Data Support JANUMETâ„¢, an Investigational Combination Therapy of Sitagliptin Phosphate Plus Metformin for Type 2 Diabetes

December 5, 2006 (BUSINESS WIRE) - CAPE TOWN, South Africa --Initial treatment with sitagliptin phosphate 50 mg twice daily in combination with metformin 1,000 mg twice daily provided substantial reductions of post prandial, or post-meal, glucose (PPG) levels and fasting plasma glucose (FPG) levels in patients with type 2 diabetes, according to new data presented for the first time today at the 19th World Diabetes Congress in Cape Town. Patients with a mean baseline 2-hour PPG of 287 mg/dL (n=152) achieved reductions of 117 mg/dL, and patients with a mean baseline FPG of 197 mg/dL (n=180) achieved reductions of 70 mg/dL, compared to placebo (primary analysis of all patients treated, p<0.001).
"Typically, oral medications for type 2 diabetes principally either reduce post-meal glucose levels or reduce fasting blood glucose levels. These study data are important because they showed substantial reductions in both measures of blood glucose levels, PPG and FPG, with sitagliptin phosphate plus metformin," said John Amatruda, M.D., vice president, clinical research, Merck & Co., Inc. "These study results provide further support for the efficacy of sitagliptin phosphate."

The American Diabetes Association (ADA) recommends that post prandial (PPG) levels should be below 180 mg/dL, and pre-prandial (FPG) levels should not rise above 130 mg/dL in patients with type 2 diabetes. Blood glucose levels both after meals and after fasting contribute to the A1C level, which is a commonly used measure of a person's average blood glucose over a two- to three-month period.

This study is part of the clinical program supporting JANUMET, an investigational therapy combining Merck's sitagliptin phosphate with metformin. In the study, combination treatment with sitagliptin phosphate plus metformin was generally well tolerated and showed no meaningful differences in tolerability compared to metformin alone. Side effects of combination treatment with sitagliptin phosphate 50 mg twice daily plus metformin 1,000 mg twice daily compared to metformin 1,000 mg twice daily alone included diarrhea (9 percent vs. 10 percent, respectively), nausea (6 percent vs. 8 percent, respectively), abdominal pain/discomfort (3 percent vs. 5 percent, respectively) and vomiting (3 percent vs. 1 percent, respectively).

In other studies of sitagliptin phosphate administered in combination with metformin, the most common side effects reported include nasopharyngitis, back pain, arthralgia and cough.

A1C efficacy results of sitagliptin phosphate plus metformin as initial therapy

This 24-week, randomized, double-blind, placebo-controlled study involved 1,091 untreated patients with type 2 diabetes (mean baseline A1C = 8.8 percent). After a run-in period of diet, exercise and/or placebo, patients were randomized to receive one of six daily treatments: sitagliptin phosphate 50 mg/metformin 500 mg twice daily (n=190), sitagliptin phosphate 50 mg/metformin 1,000 mg twice daily (n=182), metformin 500 mg twice daily (n=182), metformin 1,000 mg twice daily (n=182), sitagliptin phosphate 100 mg once daily (n=179), and placebo (n=176).

As previously disclosed at a meeting of the European Association for the Study of Diabetes (EASD) in September, this study demonstrated a significant mean placebo-subtracted reduction in A1C of 2.1 percent from a mean baseline A1C of 8.7 percent (primary analysis of all patients treated, p>0.001) in the patients treated with sitagliptin phosphate 50 mg twice daily combined with metformin 1,000 mg twice daily, as initial therapy.