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). Electronic supplementary material The online version of this article (10.1007/s13300-019-0605-7) contains supplementary material, which is available to authorized users.

Evaluation of Characteristics of Gastrointestinal Adverse Events with Once-Weekly Dulaglutide Treatment in Chinese Patients with Type 2 Diabetes: A Post Hoc Pooled Analysis of Two Randomized Trials

“…The effects of GLP-1 RAs on gut other than stomach have not been extensively studied; however, the potential of GLP-1 RAs to inhibit small intestine motor function has been reported, which may contribute to lower GI symptoms such as diarrhea and constipation [ 28 , 35 ]. Although incidence of diarrhea reported in this analysis was higher when compared with a non-Asian patient population [ 9 , 12 ], it was comparable to that in a Japanese patient population treated with once-weekly dulaglutide 0.75 mg [ 36 ], indicating no major difference in GI-related safety parameters between Chinese and Japanese patient populations.…”

Immediate Glucose-Lowering Effect After the First Administration of Dulaglutide: A Retrospective, Single-Center, Observational Study

“…However, these findings are based on the long-term studies. There are only three reports on the early-phase effects of dulaglutide; however, the sample sizes in these studies were small, ranging from 12 to 43; in addition, the associations of the early effects of dulaglutide with the patient demographic characteristics or laboratory data or with switching from other incretin-based medications were also not evaluated in these studies [20][21][22]. This study presented that dulaglutide achieved reduction in BG levels within 24 h and this might be beneficial for early decision-making on the appropriate regimen for glycemic control, especially in shortterm hospitalized diabetes patients.…”

“…Their study was designed such that blood samples were collected when dulaglutide reached its maximum concentration in the blood; therefore, the data of the first 24 h were not shown. Matsushita and Inoue [20,21] reported the mean BG levels, daily glucose fluctuations, as assessed by the SD of the 6-point BG levels, mean amplitude of the glycemic excursions (MAGE), and percentage of patients with BG greater than 180 mg/dL decreased significantly by a day after the first dulaglutide administration. In present study, the daily average preprandial and postprandial BG levels also, which have not been measured in previous studies, decreased significantly by a day after the first dulaglutide administration [20][21][22].…”

“…Because these studies were focused on the long-term efficacy of dulaglutide, factors influencing the immediate blood glucose responses to dulaglutide treatment have remained unclear. There are only a few reports on the immediate BG responses to dulaglutide administration and no reports of the possible factors associated with the efficacy of the drug because of the limited number of patients [20][21][22].…”

Preference for Oral and Injectable GLP-1 RA Therapy Profiles in Japanese Patients with Type 2 Diabetes: A Discrete Choice Experiment

“…Many injectable therapies of the glucagonlike peptide 1 (GLP-1) receptor agonist (RA) class (including semaglutide, dulaglutide, exenatide, liraglutide, and lixisenatide) have also been developed and approved for use in Japan [10][11][12][13][14][15][16][17]. In addition, a new oral formulation of semaglutide has been investigated in Japanese patients with T2D [18,19].…”