Linagliptin phase III data have been presented for the first time 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 over 24 weeks and clinically meaningful reductions in blood glucose.
Linagliptin is being investigated by Boehringer Ingelheim as a once-daily oral treatment in type 2 diabetes and is currently not licensed.
In the pivotal phase III studies, linagliptin was shown to have a favourable safety profile, with an overall rate of adverse events similar to placebo.
In addition, linagliptin was well tolerated, was weight neutral, showed no increased risk of drug-drug interactions and, importantly, there was no significantly increased risk of hypoglycaemia attributed to linagliptin use in monotherapy, or combination therapy with metformin or pioglitazone.
Professor Anthony Barnett, Professor of Medicine and Clinical Directorof the Department of Diabetes and Endocrinology, University ofBirmingham and Heart of England NHS Foundation Trust, Birmingham, UK, comments:
“What is of particular interest to both patients and clinicians is that this data shows that linagliptin provides good glycaemic control, low risk of hypoglycaemia and is weight neutral from a once daily 5 mg dose. These attributes, in addition to the favourable safety profile, offer an efficacious and interesting new option for treating type two diabetes.”
Linagliptin has a primarily non-renal route of excretion, a pharmacological feature not yet seen in other drugs in this class. In the linagliptin monotherapy study trough levels in patients with mild and moderate renal impairment were comparable to patients with normal renal function.
In four multi-centre, 24 week, randomised, double-blind, controlled trials, statistically significant reductions in blood glucose were observed with linagliptin monotherapy versus placebo and when used in combination with other commonly used oral anti-diabetes drugs.
This was accompanied by significant improvements in surrogate markers for 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 (not licensed in the UK), the most commonly used alpha glucosidase inhibitor in Japan.