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)

M. Marre, J. Shaw, M. Brändle, W. M W Bebakar, Nor Azmi Kamaruddin, J. Strand, M. Zdravkovic, T. D. Le Thi, S. Colagiuri

Research output: Contribution to journalArticle

665 Citations (Scopus)

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 ± sd), 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. Diabet. Med. 26, 268-278 (2009).

Original languageEnglish
Pages (from-to)268-278
Number of pages11
JournalDiabetic Medicine
Volume26
Issue number3
DOIs
Publication statusPublished - Mar 2009

Fingerprint

rosiglitazone
Glucagon-Like Peptide 1
Type 2 Diabetes Mellitus
glimepiride
Placebos
Weights and Measures
Glucose
Body Weight Changes
Glycosylated Hemoglobin A
Liraglutide
Hypoglycemia
Nausea
Vomiting
Diarrhea
Fasting

Keywords

  • Dipeptidyl peptidase-4
  • Glucagon-like peptide-1 receptor agonist
  • Incretin
  • Insulinotropic
  • Thiazolidinedione

ASJC Scopus subject areas

  • Endocrinology
  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

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). / Marre, M.; Shaw, J.; Brändle, M.; Bebakar, W. M W; Kamaruddin, Nor Azmi; Strand, J.; Zdravkovic, M.; Le Thi, T. D.; Colagiuri, S.

In: Diabetic Medicine, Vol. 26, No. 3, 03.2009, p. 268-278.

Research output: Contribution to journalArticle

@article{889552d04b5a4869ba6117728e67afde,
title = "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)",
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 ± sd), 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. Diabet. Med. 26, 268-278 (2009).",
keywords = "Dipeptidyl peptidase-4, Glucagon-like peptide-1 receptor agonist, Incretin, Insulinotropic, Thiazolidinedione",
author = "M. Marre and J. Shaw and M. Br{\"a}ndle and Bebakar, {W. M W} and Kamaruddin, {Nor Azmi} and J. Strand and M. Zdravkovic and {Le Thi}, {T. D.} and S. Colagiuri",
year = "2009",
month = "3",
doi = "10.1111/j.1464-5491.2009.02666.x",
language = "English",
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pages = "268--278",
journal = "Diabetic Medicine",
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TY - JOUR

T1 - 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)

AU - Marre, M.

AU - Shaw, J.

AU - Brändle, M.

AU - Bebakar, W. M W

AU - Kamaruddin, Nor Azmi

AU - Strand, J.

AU - Zdravkovic, M.

AU - Le Thi, T. D.

AU - Colagiuri, S.

PY - 2009/3

Y1 - 2009/3

N2 - 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 ± sd), 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. Diabet. Med. 26, 268-278 (2009).

AB - 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 ± sd), 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. Diabet. Med. 26, 268-278 (2009).

KW - Dipeptidyl peptidase-4

KW - Glucagon-like peptide-1 receptor agonist

KW - Incretin

KW - Insulinotropic

KW - Thiazolidinedione

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