Issue 108 Item 9 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