De Loredo L, Waitman J, Litwak L, Rodriguez M, Vines G, Maffei L, Issa C, Lowy A, Bartley P, Kamp M, Shaw J, Russell A, Karrasch J, Colagiuri S, Karrasch J, Lowy A, Protich M, Hristov V, Hristozov K, Petrova-Gancheva A, Pavlova M, Petkova M, Kokic S, Bacun T, Balen MJ, Perusicova J, Pelikanova T, Smahelova A, Rusavy Z, Zackova V, Honka M, Strand J, Kuusisto A, Honkasalo M, Taskinen M, Ilvesmaki V, Piippo T, Rahtu M, Eriksson J, Kallioniemi V, Korsoff P, Galtier F, Gouet D, Bauduceau, Lorcy Y, Duevezin-Caubet P, Courreges JP, Le Devehat C, Marre M, Chow F, Bhansali A, Chandalia HB, Seshadri KG, Shah S, Raz I, Cohen O, Karnieli E, Pontiroli A, Santeusanio F, Squatrito S, Ho YK, Hyun BS, Taek WJ, Bebakar WW, Kamaruddin NA, Mumtaz M, Que T, Sy RA, Panelo A, Racho V, Bednarczyk-Kaluzny M, Biniszkiewicz T, Derezinski T, Filipczak R, Gaczarek-Belczyk E, Gumprecht J, Kuleta J, Lopatynski J, Majkowska L, Mader P, Miarka J, Mikolajczyk-Swatko A, Skokowska E, Wojciechowska M, Wolnik B, Serban V, Mogos T, Albota A, Pop L, Popa B, Moore R, Mitha E, Latiff G, Bhana S, Lakha D, Brändle M, Bach-Kliegel B, Lehmann R, Christ E, Gaillard R, Chuang LM, Tu ST, Chen JF, Kuo SW, Deerochanawong C, Lauhawatana S, Kittivat N, Arslan M, Balci MK, Sargin H, Comlekci A, Karsidag K, Dayan A.
Source
Service d'Endocrinologie Diabétologie Nutrition, Groupe Hospitalier Bichat-Claude Bernard, Paris, France. michel.marre@bch.ap-hop-paris.fr
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.