Low doses of the diabetes drugs Avandia and metformin can help patients in the earliest stages of adult-onset diabetes from fully developing the illness, Canadian doctors report in The Lancet.
The pill combination appeared to reduce by two-thirds the risk that patients would progress from- pre-diabetes to full type 2 diabetes.
The drug combo lowered a person's absolute risk of developing the disease by 26 per cent. That means one case of Type 2 diabetes was averted for every four people who took the drug combo.
The study was conducted on 207 patients who had elevated levels of blood sugar and impaired glucose tolerance, indicating they had pre-diabetes. Half the patients were given them either half doses of Avandia and metformin a day, or placebos.
Fourteen per cent of the patients treated with the drugs developed diabetes after four years, compared to 39 per cent of those given placebo, the researchers found.
While the researchers used Avandia (rosiglitazone) for this study, they say the effect would likely be the same with another drug in the same class, Actos. Both medications are thiazolidinediones, a class of drugs that help the body better use insulin.
Metformin works another way by helping to reduce liver glucose production. While each medication has been shown to reduce the development of diabetes in patients in at-risk patients, for this study, researchers wanted to see the effect of combining the two.
By using half doses of each drugs, the researchers say they were able to avoid the side effects associated with the meds, including fluid retention and gastrointestinal problems.
Avandia has also been the subject of hot debate in the medical community, with some studies showing it raises a user's risk of heart failure and death.
Just this week, Avandia's maker, GlaxoSmithKline, settled more lawsuits alleging Avandia caused heart attacks. And last month, Dr. David Juurlink of Sunnybrook Health Sciences Centre and the U.S. watchdog group Public Citizen called on the U.S. Food and Drug Administration to scrap a large international trial comparing Avandia to Actos, saying it was unethical to proceed, given Avandia's safety profile.
GSK helped pay for this study, called the CANOE trial -- short for Canadian Normoglycemia Outcomes Evaluation.
While this study did not show any cardiac side effects from the drug combo, the researchers note the study was relatively short, at four years.
Still, lead author Dr. Bernard Zinman, a diabetes expert at Toronto's Mount Sinai Hospital, said they noticed no fluid retention in the patients, which often points to future potential heart effects.
Referring to the controversy surrounding Avandia, the authors say: "Larger long-term studies assessing low-dose combination therapy with these agents will be needed to establish cardiovascular benefit and risk, and overall long-term safety, including fracture risk."
Dr. Baiju Shah, an endocrinologist who works with Juurlink at Sunnybrook, expressed some reservations about the study. He noted the trial compared the drug combination against placebo, not against metformin alone or Avandia alone. Therefore, it's not clear whether low-dose Avandia or low-dose metformin on their own might be better than regular doses of each of the drugs.
He also says he's long been skeptical of drug treatment studies for diabetes prevention and says he'd like to see research on what happens to patients after they halt preventative drug regimens and whether they go to develop the condition anyway.
In an editorial accompanying the report, Dr. Thomas A. Buchanan of University of Southern California and Dr. Anny H. Xiang of Kaiser Permanente Southern California noted that the regimen did not affect the progression of beta-cell disease in the pancreas, which is the ultimate source of the diabetes. They said only what a treatment can do that will it be effective.
