Once-weekly glucagon-like peptide-1 receptor agonist dulaglutide significantly decreases glycated haemoglobin compared with once-daily liraglutide in Japanese patients with type 2 diabetes: 52 weeks of treatment in a randomized phase III study

Abstract

Aims: To examine the efficacy and safety of once-weekly dulaglutide 0.75 mg monotherapy compared with once-daily liraglutide 0.9 mg in Japanese patients with type 2 diabetes (T2D) for 52 weeks.

Methods: We conducted a phase III, randomized, 52-week (26-week primary endpoint), active- and placebo-controlled trial comparing 492 Japanese patients (dulaglutide, n = 281; liraglutide, n = 141; and placebo, n = 70). Participants and investigators were blinded to treatment assignment for dulaglutide and placebo but not for liraglutide (open-label comparator); after 26 weeks, patients randomized to placebo were switched to once-weekly dulaglutide 0.75 mg (open-label). The present paper reports results for patients treated with dulaglutide and patients treated with liraglutide for 52 weeks.

Results: At week 52, dulaglutide decreased HbA1c significantly from baseline compared with liraglutide [least squares mean difference: -0.20; 95% confidence interval (CI) -0.39, -0.01; p = 0.04]. At week 52 (last observation carried forward), dulaglutide significantly decreased pre- and post-dinner blood glucose (BG) levels, the mean of seven-point self-monitored BG profiles, the mean of all postprandial BG levels and circadian variation compared with liraglutide. Body weight was generally stable in both groups through 52 weeks. The most frequently reported adverse events were nasopharyngitis, constipation, nausea and diarrhoea. Eight dulaglutide-treated (2.9%) and four liraglutide-treated (2.9%) patients reported hypoglycaemia, with no event being severe.

Conclusions: Monotherapy with once-weekly dulaglutide 0.75 mg was effective and safe in Japanese patients with T2D, with better glycaemic control compared with once-daily liraglutide 0.9 mg.

Keywords: GLP-1 receptor agonist; dulaglutide; liraglutide; type 2 diabetes.

Figure 1

Study disposition. Patients were randomized to dulaglutide or liraglutide in a 2 : 1 ratio. N, number of patients. *Includes a patient who was discontinued from the study because of a serious adverse event, rectal cancer, which was diagnosed after treatment was interrupted. Because the event began after treatment ended it is not included in the serious adverse events in Table 2 or listed in Table S2.

Figure 2

Glycated haemoglobin (HbA1c), fasting serum glucose (FSG), and body weight up to week 52. (A) Mean [standard error (s.e.)] HbA1c (%) from baseline to week 52. *p = 0.04 for between‐group difference; p < 0.001 for all within‐group changes from baseline for both treatment groups. (B) Mean (s.e.) FSG (mmol/l) from baseline to week 52. (C) Mean (s.e.) changes from baseline in body weight (kg) from baseline to week 52. LS, least squares.

Figure 3

Glycated haemoglobin (HbA1c) changes from baseline, HbA1c targets, fasting serum glucose (FSG) and self‐monitored blood glucose (SMBG). (A) Mean (s.e.) changes from baseline to week 52 in HbA1c (%). (B) Proportions of patients achieving predefined HbA1c targets at week 52 (LOCF). (C) Mean (s.e.) changes from baseline to week 52 in FSG (mmol/l). (D) Mean (s.e.) seven‐point SMBG profiles (mmol/l) at baseline and week 52 (LOCF). ^aLeast squares (LS) mean difference (95% confidence interval): treatment difference calculated as dulaglutide 0.75 mg – liraglutide 0.9 mg. *Reduction from baseline in the dulaglutide 0.75 mg group was significantly greater than reduction in the liraglutide 0.9 mg group (p < 0.05).