Aggressive Therapy Doesn't Cut Heart Risk in Diabetes


SAN FRANCISCO — Tightly controlling blood sugar to lower-than-recommended standards using insulin and other drugs does not reduce the risk of stroke and heart attacks in people with type 2 diabetes—and may even be harmful, according to two major studies presented Friday at the American Diabetes Association’s annual meeting in San Francisco.

One of the studies, known as ACCORD, was halted earlier this year when patients treated aggressively with blood-sugar-lowering medication were found to have a greater mortality risk than those treated less aggressively.

The New England Journal of Medicine published both studies, called the ACCORD and ADVANCE trials, early to coincide with the meeting.

Experts emphasized that the findings do not mean that lowering blood sugar is harmful for most patients. Lowering blood sugar can reduce the risk of other diabetes complications, such as vision loss, kidney failure, and nerve damage. And it’s still not clear if more aggressive treatment may offer some heart benefits to certain patients (e.g., those without existing heart disease) or may work with some drugs but not others.

"You can safely reduce glucose to around 6.5% by using the sort of graduated, rather gentle approach to glucose control," said Stephen MacMahon, DSc, PhD, a principal investigator in the ADVANCE study and a professor at the University of Sydney in Australia. "That won't necessarily prevent cardiovascular events, but it will improve outcomes in terms of kidney disease."

Neither trial emphasized diet and exercise as a way to lower blood sugar, and the trials used different types of drugs to lower blood sugar, with varying results.

In ACCORD, half of the 10,251 type 2 diabetes patients with a hemoglobin A1C of 8.1% tried to achieve an A1C of below 6.0% (similar to a nondiabetic) using more aggressive treatment with medication. The other half aimed for a level of 7.0% to 7.9% using standard therapy. (Currently, the American Diabetes Association recommends an A1C of less than 7%.)

About 90% of patients in the intensive-therapy group took thiazolidinediones such as rosiglitazone (Avandia), as did 58% of the standard therapy group (which also took sulfonylureas, metformin, and insulin as needed). After three and a half years—when the study was halted—those in the intensive treatment group had gained more weight, had more episodes of hypoglycemia, and had a 22% higher mortality rate than those in the standard therapy group. (Find out why drug combinations are used to treat diabetes.)

The ADVANCE study was similar in design, but less than 20% of patients took rosiglitazone or similar drugs (most took gliclazide, a type of sulfonylurea).

In that trial of 11,140 people, intensive therapy reduced the risk of kidney disease, but not the risk of death due to cardiovascular disease or any cause.

An accompanying editorial in The New England Journal of Medicine called the trials important if disappointing.

"There should be no misunderstanding that the ADVANCE trial had clearly negative results," writes William Cefalu, MD, of the Louisiana State University System in Baton Rouge. "However, by virtue of the significant reduction in nephropathy, the ADVANCE trial extended our understanding of intensive glycemic control on microvascular events in patients with type 2 diabetes."

Type 2 diabetes is the most common form of the disease, making up 90% of people with diabetes. Tight blood-sugar control has been shown to reduce the risk of heart attacks and strokes in those with type 1 diabetes, a less common autoimmune disease that most often occurs in children and young adults.

By Sean Kelley


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