The efficacy and safety of human glucagon-like peptide-1 analogue liraglutide in newly diagnosed type 2 diabetes with glycosylated hemoglobin A1c > 9

Abstract

To evaluate the efficacy and safety of human glucagon-like peptide-1 analogue liraglutide in newly diagnosed type 2 diabetes mellitus (T2DM) with glycosylated hemoglobin A1c (HbA1c) > 9%. This was an open-labelled, randomized, parallel-group, treat-to-target trial. Newly diagnosed T2DM patients with HbA1c > 9% were enrolled. These patients were treated with metformin with repaglinide and randomized to receive once-daily liraglutide (LIRA, n=25) or the insulin glargine (IGla, n=24) at bedtime. Efficacy and safety were assessed and compared after 18-month treatment. (1) Compared with the baseline, patients with LIRA had significantly reduced mean body weight,BMI and waist circumference (P < 0.01), whereas, the above indexes were increased (P < 0.01) in patients treated with IGla. (2) After 18 months of treatment, fasting plasma glucose (FPG), 2-hour plasma glucose after a 75g oral glucose load (2hPG) and HbA1c were significantly improved in all patients (P < 0.01), with 2hPG, mean blood glucose (MBG), the largest amplitude of glycemic excursions (LAGE), mean amplitude of glycemic excursions (MAGE) were significantly lower in LIRA group than in IGla group (all P < 0.05). (3) HOMA-IR decreased in both groups (P < 0.05). However, ΔI30/ΔG30, AUCCP180 and Matsuda index were only significantly increased in patients treated with LIRA (respectively, 4.88 ± 1.55 vs 7.60±1.91, 9.23 ± 2.66 vs 13.18 ± 2.72, 39.28 ± 20.35 vs 54.64 ± 23.34, all P < 0.01), while HOMA-IR reduced (4.41 ± 1.58 vs 3.52 ± 1.44, P < 0.05). But in IGla group only HOMA-IR was reduced (4.92 ± 1.84 vs 4.57 ± 1.80, P < 0.05). The index of ΔI30/ΔG30, AUCCP180 and Matsuda index in LIRA group are higher than those of indexes in IGla group(respectively, 7.60 ± 1.91 vs 4.18 ± 1.00, 13.18 ± 2.72 vs 10.53 ± 2.68,54.64 ± 23.34 vs 41.65 ± 17.84, all P < 0.05), while HOMA-IR is lower (3.52 ± 1.44 vs 4.57 ± 1.80, P< 0.05). (4) The rate of HbA1c ≤ 6.5% and the dosages of oral anti-diabetic drugs in LIRA group were significantly better than that in IGla group. (5) No significant differences were observed in hypoglycemic episodes and adverse events between two groups. It seems that liraglutide is superior to insulin glargine in newly diagnosed T2DM patients with HbA1c > 9% in improving beta-cell function, insulin sensitivity and glucose homeostasis.