Boehringer Ingelheim to present linagliptin Phase III data at 46th EASD

Sep 22 2010

New Phase III data found that investigational linagliptin therapy resulted in significant reductions in blood sugar as measured by hemoglobin A1c (HbA1c) when compared to placebo, both when added to sulfonylurea (SU) in inadequately controlled type 2 diabetes (T2D) patients, and when administered as monotherapy in T2D patients for whom metformin is inappropriate. In addition, new pharmacokinetic (PK) data demonstrate that decreases in renal function had minor effect on the elimination of linagliptin. These findings support the study conclusion that a dose adjustment may not be required in T2D patients with varying degrees of renal impairment (RI) when treated with linagliptin. Boehringer Ingelheim Pharmaceuticals, Inc. is investigating the dipeptidyl peptidase 4 (DPP-4) inhibitor linagliptin as an oral once-daily tablet, as monotherapy and combination therapy, to treat T2D. The data are being presented this week at the 46th Annual Meeting of the European Association for the Study of Diabetes (EASD) in Stockholm, Sweden.

PK study shows minor effect on excretion in T2D patients with RI

Results from this PK study show that minor changes were observed in linagliptin exposure in study participants with RI (a 1.4-fold increase in exposure at steady state in T2D patients with severe RI compared with T2D patients with normal renal function). As a result of these findings, the study authors suggest that no dose adjustment is required in T2D patients with varying degrees of RI when treated with linagliptin.

RI refers to varying degrees of kidney damage, or chronic kidney disease (CKD), and can range from mild to severe. About a third of people with diabetes develop CKD.

"These results are consistent with existing data showing that linagliptin has a primarily non-renal route of excretion," said Dr. Tu Nguyen, executive director & medical leader, medical affairs, metabolic medicine, Boehringer Ingelheim Pharmaceuticals, Inc. "The data provide more information about linagliptin clearance in people with type 2 diabetes and varying degrees of renal impairment."

Linagliptin demonstrates significant reductions in HbA1c in T2D patients for whom metformin therapy is inappropriate

In this Phase III study, statistically significant differences in HbA1c between linagliptin and placebo could be seen at week six, and at week 18 the placebo adjusted mean difference was –0.57 percent (p<0.0001). Among patients who began the trial with an HbA1c of greater than or equal to 7.0 percent, 23.5 percent taking linagliptin achieved HbA1c <7.0 percent, compared to 11.8 percent taking placebo. Linagliptin-treated patients also saw statistically significant reductions in fasting plasma glucose (FPG) levels compared to placebo (adjusted mean difference from baseline –20.5 mg/dl).

Linagliptin as add-on therapy to an SU in inadequately controlled T2D patients

In another Phase III study presented at EASD, treatment with linagliptin resulted in significant reductions in HbA1c from baseline (mean placebo adjusted HbA1c reduction –0.47 percent; p<0.0001). The most commonly reported AEs in the linagliptin arm were metabolism and nutrition disorders (4.3 percent in linagliptin group, 8.3 percent in placebo group), nervous system disorders (1.9 percent) and general disorders and administration site conditions (1.2 percent).

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.