Effects of medical therapies on retinopathy progression in type 2 diabetes

N Engl J Med. 2010 Jul 15;363(3):233-44. doi: 10.1056/NEJMoa1001288. Epub 2010 Jun 29.

Abstract

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.)

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antihypertensive Agents / therapeutic use*
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / mortality
  • Cholesterol, LDL / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Retinopathy / etiology
  • Diabetic Retinopathy / prevention & control*
  • Disease Progression
  • Drug Therapy, Combination
  • Dyslipidemias / complications
  • Dyslipidemias / drug therapy
  • Female
  • Fenofibrate / therapeutic use*
  • Follow-Up Studies
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hyperglycemia / drug therapy
  • Hypertension / complications
  • Hypertension / drug therapy
  • Hypoglycemic Agents / therapeutic use*
  • Hypolipidemic Agents / therapeutic use*
  • Male
  • Middle Aged
  • Simvastatin / therapeutic use

Substances

  • Antihypertensive Agents
  • Cholesterol, LDL
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Hypolipidemic Agents
  • Simvastatin
  • Fenofibrate

Associated data

  • ClinicalTrials.gov/NCT00000620
  • ClinicalTrials.gov/NCT00542178