Eye Benefits Last 4 Years Past Tight Glucose Control: ACCORDION

Marlene Busko

June 13, 2016

NEW ORLEANS — In a study of patients with type 2 diabetes who were part of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study and of the ACCORD Follow-On (ACCORDION) Eye Study, a 3.7-year period of tight glycemic control halved the risk of retinopathy several years later—in an example of a "legacy effect" or "metabolic memory" — researchers report.

Specifically, 8 years after a baseline exam, diabetic retinopathy had progressed 3 or more steps on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale in 12.7% of patients who had received standard glycemic control vs 5.8% who had received intensive glycemic control.

Emily Y Chew, MD, deputy director of the National Eye Institute's Division of Epidemiology and Clinical Applications in Bethesda, Maryland, presented these findings on June 11 here at the American Diabetes Association (ADA) 2016 Scientific Sessions, and the study was simultaneously published online in Diabetes Care.

"This study sends a powerful message to people with type 2 diabetes who worry about losing vision," said Dr Chew. "Well-controlled glycemia, or blood sugar level, has a positive, measurable, and lasting effect on eye health."

Does Fenofibrate Therapy Need to Be Ongoing?

Dr Emily Y Chew

The ACCORD Eye Study also assessed 3.7 years of lipid-lowering therapy with fenofibrate (160 mg/day) plus simvastatin, which reduced the risk of retinopathy progression compared with therapy with simvastatin alone. In the ACCORDION Eye study, however, at 8 years, 11.8% of patients who had received fenofibrate plus simvastatin vs 10.2% of patients who had simvastatin had retinopathy progression, which was not significantly different.

This finding suggests that fenofibrate treatment may need to be ongoing to maintain benefit, but "further evaluation is required," Dr Chew said.

Intensive blood-pressure control, another aspect of the trials, had no effect on retinopathy in the ACCORD Eye Study nor in the ACCORDION Eye Study.

"This is the first study in people with type 2 diabetes of 10 years' duration and established cardiovascular disease — unlike the newly diagnosed participants of the UK Prospective Diabetes Study — to demonstrate this effect" of intensive glycemic control on later progression of retinopathy, according to Dr Chew.

The benefit of fenofibrate, however, did not persist, and intensive blood-pressure control had no effect on retinopathy, she summarized.

Fenofibrate was approved in Australia in 2013 to slow the progression of diabetic retinopathy in patients with type 2 diabetes, the first country in the world to approve this use of the agent, based on the findings of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial.

The National Eye Institute–funded Diabetic Retinopathy Clinical Research Network is currently planning a clinical trial to further explore ongoing use of fenofibrate to control diabetic retinopathy.

Balancing Eye Benefits vs Mortality Signal in ACCORD

As previously reported by Medscape Medical News, Dr Chew presented some of the current study findings at the International Diabetes Federation (IDF) 2015 World Congress.

Participants in ACCORD had had type 2 diabetes on average for 10 years at the time of enrollment and had known heart disease or at least two risk factors in addition to diabetes, including high blood pressure, high cholesterol levels, obesity, and smoking.

The ACCORD Eye Study analyzed a subset of 2856 participants in ACCORD who had not received laser photocoagulation or vitrectomy for proliferative diabetic retinopathy and who had baseline and 4-year data for seven-field stereoscopic fundus photographs.

The ACCORDION Eye Study had 1310 participants including 762 who were in the lipid-lowering substudy and 548 who were in the blood-pressure–lowering substudy.

At the beginning of the ACCORD Eye Study in 2003, participants in the intensive and standard glycemic control arms had a baseline HbA1c of 8.1% and 8.2%, respectively. When the ACCORD trial was stopped at 3.7 years due to an increased risk of death with intensive glycemic control, participants in the intensive vs standard glycemic control arms had an HbA1c of 6.4% and 7.7%, respectively.

The ACCORDION Eye Study — which was done from 2010 to 2014 — found that the lower risk of retinopathy progression in the participants who had received the intensive glycemic control in ACCORD persisted.

Diabetic Retinopathy Progression, Intensive vs Standard Therapy

Intensive vs Standard Adjusted Odds Ratio (95% CI) P
Glycemic control 0.42 (0.28–0.63) <0.0001
Lipid lowering 1.13 (0.71–1.79) 0.60
Blood-pressure treatment 0.21 (0.61–2.40) 0.59

"Results from ACCORDION suggest that lowering blood glucose can reduce progression of retinal disease relatively late in the course of type 2 diabetes and that even short-term changes in glucose have an effect....But the benefits of intensive glycemic therapy must be weighed against the potential risks — most notably the increased risk of death observed in ACCORD," according to a press release issued by the US National Eye Institute, to announce these latest study results.

The findings were presented in a session entitled "Lagniappe — A Little Something Different," which is appropriate, since "lagniappe," which roughly translates as "something extra," usually a small "freebie" given to a buyer by the seller, entered the English language from New Orleans, Louisiana.

ACCORD was supported by the Heart, Lung, and Blood Institute, and various companies provided study medications. ACCORDION was supported by the National Heart, Lung, and Blood Institute and by the National Institutes of Health's National Eye Institute (NEI). Dr Chew reports having no relevant financial relationships. Disclosures for the coauthors are listed in the article.

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Diabetes Care.Published online June 11, 2016. Article


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