What the flurry's all about is the recent annoucement of results from the DREAM study (Diabetes Reduction Assessment with ramipril and rosiglitazone Medication) -- the largest diabetes prevention study ever conducted, which shows convincing evidence that the insulin sensitizer drug rosiglitazone (Avandia) dramatically
reduces the chance that people at risk of diabetes will go on to
develop the disease. Avandia appeared to cut the risk of developing Type 2 diabetes by more than half, doctors reported. Pretty significant! The media is having a field day...
But as one colleague points out, we'd do well to ask: just how groundbreaking is this study, really? Or is it just more hype?
After all, the Canadian-led study was funded by funded by the Canadian Institutes of Health Research, Sanofi-Aventis and King Pharmaceuticals (manufacturers of ramipril), as well as GlaxoSmithKline (GSK - manufacturer of rosiglitazone, aka Avandia). I recently posted here about information bias in research. And all you shrewd readers are diligent about reminding me that one always has to look at who's funding the research, and to what end.
On these matters, I often turn to well-respected diabetes consultant Kelly Close, whose group travels around the world attending industry events and evaluating advancements. She reported from Copenhagen, where the DREAM results were presented at the recent EASD (European Association for the Study of Diabetes) event:
(*you can watch the official DREAM results presentation HERE)
"What I liked most of all today was the DREAM trial. I liked it not because of what it means commercially for GSK, but because of what it meant for the disease. ... This trial showed that they could change the course of this ravaging disease — what congratulations they deserve! They will look back, I hope, and be proud for moving forward the research that makes the world realize that it can be done..."
Cynics say that since lifestyle changes alone can reduce diabetes progression 58%, and Avandia reduces risk by 60%, the need for Avandia is not clear. "For sure, no one is saying to forget lifestyle (changes)," Close reports. "But from a public health (or any) perspective, altering lifestyle obviously doesn't work so well -- we need other tools..."
Furthermore, Close is critical, saying the DREAM study was "not done perfectly by any stretch and there are some truly unsettling aspects of the trial results. But, ... despite everything that remains uncertain, the initial results in our view are promising enough that they should make Merck, Novartis, BMS, Lilly, and J&J and others realize that the ROI on prevention might well be positive — and that they better go for it because if they don't, someone else will — and because prevention is the right thing to do for past, future, and present patients."
Here's a summary of Close's key thoughts on the trial:
1. Results suggest that underlying physiology can be changed. It's not just about glucose, and it's not just about getting good numbers somewhat consistently. It's about avoiding the disease. There was a 62% reduction in progression to diabetes for the rosiglitizone treated group -- meaning 10.6% of the 5,279 people in the trial progressed to diabetes compared to 25% of people on placebo.
2. Better yet, over half (51%) of the people with pre-diabetes returned to normal blood glucose levels after just one year of Avandia treatment, compared to about 30% of people on placebo.
3. In terms of safety, "there were troubling results regarding congestive heart failure and weight gain." The trial had hopes of showing cardiovascular benefits, but none were seen.
4. Fourteen people in the treatment group developed heart disease, versus just two in the placebo group. The messaging seemed to focus more on "only 14 out of 5,279" rather than on relative risk. If you do the math to extrapolate percentages, that's a significant risk for thousands of people in the population.
5. Weight gain seen by those treated with the drugs was an average 2.2 kg, while the placebo group actually lost a little weight. Aren't patients going to be thinking, "So I have pre-diabetes and now you want me to take a drug that is going to make me gain weight?! And, it's possible I might have a heart attack? What?"
6. There are many open questions with regards to safety, topped by CHF (congestive heart failure) risk(!) There were no deaths in the study, but the study only lasted three years... Regarding minimizing weight gain? Beta cell health? etc.
Despite all this, the results of DREAM were so promising that Close concludes: "It's a whole new world in terms of companies working on metabolic disease — onward!"
From GSK's side, the company claims they are as surprised as anyone that the results are so "very compelling indeed." Now that the news is out, they're naturally "coordinating a publicity program around the study release" -- but have said that it's too early to officially (i.e. legally) promote Avandia for preventive purposes, because they first need regulatory approval for that use in both Europe and the United States (as in FDA approval). Stay tuned.