October 24, 2006 (Toronto) — The results of the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study indicate that rosiglitazone is effective as a diabetes prevention strategy. But one of the investigators notes that lifestyle modification can first be adopted as a prevention strategy before pharmacotherapy is considered.
"This is another agent that we can add to our toolbox," said Hertzel C. Gerstein, MD, FRCPC, MSc, a co-principal investigator of the DREAM trial and a professor of medicine at McMaster University/Hamilton Health Sciences Centre in Hamilton, Ontario, Canada. "It is another drug that can be added to our arsenal. It remains to be seen how it will be used."
Dr. Gerstein noted that the arsenal includes drugs such as metformin and acarbose. Rosiglitazone, a thiazolidinedione, is approved for the treatment of hyperglycemia in patients with type 2 diabetes.
Results of the multicenter study that involved 5269 patients and evaluated the strength of rosiglitazone in preventing type 2 diabetes in patients at high risk for the condition were presented here at the annual meeting of the Canadian Diabetes Association (CDA)/Canadian Society for Endocrinology and Metabolism (CSEM).
The study found that 8 mg daily of rosiglitazone given to 2365 patients resulted in 306 cases of diabetes or death (11.6%) compared with 686 cases of diabetes or death (26.0%) in 2634 patients given a placebo, a difference that was highly statistically significant at P < .0001. In terms of reaching normal glycemic levels, 1330 patients (50.5%) in the rosiglitazone group and 798 patients (30.3%) receiving placebo achieved normal glycemic levels, a difference that was also statistically significant ( P < .0001). Patients in the trial were followed for a median of 3 years.
The 2 groups were similar in terms of their rates of cardiovascular events, but the incidence of congestive heart failure (CHF) was greater in patients receiving rosiglitazone, with 14 patients (0.5%) who received rosiglitazone compared with 2 patients (0.1%) receiving placebo who developed CHF ( P = .01).
"The aim of the study was to answer if rosiglitazone prevented diabetes," said Dr. Gerstein in an interview with Medscape. "We showed that it did. In fact, rosiglitazone prevented diabetes by 50% during the 3-year treatment period. We know that diet and exercise can also reduce the risk of diabetes substantially. If patients make modifications to their diet and they exercise, and are still at high risk of developing diabetes, then pharmacotherapy should perhaps be considered."
Edmond Ryan, MD, cochair of the CDA/CSEM annual meeting and professor of medicine in the department of endocrinology at the University of Alberta in Edmonton, Canada, notes that there are some toxicities associated with rosiglitazone that do not make it entirely attractive to patients.
"The message is that the advantage [in preventing diabetes] lies with rosiglitazone and not ramipril," said Dr. Ryan, who moderated the CDA session in which the trial results were discussed. "It's clear that rosiglitazone is effective in lowering blood glucose in these patients. In effect, what you are doing is treating prediabetes."
It is important to note the risk of adverse events that can be produced with rosiglitazone, Dr. Ryan said, such as weight gain and CHF; a patient would have to weigh those considerations before taking the medication.
Dr. Ryan said the finding that 798 of 2634 patients receiving placebo reverted to normal glycemic levels during the course of the study would support that a clinician can choose to monitor prediabetes patients before prescribing drug therapy.
"The study showed that nearly a third of patients on placebo reverted to normal in their blood sugar," said Dr. Ryan. "Given those findings, my instincts as a clinician are to advise diet and exercise changes before jumping in with rosiglitazone. We don't need to treat them unnecessarily [with medication]."
Dr. Gerstein described the weight gain that occurred in the trial among patients receiving rosiglitazone as "safe" because it was stored on the hips and not the abdomen. Mean body weight rose by 2.2 kg in the rosgilitazone group compared with the placebo group ( P < .0001). That weight gain was associated with a lower waist-to-hip ratio ( P < .0001) due to an increase in hip circumference of 1.8 cm and no increase in waist circumference.
"Nature wants us to store fat in our hips," said Dr. Gerstein. "Rosiglitazone is increasing the body's storage capacity in healthy places. It's better to store fat in the hip than where it can do mischief, which is in the abdomen."
The Canadian Institutes of Health Research, GlaxoSmithKline, Sanofi-Aventis, and King Pharmaceuticals funded the DREAM study. Dr. Gerstein is a member of advisory boards for GlaxoSmithKline and Pfizer. Dr. Ryan has received grant funding from GlaxoSmithKline and Pfizer.
CDA/CSEM Professional Conference and Annual Meeting: Hot Topic Lecture: To DREAM...Perchance to Prevent Diabetes. Presented October 20, 2006.
Medscape Medical News © 2006
Cite this: Louise Gagnon. DREAM: Rosiglitazone Effective in Preventing Diabetes - Medscape - Oct 24, 2006.