The phase III study results for linagliptin 5 mg once-daily has been announced by Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company. The results showed significant haemoglobin A1c (HbA1c or A1C) reduction of 0.88 per cent compared to 0.24 per cent in the placebo group (p=0.0002) at 24 weeks in black or African American adult patients with type 2 diabetes whose blood sugar was not adequately controlled.

The data were presented at the American Association of Clinical Endocrinologists (AACE) 21st annual Scientific and Clinical Congress.

Linagliptin is marketed as Tradjenta 5mg once-daily tablets in the US, and is the first and only member of the dipeptidyl peptidase-4 (DPP-4) inhibitor class to be approved at one dosage strength.

Tradjenta is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Tradjenta is a DPP-4 inhibitor that does not require dose adjustments regardless of declining renal function or hepatic impairment. Tradjenta should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis (increased ketones in the blood or urine). It has not been studied in combination with insulin.

In the US, African Americans and other ethnic minorities are significantly under represented in clinical trials. This is the first published trial of a DPP-4 inhibitor specifically conducted in black or African American adult patients with type 2 diabetes.

“These findings support the efficacy and safety profile of linagliptin as a treatment option for African American adult patients with type 2 diabetes,” said lead investigator James Thrasher, MD, FACE, Arkansas Diabetes and Endocrinology Centre. “As there may be differences in response to treatment among ethnic groups, an important finding of this trial is that the results are consistent with the A1C reduction seen in the linagliptin pivotal trials, which included a small sample of African American patients.”

African American adults are disproportionately affected by diagnosed diabetes. In the US, the risk of diabetes is 77 per cent greater for non-Hispanic black adults, when compared to non-Hispanic white adults, with an estimated 18.7 per cent (4.9 million) of all non-Hispanic black adults living with the disease.

In the 24-week study, 226 patients were randomized (106 to linagliptin, and 120 to placebo), and received at least one dose of the study drug in order to be included in the safety analyses. Patients who had a measurement of A1C at baseline (linagliptin 8.63 per cent +/-0.11; placebo 8.70 per cent +/-0.11) and at least one measurement post-baseline (200) were included in the analyses of efficacy. A1C was measured every six weeks during the study and the difference between the groups was significantly different by six weeks and remained so throughout the study.

The number of patients experiencing adverse events was similar for the linagliptin and placebo groups. The most common adverse events reported in this trial were hyperglycaemia (high blood sugar levels [linagliptin 2.8 per cent; placebo 9.2 per cent]) and nasopharyngitis (inflammation of the nose or pharynx [linagliptin 3.8 per cent; placebo 5 per cent]). Hypoglycaemia occurred in three patients in the linagliptin group and one patient in the placebo group, and none of the events required external assistance.

“These data are important because we know that African Americans are significantly more likely to have diabetes than non-Hispanic Whites,” said John Smith, MD, PhD, senior vice president for clinical development and medical affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “This study suggests that linagliptin provides black or African American adult patients with another option to improve control of their blood sugar, and it also reaffirms Boehringer Ingelheim and Lilly Diabetes' shared commitment to address the needs of the millions of Americans living with type 2 diabetes.”

A secondary endpoint of the study looked at the proportion of patients with an A1C value of less than 7.0 per cent, a target level recommended by the American Diabetes Association. Although the study was designed to recruit patients with an A1C of at least 7.5 per cent at screening, a few patients were below 7.0 per cent at the baseline measurement, and these patients were excluded from this analysis. All other patients with a baseline and at least one on-treatment measurement were included. At week 24, patients in the linagliptin group were significantly more likely to meet this target (28.0 per cent versus 8.7 per cent, p=0.001).

Patients in the linagliptin group were also significantly more likely to see an A1C reduction of at least half a per cent at week 24, with more than half the patients (55.3 per cent) in the linagliptin group having a reduction of 0.5 per cent or more, compared with 28.3 per cent in the placebo group (p < 0.0001).

In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an alliance in the field of diabetes that centres on four pipeline compounds representing several of the largest treatment classes. This alliance leverages the companies' strengths as two of the world's leading pharmaceutical companies, combining Boehringer Ingelheim's solid track record of research-driven innovation and Lilly's innovative research, experience, and pioneering history in diabetes. By joining forces, the companies demonstrate commitment in the care of patients with diabetes and stand together to focus on patient needs.