Linagliptin is a dipetidyl peptidase 4 (DPP4) inhibitor: it prevents the breakdown of incretin hormones, leading to a glucose-dependent improvement in glycaemic control. Linagliptin excretion occurs primarily via the faeces, with approximately 5% undergoing renal excretion. Consequently, there is no requirement for dose adjustment in patients
with renal impairment. As a result of its long half-life, linagliptin requires only once daily administration.1
The efficacy, safety and tolerability of linagliptin monotherapy in 227 patients for whom metformin was inappropriate were assessed in an 18-week, randomised, double-blind, placebo-controlled study. At 18 weeks, the adjusted mean treatment difference for HbA1c between linagliptin and placebo was -0.57% (p<0.0001) in favour of linagliptin. In patients who had a baseline HbA1c ≥7.0%, 11.8% of those on placebo and 23.5% of those receiving linagliptin achieved an HbA1c of <7.0%. Linagliptin was also superior to placebo at reducing fasting plasma glucose from baseline to week 18 with an adjusted mean difference of -1.1mmol/l (p=0.0002).2
Linagliptin as an adjunct to metformin was assessed in a 24-week, randomised, double-blind, placebo-controlled, multicentre study (n=701). This study evaluated the efficacy and safety in patients with type II diabetes with inadequate glycaemic control. Participants had HbA1c levels of 7.0–10.0% (mean 8.1%) on metformin and were taking a maximum of one other antidiabetic agent, which was discontinued on study entry. After 24 weeks, linagliptin had reduced the adjusted mean HbA1c to a greater extent than placebo (adjusted mean treatment difference -0.64%; p<0.0001). A significant reduction in adjusted mean fasting plasma glucose levels was also seen for linagliptin compared with placebo, representing a treatment effect of -1.2mmol/l (p<0.0001).3
The safety and efficacy of linagliptin was compared with placebo as adjunct to metformin and a sulfonylurea in 1058 patients with type II diabetes with inadequate glycaemic control was evaluated in a phase 3 study. After 24 weeks, linagliptin had reduced the adjusted mean HbA1c to a greater extent than placebo (adjusted mean treatment difference -0.62%; p<0.0001). More patients with a baseline HbA1c ≥7.0% achieved an HbA1c <7.0% with linagliptin (29.2%) than with placebo (8.1%; p<0.0001).4
Adverse events occurred at a similar rate in the placebo and active treatment groups of the linagliptin studies.1 The most common side-effect was hypoglycaemia, seen in triple therapy.
- Barnett AH et al. Poster presented at the 46th annual meeting of European Association for the Study of Diabetes. Stockholm, Sweden, September 2010; P823.
Further information: Boehringer Ingelheim Ltd