Study compares insulin regimens
Adding insulin injections to oral diabetes drugs does not bring most patients with Type 2 diabetes into control of their blood-sugar levels, according to early results from a major British study released Friday.
The study is the first designed to determine which type of insulin should be used initially in such patients, and researchers concluded that a single daily injection of long-acting insulin was better than shots two or three times a day at meals.
Disappointingly, however, only about a quarter of patients were successful with the best regimen.
“This is showing us that to really manage diabetes is a lot more complicated than a lot of us had hoped for,” said Dr. Larry C. Deeb, a Tallahassee, Fla., endocrinologist and former president of science and medicine at the American Diabetes Assn. “The best they got was 25%. That’s scary.”
The results, added Dr. Rury R. Holman of Oxford University, “suggest that most patients are likely to need more than one type of insulin if they are to maintain recommended glucose levels in the long term.”
Holman presented the findings Friday at an Amsterdam meeting of the European Assn. for the Study of Diabetes. They were also published online by the New England Journal of Medicine and will appear in the Oct. 25 issue.
About 18 million Americans suffer from Type 2 diabetes, in which body tissues lose their sensitivity to insulin. Patients are initially treated with drugs such as metformin and sulfonylureas, but most eventually require increasingly larger doses of insulin as well.
Numerous studies have shown that tight control of diabetes is essential to preventing complications of the disease such as peripheral neuropathy, diabetic retinopathy and cardiovascular complications.
But there had been no studies about how the insulin regimen should be started, Holman said.
He and his colleagues enrolled 708 patients who were taking the maximum doses of metformin and a sulfonylurea and whose glycated hemoglobin levels were 7% or above. Glycated hemoglobin levels are a measure of average sugar levels in the blood, and levels above 7% indicate that the diabetes is not being controlled adequately.
The team randomly assigned the patients to receive either twice daily shots of a form of insulin called biphasic aspart 30, shots before meals of a form called aspart or a single daily injection of long-acting insulin.
At the end of one year, 17% of those taking shots twice daily had glycated hemoglobin levels of 6.5% or lower, compared with 23.9% of those taking it at meals and 8.1% of those taking single daily shots.
But those taking two or three shots daily had the most episodes of hypoglycemia -- dangerously low blood sugar -- and gained the most weight. The team therefore concluded that it is probably best to start patients with a single daily shot of long-acting insulin.
The study provides a clear indication that the twice-daily shots and shots at meals “are suboptimal choices for insulin initiation and probably expose patients to an unnecessarily high risk of hypoglycemia without clinically important benefit,” editors wrote in an editorial accompanying the paper.
They also noted that the risk of hypoglycemia could probably be reduced by stopping administration of sulfonylureas, which provide no benefit when given with insulin.
The trial, commonly known as the 4-T study, is ongoing. In the second and third years, the researchers are using more complex insulin regimens in an effort to help a larger number of patients achieve control of sugar levels.
“Ultimately, people with diabetes are going to have to realize that where they start at the time of diagnosis is just the beginning of their journey,” said Dr. Francine R. Kaufman, head of the Center for Diabetes, Endocrinology and Metabolism at Childrens Hospital Los Angeles. “Eventually, oral agents aren’t enough.”
It is important to convince both patients and providers, she said, that “insulin is the friend of someone with diabetes.”
The study is sponsored by Novo Nordisk, which makes all three types of insulin used. All of the researchers have received financial support from pharmaceutical companies.
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