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

Abstract

AimsTo 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 methodsIn 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.ResultsA 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.ConclusionsDulaglutide (both doses) demonstrated superior glycaemic control vs glimepiride, with a favourable tolerability and safety profile in East‐Asian patients with T2D.

Achieving the composite end‐point of glycated hemoglobin <7.0% without weight gain or hypoglycemia with once‐weekly dulaglutide in Chinese patients with type 2 diabetes: A post‐hoc analysis

“…In both Chinese studies, DU (1.5/0.75 mg) has an acceptable safety and tolerability profile, which is similar to the GLP‐1RA class of drugs, suggesting a satisfactory risk‐to‐benefit ratio for DU. The findings of the present post‐hoc analysis are similar to the findings from global studies (AWARD trials) with DU and with published studies of other GLP‐1RAs.…”

“…Post‐hoc analyses of the global AWARD program (AWARD‐1 to 3, 5 and 6), which comprised mainly Caucasian type 2 diabetes patients, showed that 37–58% of patients that received DU 1.5 mg attained the CE, with considerably larger proportions compared with active comparators. Furthermore, a considerably larger number of patients attained the CE with DU (0.75 mg), as compared with sitagliptin or GLAR. A clinical trial program of liraglutide showed that 40% of patients treated with liraglutide 1.8 mg, 32% of patients treated with liraglutide 1.2 mg and 6–25% of patients treated with active comparators attained the CE of HbA1c <7.0% without WG and hypoglycemia.…”

“…Data from two randomized, multinational, parallel‐arm, non‐inferiority, phase III trials (AWARD‐CHN1 study [NCT01644500] and AWARD‐CHN2 study [NCT01648582]) of DU in type 2 diabetes patients were analyzed. Both studies enrolled adult type 2 diabetes patients, and were intended to assess the non‐inferiority and superiority of DU with active comparators.…”

Efficacy and Safety of Dulaglutide by Baseline HbA1c in Chinese Patients with Type 2 Diabetes: A Post Hoc Analysis

“…Several lines of clinical evidences suggest a better risk-to-benefit ratio of GLP-1RAs compared with traditional antidiabetic drugs, such as glimepiride, which is widely used across East Asia. GLP-1RAs are generally well tolerated, although gastrointestinal (GI) AEs are commonly observed across the class [11][12][13][14].…”

“…Moreover, lower risk of weight gain or hypoglycemia was observed with dulaglutide compared with active comparators such as metformin, sitagliptin, exenatide twice daily, and insulin glargine. Efficacy and safety of dulaglutide were also studied in two phase III randomized trials (AWARD-China 1 [CHN1] and AWARD-CHN2 study) in Chinese adult patients with T2DM, which demonstrated significant HbA1c reduction [11,12]. However, the effects of dulaglutide in Chinese patients with T2DM and different baseline HbA1c levels (\ 8.5% and C 8.5%) have not yet been reported.…”