Clinical factors associated with the occurrence of nausea and vomiting in type 2 diabetes patients treated with glucagon‐like peptide‐1 receptor agonists

Shiomi, Megumi; Takada, Tesshu; Tanaka, Yoïchi; Yajima, Keiko; Isomoto, Akira; Sakamoto, Masaki; Otori, Katsuya

doi:10.1111/jdi.12900

Cited by 11 publications

(8 citation statements)

References 71 publications

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“…Treatment-by-subgroup analysis of GI TEAEs yielded significant treatment-by-sex interactions for nausea and diarrhea due to different patterns of incidence across dose groups in males and females. While the higher incidence rates in females were not observed in previous dulaglutide trials, higher rates of nausea in females have been documented in other studies involving GLP-1 RA therapies [19,27,28]. Indeed, for reasons not well understood, gastrointestinal symptoms are consistently reported more frequently in females than in males, with or without diabetes [29].…”

Section: Discussionmentioning

confidence: 70%

“…These events are typically mild and tend to peak soon after treatment initiation before decreasing in the following weeks [15,17]. While the frequency of gastrointestinal (GI) TEAEs can be dose dependent [18,19], previous studies involving GLP-1 RA therapies have shown that escalating the dose in a measured, stepwise manner can lessen the occurrence and severity of GI events [20,21]. The AWARD-11 trial compared the efficacy and safety of dulaglutide at once-weekly doses of 3.0 mg and 4.5 mg with its efficacy and safety at the previously approved 1.5-mg dose [22], with dose escalation occurring every 4 weeks from the 0.75-mg starting dose to mitigate potential tolerability issues at higher doses.…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2021

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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 (B 8%), vomiting (B 2%), and diarrhea (B 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 B 0.6% of patients. Treatment discontinuation due to nausea was low across treatment groups (B 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

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Section: Discussionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…In rats, peripheral administration of LiCl induces cFos neuronal activity in the IPBN, the AP and the NTS [726,729] with remarkable overlap in the cFos activity pattern induced by centrally administered GLP-1 [726]. Apart from inducing cFos activity in the same brain areas [696,726,730], LiCl and central GLP-1R agonism both decrease locomotor activity [668,731], slow GI motility and gastric emptying [573,732], reduce body temperature [732,733], and induce adverse gastrointestinal effects including nausea, emesis, and taste avoidance [696,[724], [725], [726],[734], [735], [736], [737]]. Selective ablation of NTS PPG neurons prevents stress-induced hyperphagia in mice but has no effect on long-term ad libitum food intake, body weight, or glucose tolerance [90].…”

Section: Glp-1 Effects On Food Intake and Body Weightmentioning

confidence: 99%

Glucagon-like peptide 1 (GLP-1)

Müller¹,

Finan²,

Bloom³

et al. 2019

Molecular Metabolism

1,158

861

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BackgroundThe glucagon-like peptide-1 (GLP-1) is a multifaceted hormone with broad pharmacological potential. Among the numerous metabolic effects of GLP-1 are the glucose-dependent stimulation of insulin secretion, decrease of gastric emptying, inhibition of food intake, increase of natriuresis and diuresis, and modulation of rodent β-cell proliferation. GLP-1 also has cardio- and neuroprotective effects, decreases inflammation and apoptosis, and has implications for learning and memory, reward behavior, and palatability. Biochemically modified for enhanced potency and sustained action, GLP-1 receptor agonists are successfully in clinical use for the treatment of type-2 diabetes, and several GLP-1-based pharmacotherapies are in clinical evaluation for the treatment of obesity.Scope of reviewIn this review, we provide a detailed overview on the multifaceted nature of GLP-1 and its pharmacology and discuss its therapeutic implications on various diseases.Major conclusionsSince its discovery, GLP-1 has emerged as a pleiotropic hormone with a myriad of metabolic functions that go well beyond its classical identification as an incretin hormone. The numerous beneficial effects of GLP-1 render this hormone an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, and neurodegenerative disorders

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“…Conversely, the most common side effects associated with treatment for obesity and type 2 diabetes with GLP-1 analogs are nausea and vomiting. These symptoms may be more frequent in women and those also treated with metformin, proton pump inhibitors, and/or anti-histamines [ 165 , 166 ]. While nausea and vomiting associated with weight loss from liraglutide treatment is often transient [ 167 ], occurrence of these side effects still limits the therapeutic potential of GLP-1 analogs.…”

Section: Aversionmentioning

confidence: 99%

Ghrelin and Glucagon-Like Peptide-1: A Gut-Brain Axis Battle for Food Reward

Décarie-Spain

Kanoski

2021

Nutrients

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Eating behaviors are influenced by the reinforcing properties of foods that can favor decisions driven by reward incentives over metabolic needs. These food reward-motivated behaviors are modulated by gut-derived peptides such as ghrelin and glucagon-like peptide-1 (GLP-1) that are well-established to promote or reduce energy intake, respectively. In this review we highlight the antagonizing actions of ghrelin and GLP-1 on various behavioral constructs related to food reward/reinforcement, including reactivity to food cues, conditioned meal anticipation, effort-based food-motivated behaviors, and flavor-nutrient preference and aversion learning. We integrate physiological and behavioral neuroscience studies conducted in both rodents and human to illustrate translational findings of interest for the treatment of obesity or metabolic impairments. Collectively, the literature discussed herein highlights a model where ghrelin and GLP-1 regulate food reward-motivated behaviors via both competing and independent neurobiological and behavioral mechanisms.

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Clinical factors associated with the occurrence of nausea and vomiting in type 2 diabetes patients treated with glucagon‐like peptide‐1 receptor agonists

Abstract: The present study showed a significant correlation of PPIs or H2RAs, female sex, and diabetic retinopathy with nausea and vomiting in patients with type 2 diabetes treated with GLP-1 RAs. Hence, the occurrence of nausea and vomiting in patients with these factors warrants attention.

Cited by 11 publications

References 71 publications

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

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

Glucagon-like peptide 1 (GLP-1)

Ghrelin and Glucagon-Like Peptide-1: A Gut-Brain Axis Battle for Food Reward

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