Dr.Vad
24.09.2006, 01:43
DREAM trial findings released early online in two major general medical journals indicate that rosiglitazone reduces the risk of diabetes in patients with impaired glucose tolerance or fasting glucose compared with placebo, but ramipril does not.
Both drugs increased the likelihood of regression to normoglycemia, however, say the researchers reporting the rosiglitazone results in the Lancet and the ramipril results in the New England Journal of Medicine (NEJM).
The findings have been released to coincide with their presentation at the European Association for the Study of Diabetes 2006 meeting in Copenhagen, Denmark.
The Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial included 5269 patients with impaired plasma glucose levels after overnight fast (≥110 mg/dl but <126 mg/dl) or impaired glucose tolerance (2-hour post-load plasma glucose ≥140 mg/dl but <200 mg/dl), and no diabetes or cardiovascular disease (CVD).
In a 2x2 factorial design, participants were randomly assigned to receive the thiazolidinedione rosiglitazone 8 mg or placebo daily and concurrently assigned to the ACE inhibitor ramipril up to 15 mg or placebo and followed for a median of 3 years.
The primary composite endpoint of incident diabetes or death occurred less frequently with rosiglitazone than placebo, at 11.6% and 26.0%, respectively, giving a hazard ratio (HR) of 0.40 with active treatment (p<0.0001).
In contrast, there was no significant difference in the primary endpoint with ramipril, with events occurring in 18.1% versus 19.5% in the placebo arm.
Both rosiglitazone and ramipril did, however, increase the likelihood of the secondary outcome of regression to normoglycemia, compared with placebo, with HRs of 1.71 and 1.16, respectively (p<0.0001 and p=0.001).
In the ramipril group, glucose levels measured 2 hours after oral glucose challenge were also significantly lower than with placebo, although median fasting glucose level by the end of the study was unaffected.
This leads the researchers to suggest in the NEJM that “ramipril may have favorable effects on glucose metabolism” - a view endorsed in an editorial by Julie Ingelfinger and Caren Solomon, both deputy editors of the journal.
CVD event rates were similar with rosiglitazone and placebo, although heart failure was more likely in the active treatment group, occurring in 0.5% versus 0.1% of patients (p=0.01).
“Balancing both the benefits and risks suggests that for every 1000 people treated with rosiglitazone for 3 years, about 144 cases of diabetes will be prevented, with an excess of four to five cases of congestive heart failure,” report Herzel Gerstein (McMaster University, Hamilton, Ontario, Canada) and fellow DREAM investigators in the Lancet.
In an accompanying editorial, Jaakko Tuomiehto (University of Helsinki, Finland) and Nicholas Wareham (MRC Epidemiology Unit, Cambridge, UK) calculate that the 0.5-mmol/l difference in fasting glucose seen with rosiglitazone versus placebo should lower the risk of CVD events “by about 8.6%.”
They add: “If this estimate were the true value, the number needed to treat people like those in DREAM for 3 years to prevent one CVD event would be 554, which is very high.”
Both drugs increased the likelihood of regression to normoglycemia, however, say the researchers reporting the rosiglitazone results in the Lancet and the ramipril results in the New England Journal of Medicine (NEJM).
The findings have been released to coincide with their presentation at the European Association for the Study of Diabetes 2006 meeting in Copenhagen, Denmark.
The Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial included 5269 patients with impaired plasma glucose levels after overnight fast (≥110 mg/dl but <126 mg/dl) or impaired glucose tolerance (2-hour post-load plasma glucose ≥140 mg/dl but <200 mg/dl), and no diabetes or cardiovascular disease (CVD).
In a 2x2 factorial design, participants were randomly assigned to receive the thiazolidinedione rosiglitazone 8 mg or placebo daily and concurrently assigned to the ACE inhibitor ramipril up to 15 mg or placebo and followed for a median of 3 years.
The primary composite endpoint of incident diabetes or death occurred less frequently with rosiglitazone than placebo, at 11.6% and 26.0%, respectively, giving a hazard ratio (HR) of 0.40 with active treatment (p<0.0001).
In contrast, there was no significant difference in the primary endpoint with ramipril, with events occurring in 18.1% versus 19.5% in the placebo arm.
Both rosiglitazone and ramipril did, however, increase the likelihood of the secondary outcome of regression to normoglycemia, compared with placebo, with HRs of 1.71 and 1.16, respectively (p<0.0001 and p=0.001).
In the ramipril group, glucose levels measured 2 hours after oral glucose challenge were also significantly lower than with placebo, although median fasting glucose level by the end of the study was unaffected.
This leads the researchers to suggest in the NEJM that “ramipril may have favorable effects on glucose metabolism” - a view endorsed in an editorial by Julie Ingelfinger and Caren Solomon, both deputy editors of the journal.
CVD event rates were similar with rosiglitazone and placebo, although heart failure was more likely in the active treatment group, occurring in 0.5% versus 0.1% of patients (p=0.01).
“Balancing both the benefits and risks suggests that for every 1000 people treated with rosiglitazone for 3 years, about 144 cases of diabetes will be prevented, with an excess of four to five cases of congestive heart failure,” report Herzel Gerstein (McMaster University, Hamilton, Ontario, Canada) and fellow DREAM investigators in the Lancet.
In an accompanying editorial, Jaakko Tuomiehto (University of Helsinki, Finland) and Nicholas Wareham (MRC Epidemiology Unit, Cambridge, UK) calculate that the 0.5-mmol/l difference in fasting glucose seen with rosiglitazone versus placebo should lower the risk of CVD events “by about 8.6%.”
They add: “If this estimate were the true value, the number needed to treat people like those in DREAM for 3 years to prevent one CVD event would be 554, which is very high.”