WASHINGTON — Once-daily saxagliptin added to metformin resulted in statistically significant reductions in hemoglobin A1c, fasting plasma glucose, and postprandial glucose levels for up to 24 weeks in a placebo-controlled trial involving 743 patients with type 2 diabetes who were inadequately controlled with metformin alone.
Results of the multicenter phase III study were reported in a poster at the annual meeting of the American Association of Diabetes Educators by Dr. Shoba Ravichandran, an endocrinologist with Bristol-Myers Squibb, and Laureen MacEachern, director of scientific communications for the company. Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor jointly developed by Bristol-Myers Squibb and AstraZeneca PLC, which cosponsored the study.
At baseline, the patients had a mean diabetes duration of 6.5 years, mean hemoglobin A1c of 8.0%, fasting plasma glucose of 176 mg/dL, and 2-hour postprandial glucose of 286 mg/dL.
All of the patients were on stable doses of metformin—between 1,500 and 2,550 mg/day—for at least 8 weeks prior to the study, and remained on the same dosage during the study. They were randomized to one of four groups: saxagliptin in daily doses of 2.5, 5, or 10 mg, or placebo.
The investigators found statistically significant reductions in both HbA1c and fasting plasma glucose (FPG) were seen with all the saxagliptin doses, but the maximal benefit occurred with the 5.0- mg/day dose.
At week 24, placebo-corrected mean reductions from baseline in HbA1c were 0.73, 0.83, and 0.72 percentage points for the 2.5-, 5-, and 10-mg/day doses, respectively. Placebo-corrected FPG was reduced from baseline by 16, 23, and 22 mg/dL, respectively.
Reductions in FPG were observed as early as week 2, Dr. Ravichandran and Ms. MacEachern said.
The investigators also reported significant placebo-adjusted reductions in 2-hour postprandial glucose levels from baseline—44, 40, and 32 mg/dL, for the 2.5- 5-, and 10-mg doses, respectively. Saxagliptin did not have a significant impact on body weight, with mean reductions from baseline at week 24 of 1.4, 0.9, and 0.5 kg, respectively, and of 0.9 kg in the placebo group.
Saxagliptin was generally well-tolerated. A total of 74% of patients in the three treatment groups and 65% of the placebo group reported at least one adverse event, including nasopharyngitis in 9% of the saxagliptin patients and 8% of the placebo group, headache in 8% vs. 7%, and diarrhea in 7% vs. 11%, respectively.
The incidence of hypoglycemia was similar in the saxagliptin plus metformin-treated patients (5.7%) and the placebo plus metformin patients (5.0%).
Events of hypoglycemia that were confirmed by a fingerstick glucose value of 50 mg/dL or less were 0.5% for the saxagliptin groups and 0.6% with placebo, the investigators reported.
In July, Bristol-Myers Squibb and AstraZeneca announced the submission of a New Drug Application to the U.S. Food and Drug Administration and validation of a Marketing Authorization Application to the European Medicines Agency for saxagliptin under the proposed trade name Onglyza.