New
Treatment for Early and Pre Type 2 Diabetes
Inhibition
of dipeptidyl peptidase IV (DPP IV), could be an early treatment for
Type 2 diabetes.
A
new treatment paradigm for early type 2 diabetes, described in the May
issue of Diabetes Care, involves inhibition of dipeptidyl
peptidase IV (DPP IV).
"This
study provides the first evidence that pharmacological DPP IV
inhibition is feasible for the treatment of type 2 diabetes in
humans," write Bo Ahren, MD, from Lund University in Malmo,
Sweden, and colleagues.
Although
glucagon-like peptide-1 (GLP-1) has potential for treatment of type 2
diabetes, its short half-life prompted investigation of inhibitors of
the GLP-1-degrading enzyme DPP IV, which improve glucose tolerance in
insulin-resistant rats and mice.
This
double-blind, multicenter trial involved the selective, orally active
DPP IV inhibitor NVP DPP728. Over the 4-week treatment period, 61 men
and 32 women with diet-controlled type 2 diabetes (mean age, 64 years)
received placebo or the inhibitor at a dose of 100 mg three times
daily or 150 mg twice daily. There were no significant adverse
effects.
Compared
with placebo, NVP DPP728 at 100 mg three times daily reduced mean
fasting glucose by 1.0 mmol/L, prandial glucose excursions by 1.2
mmol/L, and mean 24-hour glucose levels by 1.0 mmol/l (all P<.001).
Reductions were similar in subjects receiving 150 mg twice daily, and
mean 24-hour insulin levels were reduced by 26 pmol/L in both active
treatment groups. An unexpected benefit was that HbA1c in
the combined active treatment groups decreased by 0.6% (P<.001).
"There
was no difference between a three-times-daily treatment schedule
versus a twice-daily treatment schedule with NVP DPP728, indicating
that either dosing regimen could probably be used with equal
efficacy," the authors write. "Further long-term studies
will be needed to examine the long-term effects of DPP IV inhibition
as well as to fully understand the mechanism of the effects and to
define the use of this approach in patients with more advanced
diabetes and in combination with other antidiabetic drugs."
Diabetes
Care. 2002;25(5):869-875
