Phase three data show linagliptin significantly lowered blood glucose

At the 70th Scientific Sessions of the American Diabetes Association (ADA), phase three data was presented showing that an investigational compound, a dipeptidyl peptidase (DPP)-4 inhibitor, achieved significant, sustained and clinically meaningful reductions in blood glucose as measured by the diabetes triad – haemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and postprandial glucose (PPG) concentrations.

Linagliptin is being investigated by Boehringer Ingelheim as a once-daily oral treatment in type two diabetes.

Once considered a disease of the West, type-two diabetes is an increasing epidemic in Asia, affecting a disproportionately high number of young to middle-aged adults. Within the next 15 years, it is anticipated there will be 380 million people around the world with diabetes; 60 percent of which will reside in Asia. Diabetes, and particularly un-controlled diabetes is associated with an increase risk of cardiovascular disease.

In the phase three studies, which included more than 1,000 patients from across Asia, 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, 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.

The data suggests that linagliptin would not need dose adjustment in patients with type two diabetes regardless of the stage of renal impairment.

The incidence of diabetic kidney disease is increasing in the developing world with Asia Pacific being the most severely affected, so it’s important that research and development efforts are focused on options suitable for this growing group of patients.

In four multi-centre, 24 weeks, 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 beta-cell function. Declining beta-cell function is a key factor driving the progression of type two 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.