AACE: The First Study to Show That an Ethnic Group Can Gain Benefits from a DPP-4 Compound

"We found that this drug had clinically significant and clinically relevant reductions in all measures of hyperglycemia that we looked at," said lead researcher James Thrasher, MD, from the Arkansas Diabetes and Endocrinology Center in Little Rock. The study was sponsored by the drug's manufacturers.

The multicenter, randomized, placebo-controlled, double-blind trial -- the first study of a DPP-4 inhibitor specifically conducted in black adults -- showed that linagliptin 5 mg once daily reduced HbA_1c by 0.88% over 24 weeks, compared with 0.24% with placebo (P = .0002).

Black adults tend to suffer from diabetes at a higher rate than white non-Hispanic adults, and "they have higher rates of complications," said Dr. Thrasher during a press conference.

"In most clinical trials, the majority of participants are white non-Hispanic patients. We wanted to do this first-of-a-kind study of a DPP-4 inhibitor to look at a minority group, specifically blacks," he said. "This is...something relatively new for us to do, to look at ethnic groups specifically with a clinical trial and a drug."

The study involved 226 patients who were randomized to linagliptin 5 mg (n = 106) or placebo (n = 120) once daily for 24 weeks. Slightly more than half (54%) of the patients were men, mean age was 54 years, and mean body mass index was 32.7 kg/m².

Almost three quarters (72%) of the patients had hypertension, and most patients were on metformin or a sulfonylurea, which they continued throughout the study period. The remaining 12% were treatment-naïve.

HbA_1c levels were similar in the linagliptin and placebo groups at baseline (8.63% vs 8.70%), and were measured every 6 weeks during the study.

Patients who had a baseline HbA_1c measurement and at least 1 post-baseline measurement (n = 200) were included in the efficacy analysis; those who received at least 1 dose of the study drug were included in the safety analysis.

In terms of efficacy, HbA_1c levels were significantly different at 6 weeks, and remained so for the rest of the study.

Patients in the linagliptin group were significantly more likely than those in the placebo group to see an HbA_1c reduction of 0.5% by week 24 (55.3% vs 28.3%; P < .0001). In addition, significantly more patients in the linagliptin group than in the placebo group achieved an HbA_1c level below 7.0% (28.0% vs 8.7%; P = .001), a target recommended by the American Diabetes Association.

The rates of adverse events were similar in the 2 groups, were mostly mild or moderate, and were considered to be unrelated to the study drug.

The most common adverse events were hyperglycemia (2.8% with linagliptin and 9.2% with placebo) and nasopharyngitis (3.8% with linagliptin and 5.0% with placebo). Researcher-defined hypoglycemia occurred in 3 patients in the linagliptin group and in 1 patient in the placebo group; none of the events required external assistance. "In this high-risk group, this is a drug that's efficacious, has a similar side-effect profile to placebo, and is a treatment option for patients who have inadequate control of their type 2 diabetes," concluded Dr. Thrasher. 

Presented at the American Association of Clinical Endocrinologist (AACE) May 24, 2012. Abstract 206.