Today we have even more bad news in two separate studies about the diabetes drug Avandia. With the bad news we get all the time about diabetes you might wonder why I report more negative stuff.
It’s because we have much better alternatives.
I have been studying a pre-print of a report scheduled to appear in the highly-respected Cochrane Library, a journal devoted to systematic reviews of health care interventions. The abstract is online. This is a publication of the Cochrane Collaboration, which has worldwide chapters in 50 medical specialties. The name comes from Archie Cochrane, who wrote a history of fatal flaws in medical practice, like the refusal by 19th century doctors to wash their hands between dissecting corpses and examining patients.
Embargoed until just this hour, The Cochrane Library reports a systematic review of data by German researchers. Led by Bernd Richter, M.D., of Heinrich-Heine University, the study pooled data from 18 randomized controlled trials including more than 8,000 participants.
The new study is unlike the sensational meta-analysis that came out in May indicating that Avandia causes some people to use it to have heart attacks. That seems to affect only a small percentage of people who take it.
The new study reports on negative side effects of Avandia that affect the average user. It seems that even if you don’t die of a heart attack while taking this drug, you will probably gain a lot of weight in the meanwhile.
The pooled data that the study looked at revealed that people who take Avandia gained up to 11 pounds in body weight and that the chance of developing swelling doubled. These changes indicate that the drug causes fluid retention, which can lead to shortness of breath and heart failure.
It was the Rosiglitazone Clinical Trials Study Group, headed by Martin St. John Sutton, that reported the 11 pound weight gain on Avandia in a 2002 issue of Diabetes Care. That was just in the first year of use.
It happens that another study, which the new review did not include, showed the same 11-pound weight gain. Kaiser Permanente Northwest members who started taking Avandia or Actos (a similar drug in the same class) between 1996 and 2002 and continued to use it for at least a year without adding any other diabetes medication gained an average of 11 pounds in the first year they used it. That’s more than any other drug that we take to control our diabetes, including insulin and the sulfonylureas. Gregory A. Nichols and Andres Gomez first reported this finding in “Weight Changes Associated with Anti-Hyperglycemic Therapies for Type 2 Diabetes,” in abstract 13-OR presented at the 65th Annual Scientific Sessions of the American Diabetes Association, San Diego in 2005.
Even without taking Avandia, people with diabetes usually have a big enough problem with weight. U.S. government statistics show that 85 percent of us are overweight or obese.
The new Cochrane study has a damning conclusion as I ever remember reading in a scientific study. “New safety data on increased rates of fractures and possibly the risk of myocardial infarction and cardiovascular disease should lead to a very cautious approach to rosiglitazone use. If possible, other antidiabetic medications should be employed.”
It doesn’t even make sense to study Avandia more. “It appears
questionable whether new studies with rosiglitazone will be ethical
given the fact that less dangerous therapeutic alternatives exist.”
Since weight is such a big issue to people with diabetes, the clinical studies of all diabetes drugs look at it. But the drug’s ability to reduce our blood glucose levels, as measured by a drop in A1C, is what interests the researchers the most.
In this respect Avandia works quite well. People in a 26-week clinical trial were able to bring down their A1C by 1.5 percent more than those taking a placebo.
But some other drugs that don’t lead to weight gain also improve our A1C even more than Avandia does. Metformin, which is now a generic drug and is also sold under the Glucophage brand, typically reduced A1C by 1.8 percent in a 29 week trial.
Januvia didn’t do as well, bringing down A1C just 0.8 percent more than those on a placebo in 24 weeks. Byetta also reduces A1C, although the only published studies so far show the results when used with another diabetes drug. Amylin Pharmaceuticals tells me that studies of Byetta used alone are due out at the end of the year.
Importantly, none of these drugs – metformin, Januvia, or Byetta – lead to weight gain. Januvia and Byetta are new on the market, but metformin has been available since 1995, even longer than Avandia, which the Food and Drug Administration approved in 1999.
Some people avoid taking metformin because it might cause a rare but dangerous side effect called lactic acidosis, the buildup of lactic acid in the blood. So doctors don’t prescribe it to people who have moderate kidney disease or heart failure.
However, another new study questions the basis of this concern about lactic acidosis from taking metformin. The Annals of Internal Medicine will publish this study in September, but it’s already online.
The federal Agency for Healthcare Research and Quality commissioned this analysis of diabetes drugs in 2005. Its goal was to do the first in-depth comparison of the many oral medications that came out in the previous decade, as well as the sulfonylureas, which been available for half a century. The report didn’t evaluate insulin or other injected diabetes drugs like Byetta.
A key finding of this report is that they found no “evidence of an elevated risk for lactic acidosis in patients taking metformin compared with other oral diabetes agents.” The evidence for metformin-induced lactic acidosis stems mainly from about 300 case reports. “We suspect that apparent cases of ‘metformin-induced lactic acidosis’ may have been overreported,” because an earlier drug in the same class, phenformin, unequivocally did cause lactic acidosis.
Aside from this concern, metformin appears remarkably safe and effective in reducing blood glucose. It certainly doesn’t cause weight gain, and may in fact lead to a little weight loss. It is even much less expensive than Avandia.
Why then don’t doctors prescribe metformin even more often than they do? Partly it is because some people experience nausea from it. But I know from my own experience of taking metformin up until a year ago that when people start it at small doses and work up to larger ones, you can usually avoid that problem.
I suspect that the reason so many people are still using Avandia is because the manufacturer, GlaxoSmithKline, markets it so well. Because metformin is an inexpensive generic drug, there’s just not that much money in it for the pharmaceutical companies. And cost is all the more reason for people who are still using Avandia to try to persuade their doctors to switch them to metformin.
Januvia and Byetta are more expensive than metformin. But unlike Avandia, they help us control our blood glucose while not causing cause heart attacks or weight gain. And as I have reported here in several articles, Byetta can help us to lose a lot of weight.
This article is based on an earlier version of my article published by HealthCentral.
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