Saxagliptin Improves Glycemic Control in Type 2 Diabetes Patients

Saxagliptin added to a thiazolidinedione improved glycemic control in Type 2 diabetes patients, in a phase III trial.

“Saxagliptin is a potent, selective inhibitor of DPP-4,” the authors explain. This is significant, they continue, because DPP-4 blocks the activity of glucagon-like peptide 1, which has a critical role in regulating blood glucose levels.

The 24-week multicenter trial involved 565 patients who had been taking a stable dose of thiazolidinediones but who had hemoglobin A1c (HbA1c) levels at or above 7% (but no higher than 10%).

Participants continued to take their usual thiazolidinedione dose, and in addition were randomized to receive either 2.5 mg or 5.0 mg of saxagliptin per day, or placebo.

As Dr. Priscilla Hollander from Baylor University Medical Center, Dallas, and her colleagues report, saxagliptin produced significant declines in HbA1c. Specifically, from baseline to week 24, HbA1c fell from 8.3% to 7.6% in the 2.5-mg group and from 8.4% to 7.4% in the 5.0 mg. The decline in the placebo group (from 8.2% to 7.9%) was not statistically significant.

More than half of saxagliptin-treated patients had HbA1c reductions of at least 0.7%, the authors report.

The proportion of patients achieving an HbA1c level below 7.0% was higher for saxagliptin 2.5 mg (42.2%) and 5 mg (41.8%) than for placebo (25.6%), as was the proportion of patients achieving an HbA1c level below 6.5% (19.3% for 2.5 mg, 20.7% for 5 mg, and 9.4% for placebo).

Fasting plasma glucose declines were significantly greater in both saxagliptin groups (0.8 mmol/L for 2.5 mg and 1.0 mmol/L for 5 mg) than in the placebo group (0.2 mmol/L).

Significant HbA1c reductions were seen by week 4, and significant fasting plasma glucose reductions were seen as early as week 2.

Beta-cell function improved in both saxagliptin groups compared with placebo, as did early insulin response to a glucose load and insulin sensitivity.

Saxagliptin was generally well tolerated, the investigators say, and rates of hypoglycemia were low in both groups.

“The glycemic benefits demonstrated in this study combined with a low propensity for hypoglycemia support the use of saxagliptin as add-on therapy to thiazolidinediones in patients with Type 2 diabetes and inadequate glycemic control in need of combination therapy,” the researchers conclude.