SAN DIEGO – Type 2 diabetes patients treated with linagliptin showed statistically significant improvements in hemoglobin A1c level after 24 weeks, regardless of their body mass index, on the basis of data from a pooled analysis of 2,224 patients.
Linagliptin, a dipeptidyl peptidase–4 (DPP-4) inhibitor, was approved by the U.S. Food and Drug Administration on May 2 as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. Two other DPP-4 inhibitors have been previously approved for the same indication – sitagliptin (Januvia) and saxagliptin (Onglyza).
In three phase III, randomized, double-blind, placebo-controlled trials, the primary efficacy outcome was the change in HbA1c level from baseline to 24 weeks. The average reduction in HbA1c was similar between BMI groups: –0.79 for those with a BMI less than 25 kg/m2, –0.57 for those with a BMI of 25-30, and –0.62 for those with a BMI above 30, Dr. Angelina Trujillo of Boehringer Ingelheim Pharmaceuticals in Ridgefield, Conn., reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.
One study evaluated linagliptin as monotherapy in patients previously untreated with oral diabetes medications or taking a single nonthiazolidinedione medication. The second study evaluated linagliptin when added to metformin in patients whose diabetes was not well controlled, some of whom were taking one additional oral antidiabetic medication. The third study evaluated linagliptin as additional therapy for patients whose diabetes was not well controlled on both metformin and a sulfonylurea.
The mean age of the patients ranged from 55 to 58 years, and about half were women. The average BMI ranged from 23 to 34 kg/m2.
The overall rate of adverse events was similar among the three groups, Dr. Trujillo and her associates found. In particular, the overall incidence of hyperglycemia was lower in the linagliptin group, compared with the placebo group, across all BMI categories. A higher incidence of hypoglycemia in the linagliptin group compared with the placebo group was seen in the linagliptin patients who were taking both metformin and a sulfonylurea.
"This was expected, as previously described in the literature, due to the combination with a sulfonylurea," she wrote in the poster. "The overall hypoglycemic event rate with linagliptin in monotherapy and add-on to metformin therapy was very low (less than 1.0%)," she added.
The incidence of serious adverse events based on BMI categories in the linagliptin and placebo groups were 4% and 5%, respectively, in those with BMIs of less than 25 kg/m2; 3% and 4% in those with BMIs of 25-30 kg/m2; and 3% and 2% in those with BMIs above 30.
"The safety and tolerability of linagliptin was comparable to placebo across baseline categories of normal, overweight, and obese BMI in this pooled analysis," she reported.
Litagliptin will be marketed as Tradjenta by Boehringer Ingelheim Pharmaceuticals and Eli Lilly. The study was supported by Boehringer Ingelheim Pharmaceuticals.