scholarly journals A Review on the Association between Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Wei-Yih Chiu ◽  
Shyang-Rong Shih ◽  
Chin-Hsiao Tseng
Keyword(s):  
Clinical Trials ◽  
Thyroid Cancer ◽  
Cell Cancer ◽  
Adverse Event Reporting System ◽  
C Cells ◽  
C Cell ◽  
Increased Risk ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Impact

There is a concern on the risk of thyroid cancer associated with glucagon-like peptide-1 (GLP-1) analogs including liraglutide and exenatide. In this article, we review related experimental studies, clinical trials and observational human studies currently available. In rodents, liraglutide activated the GLP-1 receptors on C-cells, causing an increased incidence of C-cell neoplasia. Animal experiments with monkeys demonstrated no increase in calcitonin release and no C-cell proliferation after long-term liraglutide administration. Longitudinal 2-year data from clinical trials do not support any significant risk for the activation or growth of C-cell cancer in humans in response to liraglutide. However, an analysis of the FDA adverse event reporting system database suggested an increased risk for thyroid cancer associated with exenatide after its marketing. Noticeably, a recent study discovered that GLP-1 receptor could also be expressed in human papillary thyroid carcinomas (PTC), but the impact of GLP-1 analogs on PTC is not known. Therefore, GLP-1 analogs might increase the risk of thyroid C-cell pathology in rodents, but its risk in humans awaits confirmation. Since GLP-1 receptor is also expressed in PTC besides C-cells, it is important to investigate the actions of GLP-1 on different subtypes of thyroid cancer in the future.

scholarly journals Glucagon-Like Peptide-1 Receptor Agonists Activate Rodent Thyroid C-Cells Causing Calcitonin Release and C-Cell Proliferation

2010 ◽  
Vol 95 (3) ◽  
pp. 1476-1477
Author(s):  
Lotte Bjerre Knudsen ◽  
Lars Wichmann Madsen ◽  
Søren Andersen ◽  
Kasper Almholt ◽  
Anne S. de Boer ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
C Cells ◽  
Receptor Agonists ◽  
C Cell ◽  
Thyroid C Cells ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Medullary Carcinoma of Thyroid Due to GLP-1 Receptor Agonist

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A893-A893
Author(s):  
Hasitha Vemula ◽  
Fiorella Sotomayor Villanueva ◽  
Huong Diem Nguyen ◽  
Akhila Mohan ◽  
Sriravali Potluri
Keyword(s):  
Thyroid Tissue ◽  
Medullary Carcinoma ◽  
Human Thyroid ◽  
C Cells ◽  
Men 2 ◽  
C Cell ◽  
Thyroid C Cells ◽  
Increased Risk ◽  
Glucagon Like Peptide 1

Abstract Introduction: The first GLP-1 receptor agonist (GLP-1 RA) was approved for the treatment of type 2 Diabetes mellitus in 2005. This class has gained popularity due to its anti-glycemic effect, weight loss and reduction in Cardiovascular disease outcomes1. The effects of this drug class on human thyroid cells are not well known. We hereby report a case of a woman who developed medullary carcinoma of thyroid (MTC) after using Dulaglutide. CaseA 63-year-old female with T2DM for 3 years, taking dulaglutide for 2 years, who presented with a lump in the neck. She had no personal or family history of MEN 2 syndrome, radiation exposure or cancer. Examination showed a 2cm firm nodule in the left lower neck. Thyroid ultrasound revealed a large nodule in the left upper lobe of thyroid. Lab work showed TSH of 1.55mIU/L (0.27-4.2 mIU/L) and serum calcitonin level of 1903 pg/ml (0.0-5.1 pg/mL). FNA biopsy of the nodule showed MTC. She tested negative for RET MEN 2 gene mutation. She underwent total thyroidectomy and neck dissection. Pathological examination confirmed MTC. Post-op calcitonin improved to 2.1 pg/ml. Discussion: GLP-1 RAs provide glycemic control by many mechanisms, including increase in insulin secretion, reduction in postprandial glucagon secretion, delaying gastric emptying, increasing satiety and weight loss. Although they have proved effective in T2DM management, the potential effects on thyroid C-cells should not be ignored. Several in-vitro studies have shown GLP-1 receptors on the rat thyroid tissue C-cells. Stimulation of these receptors resulted in increased production of calcitonin in a dose dependent manner and increased risk of C-cell tumor formation at 104 weeks. Studies initially done by Knudsen et al2 showed that this effect was not seen in humans due to lower expression of GLP-1 receptors in human thyroid tissue C cells. However, a study conducted by Gier et al showed the expression of GLP-1 receptor in some patients with C-cell hyperplasia as well as papillary and medullary carcinoma3. FDA adverse event reporting system database suggested an increased risk of thyroid cancer associated with GLP-1 RAs. It is unclear whether dulaglutide contributed to the development of MTC in this patient. She had not had a baseline calcitonin level prior to the initiation of dulaglutide. The consequence of long-term use of GLP-1 RAs in the thyroid gland in humans still remains unknown and further studies to determine if they increase the risk of MTC are warranted. References: 1. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016;375(4):311. Epub 2016 Jun 13. 2. Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. Endocrinology. 2010;151(4):1473. Epub 2010 Mar 3. Glucagon Like Peptide-1 Receptor Expression in the Human Thyroid Gland

scholarly journals Glucagon-Like Peptide-1 Receptor Agonists Activate Rodent Thyroid C-Cells Causing Calcitonin Release and C-Cell Proliferation

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1473-1486 ◽  
Author(s):  
Lotte Bjerre Knudsen ◽  
Lars Wichmann Madsen ◽  
Søren Andersen ◽  
Kasper Almholt ◽  
Anne S. de Boer ◽  
...  
Keyword(s):  
Receptor Expression ◽  
C Cells ◽  
Cell Hyperplasia ◽  
Receptor Agonists ◽  
C Cell Hyperplasia ◽  
C Cell ◽  
Thyroid C Cells ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Liraglutide is a glucagon-like peptide-1 (GLP-1) analog developed for type 2 diabetes. Long-term liraglutide exposure in rodents was associated with thyroid C-cell hyperplasia and tumors. Here, we report data supporting a GLP-1 receptor-mediated mechanism for these changes in rodents. The GLP-1 receptor was localized to rodent C-cells. GLP-1 receptor agonists stimulated calcitonin release, up-regulation of calcitonin gene expression, and subsequently C-cell hyperplasia in rats and, to a lesser extent, in mice. In contrast, humans and/or cynomolgus monkeys had low GLP-1 receptor expression in thyroid C-cells, and GLP-1 receptor agonists did not activate adenylate cyclase or generate calcitonin release in primates. Moreover, 20 months of liraglutide treatment (at >60 times human exposure levels) did not lead to C-cell hyperplasia in monkeys. Mean calcitonin levels in patients exposed to liraglutide for 2 yr remained at the lower end of the normal range, and there was no difference in the proportion of patients with calcitonin levels increasing above the clinically relevant cutoff level of 20 pg/ml. Our findings delineate important species-specific differences in GLP-1 receptor expression and action in the thyroid. Nevertheless, the long-term consequences of sustained GLP-1 receptor activation in the human thyroid remain unknown and merit further investigation.

scholarly journals Glucagon-like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review

2020 ◽  
Vol 41 (1) ◽  
pp. 14-30 ◽  
Author(s):  
Mark P Maskery ◽  
Christian Holscher ◽  
Stephanie P Jones ◽  
Christopher I Price ◽  
W David Strain ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Scoping Review ◽  
Clinical Studies ◽  
Neuroprotective Agents ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Retrospective Database

Stroke mortality and morbidity is expected to rise. Despite considerable recent advances within acute ischemic stroke treatment, scope remains for development of widely applicable neuroprotective agents. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally licensed for the management of Type 2 Diabetes Mellitus, have demonstrated pre-clinical neuroprotective efficacy in a range of neurodegenerative conditions. This systematic scoping review reports the pre-clinical basis of GLP-1RAs as neuroprotective agents in acute ischemic stroke and their translation into clinical trials. We included 35 pre-clinical studies, 11 retrospective database studies, 7 cardiovascular outcome trials and 4 prospective clinical studies. Pre-clinical neuroprotection was demonstrated in normoglycemic models when administration was delayed by up to 24 h following stroke induction. Outcomes included reduced infarct volume, apoptosis, oxidative stress and inflammation alongside increased neurogenesis, angiogenesis and cerebral blood flow. Improved neurological function and a trend towards increased survival were also reported. Cardiovascular outcomes trials reported a significant reduction in stroke incidence with semaglutide and dulaglutide. Retrospective database studies show a trend towards neuroprotection. Prospective interventional clinical trials are on-going, but initial indicators of safety and tolerability are favourable. Ultimately, we propose that repurposing GLP-1RAs is potentially advantageous but appropriately designed trials are needed to determine clinical efficacy and cost-effectiveness.

scholarly journals Antidiabetic Drugs for the Risk of Alzheimer Disease in Patients With Type 2 DM Using FAERS

2020 ◽  
Vol 35 ◽  
pp. 153331751989954 ◽  
Author(s):  
Hayato Akimoto ◽  
Akio Negishi ◽  
Shinji Oshima ◽  
Haruna Wakiyama ◽  
Mitsuyoshi Okita ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Antidiabetic Drug ◽  
Type 2 Dm ◽  
Metformin Monotherapy ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Alzheimer disease (AD) may develop after the onset of type 2 diabetes mellitus (T2DM), and the risk of AD may depend on the antidiabetic drug administered. We compared the risk of AD among 66 085 patients (≥ 65 years) with T2DM (1250 having concomitant AD) who had been administered antidiabetic drug monotherapy for T2DM who had voluntarily reported themselves in the Food and Drug Administration Adverse Event Reporting System. The risk of AD from the use of different antidiabetic drug monotherapies compared to that of metformin monotherapy was assessed by logistic regression. Rosiglitazone (adjusted reporting odds ratio [aROR] = 0.11; 95% confidence interval [CI]: 0.07-0.17; P < .001), exenatide (aROR = 0.22; 95% CI: 0.11-0.37; P < .001), liraglutide (aROR = 0.36; 95% CI: 0.19-0.62; P < .001), dulaglutide (aROR = 0.39; 95% CI: 0.17-0.77; P = .014), and sitagliptin (aROR = 0.75; 95% CI: 0.60-0.93; P = .011) were found to have a significantly lower associated risk of AD than that of metformin. Therefore, the administration of glucagon-like peptide 1 receptor agonists and rosiglitazone may reduce the risk of AD in patients with T2DM.

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