Dataset Information

Gastrointestinal Tolerability of Once-Weekly Dulaglutide 3.0 mg and 4.5 mg: A Post Hoc Analysis of the Incidence and Prevalence of Nausea, Vomiting, and Diarrhea in AWARD-11.

ABSTRACT:

Background

Gastrointestinal (GI) events are the most frequent treatment-emergent adverse events (TEAEs) reported for glucagon-like peptide-1 receptor agonist therapies. This post hoc analysis of the AWARD-11 phase 3 trial assessed the GI tolerability of dulaglutide at once-weekly doses of 1.5, 3.0, and 4.5 mg.

Methods

The AWARD-11 trial randomized patients to once-weekly dulaglutide 1.5 mg (n = 612), 3.0 mg (n = 616), or 4.5 mg (n = 614) for 52 weeks. Patients started on dulaglutide 0.75 mg for 4 weeks before escalating stepwise every 4 weeks until the final randomized dose was reached. This study analyzes the onsets, incidences, prevalences, and severities of nausea, vomiting, and diarrhea events reported through 52 weeks.

Results

The highest incidences of nausea (≤ 8%), vomiting (≤ 2%), and diarrhea (≤ 4%) were primarily observed soon after the initiation of dulaglutide treatment at 0.75 mg. Incidence then declined throughout the remainder of the study, even with dose escalation to 1.5, 3.0, and 4.5 mg. Most of these GI TEAEs were mild to moderate in severity, with severe nausea, vomiting, or diarrhea events occurring in ≤ 0.6% of patients. Treatment discontinuation due to nausea was low across treatment groups (≤ 1.5%).

Conclusions

The tolerability profiles of dulaglutide 3.0 mg and 4.5 mg were consistent with that of the 1.5-mg dose. Patients experiencing GI events were most likely to do so within 2 weeks of treatment initiation, and few patients experienced a new GI event after escalating to the 3.0-mg or 4.5-mg dose. Severe events were infrequent, and when they did occur, no relationship with dose at time of event was observed. Supplementary file1 (MP4 33880 kb).

SUBMITTER: Van J

PROVIDER: S-EPMC8479017 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo compare efficacy and safety of dulaglutide at doses of 3.0 and 4.5 mg versus 1.5 mg in patients with type 2 diabetes inadequately controlled with metformin.Research design and methodsPatients were randomly assigned to once-weekly dulaglutide 1.5 mg, 3.0 mg, or 4.5 mg for 52 weeks. The primary objective was determining superiority of dulaglutide 3.0 mg and/or 4.5 mg over 1.5 mg in HbA1c reduction at 36 weeks. Secondary superiority objectives included change in body weight. Two estimands addressed efficacy objectives: treatment regimen (regardless of treatment discontinuation or rescue medication) and efficacy (on treatment without rescue medication) in all randomly assigned patients.ResultsMean baseline HbA1c and BMI in randomly assigned patients (N = 1,842) was 8.6% (70 mmol/mol) and 34.2 kg/m2, respectively. At 36 weeks, dulaglutide 4.5 mg provided superior HbA1c reductions compared with 1.5 mg (treatment-regimen estimand: -1.77 vs. -1.54% [-19.4 vs. -16.8 mmol/mol], estimated treatment difference [ETD] -0.24% (-2.6 mmol/mol), P < 0.001; efficacy estimand: -1.87 vs. -1.53% [-20.4 vs. -16.7 mmol/mol], ETD -0.34% (-3.7 mmol/mol), P < 0.001). Dulaglutide 3.0 mg was superior to 1.5 mg for reducing HbA1c, using the efficacy estimand (ETD -0.17% [-1.9 mmol/mol]; P = 0.003) but not the treatment-regimen estimand (ETD -0.10% [-1.1 mmol/mol]; P = 0.096). Dulaglutide 4.5 mg was superior to 1.5 mg for weight loss at 36 weeks for both estimands (treatment regimen: -4.6 vs. -3.0 kg, ETD -1.6 kg, P < 0.001; efficacy: -4.7 vs. -3.1 kg, ETD -1.6 kg, P < 0.001). Common adverse events through 36 weeks included nausea (1.5 mg, 13.4%; 3 mg, 15.6%; 4.5 mg, 16.4%) and vomiting (1.5 mg, 5.6%; 3 mg, 8.3%; 4.5 mg, 9.3%).ConclusionsIn patients with type 2 diabetes inadequately controlled by metformin, escalation from dulaglutide 1.5 mg to 3.0 mg or 4.5 mg provided clinically relevant, dose-related reductions in HbA1c and body weight with a similar safety profile.

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