Liraglutide, a Once-daily Human GLP-1 Analog, In Type 2 Diabetes Provides Similar Glycemic Control with Reduced Body Weight Compared with Glimepiride when Added to Metformin.

Abstract

This placebo-controlled (plb), double-blind, randomized 26-week trial investigated the effect on glycemic control (HbA1c) of three liraglutide doses (lira; 0.6, 1.2 or 1.8 mg sc, QD) added to metformin (met; 1 g BD) compared with met monotherapy (plb+met) or glimepiride (glim, 4 mg QD) added to met (glim+met). The trial included 1091 subjects with T2DM previously treated with oral antidiabetic drug (OAD) mono-therapy (35%) or combination therapy (65%), with mean±SD baseline HbA1c 8.4±1.0% and body weight (BW) 88.6±17.3 kg. HbA1c was significantly reduced in all lira groups vs plb+met. Reduction in HbA1c was greater in subjects previously treated with OAD mono vs combination therapy. The fraction of subjects achieving HbA1c<7.0% or <6.5% was significantly higher in lira+met vs plb+met, with no difference between lira+met vs glim+met. Change in fasting plasma glucose followed the same pattern as for HbA1c. BW decreased significantly in all lira groups vs glim+met. Reduction in BW was significantly greater in lira1.2+met and lira1.8+met vs plb+met. Presence of lira antibodies was 0-4% (only patients not entering the extension phase of the study were included: lira0.6, n=28; lira1.2, n=25; lira1.8, n=32). Minor hypoglycemia (<3.1 mmol/L) occurred in <4% of subjects in lira+met and plb+met, and in 16.9% in glim+met. There was no major hypoglycemia. The most common adverse events in lira+met were GI disorders (mainly nausea). Nausea initially occurred in 6-12% of subjects in lira+met, declining to plb+ met levels (2%) after 8–16 weeks' treatment. Liraglutide was well tolerated, produced a clinically significant reduction in HbA1c, and in contrast to met+glim resulted in few hypoglycemic episodes and weight loss in T2DM subjects. Tabled 1 Lira 0.6 mg + met Lira 1.2 mg + met Lira 1.8 mg + met Plc + met Glim + met Final HbA1c, % (SD) a No statistical analysis Change HbA1c, % (SE) 7.8 (1.1)−0.7 (0.1) * p<0.05 compared to plb+met 7.5 (1.1)−1.0 (0.1) * p<0.05 compared to plb+met 7.5 (1.2)−1.0 (0.1) * p<0.05 compared to plb+met 8.6 (1.4)+ 0.1 (0.1) 7.5 (1.1)−1.0 (0.1) Mono/combi changeHbA1c, % (SD) a No statistical analysis −0.8 (0.8)/−0.5 (1.1) −1.3 (1.2)/−0.6 (0.9) −1.3 (1.1)/−0.7 (1.1) −0.5 (1.3)/+ 0.5 (1.0) −1.1 (0.1)/−0.8 (1.0) % HbA1c <7.0% HbA1c <6.5 28.0 * p<0.05 compared to plb+met † p<0.05 compared to glim+met 11.3 * p<0.05 compared to plb+met † p<0.05 compared to glim+met , 35.3 * p<0.05 compared to plb+met 19.8 * p<0.05 compared to plb+met 42.4 * p<0.05 compared to plb+met 24.6 * p<0.05 compared to plb+met 10.84.2 36.322.2 Final FPG, mmol/L (SD) a No statistical analysis Change FPG, mmol/L (SE) 9.1 (2.6)−1.1 (0.2) * p<0.05 compared to plb+met 8.4 (2.6)−1.6 (0.2) * p<0.05 compared to plb+met 8.5 (2.3)−1.7 (0.2) * p<0.05 compared to plb+met 10.7 (57)+ 0.4 (0.2) 8.8 (2.4)−1.3 (0.2) Weight change, kg (SE) −1.8 (0.2) † p<0.05 compared to glim+met −2.6 (0.2) * p<0.05 compared to plb+met † p<0.05 compared to glim+met −2.8 (0.2) * p<0.05 compared to plb+met † p<0.05 compared to glim+met −1.5 (0.3) +1.0 (0.2) % minor hypos reported a No statistical analysis 3.3 0.8 2.5 2.5 16.9 * p<0.05 compared to plb+met † p<0.05 compared to glim+met a No statistical analysis Open table in a new tab