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Phase III data demonstrated that Saxagliptin, an inhibitor of dipeptidyl-peptidase-4 ( DPP-4 ), in combination with Metformin, exhibited a statistically significant improvement in glycemic control in subjects with type 2 diabetes compared to Metformin alone through 24 weeks of treatment.

A group of 743 subjects ( ages 18-77 ) with type 2 diabetes whose hemoglobin A1C level was within the range of greater than or equal to 7 percent or less than or equal to 10 percent and on a stable Metformin dose alone ( 1500 to 2550 mg/day ) were randomized 1:1:1:1 to add-on Saxagliptin 2.5 mg, 5 mg, 10 mg, or placebo once daily.

The primary endpoint of the study was the change from baseline in HbA1C levels. After 24 weeks, the subjects receiving Saxagliptin + Metformin demonstrated statistically significant decreases in hemoglobin A1C levels compared to Placebo + Metformin: -0.73 percent, -0.83 percent, and -0.72 percent at the 2.5 mg, 5 mg and 10 mg doses, respectively ( p-value at all dosage levels less than 0.0001 versus Placebo + Metformin ).

Saxagliptin plus Metformin also statistically significantly reduced fasting plasma glucose ( secondary endpoint ) as compared to Placebo plus Metformin: -16 mg/dL, -23 mg/dL, and -22 mg/dL for Saxagliptin 2.5 mg, 5 mg and 10 mg, respectively ( p-value at all dosage levels less than 0.0001 vs. Placebo + Metformin ).

The percentage of subjects with HbA1C less than 7 percent at week 24 ( secondary endpoint ) was 17 percent for Placebo + Metformin and 37 percent, 44 percent and 44 percent for the 2.5 mg, 5 mg and 10 mg doses of Saxagliptin respectively ( p-value at all dosage levels less than 0.0001 vs. Placebo + Metformin ).

The number of subjects with investigator-reported hypoglycemia, with or without confirmation, were: 9 on Placebo + Metformin, and 15, 10 and 7, for 2.5 mg, 5 mg, and 10 mg on Saxagliptin + Metformin, respectively.
The most common adverse events seen in more than 5 percent of subjects randomized to either Placebo + Metformin or Saxagliptin + Metformin ( all doses combined ) were: nasopharyngitis 7.8% vs. 8.7 %, headache 7.3% vs. 8.0%, diarrhea 11.2% vs. 7.1%, upper respiratory infection 5.0% vs. 6.6%, influenza 7.3% vs. 6.0%, and urinary tract infection 4.5% vs. 5.1%.

Source: American Diabetes Association ( ADA ) – Meeting, 2007

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