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Effects of Medical Therapies on Retinopathy Progression in Type 2 Diabetes
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BACKGROUND: We investigated whether intensive glycemic control, combination therapy for dyslipidemia, and intensive blood-pressure control would limit the progression of diabetic retinopathy in persons with type 2 diabetes. Previous data suggest that these systemic factors may be important in the development and progression of diabetic retinopathy. METHODS: In a randomized trial, we enrolled 10,251 participants with type 2 diabetes who were at high risk for cardiovascular disease to receive either intensive or standard treatment for glycemia (target glycated hemoglobin level, <6.0% or 7.0 to 7.9%, respectively) and also for dyslipidemia (160 mg daily of fenofibrate plus simvastatin or placebo plus simvastatin) or for systolic blood-pressure control (target, <120 or <140 mm Hg). A subgroup of 2856 participants was evaluated for the effects of these interventions at 4 years on the progression of diabetic retinopathy by 3 or more steps on the Early Treatment Diabetic Retinopathy Study Severity Scale (as assessed from seven-field stereoscopic fundus photographs, with 17 possible steps and a higher number of steps indicating greater severity) or the development of diabetic retinopathy necessitating laser photocoagulation or vitrectomy. RESULTS: At 4 years, the rates of progression of diabetic retinopathy were 7.3% with intensive glycemia treatment, versus 10.4% with standard therapy (adjusted odds ratio, 0.67; 95% confidence interval [CI], 0.51 to 0.87; P=0.003); 6.5% with fenofibrate for intensive dyslipidemia therapy, versus 10.2% with placebo (adjusted odds ratio, 0.60; 95% CI, 0.42 to 0.87; P=0.006); and 10.4% with intensive blood-pressure therapy, versus 8.8% with standard therapy (adjusted odds ratio, 1.23; 95% CI, 0.84 to 1.79; P=0.29). CONCLUSIONS: Intensive glycemic control and intensive combination treatment of dyslipidemia, but not intensive blood-pressure control, reduced the rate of progression of diabetic retinopathy. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov numbers, NCT00000620 for the ACCORD study and NCT00542178 for the ACCORD Eye study.)
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“The primary composite major CV outcomes (nonfatal MI, nonfatal stroke or death from CV causes) were not reduced significantly in ACCORD (hazard ratio [HR] 0.90, p=0.16).”
From Targets for Glycemic Control (2018) · cites this paper as [21]
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In the citing paper
“In people with type 2 diabetes, an A1C ≤6.5% may be targeted to reduce the risk of CKD [Grade A, Level 1A (23)] and retinopathy [Grade A, Level 1A (21)], if they are assessed to be at low risk of hypoglycemia based on class of antihyperglycemic medication(s) utilized and the person's characteristics [Grade D, Consensus].”
From Targets for Glycemic Control (2018) · cites this paper as [21]
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“The UK Prospective Diabetes Study randomly assigned 4209 patients with newly diagnosed type 2 diabetes to receive conventional (primarily diet) vs intensive (insulin, sulfonylurea, or, if overweight, metformin) treatment, with mean attained HbA1C of 7.9% vs 7.0%, respectively.36,37”
From Diagnosis and Treatment of Type 2 Diabetes in Adults (2025) · cites this paper as [36]
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“Other options that can stabilize retinopathy include lifestyle intervention or bariatric surgery in persons with T2D or physical activity in persons with T1D.524–527”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [527]
Experimental — accuracy not yet measuredIn the citing paper
“Fenofibrate reduces the progression of diabetic retinopathy.413,414”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [414]
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Emerging Concepts in the Treatment of Diabetic Retinopathy
Ellis, M., Lent-Schochet, D., Lo, T., & Yiu, G. C. (2019) · Current Diabetes Reports · doi:10.1007/s11892-019-1276-5 · Cited by 39
Hypertriglyceridaemia: an update
Wierzbicki, A. S., Kim, E. J., Esan, O., & Ramachandran, R. (2022) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2021-207719 · Cited by 42
Activation of AMP-Activated Protein Kinase Prevents Lipotoxicity in Retinal Pericytes
Cacicedo, J. M., Benjachareonwong, S., Chou, E. L., Yagihashi, N., Ruderman, N. B., & Ido, Y. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-5784 · Cited by 44
Kim, Y. J., Kim, J.-G., Lee, J. Y., Lee, K. S., Joe, S. G., Park, J., Kim, M., & Yoon, Y. H. (2014) · Journal of Korean Medical Science · doi:10.3346/jkms.2014.29.12.1699 · Cited by 39
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Lipids and Diabetic Retinopathy
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Metadata
- Authors
- The ACCORD Study Group and ACCORD Eye Study Group
- Corresponding author
- The ACCORD Study Group and ACCORD Eye Study Group
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2010-07-15
- Volume
- 363
- Issue
- 3
- Pages
- 233-244
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC4026164
- OpenAlex
- W2219384223
- Semantic Scholar
- 9a607a3bfd9432a917f703d573fdaa1052647711
- Cited by
- 1,311
- References
- 36
- Citations by year
- 2026: 54 · 2025: 60 · 2024: 66 · 2023: 86 · 2022: 73 · 2021: 94 · 2020: 96 · 2019: 57 · 2018: 78 · 2017: 87 · 2016: 82 · 2015: 84 · 2014: 74 · 2013: 81 · 2012: 93
- FWCI
- 111.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Abbott Laboratories
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Gilead Sciences
- Regeneron Pharmaceuticals
- Massachusetts Medical Society
- Omron Healthcare
- Bayer HealthCare
- Daiichi-Sankyo
- Novo Nordisk
- Servier
- National Institutes of Health (n01hc95183-23-0-0, n01hc95180-24-0-1, n01hc95184-24-0-1, n01hc95181-23-0-1, n01hc95182-23-0-1, Z99 EY999999, n01hc95178-28-0-1, n01hc95179-25-0-0)
- Centers for Disease Control and Prevention
- National Institute on Aging
- National Heart, Lung, and Blood Institute (N01- HC-95181, R01HL073030, N01 HC095184, N01-HC- 95180, N01-HC-95178, N01 HC095182, N01 HC095181, Y01 HC001010, N01-HC-095183, N01 HC095178, N01-HC-95184, N01HC95179, IAAY1-HC-1010, IAA #Y1-HC-9035, N01 HC095180, Y01 HC009035, N01‐HC‐95183, N01-HC-95182, N01 HC095179)
- National Eye Institute (ZIAEY000410)
- National Institute of Diabetes and Digestive and Kidney Diseases
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- diabetic retinopathy, retinopathy progression, type 2 diabetes, tight glycemic control, HbA1c, fenofibrate, simvastatin, dyslipidemia, blood pressure control, laser photocoagulation, vitrectomy, cardiovascular risk reduction, combination therapy, Early Treatment Diabetic Retinopathy Study
- MeSH terms
- Antihypertensive Agents, Hypolipidemic Agents, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Drug Therapy, Combination, Female, Follow-Up Studies, Glycated Hemoglobin, Humans, Hyperglycemia, Hypertension, Hypoglycemic Agents, Cholesterol, LDL, Male, Middle Aged, Fenofibrate, Disease Progression, Simvastatin, Dyslipidemias
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