The
effect of rosiglitazone is similar to that reported for lifestyle changes.
Among
patients at risk for progression to diabetes, metformin and acarbose
therapy each modestly reduce the likelihood of progression; dietary
modifications and increased exercise are more effective but are also
more difficult to maintain (Journal
Watch Feb 19 2002). In a new industry-funded multinational trial,
researchers explored the effectiveness of rosiglitazone, ramipril, or
both in patients at risk for diabetes; ramipril was studied because
angiotensin-converting–enzyme inhibitors have been associated with
a lower incidence of diabetes in previous trials (done for other
purposes).
Researchers
randomized more than 5000 nondiabetic patients with either elevated
fasting glucose levels (110–125 mg/dL) or impaired glucose
tolerance (plasma glucose, 140–199 mg/dL 2 hours after a 75-gm
glucose challenge) to receive daily rosiglitazone (titrated to 8 mg),
daily ramipril (titrated to 15 mg), both, or neither. Patients with
cardiovascular disease, including heart failure or reduced ejection
fraction, were excluded. All patients were encouraged to maintain
healthy diets and lifestyles.
After
a median 3 years of follow-up, the primary outcome of diabetes or
death occurred significantly less often in patients who received
rosiglitazone than in those who received placebo (12% vs. 26%); the
difference was due entirely to a reduction in incident diabetes.
Significantly more rosiglitazone patients than placebo patients
regressed to normoglycemia (50% vs. 30%). Ramipril recipients were
significantly more likely than placebo recipients to regress to
normoglycemia (42% vs. 38%), but a trend toward a lower rate of
incident diabetes in patients who received ramipril did not reach
statistical significance.
Comment:
The effect of rosiglitazone on progression to diabetes is similar to
that reported for lifestyle changes and greater than that reported
for acarbose or metformin. Rosiglitazone might simply have masked
progression to diabetes by reducing hyperglycemia; data collected
during the post-trial washout period (but not reported here) will
test this hypothesis. Ramipril had only a modest effect on glucose
metabolism; a longer or larger trial might have yielded significant
results.
With
regard to preventing end-organ complications, we don’t yet know
whether starting these interventions in prediabetic patients is
more effective than starting them after progression to overt diabetes.
—
Bruce Soloway, MD
Published
in Journal
Watch October 12, 2006
Citation(s):
DREAM
(Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial
Investigators. Effect of rosiglitazone on the frequency of diabetes in patients
with impaired glucose tolerance or impaired fasting glucose: A randomised
controlled trial. Lancet 2006 Sep 23; 368:1096-105.
[Medline
abstract]
The DREAM Trial Investigators. Effect of ramipril on the incidence of diabetes. N Engl J Med 2006 Oct 12; 355:1551-62.