Efficacy and safety of dulaglutide monotherapy compared with glimepiride in East‐Asian patients with type 2 diabetes in a multicentre, double‐blind, randomized, parallel‐arm, active comparator, phase III trial

摘要

Aims To compare the efficacy and safety of once‐weekly glucagon‐like peptide‐1 receptor agonist dulaglutide 1.5 and 0.75 mg with glimepiride in East‐Asian patients with type 2 diabetes (T2D). Materials and methods In this phase III, multinational, multicentre, double‐blind, randomized, parallel‐arm, 26‐week study, patients with inadequate glycaemic control were randomized 1:1:1 to once‐weekly dulaglutide 1.5 or 0.75 mg or daily glimepiride (1‐3 mg/d). The primary endpoint was assessment of the non‐inferiority of dulaglutide (1.5 mg), as measured by change in glycated haemoglobin (HbA1c), compared with glimepiride using a 0.4% non‐inferiority margin. Results A total of 737 patients were randomized (dulaglutide 1.5 mg, n = 244; dulaglutide 0.75 mg, n = 248; glimepiride, n = 245). At week 26, both doses of dulaglutide were non‐inferior and also superior to glimepiride for HbA1c reduction from baseline with a least squares mean difference of ?6.34 mmol/mol (95% confidence interval [CI] ?8.31, ?4.26) or ‐0.58% (95% CI ?0.76, ?0.39) for dulaglutide 1.5 mg and ?3.50 mmol/mol (95% CI ?5.47, ?1.42) or ?0.32% (95% CI ?0.50, ?0.13) for dulaglutide 0.75 mg ( P .001). A greater proportion of patients in the dulaglutide 1.5 mg group achieved the HbA1c target of 53 mmol/mol (7.0%) compared with the glimepiride group (74.1% vs 57.4%; P .001). The mean body weight decreased ( P .005) and total hypoglycaemia rates were lower ( P .001) in the dulaglutide groups compared with the glimepiride group. The most common drug‐related adverse events in both dulaglutide groups (≥5% of patients) included diarrhoea, nausea, increased lipase, decreased appetite, abdominal distension and vomiting. Conclusions Dulaglutide (both doses) demonstrated superior glycaemic control vs glimepiride, with a favourable tolerability and safety profile in East‐Asian patients with T2D.