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

AimsTo 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.MethodsWe 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.ResultsAt 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.ConclusionsMonotherapy 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.

Effects of Once-Weekly Dulaglutide on Glycemic Control and Renal Function in Patients with Advanced-Stage Diabetic Nephropathy

“…Hence, it requires no dose adjustment for use in patients with renal impairment. Furthermore, a phase III clinical study reported that once-weekly dulaglutide significantly reduced HbA1c levels in type 2 diabetes mellitus patients with normal renal function compared to once-daily liraglutide after 52 weeks (11). In our study, once-weekly dulaglutide significantly reduced HbA1c levels with no adverse effects in patients with advanced-stage diabetic nephropathy after changing from once-daily liraglutide.…”

“…Dulaglutide, a long-acting GLP-1 receptor agonist, can be used by once-weekly administration in patients with diabetes mellitus and impaired renal function without any dose adjustment (8)(9)(10). Dulaglutide showed better glucose control compared to liraglutide, a once-daily GLP-1 receptor agonist, in patients with type 2 diabetes mellitus and normal renal function (11). Dulaglutide has also been reported to show nephroprotective effects in patients with type 2 diabetes mellitus with mild renal impairment (12).…”

Subgroup analysis of phase 3 studies of dulaglutide in Japanese patients with type 2 diabetes

“…gov (NCT01584232, NCT01558271, NCT01468181). Study design and methods for each study have been previously reported [7][8][9][10].…”

“…In phase 3 studies in Japanese patients with T2D, once weekly dulaglutide 0.75 mg has shown superiority to insulin glargine (in a randomized, 26-week, open-label study of dulaglutide in combination with sulfonylureas [SU] and/or biguanides [BG]) and non-inferiority to liraglutide 0.9 mg/day (in a randomized monotherapy study in which dulaglutide was compared to placebo [double-blind] and to liraglutide 0.9 mg/day [open-label]; the study had a 26-week primary endpoint and a 52-week treatment period) in HbA1c changes [7][8][9]. Also, in a nonrandomized, open-label, long-term (52-week) phase 3 safety study in Japanese patients with T2D, once weekly dulaglutide 0.75 mg was overall well-tolerated in combination with a single oral hypoglycemic agent (SU, BG, α-glucosidase inhibitors, thiazolidinediones, or glinides) [10].…”

Analysis of efficacy and safety of dulaglutide 0.75 mg stratified by sex in patients with type 2 diabetes in 2 randomized, controlled phase 3 studies in Japan

“…Dulaglutide is a once weekly GLP-1 receptor agonist approved in Japan at a dose of 0.75 mg. After 26 apy study" [8,12], which was a 52-week study that had the primary endpoint at 26 weeks, and 2) "the combination study" [9], which was a 26-week study. The monotherapy study randomized patients to dulaglutide, liraglutide 0.9 mg, or placebo; after 26 weeks of treatment, patients treated with placebo were switched to dulaglutide.…”