Long-term effect of rosiglitazone and/or ramipril on the incidence of diabetes.
OBJECTIVE
The Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial reported that 3 years of therapy with rosiglitazone reduced the primary outcome of diabetes or death by 60%. Here we investigated whether an effect on diabetes prevention persists more than 1.5 years after therapy has been discontinued.


METHODS
The DREAM On passive follow-up study was conducted at 49 of the 191 DREAM sites. Consenting participants were invited to have a repeat OGTT 1-2 years after active therapy ended. A diagnosis of diabetes at that time was based on either a fasting or 2 h plasma glucose level of ≥7.0 mmol/l or ≥11.1 mmol/l, respectively, or a confirmed diagnosis by a non-study physician. Regression to normoglycaemia was defined as a fasting and 2 h plasma glucose level of <6.1 mmol/l and <7.8 mmol/l, respectively.


RESULTS
After a median of 1.6 years after the end of the trial and 4.3 years after randomisation, rosiglitazone participants had a 39% lower incidence of the primary outcome (hazard ratio [HR] 0.61, 95% CI 0.53-0.70; p < 0.0001) and 17% more regression to normoglycaemia (95% CI 1.01-1.34; p = 0.034). When the analysis was restricted to the passive follow-up period, a similar incidence of both the primary outcome and regression was observed in people from both treatment groups (HR 1.00, 95% CI 0.81-1.24 and HR 1.14, 95% CI 0.97-1.32, respectively). Similar effects were noted when new diabetes was analysed separately from death. Ramipril did not have any significant long-term effect.


CONCLUSIONS
Time-limited exposure to rosiglitazone reduces the longer term incidence of diabetes by delaying but not reversing the underlying disease process.
H C
HC
Gerstein
V
V
Mohan
A
A
Avezum
R M
RM
Bergenstal
J-L
JL
Chiasson
M
M
Garrido
I
I
MacKinnon
P V
PV
Rao
B
B
Zinman
H
H
Jung
L
L
Joldersma
J
J
Bosch
S
S
Yusuf
D000368:Aged; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000517:prevention & control; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017257:Ramipril / Q000627:therapeutic use*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D017257:Ramipril