USA: Slashing Blood Sugar Helps Kidneys, Not Hearts of Diabetics

NEW YORK (Bloomberg), June 7, 2008:

By Rob Waters

Diabetes drugs aimed at drastically cutting blood sugar levels increased deaths from heart disease in one study and reduced kidney illness in another, results that suggest each patient can't be treated the same.

The two trials, which followed more than 21,000 elderly, often obese diabetics, used multiple drugs to tightly control blood sugar levels to help patients avoid complications that can cause disability and death. While cutting kidney disease in one trial, the treatments failed to protect diabetics from heart disease and stroke in the second.

Both studies, the largest ever for diabetes, were published yesterday by the New England Journal of Medicine. The conflicted findings challenge the common use of powerful drug combinations to slash the blood sugar of diabetics to levels seen in non- diabetics, said Harlan Krumholz, a Yale University cardiologist who wasn't involved in the studies.

``The results are surprising and question the conventional wisdom that the lower you get blood sugar, the better off patients are and the lower their risk,'' Krumholz said in a telephone interview. ``These studies should give us pause'' about the current standard of treatment.

The most frequently used drug in the two trials was GlaxoSmithKline's Avandia. Patients also received Takeda Pharmaceutical Co.'s Actos, Eli Lilly & Co.'s Byetta, Bayer AG's Precose and generic medications. Most also used insulin.

Double by 2030

An estimated 180 million people around the world have diabetes, according to the Geneva-based World Health Organization, which predicts the number will double by 2030. The blood sugar studies will be discussed by researchers at the annual meeting of the American Diabetes Association, which began yesterday in San Francisco.

More than 90 percent of diabetes patients have the Type 2 form, which occurs when the pancreas doesn't produce enough insulin, a hormone that allows cells to convert glucose, or sugar, into energy. Glucose collects in the blood and can impair circulation, leading to complications involving small blood vessels such as kidney failure, blindness, and amputations as well as those that impair larger arteries such as heart disease and stroke. Type 2 diabetes is linked to obesity.

The first of the two studies, called the ACCORD trial, was aimed at learning which of two approaches would better protect Type 2 diabetics from developing serious cardiovascular problems. The patients, whose average age was 62, entered the study with an average glucose level of 8.1 percent, about 2 points higher than healthy non-diabetics.

Two Groups in Trial

One group in the trial received intensive therapy and multiple drugs aimed at lowering their glucose level to 6 percent or below. Others in the trial received less rigorous treatment that aimed for blood sugar levels that ranged from 7 percent to 7.9 percent.

While the intensively treated patients had a slightly lower risk of heart attacks and strokes, patients in that group were more likely to die from such events and from other causes. These findings led the U.S. National Heart, Lung and Blood Institute to halt the trial in February, 18 months early, after following patients for 3 1/2 years.

Avandia, the most commonly used drug, was connected to increased risk of heart attacks in findings released last May. ACCORD investigators who analyzed differences between the patients ``didn't see any link between Avandia and increased cardiovascular events,'' said Nikheel Kolatkar, Glaxo's director of clinical development for cardiovascular and metabolic drugs, in a telephone interview yesterday.

Advance Study

The second study, released for the first time yesterday, focused on reducing complications involving small blood vessels.

Dubbed the Advance trial, this study found that patients given an intensive regimen that included the drug Diamicron, marketed in Europe by Les Laboratoires Servier, a closely held French company, slashed glucose levels to 6.5 percent and cut the number of patients with kidney disease by 21 percent.

That's significant, said Stephen MacMahon, a cardiologist at the George Institute for International Health in Sydney, Australia and a study leader, who called kidney disease ``a massive problem. One in two diabetics will get kidney disease and one in five will die of it in their lifetime,'' he said in a telephone interview yesterday. ``This shows that you can do something about that complication.''

The dueling results ``do add to confusion because you're seeing different outcomes in groups of patients that are fairly similar,'' said Martin J. Abrahamson, medical director of the Joslin Clinic, a Boston center affiliated with Harvard Medical School. While the use of multiple drugs seems to be contributing to good and bad outcomes, trying to push glucose too low may be dangerous, he said.

Caution

Yale's Krumholz said the results were another reminder that drugs that change results on laboratory tests don't always translate into real benefit for patients. He pointed to torcetrapib, the cholesterol drug Pfizer Inc. abandoned last year after studies showed it increased patient deaths. New York-based Pfizer, the world's largest pharmaceutical company, invested $1 billion developing the medicine.

``They had a drug that really boosted HDL cholesterol and lowered LDL, and by all rights, it should have been amazing,'' Krumholz said. ``Just because we know what a drug is doing to risk factors doesn't mean we know what's happening with patients.''

Robin Goland, the co-director of the Naomi Berrie Diabetes Center at Columbia University Medical Center in New York, said the results show that treatment of diabetics can't follow stock formulas. Patients who have had already had heart attacks or strokes may not be able to handle multiple drugs and intensive lowering of glucose, she said.

The results also strengthened her resolve to offer patients ``the least sexy advice in medicine: to eat less and exercise more. That should be the first line of therapy for everybody.''

Rob Waters, San Francisco
rwaters5@bloomberg.net
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