Boehringer Ingelheim (BI) has released a fistful of data from Phase III clinical trials showing that the DPP-4 inhibitor linagliptin, the most advanced compound in the company’s diabetes portfolio, can achieve “significant, sustained … and clinically meaningful” reductions in blood glucose levels.

The data from four Phase III trials with linagliptin, used either alone or in combination as a once-daily oral treatment for type 2 diabetes, were presented at the 70th Scientific Sessions of the American Diabetes Association (ADA) in Orlando, US.

Along with statistically significant reductions in blood glucose and significant improvements in surrogate markers of beta-cell function, linagliptin demonstrated a favourable safety profile, with no increased risk of drug-drug interactions, and was weight-neutral, BI reported.

Moreover, linagliptin was not associated with any marked increase in the risk of hypoglycaemia, either as monotherapy or when combined with metformin or pioglitazone (Actos).

The four multicentre, randomised, placebo-controlled, double-blinded trials looked at the efficacy, safety and tolerability of linagliptin 5mg administered once daily over 24 weeks in type 2 diabetes mellitus patients with insufficient glycaemic control. Blood levels of glycated haemoglobin (HbA1c) ranged from around 6.5% to 11%.

The treatment combinations were linagliptin as monotherapy, together with exercise and diet; as an add-on to metformin alone; as an add-on to metformin plus a sulfonylurea; and as an initial combination with pioglitazone.

Among the key efficacy highlights were:

- Linagliptin as monotherapy showed a mean placebo-adjusted reduction of -0.69% in HbA1c levels from baseline.

- Linagliptin monotherapy patients were significantly more likely to achieve HbA1c reductions of _ 0.5% at 24 weeks than those on placebo (47.1% versus 19.0% respectively).

- As an add-on to metformin, linagliptin achieved a placebo-adjusted mean change in HbA1c of -0.64% from baseline after 24 weeks of treatment, while post-prandial glucose levels were down by 67.1mg/dl.

- When linagliptin was added to metformin plus a sulfonylurea, mean placebo-adjusted HbA1c was down by 0.62% after 24 weeks, while patients with baseline HbA1c of _ 7.0% were significantly more likely to reach a target HbA1c of <7.0% when treated with linagliptin (29.2%) versus placebo (8.1%).

- Linagliptin in combination with pioglitazone produced a mean placebo-adjusted reduction of 1.06% from baseline in HbA1c and a change of -0.51% compared with the pioglitazone and placebo group.

In another Phase III study presented at the ADA scientific sessions, linagliptin monotherapy given over 12 or 26 weeks to drug-naïve or previously treated Japanese patients with type 2 diabetes achieved significant placebo-adjusted improvements in HbA1c levels (-0.87% for linagliptin 5mg versus placebo, -0.88% for linagliptin 10mg) at week 12.

At week 26, the placebo-adjusted mean changes from baseline HbA1c with linagliptin versus voglibose, the most commonly used alpha glucosidase inhibitor in Japan, were -0.32% for the 5mg dose and -0.39% for linagliptin 10mg, BI said.