Linagliptin fase III data

Linagliptine fase III resultaten, gepresenteerd op ADA

Ingelheim, Germany, 26 June 2010 - Linagliptin phase III data were presented for the first time this week at the 70th Scientific Sessions of the American Diabetes Association (ADA), showing that this investigational compound, a dipeptidyl peptidase (DPP)-4 inhibitor, achieved significant, sustained and clinically meaningful reductions in blood glucose as measured by haemoglobin A 1c (HbA 1c), fasting plasma glucose (FPG), and postprandial glucose (PPG) concentrations. 1-6 Linagliptin is being investigated by Boehringer Ingelheim as a once-daily oral treatment in type 2 diabetes.

In the pivotal phase III studies, linagliptin was shown to have a very favourable safety profile, with an overall rate of adverse events similar to placebo. In addition, linagliptin showed an excellent tolerability, was weight neutral, showed no increased risk of drug-drug interactions and, importantly, there was no increased risk of hypoglycaemia attributed to linagliptin use in monotherapy, or combination therapy with metformin or pioglitazone.

Notably, in diabetes patients with mild and moderate renal impairment, linagliptin blood plasma levels were comparable to those seen in diabetes patients with normal renal function, 1 suggesting that linagliptin, which has a primarily non-renal route of excretion, may have distinct pharmacological features not yet seen in this novel class of drugs. 8 The data suggest that linagliptin would not need dose adjustment in patients with type 2 diabetes regardless of the stage of renal impairment.

In four multi-centre, 24 weeks, randomised, double-blind, controlled trials, statistically significant reductions in blood glucose were observed with linagliptin monotherapy versus placebo 1 and when used in combination with other commonly used oral anti-diabetes drugs. This was accompanied by significant improvements in beta-cell function. Declining beta-cell function is a key factor driving the progression of type 2 diabetes.

In a further study, linagliptin monotherapy showed superiority in glucose lowering versus placebo and versus voglibose, the most commonly used alpha glucosidase inhibitor in Japan.

“Many type 2 diabetes patients treated with traditional anti-diabetes agents fail to achieve their glycaemic targets or maintain them over time, which can leave them at a higher likelihood of developing diabetic complications, including renal disease. Although renal impairment is very common in patients with type 2 diabetes, early stage renal dysfunction often goes undiagnosed. It is important to identify those patients as they will require effective and safer drugs with low risk of hypoglycaemia”, commented Julio Rosenstock, M.D., Director of Dallas Diabetes and Endocrine Center at Medical City and also a Clinical Professor of Medicine, University of Texas Southwestern Medical School, Dallas, Texas, USA. “For linagliptin, we see from studies that only approximately five percent of the orally administered drug is excreted via the kidneys. Data to date appear to indicate that linagliptin would not require dose adjustment, which could translate into an important benefit for physicians when choosing a treatment, not only for the type 2 diabetes patient population with diagnosed renal impairment, but also for those patients at risk of developing renal complications”, he added.

SOURCE: Boehringer Ingelheim