Mengyuan Sun, PhD; Daphne Yang, BS; Catherine Psaras, BA; Jacquelyn Callander, MD; Christina Flaxel, MD; Amani A. Fawzi, MD; Thomas K. Schlesinger, MD, PhD; Robert W. Wong, MD; Loh-Shan Bryan Leung, MD; Alexander M. Eaton, MD; Nathan C. Steinle, MD; David G. Telander, MD; Armin R. Afshar, MD; Melissa D. Neuwelt, MD; Jennifer I. Lim, MD; Glenn C. Yiu, MD, PhD; Jay M. Stewart, MD

Ophthalmology Science (May 2024)

METformin for the MINimization of Geographic Atrophy Progression (METforMIN): A Randomized Trial

Liangbo Linus Shen, MD,
Jeremy D. Keenan, MD, MPH,
Noor Chahal, BS,
Abu Tahir Taha, BS,
Jasmeet Saroya, BS,
Chu Jian Ma, MD,
Mengyuan Sun, PhD,
Daphne Yang, BS,
Catherine Psaras, BA,
Jacquelyn Callander, MD,
Christina Flaxel, MD,
Amani A. Fawzi, MD,
Thomas K. Schlesinger, MD, PhD,
Robert W. Wong, MD,
Loh-Shan Bryan Leung, MD,
Alexander M. Eaton, MD,
Nathan C. Steinle, MD,
David G. Telander, MD,
Armin R. Afshar, MD,
Melissa D. Neuwelt, MD,
Jennifer I. Lim, MD,
Glenn C. Yiu, MD, PhD,
Jay M. Stewart, MD

Affiliations

Liangbo Linus Shen, MD: Department of Ophthalmology, University of California, San Francisco, San Francisco, California
Jeremy D. Keenan, MD, MPH: Department of Ophthalmology, University of California, San Francisco, San Francisco, California; Francis I. Proctor Foundation for Research in Ophthalmology, University of California, San Francisco, San Francisco, California
Noor Chahal, BS: Department of Ophthalmology, University of California, San Francisco, San Francisco, California
Abu Tahir Taha, BS: Department of Ophthalmology, University of California, San Francisco, San Francisco, California
Jasmeet Saroya, BS: Department of Ophthalmology, University of California, San Francisco, San Francisco, California
Chu Jian Ma, MD: Department of Ophthalmology, University of California, San Francisco, San Francisco, California
Mengyuan Sun, PhD: Institute of Cardiovascular Diseases, Gladstone Institute, San Francisco, California
Daphne Yang, BS: Department of Ophthalmology, University of California, San Francisco, San Francisco, California
Catherine Psaras, BA: Department of Ophthalmology, University of California, San Francisco, San Francisco, California
Jacquelyn Callander, MD: Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, San Francisco, California
Christina Flaxel, MD: Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
Amani A. Fawzi, MD: Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
Thomas K. Schlesinger, MD, PhD: North Bay Vitreoretinal Consultants, Santa Rosa, California
Robert W. Wong, MD: Austin Retina Associates, Austin, Texas
Loh-Shan Bryan Leung, MD: Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California
Alexander M. Eaton, MD: Retina Health Center, Fort Myers, Florida
Nathan C. Steinle, MD: California Retina Consultants, Santa Barbara, California
David G. Telander, MD: Retinal Consultants Medical Group, Sacramento, California
Armin R. Afshar, MD: Department of Ophthalmology, University of California, San Francisco, San Francisco, California
Melissa D. Neuwelt, MD: Department of Ophthalmology, University of California, San Francisco, San Francisco, California
Jennifer I. Lim, MD: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois
Glenn C. Yiu, MD, PhD: Department of Ophthalmology & Visual Sciences, UC Davis Medical Center, Sacramento, California
Jay M. Stewart, MD: Department of Ophthalmology, University of California, San Francisco, San Francisco, California; Correspondence: Jay M. Stewart, MD, Department of Ophthalmology, University of California, San Francisco, 490 Illinois Street, Floor 5, San Francisco, CA 94143-4081.

Journal volume & issue: Vol. 4, no. 3
p. 100440

Abstract

Read online

Purpose: Metformin use has been associated with a decreased risk of age-related macular degeneration (AMD) progression in observational studies. We aimed to evaluate the efficacy of oral metformin for slowing geographic atrophy (GA) progression. Design: Parallel-group, multicenter, randomized phase II clinical trial. Participants: Participants aged ≥ 55 years without diabetes who had GA from atrophic AMD in ≥ 1 eye. Methods: We enrolled participants across 12 clinical centers and randomized participants in a 1:1 ratio to receive oral metformin (2000 mg daily) or observation for 18 months. Fundus autofluorescence imaging was obtained at baseline and every 6 months. Main Outcome Measures: The primary efficacy endpoint was the annualized enlargement rate of the square root-transformed GA area. Secondary endpoints included best-corrected visual acuity (BCVA) and low luminance visual acuity (LLVA) at each visit. Results: Of 66 enrolled participants, 34 (57 eyes) were randomized to the observation group and 32 (53 eyes) were randomized to the treatment group. The median follow-up duration was 13.9 and 12.6 months in the observation and metformin groups, respectively. The mean ± standard error annualized enlargement rate of square root transformed GA area was 0.35 ± 0.04 mm/year in the observation group and 0.42 ± 0.04 mm/year in the treatment group (risk difference = 0.07 mm/year, 95% confidence interval = −0.05 to 0.18 mm/year; P = 0.26). The mean ± standard error decline in BCVA was 4.8 ± 1.7 letters/year in the observation group and 3.4 ± 1.1 letters/year in the treatment group (P = 0.56). The mean ± standard error decline in LLVA was 7.3 ± 2.5 letters/year in the observation group and 0.8 ± 2.2 letters/year in the treatment group (P = 0.06). Fourteen participants in the metformin group experienced nonserious adverse events related to metformin, with gastrointestinal side effects as the most common. No serious adverse events were attributed to metformin. Conclusions: The results of this trial as conducted do not support oral metformin having effects on reducing the progression of GA. Additional placebo-controlled trials are needed to explore the role of metformin for AMD, especially for earlier stages of the disease. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Published in Ophthalmology Science

ISSN: 2666-9145 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Ophthalmology
Website: https://www.journals.elsevier.com/ophthalmology-science/

About the journal

Abstract

Keywords