DDP-4 inhibitors: A New Class of Oral Antidiabetic Drugs – Coming Soon

Data emerging on the safety and efficacy of the new oral antidiabetic agents were presented at the European Association for the Study of Diabetes 2006 Meeting.

Two new oral (DDP-4 inhibitors) antidiabetic agents, both vildagliptin (Galvus-Novartis), and sitagliptin (Januvia- Merck & Co) showing positive results for reductions in hemoglobin A1c (HbA1c) without associated weight gain or adverse gastrointestinal effects.

One study, led by Dr Emmanuele Bosi (Instituto Scientifico San Raffaele, Italy), showed that vildagliptin produced clinically meaningful, dose-related decreases in fasting plasma glucose, postprandial glucose levels, and HbA1c in type 2 diabetes mellitus patients treated with metformin.

In the study by Bosi and colleagues, investigators randomized 416 patients who had been treated with metformin for three or more months and had received a stable dose regimen of metformin (>1500 mg/day) to placebo, to vildagliptin 50 mg, or to vildagliptin 100 mg. The average HbA1c was 8.4% before treatment.

In both active-treatment arms, HbA1c decreased progressively from baseline to week 12 and then remained stable until the completion of the trial at week 24. The adjusted mean change in HbA1cwas -0.7% in patients treated with vildagliptin 50 mg and -1.1% in patients treated with vildagliptin 100 mg (p<0.001 vs placebo). The proportion of patients reaching the HbA1c target of <7.0% was three to four times higher in the vildagliptin-treated patients compared with placebo.

In addition to improvements in HbA1c, there were also improvements in fasting plasma glucose. The between-group difference in the adjusted mean change in fasting plasma glucose was -0.8 mmol and -1.7 mmol in patients treated with the 50 mg and 100 mg dose of vildagliptin, respectively, both significant when compared with placebo. A standard meal test performed in patients who volunteered to participate also showed that postprandial glucose levels were significantly decreased among those treated with the DDP-4 inhibitor.

Bosi also noted that beta-cell function was also improved with the active treatment and said that despite the improved glycemic control in patients adding vildagliptin to metformin treatment, relative to baseline, there was no change in body weight.

In another study, data on the safety and efficacy of sitagliptin added to metformin therapy were also presented, with the findings showing the combination to be well tolerated. Sitagliptin added to metformin provided sustained improvement in HbA1c, fasting blood glucose, and postprandial glucose levels, as well as improvements in insulin secretion and beta-cell function.

Patients treated with sitagliptin 50 mg twice daily and metformin 1000 mg twice daily had a significant mean placebo-subtracted 2.1% reduction in HbA1c. Significant HbA1c placebo-subtracted reductions and better goal attainment were also seen with sitagliptin 50 mg twice daily when a 500-mg twice-daily dose of metformin was administered. Investigators report adverse events were similar to those among patients treated with metformin alone. The most commonly reported adverse effects were gastrointestinal, including diarrhea, nausea, abdominal pain or discomfort, and vomiting.

In addition, a study by Dr Julio Rosenstock (University of Texas Southwestern Medical School, Dallas) showed that sitagliptin can be safely added to pioglitazone. In that 24-week trial in patients with type 2 diabetes mellitus and inadequate glycemic control on pioglitazone, the addition of sitagliptin led to significant lowering of HbA1c and fasting plasma glucose, all without additional weight gain and with good tolerance.

Source: Diabetes In Control: Presented at the European Association for the Study of Diabetes 2006 Meeting