pile of pills

We know that diet and exercise can prevent the onset of type 2 diabetes in people with impaired glucose tolerance. We also know that healthy lifestyle measures are more effective than even the most effective drugs. That being said, we also know that in the real world with Mickey Ds and Starbucks on every corner, long work hours, longer hours in front of the computer, and way too few hours exercising our body parts, medications will be a part of the treatment armamentarium utilized to prevent type 2 diabetes.

So the question before us today is which drug should be used. An editorial in the March 20, 2007 issue of the Annals of Internal Medicine takes a stab at answering that question.

David Nathan, MD from the Massachusetts General Hospital Diabetes Unit and Michael Berkwits, MD, Deputy Editor of the Annals review the results of the DREAM trial (a.k.a. the Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication trial—seems like you can’t have an important trial nowadays without a cute acronym).

The DREAM trial randomly assigned more than 5,000 patients with impaired fasting glucose (>110 mg/dL, but less than 126 mg/dL) or impaired glucose tolerance (a glucose level 2 hours after an oral glucose load between 140 mg/dL and 199 mg/dL) into one of four groups. One group received ramipril (an ACE inhibitor), one received rosiglitazone (an insulin sensitizer), one group received both drugs, and one group received a placebo.

The participants were evaluated after 2, 6, and 12 months and annually thereafter to determine if they had either developed diabetes or died. They were also evaluated to see if their glucose levels improved during those time frames. The participants were middle-aged and they were obese (mean BMI 31 kg/m2).

Here is what the study showed:

  • Participants taking the drugs had a significant reduction in the progression to type 2 diabetes
  • The reduction was entirely attributable to taking rosiglitazone.
  • More patients taking rosiglitazone regressed to normal blood glucose levels (almost 39% in the rosi group compared to 20% in the placebo group.
  • Although both medications were generally safe, rosiglitazone was associated with a higher prevalence of peripheral edema (swollen ankles) and a ~2.2 kg weight gain. In addition, there was an increased frequency of heart failure in a small number of patients (0.5% in the rosi group compared to 0.1% in the placebo group)

The authors talk about what clinicians (and patients) should do in light of this new information. First of all, they point out that rosiglitazone is expensive and has some uncommon but serious side effects. There are, they remind us, other medications that have been shown to prevent progression from impaired glucose tolerance to type 2 diabetes.

Metformin is available as an inexpensive generic formulation. At least in people with BMIs of 35 or higher, the percent reduction in progression to diabetes is only slightly lower than that described with rosiglitazone (53% vs. 60%). In addition, it is well tolerated except for some minor gastrointestinal symptoms, and it is much cheaper. The other effective drug, acarbose, is poorly tolerated because of adverse GI side effects.

So what’s a clinician to do?

  • Continue to counsel and support patients with impaired glucose tolerance or impaired fasting glucose to adhere to a healthy lifestyle (you know, diet and exercise).
  • For patients unable to unwilling to make these changes, they recommend considering metformin, as opposed to rosiglitazone, as a medication to prevent type 2 diabetes.

It is noteworthy, that Dr. Nathan lists GlaxoSmithKline, makers of Avandia, the brand name for rosiglitazone, as a potential financial conflict of interest. His recommendation to not go with rosi as a first line diabetes prevention drug must surely have caused some heartburn in GSK marketing circles.