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Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU)

Identifieur interne : 008996 ( Main/Merge ); précédent : 008995; suivant : 008997

Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU)

Auteurs : M. Marre [France] ; J. Shaw [Australie] ; M. Br Ndle [Suisse] ; W. M. W. Bebakar [Malaisie] ; N. A. Kamaruddin [Malaisie] ; J. Strand [Finlande] ; M. Zdravkovic [Danemark] ; T. D. Le Thi [Danemark] ; S. Colagiuri [Australie]

Source :

RBID : Pascal:09-0162156

Descripteurs français

English descriptors

Abstract

Aim To compare the effects of combining liraglutide (0.6, 1.2 or 1.8 mg/day) or rosiglitazone 4 mg/day (all n ≥228) or placebo (n = 114) with glimepiride (2-4 mg/day) on glycaemic control, body weight and safety in Type 2 diabetes. Methods In total, 1041 adults (mean ± so), age 56 ± 10 years, weight 82 ± 17 kg and glycated haemoglobin (HbA1c) 8.4 ± 1.0% at 116 sites in 21 countries were stratified based on previous oral glucose-lowering mono: combination therapies (30: 70%) to participate in a five-arm, 26-week, double-dummy, randomized study. Results Liraglutide (1.2 or 1.8 mg) produced greater reductions in HbA1c from baseline, (-1.1%, baseline 8.5%) compared with placebo (+0.2%, P < 0.0001, baseline 8.4%) or rosiglitazone (-0.4%, P < 0.0001, baseline 8.4%) when added to glimepiride. Liraglutide 0.6 mg was less effective (-0.6%, baseline 8.4%). Fasting plasma glucose decreased by week 2, with a 1.6 mmol/l decrease from baseline at week 26 with liraglutide 1.2 mg (baseline 9.8 mmol/l) or 1.8 mg (baseline 9.7 mmol/l) compared with a 0.9 mmol/l increase (placebo, P < 0.0001, baseline 9.5 mmol/l) or 1.0 mmol/l decrease (rosiglitazone, P < 0.006, baseline 9.9 mmol/l). Decreases in postprandial plasma glucose from baseline were greater with liraglutide 1.2 or 1.8 mg [-2.5 to -2.7 mmol/l (baseline 12.9 mmol/l for both)] compared with placebo (-0.4 mmol/l, P< 0.0001, baseline 12.7 mmol/l) or rosiglitazone (-1.8 mmol/l, P < 0.05, baseline 13.0 mmol/l). Changes in body weight with liraglutide 1.8 mg (-0.2 kg, baseline 83.0 kg), 1.2 mg (+0.3 kg, baseline 80.0 kg) or placebo (-0.1 kg, baseline 81.9 kg) were less than with rosiglitazone (+2.1 kg, P < 0.0001, baseline 80.6 kg). Main adverse events for all treatments were minor hypoglycaemia (< 10%), nausea (<11%), vomiting (< 5%) and diarrhoea (< 8%). Conclusions Liraglutide added to glimepiride was well tolerated and provided improved glycaemic control and favourable weight profile.

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Pascal:09-0162156

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<title xml:lang="en" level="a">Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU)</title>
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<name sortKey="Bebakar, W M W" sort="Bebakar, W M W" uniqKey="Bebakar W" first="W. M. W." last="Bebakar">W. M. W. Bebakar</name>
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<country>Malaisie</country>
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<name sortKey="Kamaruddin, N A" sort="Kamaruddin, N A" uniqKey="Kamaruddin N" first="N. A." last="Kamaruddin">N. A. Kamaruddin</name>
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<country>Malaisie</country>
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<country>Finlande</country>
<wicri:noRegion>Oulun Diakonissalaitos</wicri:noRegion>
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<title level="j" type="main">Diabetic medicine</title>
<title level="j" type="abbreviated">Diabetic med.</title>
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<date when="2009">2009</date>
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<title level="j" type="main">Diabetic medicine</title>
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<idno type="ISSN">0742-3071</idno>
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<keywords scheme="KwdEn" xml:lang="en">
<term>Agonist</term>
<term>Analog</term>
<term>Body weight</term>
<term>Comparative study</term>
<term>Daily dose</term>
<term>Endocrinology</term>
<term>Glucagon like peptide 1</term>
<term>Glycemia</term>
<term>Human</term>
<term>Hypoglycemic agent</term>
<term>Improvement</term>
<term>Incretin</term>
<term>Lead</term>
<term>Liraglutide</term>
<term>Metabolic diseases</term>
<term>Nutritional status</term>
<term>Peptidases</term>
<term>Placebo</term>
<term>Rosiglitazone</term>
<term>Surveillance</term>
<term>Thiazolidinedione derivatives</term>
<term>Type 2 diabetes</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Liraglutide</term>
<term>Dose journalière</term>
<term>Homme</term>
<term>Rosiglitazone</term>
<term>Peptide GLP1</term>
<term>Analogue</term>
<term>Diabète de type 2</term>
<term>Amélioration</term>
<term>Glycémie</term>
<term>Poids corporel</term>
<term>Surveillance</term>
<term>Etude comparative</term>
<term>Placebo</term>
<term>Plomb</term>
<term>Peptidases</term>
<term>Agoniste</term>
<term>Dérivé de la thiazolidinedione</term>
<term>Endocrinologie</term>
<term>Maladie métabolique</term>
<term>Hypoglycémiant</term>
<term>Etat nutritionnel</term>
<term>Récepteur GLP-1</term>
<term>Incrétine</term>
</keywords>
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<front>
<div type="abstract" xml:lang="en">Aim To compare the effects of combining liraglutide (0.6, 1.2 or 1.8 mg/day) or rosiglitazone 4 mg/day (all n ≥228) or placebo (n = 114) with glimepiride (2-4 mg/day) on glycaemic control, body weight and safety in Type 2 diabetes. Methods In total, 1041 adults (mean ± so), age 56 ± 10 years, weight 82 ± 17 kg and glycated haemoglobin (HbA
<sub>1c</sub>
) 8.4 ± 1.0% at 116 sites in 21 countries were stratified based on previous oral glucose-lowering mono: combination therapies (30: 70%) to participate in a five-arm, 26-week, double-dummy, randomized study. Results Liraglutide (1.2 or 1.8 mg) produced greater reductions in HbA
<sub>1c</sub>
from baseline, (-1.1%, baseline 8.5%) compared with placebo (+0.2%, P < 0.0001, baseline 8.4%) or rosiglitazone (-0.4%, P < 0.0001, baseline 8.4%) when added to glimepiride. Liraglutide 0.6 mg was less effective (-0.6%, baseline 8.4%). Fasting plasma glucose decreased by week 2, with a 1.6 mmol/l decrease from baseline at week 26 with liraglutide 1.2 mg (baseline 9.8 mmol/l) or 1.8 mg (baseline 9.7 mmol/l) compared with a 0.9 mmol/l increase (placebo, P < 0.0001, baseline 9.5 mmol/l) or 1.0 mmol/l decrease (rosiglitazone, P < 0.006, baseline 9.9 mmol/l). Decreases in postprandial plasma glucose from baseline were greater with liraglutide 1.2 or 1.8 mg [-2.5 to -2.7 mmol/l (baseline 12.9 mmol/l for both)] compared with placebo (-0.4 mmol/l, P< 0.0001, baseline 12.7 mmol/l) or rosiglitazone (-1.8 mmol/l, P < 0.05, baseline 13.0 mmol/l). Changes in body weight with liraglutide 1.8 mg (-0.2 kg, baseline 83.0 kg), 1.2 mg (+0.3 kg, baseline 80.0 kg) or placebo (-0.1 kg, baseline 81.9 kg) were less than with rosiglitazone (+2.1 kg, P < 0.0001, baseline 80.6 kg). Main adverse events for all treatments were minor hypoglycaemia (< 10%), nausea (<11%), vomiting (< 5%) and diarrhoea (< 8%). Conclusions Liraglutide added to glimepiride was well tolerated and provided improved glycaemic control and favourable weight profile.</div>
</front>
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<li>Australie</li>
<li>Danemark</li>
<li>Finlande</li>
<li>France</li>
<li>Malaisie</li>
<li>Suisse</li>
</country>
<region>
<li>Nouvelle-Galles du Sud</li>
<li>Victoria (État)</li>
<li>Île-de-France</li>
</region>
<settlement>
<li>Melbourne</li>
<li>Paris</li>
<li>Sydney</li>
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<name sortKey="Shaw, J" sort="Shaw, J" uniqKey="Shaw J" first="J." last="Shaw">J. Shaw</name>
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<name sortKey="Colagiuri, S" sort="Colagiuri, S" uniqKey="Colagiuri S" first="S." last="Colagiuri">S. Colagiuri</name>
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<noRegion>
<name sortKey="Bebakar, W M W" sort="Bebakar, W M W" uniqKey="Bebakar W" first="W. M. W." last="Bebakar">W. M. W. Bebakar</name>
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<name sortKey="Kamaruddin, N A" sort="Kamaruddin, N A" uniqKey="Kamaruddin N" first="N. A." last="Kamaruddin">N. A. Kamaruddin</name>
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<noRegion>
<name sortKey="Strand, J" sort="Strand, J" uniqKey="Strand J" first="J." last="Strand">J. Strand</name>
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<country name="Danemark">
<noRegion>
<name sortKey="Zdravkovic, M" sort="Zdravkovic, M" uniqKey="Zdravkovic M" first="M." last="Zdravkovic">M. Zdravkovic</name>
</noRegion>
<name sortKey="Le Thi, T D" sort="Le Thi, T D" uniqKey="Le Thi T" first="T. D." last="Le Thi">T. D. Le Thi</name>
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