No Evidence of Increase in Calcitonin Concentrations or Development of C-Cell Malignancy in Response to Liraglutide for Up to 5 Years in the LEADER Trial

Sherman, Steven I.; Tuttle, R. Michael; Scholten, Bernt Johan von; Rasmussen, Søren; Karsbøl, Julie Derving; Daniels, Gilbert H.

doi:10.2337/dc17-1956

Cited by 44 publications

(28 citation statements)

References 10 publications

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“…There was also no evidence of increased calcitonin levels with increasing semaglutide exposure. No evidence of increased calcitonin concentrations was likewise found with liraglutide compared with placebo after 3 years …”

Section: Discussionmentioning

confidence: 93%

Exposure‐response analysis for evaluation of semaglutide dose levels in type 2 diabetes

Petri

Ingwersen

Flint

et al. 2018

Diabetes Obesity Metabolism

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AimsTo evaluate dose levels for semaglutide, a glucagon‐like peptide‐1 analogue approved for the treatment of type 2 diabetes, by examining the effects of demographic factors on efficacy and safety in an exposure‐response analysis.MethodsWe analysed data from 1552 adults from four randomized phase III trials of 30 to 56 weeks' duration, investigating once‐weekly semaglutide doses 0.5 and 1.0 mg. Exposure‐response relationships were investigated using graphical and model‐based techniques to assess the two dose levels and subgroups with the highest and lowest exposure and response.ResultsThe population had the following demographic characteristics: baseline mean age between 53.2 and 58.4 years, glycated haemoglobin (HbA1c) between 64 and 67 mmol/mol (8.0% and 8.3%), body weight between 71.3 and 96.2 kg, and diabetes duration between 4.2 and 8.9 years. Exposure‐response analysis showed a clear HbA1c and weight reduction across exposures after 30 weeks, irrespective of baseline values. The exposure‐response for HbA1c was influenced by baseline HbA1c, and body weight exposure‐response was influenced by sex, with limited impact of other factors. Analyses for relevant subgroups of baseline body weight, baseline HbA1c and sex indicated clinically relevant additional benefits with regard to HbA1c and weight with 1.0 vs 0.5 mg semaglutide. The proportion of participants reporting gastrointestinal (GI) side effects increased with increasing exposure, but was counteracted by tolerance development.ConclusionsThe analysis showed that all subgroups obtained a clinically relevant benefit with semaglutide 0.5 mg and an additional benefit with semaglutide 1.0 mg. The increase in GI side effects with higher exposure was mitigated by gradually increasing the dose.

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Section: Discussionmentioning

confidence: 93%

Exposure‐response analysis for evaluation of semaglutide dose levels in type 2 diabetes

Petri

Ingwersen

Flint

et al. 2018

Diabetes Obesity Metabolism

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“…A large population-based randomized study (the LEADER Trial) assessed the long-term effects of the GLP-1 receptor agonist liraglutide on serum CT concentrations over a 3.5-5-year period. Unstimulated serum CT concentrations were measured in over 9,340 patients with T2D receiving liraglutide or placebo (253). The results did not support any effect of GLP-1 receptor activation on serum CT levels, C-cell hyperplasia or C-cell malignancy in humans suggesting that the findings previously reported in rodents may not apply to humans (253).…”

Section: Advance Article: Endocrine Reviewsmentioning

confidence: 87%

“…Unstimulated serum CT concentrations were measured in over 9,340 patients with T2D receiving liraglutide or placebo (253). The results did not support any effect of GLP-1 receptor activation on serum CT levels, C-cell hyperplasia or C-cell malignancy in humans suggesting that the findings previously reported in rodents may not apply to humans (253). Therefore, there is no evidence for adverse effects of liraglutide in humans.…”

Section: Advance Article: Endocrine Reviewsmentioning

confidence: 89%

Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders

2019

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“…In rodents administered incretin-based medications, pancreatic, intestinal, and breast neoplasms were found to develop more frequently; however, these results were not found in human studies [66][67][68]. A phase IIIb RCT reported no difference in calcitonin levels and medullary thyroid carcinoma rates between liraglutide (≤1.8 mg) and placebo during a follow-up of 3.5-5 years [69]. Additionally, the total risk of malignant and benign neoplasms, including pancreatic cancer, was not found to increase in the liraglutide vs. placebo group [63,64,70].…”

Section: ) Clinical Efficacymentioning

confidence: 98%

Anti-Obesity Drugs: Long-Term Efficacy and Safety: An Updated Review

Tak

Lee

2021

World J Mens Health

102

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Recently, the "epidemic of obesity" has emerged as one of the major global health concerns. Between 1975 and 2016, the worldwide prevalence of obesity tripled and was primarily attributed to the intake of a high calorie diet and a sedentary lifestyle [1]. Although the prevalence of being overweight was similar between men (39%) and women (40%) in 2016 according to the World Health Organization, recent studies have reported more rapid increases in obesity-related indicators in men than in women [2,3]. This sex disparity can be explained by genetic, sociocultural, socioeconomic, and behavioral factors [4]. After starting a career, men might succumb to obesogenic environmental changesfrequent dining outside the home, drinking, and stress,

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No Evidence of Increase in Calcitonin Concentrations or Development of C-Cell Malignancy in Response to Liraglutide for Up to 5 Years in the LEADER Trial

Abstract: There was no evidence of a difference in calcitonin concentrations between the liraglutide and placebo groups, and no C-cell malignancies occurred in the liraglutide group.

Cited by 44 publications

References 10 publications

Exposure‐response analysis for evaluation of semaglutide dose levels in type 2 diabetes

Exposure‐response analysis for evaluation of semaglutide dose levels in type 2 diabetes

Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders

Anti-Obesity Drugs: Long-Term Efficacy and Safety: An Updated Review

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