Effect of Once-Weekly Dulaglutide on Glucose Levels in Japanese Patients with Type 2 Diabetes: Findings from a Phase 4, Randomized Controlled Trial

Abstract

Introduction: Dulaglutide is a recombinant glucagon-like peptide-1 immunoglobulin G4 Fc fusion protein approved for treating patients with type 2 diabetes (T2D). The aim of this study was to assess postprandial data over 4 weeks for dulaglutide (0.75 mg) versus placebo after a standardized test meal in Japanese patients with T2D.

Methods: The pharmacodynamic (PD) effects of once-weekly dulaglutide (0.75 mg) in Japanese patients with T2D on diet and exercise therapy (N = 12) were evaluated by assessing postprandial data up to week 4 in a phase 4, single-center, randomized, cross-over, single-blind, placebo-controlled study. The primary end point was the change in 4-h glucose area under the concentration versus time curve [AUC (0-4 h)] from baseline to week 4. Secondary end points included changes from baseline in other PD parameters (insulin, C-peptide, glucagon, and triglycerides) at weeks 1, 2, and 4 and the safety and tolerability of dulaglutide 0.75 mg. Continuous glucose monitoring (CGM) during the 1st week was performed as an exploratory measure in each treatment period.

Results: The decrease in AUC (0-4 h) from baseline to week 4 following dulaglutide administration was statistically significant compared with placebo at weeks 1, 2, and 4 (P < 0.0001). Insulin and C-peptide levels were also significantly increased (P < 0.05) with dulaglutide versus placebo at weeks 2 and 4. There were no statistically significant differences between groups in glucagon and triglyceride levels. Daily average glucose concentrations were decreased on the day after the first administration of dulaglutide and remained at similar levels for 4 days. The incidence of treatment-emergent adverse events was slightly higher with dulaglutide versus placebo.

Conclusion: In conclusion, dulaglutide decreased postprandial glucose from week 1 in Japanese patients with T2D, indicating that dulaglutide treatment is associated with favorable PD effects soon after treatment begins.

Trial registration: ClinicalTrials.gov identifier: NCT03315780.

Funding: Eli Lilly Japan K.K. (Kobe, Japan).

Keywords: Dulaglutide; Glucagon-like peptide-1; Meal tolerance test; Pharmacodynamic effect; Type 2 diabetes.

Figures

Fig. 1

Study design. CGM continuous glucose monitoring

Fig. 2

Time course of pharmacodynamic parameters, including a, b serum glucose, c, d insulin, e, f C-peptide, g, h glucagon, and i, j triglyceride concentrations at weeks 0, 1, 2, and 4 in Japanese patients with type 2 diabetes who were treated once weekly with dulaglutide 0.75 mg or placebo. Blood samples were taken before and 30, 60, 90, 120, 180, and 240 min after patients consumed a standardized test meal. Data are mean ± standard deviation

Fig. 3

Time course of continuous glucose monitoring parameters in Japanese patients with type 2 diabetes who were treated QW with dulaglutide 0.75 mg or placebo: a daily average glucose concentration, b time glucose concentration was < 70 mg/dl, c time glucose concentration was > 180 mg/dl, d daily within-day SD, and e daily mean amplitude glycemic excursion. *P < 0.05 for dulaglutide versus placebo (paired t test). MAGE mean amplitude of glycemic excursion, QW once weekly, SD standard deviation. Data are mean ± SD