Efficacy and Safety of a Biosimilar Liraglutide (Melitide(®)) Versus the Reference Liraglutide (Victoza(®)) in People with Type 2 Diabetes Mellitus: A Randomized, Double-Blind, Noninferiority Clinical Trial

生物类似药利拉鲁肽(Melitide®)与参考药物利拉鲁肽(Victoza®)在2型糖尿病患者中的疗效和安全性:一项随机、双盲、非劣效性临床试验

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Abstract

INTRODUCTION: Liraglutide effectively controls blood glucose level and reduces body weight. The aim of this study was to compare the efficacy and safety of a biosimilar liraglutide (Melitide(®); CinnaGen, Tehran, Iran) to the reference liraglutide (Victoza(®); Novo Nordisk, Bagsvaerd, Denmark) in people with type 2 diabetes mellitus (T2DM). METHODS: In this phase 3 clinical noninferiority trial, adult patients with inadequately controlled T2DM and with hemoglobin A(1C) (HbA(1C)) levels of 7-10.5% on at least two oral glucose-lowering drugs with stable doses for at least 3 months were randomized to receive Melitide(®) (n = 150) or Victoza(®) (n = 150) 1.8 mg/day for 26 weeks. The primary outcome was assessment of the noninferiority of Melitide(®) to Victoza(®) in terms of change in HbA(1C) level with a prespecified margin of 0.4%. The secondary outcomes were the assessment of additional efficacy parameters (including the proportion of patients achieving HbA(1C) levels of < 7%), the incidence of adverse events, and immunogenicity. RESULTS: Of the 300 participants enrolled in this study, 235 were included in the per-protocol analysis (112 in the Melitide(®) group and 123 in the Victoza(®) group). The mean (standard deviation) changes in HbA(1C) were - 1.76% (1.22) in the Melitide(®) group and - 1.59% (1.31) in the Victoza(®) group. The upper limit of the 95% one-sided confidence interval (CI) of the mean difference between Melitide(®) and Victoza(®) in lowering HbA(1C) was lower than the predefined margin (mean difference - 0.18, 95% CI - 0.5 to 0.15). Similar findings were obtained with the intention-to-treat analysis. No statistically significant differences were observed between the two study arms regarding the proportion of patients achieving HbA(1C) < 7% (p = 0.210), other efficacy parameters (p > 0.05), and reported adverse events (p = 0.916). Furthermore, none of the patients developed anti-liraglutide antibodies. CONCLUSION: The biosimilar liraglutide (Melitide(®)) was noninferior in efficacy and comparable in safety when compared with the reference liraglutide. TRIAL REGISTRATION: NCT03421119.

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