PHILADELPHIA – Linagliptin was associated with significant improvements in hyperglycemia in a multicenter, randomized, placebo-controlled, double-blind trial of 226 African-American patients with type 2 diabetes.
"African Americans have a 77% greater likelihood of developing diabetes yet tend to be underrepresented in clinical trials of antidiabetic drugs," said Dr. James R. Thrasher, director of medical investigation at Arkansas Diabetes and Endocrinology Center, Little Rock. "We wanted to look at this group with higher rates of diabetes and higher risk for complications of diabetes."
Linagliptin (Tradjenta) is a once-daily dipeptidyl peptidase-4 inhibitor, licensed for the treatment of type 2 diabetes. Unlike other DPP-4 inhibitors, it does not require dose adjustment for patients with renal or hepatic impairment, Dr. Thrasher noted in an interview at the annual meeting of the American Association of Clinical Endocrinologists.
Patients were randomized to 24 weeks of 5 mg/day linagliptin or placebo. Overall, 54% of the patients were men. The mean age was 54 years and mean body mass index was 32.7 kg/m2. Nearly two-thirds (72%) had hypertension. In the efficacy analysis set of 100 linagliptin and 111 placebo patients, mean baseline hemoglobin A1c was 8.6% for the linagliptin group and 8.7% for the placebo group. Most patients were already taking metformin or a sulfonylurea, which did not change. Twelve percent were treatment naive.
By 24 weeks, mean HbA1c had dropped by 0.88 percentage points with linagliptin and 0.24 with placebo, a highly significant difference (P = 0.0002). Roughly three times more linagliptin patients achieved an HbA1c of less than 7.0% (28.0% vs. 8.7%) and almost twice as many had an HbA1c reduction of 0.5% or more (55.3% vs. 28.3%), Dr. Thrasher reported.
In the safety analysis set comprising 106 linagliptin and 120 placebo patients, most adverse events were mild or moderated and were considered unrelated to the study drug. The most common of these were hyperglycemia (2.8% in the linagliptin group and 9.2% in the placebo group) and nasopharyngitis (3.8% and 5.0%, respectively). Serious adverse events were reported in one linagliptin patient and two placebo patients. Hypoglycemia occurred in three linagliptin patients and one placebo patient. No event required external assistance, he said.
The responses among the African Americans in this study were comparable to those seen in the pivotal trials for linagliptin. "We know from studies of blood pressure medications that African Americans respond differently to different medications. In the area of diabetes, this is kind of landmark. It’s something new for us to look at ethnic groups specifically with a clinical trial for a drug. ... I hope this opens up the door to more [such] research with other drugs," Dr. Thrasher said.
Dr. Thrasher disclosed that he has received research grants and is a speaker for Boehringer Ingelheim, which manufactures linagliptin, and Lilly.