Pharmacodynamic characteristics of lixisenatide once daily versus liraglutide once daily in patients with type 2 diabetes insufficiently controlled on metformin. Issue 7 (25th February 2013)

• Record Type: Journal Article
• Authors: Kapitza, C.; Forst, T.; Coester, H.‐V.; Poitiers, F.; Ruus, P.; Hincelin‐Méry, A.
• Is Part Of: Diabetes, obesity & metabolism. Volume 15:Issue 7(2013:Jul.)
• Page Start: 642
• Page End: 649
• Publication Date: 2013-02-25
• Subjects: Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.12076
• Languages: English
• ISSNs: 1462-8902

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <sec id="dom12076-sec-0001" sec-type="section"> <title>Aim</title> <p>Assess the pharmacodynamics of lixisenatide once daily (QD) versus liraglutide QD in type 2 diabetes insufficiently controlled on metformin.</p> </sec> <sec id="dom12076-sec-0002" sec-type="section"> <title>Methods</title> <p>In this 28‐day, randomized, open‐label, parallel‐group, multicentre study (NCT01175473), patients (mean HbA1c 7.3%) received subcutaneous lixisenatide QD (10 µg weeks 1–2, then 20 µg; n = 77) or liraglutide QD (0.6 mg week 1, 1.2 mg week 2, then 1.8 mg; n = 71) 30 min before breakfast. Primary endpoint was change in postprandial plasma glucose (PPG) exposure from baseline to day 28 during a breakfast test meal.</p> </sec> <sec id="dom12076-sec-0003" sec-type="section"> <title>Results</title> <p>Lixisenatide reduced PPG significantly more than liraglutide [mean change in AUC<sub>0</sub><sub>:30–4:30h</sub>: −12.6 vs. −4.0 h·mmol/L, respectively; p < 0.0001 (0:30 h = start of meal)]. Change in maximum PPG excursion was −3.9 mmol/l vs. −1.4 mmol/l, respectively (p < 0.0001). More lixisenatide‐treated patients achieved 2‐h PPG <7.8 mmol/l (69% vs. 29%). Changes in fasting plasma glucose were greater with liraglutide (−0.3 vs. −1.3 mmol/l, p < 0.0001). Lixisenatide provided greater decreases in postprandial glucagon (p < 0.05), insulin (p < 0.0001) and C‐peptide (p < 0.0001). Mean HbA1c decreased in both treatment groups (from 7.2% to 6.9% with lixisenatide vs. 7.4% to 6.9% with liraglutide) as did body weight (−1.6 kg vs. −2.4 kg, respectively). Overall incidence of adverse events was lower with lixisenatide (55%) versus liraglutide (65%), with no serious events or hypoglycaemia reported.</p> </sec> <sec id="dom12076-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Once daily prebreakfast lixisenatide provided a significantly greater reduction in PPG (AUC) during a morning test meal versus prebreakfast liraglutide. Lixisenatide provided significant decreases in postprandial insulin, C‐peptide (vs. an increase with liraglutide) and glucagon, and better gastrointestinal tolerability than liraglutide.</p> </sec> </abstract>