New Class of Drug Adds Options for Diabetics
Federal regulators Tuesday approved a new class of oral drugs for Type 2 diabetes that is as effective as most existing treatments and avoids common side effects, such as dangerously low blood sugar.
The Food and Drug Administration said that Merck & Co.'s Januvia, a once-daily tablet, could be taken alone or in combination with the common oral diabetes medicines metformin, Actos and Avandia.
Dr. Robert Meyer of the FDA’s Office of Drug Evaluation called Januvia a “useful addition” to the treatment arsenal.
“Not everybody optimally responds to each medication, or not everybody can tolerate each medication,” he said at a news conference. “Having a new drug in a new class for such a widely prevalent disease is important.”
But Dr. John Buse, director of the diabetes center at the University of North Carolina School of Medicine and president-elect of the American Diabetes Assn., said it was still uncertain how valuable the drug would prove to be.
Some commonly used older drugs “are very effective and are ridiculously cheap,” said Buse, who has consulted for many pharmaceutical companies. “The only sin they committed was becoming generic” and losing corporate marketing support.
Januvia will cost $4.86 a day, adding about $1,800 to the annual cost of treatment.
The drug is among several medicines recently approved for Type 2 diabetes, an illness linked to obesity that is reaching epidemic proportions worldwide and affects 20 million people in the U.S.
Annual worldwide sales of diabetes drugs are expected to double to $20 billion over the next five years as more people develop the disease and pharmaceutical companies continue to bring out new and more expensive treatments.
Galvus, a Novartis drug similar to Januvia, is expected to receive FDA approval next month.
People with Type 2 diabetes progressively lose their ability to produce or properly use insulin, a hormone made in the pancreas that moves sugar from the blood into cells, where it is used as fuel. A buildup of sugar in the blood not only starves cells of energy but can cause serious health complications including blindness, kidney failure and amputations.
Existing drugs act to lower blood-sugar levels in one of two ways. Sulfonylurea drugs stimulate the pancreas to release insulin. Metformin works to discourage the liver from producing sugar. Patients usually start on metformin and later add a sulfonylurea or another drug, but over time the medicines lose their effectiveness, and eventually many patients need insulin shots.
Januvia and Galvus work differently. They raise the level of a hormone called GLP-1, which is produced in the intestines and stomach when blood-sugar levels are elevated. The hormone in turn stimulates the pancreas to release insulin while restraining the liver from making sugar.
The most common side effects of the new drugs, known as gliptins, include headache and a stuffy nose.
They do not appear to cause weight gain, a problem with sulfonylureas and another class of diabetes drugs known as thiazolidinediones, which includes Actos and Avandia. The latter drugs carry a small risk of congestive heart failure.
“We think this will change the landscape for how physicians manage the disease,” Merck marketing vice president Patrick Magri said.
Most doctors and analysts do not think the gliptins will dislodge metformin, a more effective blood-sugar-lowering agent, as a first treatment for Type 2 diabetes.
But some think the new medicines could eventually replace sulfonylureas as second-line drugs because they avoid the weight-gain effect.
“The fact that these drugs are weight-neutral is a real bonus,” said David Kliff, who publishes the Diabetic Investor newsletter and predicts annual sales of Januvia and Galvus will eventually reach or exceed $1 billion each.
Still, some doctors said it would take time for them to become comfortable with the new class of drugs. The longest clinical trials involved a few thousand patients and lasted no more than two years, not large enough or long enough to observe rare side effects. The gliptins increase neutrophils, a kind of white blood cell, but the companies say the reaction does not pose problems.
Dr. Alvin Powers, director of the Diabetes Research and Training Center at Vanderbilt University, said he would probably turn to a gliptin when patients couldn’t tolerate conventional drugs or no longer responded to them.
“It is very exciting to have new agents for this disease,” he said. “But I think it is going to take several years to know exactly how to use them.”
As a condition of approval, the FDA required Merck to conduct research to see whether Januvia can be safely combined with insulin and sulfonylureas, studies that might also expand the market for the drug.
Dr. Andrew Drexler, director of UCLA’s Gonda Diabetes Center, said the real promise of the drugs had been suggested by animal studies showing that gliptins could spur the growth of new insulin-producing cells.
Research is underway to find out whether the drugs can halt or reverse the course of diabetes in people.
“These drugs could be somewhat important or tremendously important,” said Drexler, who has done previous work for Merck and Novartis. “It is the $4-billion question, literally.”