Licence extensions for linagliptin and vildagliptin

2 January 2013

The dipeptidyl peptidase 4 (DPP4) inhibitors linagliptin and vildagliptin have been approved for additional indications in type II diabetes.

DPP4 inhibitors prevent the breakdown of incretin hormones, leading to a glucose-dependent improvement in glycaemic control.

Trajenta (linagliptin) and Galvus (vildagliptin) can now be used in combination with insulin (with or without metformin), when insulin alone, with diet and exercise, does not provide adequate glycaemic control. Galvus has also been licensed for triple therapy alongside metformin and a sulfonylurea. In addition, the vildagliptin/metformin combination product Eucreas has been approved for use in combination with a sulfonylurea or insulin.

Linagliptin in combination with insulin

In a double-blind 24-week study, addition of linagliptin to insulin (with or without concomitant metformin and/or pioglitazone), provided a significant -0.65% improvement in HbA_1ccompared with placebo, from a mean baseline of 8.3%. A similar improvement in HbA_1c versus placebo was seen in a double-blind 24-week study in elderly patients (≥70 years) receiving linagliptin in addition to metformin and/or sulfonylurea and/or insulin: -0.64%, from a baseline of 7.8%.

Vildagliptin plus insulin

A randomised, double-blind 24-week trial showed that vildagliptin significantly reduced HbA_1c in patients receiving a stable dose of basal or premixed insulin (n=449). The placebo-adjusted mean HbA_1c reduction in the overall study population was -0.72% from a mean baseline of 8.8%. In patients receiving and patients not receiving concomitant metformin the reductions were 0.63% and 0.84%, respectively.
In another 24-week study in patients with more advanced type 2 diabetes not adequately controlled on insulin, addition of vildagliptin produced a significantly greater mean reduction in HbA_1c than addition of placebo (0.5% vs 0.2%).

Vildagliptin plus metformin and a sulfonylurea

A randomised, double-blind 24-week trial in 318 patients showed that vildagliptin in combination with metformin and glimepiride significantly decreased HbA_1c, with a placebo-adjusted mean reduction of 0.76% from a mean baseline HbA_1c of 8.8%.

Consider reducing sulfonylurea dose when used with DPP4 inhibitor

When DPP4 inhibitors are used in combination with insulin or a sulfonylurea, a lower dose of the sulfonylurea or insulin may be needed to reduce the risk of hypoglycaemia.