File under, "... almost too strange to be true ...":
March 2, 2006
A Ray of Hope for Diabetics
By ALEX BERENSON
The users call the drug Lizzie, the Big Brother or sometimes Gilly. On blogs they rave over its uncanny ability to melt away pounds, although some are wary of its side effects, which can include nausea and strange welts.
The users are not fad dieters or methamphetamine addicts, but people with diabetes. And the subject of their rhapsodies is not a gray-market diet pill sold on late-night television but Byetta, a federally approved diabetes medicine, available only by prescription, whose popularity and sales have soared since its introduction last June.
For diabetics, the weight loss caused by Byetta comes as a welcome contrast to the weight gain that often accompanies insulin and other diabetes medicines; the extra pounds can eventually worsen the disease. Some patients say Byetta has reversed the course of a disease that can lead to severe complications like amputations, blindness and kidney failure and even death.
"I went from despair to life — no hope to lots of hope," said the Rev. John L. Dodson, a 73-year-old pastor in Felton, Calif. Mr. Dodson, 5 feet 6 inches tall, says he has lost almost 60 pounds since starting Byetta last June and now weighs 178, his lowest weight since college.
The drug seems so effective for weight loss that some nondiabetics have begun using Byetta as a diet drug — causing concern among doctors who say such use has not been medically tested and could be dangerous.
But for diabetics, weight loss from Byetta could be a particularly important benefit. Among the 21 million Americans with diabetes, about 90 percent have Type 2, which usually occurs in adulthood and has been linked to obesity and inactivity.
Byetta is not a cure-all, doctors caution. Some patients cannot tolerate its side effects. And it has never been studied as a weight-loss agent in people with normal blood sugar. Amylin Pharmaceuticals and Eli Lilly, which jointly make and market Byetta, say they strongly discourage its use solely as a diet drug. Based on tests in rats, moreover, some scientists have raised the possibility that Byetta may increase the risk of thyroid cancer, although no evidence of that link has appeared in human clinical trials.
Still, diabetic patients are embracing the drug, despite the requirement that Byetta must be kept refrigerated and injected twice daily, making it less convenient than drugs taken in pill form. Users' enthusiasm is all the more remarkable considering that Amylin and Eli Lilly do not plan to advertise Byetta to consumers until at least this summer, a year after its introduction, in keeping with voluntary advertising guidelines that the drug industry adopted last year.
Even without a big marketing push, prescriptions for Byetta are soaring, as news of the drug spreads among diabetics and doctors. From November to January, monthly prescriptions rose almost 40 percent, to almost 100,000, well ahead of analysts' forecasts. Byetta costs about $170 a month, or $2,100 a year, slightly more than most other diabetes drugs, but most insurers cover it.
Byetta's active ingredient is a protein, exenatide, that encourages digestion and the production of insulin. The fact that exenatide was initially discovered in the saliva of the Gila monster, a poisonous lizard found in the Southwest, explains the nicknames Lizzy and Gilly for Byetta — if not the pronunciation. Gilly (GILL-ee) bears little phonic resemblance to Gila (HEE-la). (The third nickname, the Big Brother, refers to the 10 microgram dose, which patients say is more likely to cause nausea than the smaller 5 microgram dose.)
Though still far behind long-acting insulin, for which nearly a million prescriptions were written in January, Byetta is already ranked eighth among the most widely prescribed drugs for diabetes.
"My patients have done strikingly well on the drug," said Dr. Alan J. Garber, a professor at Baylor College of Medicine in Houston and a former member of the national board of the American Diabetes Association. "It's a better choice for an overweight diabetic."
Dr. Garber, who says he has not consulted for Amylin or Lilly, estimates he has about 30 patients on Byetta and that none have experienced serious side effects. Byetta is also easier for patients to use than insulin, because it is less likely to cause low blood sugar than insulin is, he said.
In a clinical trial of 537 patients who tested Byetta against insulin, the average Byetta patient lost five pounds after six months, while the typical patient on insulin gained four pounds. Another trial of 146 patients showed that they lost an average of 12 pounds after two years on Byetta, with their losses increasing the longer they took the drug.
While the drug does not work for everyone, some people report much larger weight loss and say Byetta seems to suppress their appetite and leave them feeling full even on small meals.
"I used to have a love affair with my refrigerator," said John Granger, a computer consultant in Richmond, Va., who began taking Byetta in early January. "I eat about half of what I used to eat."
Mr. Granger, who is 5 feet 11 inches tall and weighs 230 pounds, says he has lost 20 pounds since starting on Byetta. His blood sugar has also dropped, he said.
"My numbers are fabulous," he said. "My numbers are good even for a nondiabetic now."
Mr. Dodson, the pastor, said he had previously used insulin to control his blood sugar, but he disliked insulin because it caused him to feel lethargic and his joints to ache. As soon as he began taking Byetta, he was able to stop using insulin, greatly improving his quality of life, he said.
"I can't tell you what it means to me," Mr. Dodson said. "I used to hate pictures, literally hate them, and now I ask people to take my picture."
The reports of weight loss raise the question of how widely Byetta will be prescribed as a diet drug to people who are not diabetic — a so-called off-label use. Doctors can legally do so, but the F.D.A. and the makers say the drug is supposed to be prescribed only to people with diabetes whose blood sugar is too high even though they are already taking other diabetes medicines. And insurers generally will not cover the drug for nonapproved uses.
Amylin and Eli Lilly say people who are not diabetic should not take Byetta. The companies say they have no plans to study Byetta as a weight-loss treatment in people with normal blood sugar.
"We do not nod and wink to off-label," said Michael Quattro, vice president for marketing at Amylin. "It's the wrong thing to do for the patient."
Many doctors also say that Byetta is probably inappropriate as a weight-loss drug. Although many diabetic patients appear to tolerate it reasonably well, the drug's most common side effect is nausea, which for some patients is so serious that they must stop using it. The drug also causes a rash, fever and chills in some patients, although those effects often fade with continued use.
Byetta is designed to work in a way that carries a lower risk than insulin of causing hypoglycemia, or low blood sugar — a dangerous condition that can lead to coma or death in severe cases. In clinical trials, a small number of people taking Byetta had mild or moderate hypoglycemia, and some patients taking the drug now report similar problems.
Despite the cautions and drawbacks, some doctors appear to be prescribing Byetta primarily as a weight-loss aid in people who do not have elevated blood sugar.
Lynn Cole, a software project manager in Rochester, says that she has been taking Byetta since October even though her blood sugar levels were at near-normal levels when she started taking it.
"I'm not hungry; I don't have a desire to eat," Ms. Cole said. "I definitely do not eat as much as I used to." Ms. Cole, who is 5 feet 4 inches and 250 pounds, said she had lost about 20 pounds taking Byetta. The weight loss has also encouraged her to join a gym and begin to work out, she said.
Jan Knorr, the director of the diabetes disease management program at the Jewish Guild for the Blind in New York, says she expects that doctors will prescribe Byetta to overweight people who are "pre-diabetic," or have moderately high blood sugar but no other complications of diabetes.
"Even though it's a needle, people are desperate to do anything to achieve weight loss or curb their appetite," she said.
Byetta's active ingredient, exenatide, works by mimicking the effects of a human hormone called GLP-1, which is normally released after meals, stimulating digestion and insulin production. GLP-1 also discourages the liver from producing too much sugar.
Exenatide was found by Dr. John Eng, an endocrinologist at the Bronx Veterans Affairs Medical Center in New York City, who struggled for years before finally convincing Amylin to test the hormone as a diabetes treatment.
The companies are testing several other versions of Byetta, including a long-acting formulation that would need to be injected only once a week. Analysts say that version has the potential to become a blockbuster drug, with sales of up to $2 billion in the United States alone, although they say it will not reach the market before 2009 at the soonest.
Meanwhile, many patients appear more than happy to inject themselves twice a day and endure upset stomachs, as long as they can keep losing weight.
"Initially, I really had quite a bit of nausea," said Karen Brady, 51, a computer programmer in Houston. But Ms. Brady, who has diabetes and takes Byetta along with metformin, another diabetes drug, said that she had stayed with Byetta and lost 50 pounds in the last five months. At 5 feet 5 inches she now weighs 150 pounds.
The drug does not permit her to overeat, she said.
"What you eat stays in your stomach forever, so if you do overeat, you're going to be in for a really unpleasant time," she said. "I've only done it once, but it was a good teacher. It keeps me honest."