TORONTO - A once-a-week injectable diabetes drug appears to lower blood sugar somewhat better than the same drug injected twice daily, creating promise that the new formulation may be a more useful part of a Type 2 diabetes control regime, a new study suggests.
The drug, exenatide, also has the advantage of triggering modest weight loss -- an average of just over 3.5 kilograms -- in people taking it, making it the only available diabetes drug to do so. While some diabetes drugs are "weight neutral," most cause weight gain, which can complicate diabetes control and undermine a person's willingness to take their medication.
The results of the study were published Monday by the journal The Lancet to coincide with their release at a scientific meeting in Rome.
Lead author Dr. Daniel Drucker, from Toronto's Mount Sinai Hospital, was attending the meeting and was not available for interview. But one of his co-investigators expressed excitement at the results.
"I think we need lots of medications to treat this very tough disease," said Dr. Gary Lewis, director of the division of endocrinology at the University of Toronto medical school.
"Here's another potentially very useful medicine coming down the line. It's not going to be for everybody but it's going to have a very, very important place, I believe, providing all goes well with the testing, etc."
Exenatide was developed as a joint venture between Amylin Pharmaceuticals Inc. and Eli Lilly and Company. The two companies funded and helped design and run this study.
Diabetes experts not involved in the research expressed enthusiasm -- albeit more tempered -- about the findings.
Dr. David Nathan, director of the Diabetes Centre at Massachusetts General Hospital, noted a large-gauge needle is needed to give the once-a-week shot -- a fact that would deter some patients.
And he suggested the once-a-week formulation has both pros and cons. The thought of 13 fewer shots a week would appeal to many patients. But medication taken weekly is easier to forgot.
"When you do something once a day, it becomes a habit," Nathan said, referring to insulin, an alternative to this drug which requires once-a-day injection. "When you do something once a week and you forget it for a week, that's a problem."
Still, he suggested the option of a once-a-week formulation -- if licensed -- might start to change the thinking of doctors who may have favoured insulin for their patients up until now.
"I think frankly many of us were reluctant to use a drug (exenatide) that was more expensive, caused nausea and vomiting, (and) required injections twice a day, especially when it wasn't that powerful a drug. But here you see with once a week injection the balance is being tilted a little bit."
Both the twice-daily and once-weekly formulations cause nausea, vomiting and diarrhea in a portion of people who take exenatide. In the study, 26.4 per cent of people on the once-a-week version and 34.5 per cent of people on the twice-daily schedule complained of nausea.
There may be another, more serious side-effect as well. The U.S. Food and Drug Administration has received six reports of pancreatitis in people using the twice-daily formulation -- sold as Byetta -- in that country. The FDA is working with Amylin, which makes the drug, to develop new label warnings to highlight the risk of the potentially fatal condition.
"There are really two groups of patients," explained Lewis, who said he has no financial ties to either company though he has acted as a consultant for Lilly in the past.
"Some of them just cannot tolerate it ... And then it's not a drug for them and there are other alternatives. But (for) those who tolerate it, it is absolutely phenomenal. I mean, I haven't seen anything as effective as this -- something causing weight loss and improved sugars at the same time and doing it in a sustained fashion so well."
So far neither formulation of exenatide has been licensed in Canada.
In the 30-week study, 259 patients were randomly assigned to receive one or the other formulation of the drug.
At the end of the period, the A1C readings for those on the once-a-week schedule had dropped by 1.9 units, compared to 1.5 for those taking the drug twice daily. A1C is a measure of glycose stuck to red blood cells; it is the test used to determine how well a diabetic is doing controlling his or her blood sugar.
Elevated blood sugar leads to the complications of diabetes -- vision loss, kidney problems, nerve damage that can lead to limb amputation and heart disease.
More people on the weekly shot (77 per cent) managed to hit the target A1C reading of seven per cent than did people (61 per cent) taking the twice-daily shots. Weight loss in both groups was nearly identical, at just over 3.5 kilograms after 30 weeks.
Dr. Hertzel Gerstein, a diabetes expert at McMaster University in Hamilton, said it still remains to be seen whether lowering of A1C levels with this drug will translate into fewer complications of diabetes.
"Just because lowering or changing a value with one compound has a benefit doesn't mean that the same change caused by another compound will have the same benefit," he cautioned.
Still, Gerstein -- who has consulted with Amylin and Lilly on this drug -- said he would use exenatide in his practice "carefully" if and when it is approved for use in Canada.
"We don't have the ideal drug. There is no such thing as the ideal drug that has no side-effects, does exactly what you want it to do and that solves the problem completely," he said, saying it will be important to follow the drug for a number of years to get a more complete picture of its effectiveness.
"And so, in the end, every drug that we have . . . to treat every disease is going to have some side-effects, some things that we don't understand, some benefits. And ... the only way to know in the end is to do the long-term studies and get these data."
