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, N A Kamaruddin, J Strand, M Zdravkovic, T D Le Thi, S Colagiuri, LEAD-1 SU study group, L De Loredo, J Waitman, L Litwak, M Rodriguez, G Vines, L Maffei, C Issa, A Lowy, P Bartley, M Kamp, J Shaw, A Russell, J Karrasch, S Colagiuri, J Karrasch, A Lowy, M Protich, V Hristov, K Hristozov, A Petrova-Gancheva, M Pavlova, M Petkova, S Kokic, T Bacun, M J Balen, J Perusicova, T Pelikanova, A Smahelova, Z Rusavy, V Zackova, M Honka, J Strand, A Kuusisto, M Honkasalo, M Taskinen, V Ilvesmaki, T Piippo, M Rahtu, J Eriksson, V Kallioniemi, P Korsoff, F Galtier, D Gouet, Bauduceau, Y Lorcy, P Duevezin-Caubet, J-P Courreges, C Le Devehat, M Marre, F Chow, A Bhansali, H B Chandalia, K G Seshadri, S Shah, I Raz, O Cohen, E Karnieli, A Pontiroli, F Santeusanio, S Squatrito, Yoon K Ho, Baik S Hyun, Woo J Taek, W W Bebakar, N A Kamaruddin, M Mumtaz, T Que, R A Sy, A Panelo, V Racho, M Bednarczyk-Kaluzny, T Biniszkiewicz, T Derezinski, R Filipczak, E Gaczarek-Belczyk, J Gumprecht, J Kuleta, J Lopatynski, L Majkowska, P Mader, J Miarka, A Mikolajczyk-Swatko, E Skokowska, M Wojciechowska, B Wolnik, V Serban, T Mogos, A Albota, L Pop, B Popa, R Moore, E Mitha, G Latiff, S Bhana, D Lakha, M Brändle, B Bach-Kliegel, R Lehmann, E Christ, R Gaillard, L-M Chuang, S-T Tu, J-F Chen, S-W Kuo, C Deerochanawong, S Lauhawatana, N Kittivat, M Arslan, M K Balci, H Sargin, A Comlekci, K Karsidag, A Dayan, M Marre, J Shaw, M Brändle, W M W Bebakar, N A Kamaruddin, J Strand, M Zdravkovic, T D Le Thi, S Colagiuri, LEAD-1 SU study group, L De Loredo, J Waitman, L Litwak, M Rodriguez, G Vines, L Maffei, C Issa, A Lowy, P Bartley, M Kamp, J Shaw, A Russell, J Karrasch, S Colagiuri, J Karrasch, A Lowy, M Protich, V Hristov, K Hristozov, A Petrova-Gancheva, M Pavlova, M Petkova, S Kokic, T Bacun, M J Balen, J Perusicova, T Pelikanova, A Smahelova, Z Rusavy, V Zackova, M Honka, J Strand, A Kuusisto, M Honkasalo, M Taskinen, V Ilvesmaki, T Piippo, M Rahtu, J Eriksson, V Kallioniemi, P Korsoff, F Galtier, D Gouet, Bauduceau, Y Lorcy, P Duevezin-Caubet, J-P Courreges, C Le Devehat, M Marre, F Chow, A Bhansali, H B Chandalia, K G Seshadri, S Shah, I Raz, O Cohen, E Karnieli, A Pontiroli, F Santeusanio, S Squatrito, Yoon K Ho, Baik S Hyun, Woo J Taek, W W Bebakar, N A Kamaruddin, M Mumtaz, T Que, R A Sy, A Panelo, V Racho, M Bednarczyk-Kaluzny, T Biniszkiewicz, T Derezinski, R Filipczak, E Gaczarek-Belczyk, J Gumprecht, J Kuleta, J Lopatynski, L Majkowska, P Mader, J Miarka, A Mikolajczyk-Swatko, E Skokowska, M Wojciechowska, B Wolnik, V Serban, T Mogos, A Albota, L Pop, B Popa, R Moore, E Mitha, G Latiff, S Bhana, D Lakha, M Brändle, B Bach-Kliegel, R Lehmann, E Christ, R Gaillard, L-M Chuang, S-T Tu, J-F Chen, S-W Kuo, C Deerochanawong, S Lauhawatana, N Kittivat, M Arslan, M K Balci, H Sargin, A Comlekci, K Karsidag, A Dayan
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 >or= 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 (HbA(1c)) 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(1c) 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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Source: PubMed