Dataset Information

Once-Weekly Dulaglutide with Insulin Therapy for Type 2 Diabetes: Efficacy and Safety Results from a Phase 4, Randomized, Placebo-Controlled Study.

ABSTRACT:

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.

SUBMITTER: Ishii H

PROVIDER: S-EPMC6965529 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PURPOSE:In East Asian patients, type 2 diabetes mellitus (T2DM) is characterized primarily by β-cell dysfunction, with lower insulin secretion than in Caucasian individuals. Therefore, bolus insulin and premixed insulin containing a bolus insulin component are important therapeutic tools in Japan, in addition to basal insulin. This subgroup analysis is stratified by insulin regimen and uses data from a phase 4, randomized, placebo-controlled, double-blind and subsequent open-label study in Japan to assess the efficacy and safety of once-weekly dulaglutide combined with various insulin therapies. METHODS:This multicenter study enrolled Japanese patients with T2DM and inadequate glycemic control [glycated hemoglobin A1c (HbA1c) ≥ 7.5% to ≤ 10.5%] on insulin therapy [basal (B), premixed (PM), or basal bolus (BB)] in combination with or without one or two oral antidiabetic agents. Randomized participants received once-weekly dulaglutide 0.75 mg (n = 120) or placebo (n = 39) during a 16-week double-blind treatment period, and dulaglutide during a 36-week open-label extension. In this subgroup analysis, efficacy measures were changes from baseline in HbA1c, 7-point self-monitored blood glucose profiles, and body weight. Safety measures were incidence of adverse events and hypoglycemia during the first 16 weeks. RESULTS:At week 16, least squares mean differences (95% CI) regarding changes from baseline in HbA1c for each insulin regimen versus placebo were: B: - 1.62% (- 1.96, - 1.28), PM: - 1.78% (- 2.25, - 1.30), and BB: - 1.15% (- 1.54, - 0.77); p < 0.001 dulaglutide vs. placebo for each subgroup. No significant differences in body weight changes were observed between dulaglutide and placebo for any insulin regimen. Gastrointestinal symptoms were the most commonly observed adverse events in dulaglutide-treated patients. Hypoglycemia incidence rates were: B: dulaglutide 38.5% vs. placebo 23.5%; PM: dulaglutide 38.5% vs. placebo 44.4%; BB: dulaglutide 50.0% vs. placebo 30.8%. CONCLUSIONS:Overall, dulaglutide was generally well tolerated and improved glycemic control significantly versus placebo, regardless of insulin regimen. TRIAL REGISTRATION:ClinicalTrials.gov identifier, NCT02750410.

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