LAUSR

Introduction Although global studies have investigated the combination of dulaglutide with insulin in patients with type 2 diabetes mellitus (T2DM), differences in lean body mass and dulaglutide dosing can complicate the extrapolation of global study results to Japanese patients. This phase 4, randomized, placebo-controlled, double-blind, and subsequent open-label study aimed to assess the efficacy and safety of once-weekly dulaglutide 0.75 mg in combination with insulin therapy in patients with T2DM. Methods Patients enrolled in this multicenter study were Japanese with T2DM who had inadequate glycemic control (HbA1c 7.5–10.5%) with insulin therapy (basal insulin, premixed insulin, or basal/mealtime insulin) in combination with or without one or two oral antidiabetic agents (OADs). Patients were randomized in a 3:1 ratio to dulaglutide or placebo. The first 16 weeks was the double-blind period with stable insulin dosing, and patients taking placebo were switched to dulaglutide for an additional 36-week open-label period in which all patients took dulaglutide (52 weeks total). Results Patients ( N  = 159) were randomized to dulaglutide ( n  = 120) or placebo ( n  = 39). The least-squares (LS) mean changes from baseline in HbA1c at week 16 were dulaglutide − 1.45% and placebo 0.06%. The LS mean and 95% confidence interval for the difference were − 1.50% (− 1.73%, − 1.28%) and dulaglutide was superior to placebo. There were no significant differences between treatment groups in changes from baseline in body weight and insulin dose. The most frequently observed treatment-emergent adverse events in dulaglutide were nasopharyngitis, constipation, abdominal discomfort, nausea, and decreased appetite. The incidence rates of hypoglycemic events by week 16 were dulaglutide 42.5% and placebo 30.8% ( P  = 0.258). Conclusion Once-weekly dulaglutide 0.75 mg was superior to once-weekly placebo in glycemic control improvement and well tolerated in patients with T2DM in combination with insulin therapy with or without OADs. Trial Registration ClinicalTrials.gov, NCT02750410. Funding Eli Lilly and Company.