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

<jats:sec> <jats:title>Aims</jats:title> <jats:p> 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 <jats:styled-content style="fixed-case">J</jats:styled-content> apanese patients with type 2 diabetes ( <jats:styled-content style="fixed-case">T2D</jats:styled-content> ). </jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p> In this phase <jats:styled-content style="fixed-case">III</jats:styled-content> , randomized, open‐label, parallel‐group, 26‐week study, 361 patients with inadequately controlled <jats:styled-content style="fixed-case">T2D</jats:styled-content> receiving sulphonylureas and/or biguanides, aged ≥20 years, with glycated haemoglobin ( <jats:styled-content style="fixed-case">HbA1c</jats:styled-content> ) 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 <jats:styled-content style="fixed-case">HbA1c</jats:styled-content> at 26 weeks, analysed using a mixed‐effects model for repeated measures, with a predefined non‐inferiority margin of 0.4%. </jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p> At week 26, least‐squares ( <jats:styled-content style="fixed-case">LS</jats:styled-content> ) mean (standard error) reductions in <jats:styled-content style="fixed-case">HbA1c</jats:styled-content> 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 <jats:styled-content style="fixed-case">HbA1c</jats:styled-content> was −0.54% (95% <jats:styled-content style="fixed-case">CI</jats:styled-content> −0.67, −0.41) [−5.90 mmol/mol (95% <jats:styled-content style="fixed-case">CI</jats:styled-content> −7.32, −4.48)]; p < 0.001. Dulaglutide significantly reduced body weight compared with glargine at week 26 ( <jats:styled-content style="fixed-case">LS</jats:styled-content> mean difference −1.42 kg, 95% <jats:styled-content style="fixed-case">CI</jats:styled-content> −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. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p> In <jats:styled-content style="fixed-case">J</jats:styled-content> apanese patients with <jats:styled-content style="fixed-case">T2D</jats:styled-content> uncontrolled on sulphonylureas and/or biguanides, once‐weekly dulaglutide was superior to once‐daily glargine for reduction in <jats:styled-content style="fixed-case">HbA1c</jats:styled-content> at 26 weeks. Although dulaglutide increased gastrointestinal symptoms, it was well tolerated, with an acceptable safety profile. </jats:p> </jats:sec>