Use of GLP-1 Receptor Agonists and Occurrence of Thyroid Disorders: a Meta-Analysis of Randomized Controlled Trials

Hu, Weiting; Song, Rui; Cheng, Rui; Liu, Caihong; Guo, Rui; Tang, Wei; Zhang, Jie; Zhao, Qian; Li, Xing; Liu, Jing

doi:10.3389/fendo.2022.927859

Cited by 46 publications

(26 citation statements)

References 77 publications

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“…These disease states are often comorbid, and one affects the disease progression of the other 28 . However, the potential molecular mechanisms responsible for thyroid effects of GLP-1 RAs are insufficiently characterized and may include multiple pathways such as phosphoinositol-3 kinase/AKT serine/threonine kinase, mitogen-activated protein kinase/extracellular signal-regulated kinase pathways, expression GLP-1 receptors by C-cells, and GLP-1 association with triiodothyronine levels 21,29 . Thyroid hormone plays a pivotal role in nearly every aspect of lipid metabolism 30,31 .…”

Section: Resultsmentioning

confidence: 99%

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Thyroid hyperplasia and neoplasm adverse events associated with GLP-1 receptor agonists in FDA Adverse Event Reporting System

Makunts,

Joulfayan,

Abagyan

2023

Preprint

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Glucagon receptor-like peptide receptor agonists, GLP-1 RAs, are one of the most commonly used drugs for type-2 diabetes mellitus. The clinical guidelines recommend GLP-1 RAs as adjunct to diabetes therapy in patients with chronic kidney disease, presence or risk of atherosclerotic cardiovascular disease, obesity, and other cardiometabolic conditions. The weight loss seen in clinical trials has been explored further in healthy individuals, putting GLP-1 RAs on track to be the next weight loss treatment. Although the adverse event profile is relatively safe, most GLP-1 RAs come with a labeled black boxed warning of the risk of thyroid cancers, based on animal models and some postmarketing case reports in humans. Considering the increasing popularity of this drug class and its expansion into a new popular indication, a further review of most recent postmarketing safety data is warranted to quantify thyroid hyperplasia and neoplasms instances. In this study we analyzed over eighteen million reports from United States Food and Drug Administration Adverse Event Reporting System and identified 17,653 relevant GLP-1 RA monotherapy reports to provide the evidence of significantly increased propensity for thyroid hyperplasias and neoplasms in patients taking GLP-1 RA as monotherapy when compared to patients taking sodium-glucose cotransporter-2 inhibitor monotherapy.

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Section: Resultsmentioning

confidence: 99%

“…The thyroid cancer association in humans has been studied and observed as well in retrospective studies [18][19][20] . However, there is conflicting evidence from a meta-analysis of human randomized controlled trials which refutes this association 21 .…”

Section: Introductionmentioning

confidence: 99%

Thyroid hyperplasia and neoplasm adverse events associated with GLP-1 receptor agonists in FDA Adverse Event Reporting System

Makunts,

Joulfayan,

Abagyan

2023

Preprint

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“…Several studies have found that GLP-1 receptor agonists may cause thyroid C-cell adenomas and C-cell carcinomas in rodents ( 26 , 27 ), and thus GLP-1 receptor agonists are contraindicated in those with a history of medullary thyroid cancer. However, the LEADER trial ( 28 ) in T2DM patients and a meta-analysis ( 29 ) excluded a major increase in the risk of total malignant neoplasms (including pancreatic and thyroid neoplasms) with liraglutide treatment. In the present study, we further evaluated the relationship between thyroid function and GSEA.…”

Section: Discussionmentioning

confidence: 99%

Factors associated with gastrointestinal side effects after liraglutide treatment for type 2 diabetes

Chen

et al. 2023

Front. Endocrinol.

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AimTo identify risk factors predictive of or associated with gastrointestinal side effects (GISE) of liraglutide in patients with type 2 diabetes (T2DM).MethodsT2DM patients treated with liraglutide for the first time were obtained and grouped into patients without GSEA and patients with GSEA. Baseline variables, including age, sex, body mass index (BMI), glycemia profiles, alanine aminotransferase, serum creatinine, thyroid hormones, oral hypoglycemic drugs and history of gastrointestinal diseases, were tested for possible associations with GSEA outcome. Significant variables were entered into univariate and multivariate logistic regression (forward LR) analyses. Receiver operating characteristic (ROC) curves to determine clinically useful cutoff values.ResultsA total of 254 patients (95 female) were included in this study. 74 cases (29.13%) reported GSEA and 11 cases (4.33%) discontinued treatment. The results of univariate analyses showed that sex, age, thyroid stimulating hormone (TSH), free triiodothyronine, α-glucosidase inhibitor (AGI), and concomitant gastrointestinal diseases were associated with GSEA occurrence (all p <0.05). In the final regression model, AGI use (adjusted OR=4.01, 95%CI: 1.90-8.45, p<0.001), gastrointestinal diseases (adjusted OR=3.29, 95%CI: 1.51-7.18, p=0.003), TSH (adjusted OR=1.79, 95%CI: 1.28-2.50, p=0.001) and male sex (adjusted OR=0.19, 95%CI: 0.10-0.37, p<0.001) were independently associated with GSEA. Furthermore, ROC curve analysis confirmed that TSH values of 1.33 and 2.30 in females and males, respectively, were useful thresholds for predicting GSEA.ConclusionThis study suggests that the combination of AGI, concomitant gastrointestinal diseases, female sex and higher TSH levels are independent risk factors of GSEA of liraglutide treatment in patients with T2DM. Further research is warranted to elucidate these interactions.

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“… 21 In a meta-analysis of 11 trials, there was no increase in the risk of thyroid disorders in participants treated with semaglutide relative to placebo (RR = 0.75; 95% CI = 0.35, 1.57). 65 However, these events are rare, and people at individual or familial risk for MTC and MEN 2 and those with high baseline calcitonin were excluded from the STEP trials. In addition, most studies have been of relatively short duration.…”

Section: Candidates For Semaglutidementioning

confidence: 99%

Clinical Insight on Semaglutide for Chronic Weight Management in Adults: Patient Selection and Special Considerations

Chao

Tronieri

Amaro

et al. 2022

DDDT

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Losses of 5-10% or more of initial body weight are associated with improvements in obesity-related comorbidities. However, attaining and sustaining this level of weight loss is challenging. The novel anti-obesity medication semaglutide 2.4 mg injected subcutaneously once weekly as an adjunct to a reduced-calorie diet and physical activity helps patients achieve average losses of 9.6-17.4% of initial body weight at week 68, as well as improvements in cardiometabolic and psychosocial indices. Despite these average benefits, prescribers should carefully assess the suitability of patients for this medication. In this paper, we discuss considerations for the selection of individuals who are candidates for semaglutide and special considerations related to the use of this medication. These include its efficacy and safety, as well as its contraindications, potential adverse effects, management of comorbidities and drug interactions, insurance coverage and cost, and patient preferences.

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Use of GLP-1 Receptor Agonists and Occurrence of Thyroid Disorders: a Meta-Analysis of Randomized Controlled Trials

Cited by 46 publications

References 77 publications

Thyroid hyperplasia and neoplasm adverse events associated with GLP-1 receptor agonists in FDA Adverse Event Reporting System

Thyroid hyperplasia and neoplasm adverse events associated with GLP-1 receptor agonists in FDA Adverse Event Reporting System

Factors associated with gastrointestinal side effects after liraglutide treatment for type 2 diabetes

Clinical Insight on Semaglutide for Chronic Weight Management in Adults: Patient Selection and Special Considerations

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