Therapy with alogliptin alone is significantly reduced glycosylated hemoglobin A1c levels in patients with type 2 diabetes and inadequate glycemic control, according to a double-blind, placebo-controlled, multicenter trial reported this month.
Alogliptin is a novel high-affinity, high-specificity inhibitor of dipeptidyl peptidase-4 (DPP-4), and has been shown to significantly reduce postprandial plasma glucose concentrations in patients with type 2 diabetes, Dr. Ralph A. DeFronzo at the University of Texas Health Science Center at San Antonio and colleagues note.
For the current study, a phase III trial, the researchers recruited 329 participants who had type 2 diabetes that was inadequately controlled with diet and exercise and who were treatment-naive. Average age of the participants was 53.4 years.
The subjects were randomized 2:2:1 to receive 12.5 mg alogliptin, 25 mg alogliptin or placebo for 26 weeks. Other antidiabetes drugs were prohibited. The study’s primary endpoint was mean change from baseline in A1c levels.
Mean A1c decreased significantly more with alogliptin 12.5 mg (-0.56%) and 25 mg (-0.59%) than with placebo (-0.02%), and significant reductions were seen as soon as week 4.
In addition, decreases in fasting plasma glucose were significantly greater with alogliptin than with placebo at week 26 and as early as week 1, and the percentage of patients needing hyperglycemic rescue was significantly less with alogliptin than with placebo.
Most adverse events were mild or moderate, and rates of hypoglycemia were similar across treatment groups (1.5% – 3.0%).
Because skin and digit lesions had been seen in earlier preclinical studies of DPP-4 inhibitors other than alogliptin, Dr. DeFronzo’s team monitored participants for skin-related adverse events. Although low overall, the incidence of such events was higher with alogliptin (12.8% – 15.2%) than with placebo (6.3%). One patient discontinued treatment (25 mg) because of moderate subcorneal pustular dermatosis that was judged to be possibly related to the study drug.
The researchers concluded that “the efficacy and safety of alogliptin monotherapy were comparable with those of other DPP-4 inhibitors. Alogliptin represents an effective treatment option whether given alone or in combination with antihyperglycemic agents from other classes.”
Diabetes Care, Dec. 2008.