Efficacy and safety of once-weekly dulaglutide in combination with sulphonylurea and/or biguanide compared with once-daily insulin glargine in Japanese patients with type 2 diabetes: a randomized, open-label, phase III, non-inferiority study

一项随机、开放标签、III期非劣效性研究,旨在比较每周一次度拉糖肽联合磺脲类和/或双胍类药物与每日一次甘精胰岛素治疗日本2型糖尿病患者的疗效和安全性。

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Abstract

AIMS: To evaluate 0.75 mg of dulaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, compared with once-daily insulin glargine for glycaemic control in Japanese patients with type 2 diabetes (T2D). METHODS: In this phase III, randomized, open-label, parallel-group, 26-week study, 361 patients with inadequately controlled T2D receiving sulphonylureas and/or biguanides, aged ≥20 years, with glycated haemoglobin (HbA1c) levels 7.0-10.0% (53-86 mmol/mol), inclusive, were randomized (1 : 1) to receive dulaglutide or glargine. Participants and investigators were not masked to treatment allocation. The primary measure was change from baseline in HbA1c at 26 weeks, analysed using a mixed-effects model for repeated measures, with a predefined non-inferiority margin of 0.4%. RESULTS: At week 26, least-squares (LS) mean (standard error) reductions in HbA1c were -1.44 (0.05)% [-15.74 (0.55) mmol/mol] in the dulaglutide group and -0.90 (0.05)% [-9.84 (0.55) mmol/mol] in the glargine group. The mean between-group treatment difference in HbA1c was -0.54% (95% CI -0.67, -0.41) [-5.90 mmol/mol (95% CI -7.32, -4.48)]; p < 0.001. Dulaglutide significantly reduced body weight compared with glargine at week 26 (LS mean difference -1.42 kg, 95% CI -1.89, -0.94; p < 0.001). The most frequent adverse events with dulaglutide treatment were nasopharyngitis and gastrointestinal symptoms. The incidence of hypoglycaemia was significantly lower with dulaglutide [47/181 (26%)] compared with glargine [86/180 (48%)], p < 0.001. CONCLUSION: In Japanese patients with T2D uncontrolled on sulphonylureas and/or biguanides, once-weekly dulaglutide was superior to once-daily glargine for reduction in HbA1c at 26 weeks. Although dulaglutide increased gastrointestinal symptoms, it was well tolerated, with an acceptable safety profile.

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