Evidence map›Paper›PMID 21209033›Full record

Trial reportThe Journal of clinical endocrinology and metabolism2011

GLP-1 and calcitonin concentration in humans: lack of evidence of calcitonin release from sequential screening in over 5000 subjects with type 2 diabetes or nondiabetic obese subjects treated with the human GLP-1 analog, liraglutide.

Laszlo Hegedüs, Alan C Moses, Milan Zdravkovic, Tu Le Thi, Gilbert H Daniels

Registry-linked trialOpen access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The Journal of clinical endocrinology and metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT00318422. Cited by 75 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed, 3 pooled it
17.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00318422 phase3completed

Liraglutide Effect and Action in Diabetes (LEAD-1): Effect on Glycaemic Control After Once Daily Administration of Liraglutide in Combination With Glimepiride Versus Glimepiride Monotherapy Versus Glimepiride and Rosiglitazone Combination Therapy in Subjects With Type 2 Diabetes.

Ran2006Enrolled1,041Registered outcomes5Posted comparisons0ConditionsDiabetes, Diabetes Mellitus, Type 2ArmsGlimepiride, liraglutide, Rosiglitazone
PMID 21883806PMID 19491535PMID 23010561PMID 22055210PMID 22193143PMID 19491536PMID 25504028PMID 23186975PMID 21450987PMID 19245711PMID 19878259PMID 22862847other papers from this trial
Open the trial in the graph
3 · Its place in the literature

Who cites it

75 citing papers in PubMed, 3 syntheses or guidelines pooled it, 190 citations in OpenAlex.

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  11. Effects of Glucagon-Like Peptide-1 receptor agonists on bone health in people living with obesity.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025
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15 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 4 institutions in 2 countries.

Laszlo HegedüsDepartment of Endocrinology, Odense University Hospital, Odense, Denmark. Laszlo.Hegedus@ouh.regionsyddanmark.dk
Alan C Moses
Milan Zdravkovic
Tu Le Thi
Gilbert H Daniels
Novo Nordisk (Denmark) · DKHarvard University · USNovo Nordisk (United States) · USOdense University Hospital · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSerum calcitonin (CT) is a well-accepted marker of C-cell proliferation, particularly in medullary thyroid carcinoma. Chronic glucagon-like peptide-1 (GLP-1) receptor agonist administration in rodents has been associated with increased serum CT levels and C-cell tumor formation. There are no longitudinal studies measuring CT in humans without medullary thyroid carcinoma or a family history of medullary thyroid carcinoma and no published studies on the effect of GLP-1 receptor agonists on human serum CT concentrations.

aimThe aim of the study was to determine serum CT response over time to the GLP-1 receptor agonist liraglutide in subjects with type 2 diabetes mellitus or nondiabetic obese subjects.

methodsUnstimulated serum CT concentrations were measured at 3-month intervals for no more than 2 yr in a series of trials in over 5000 subjects receiving liraglutide or control therapy.

resultsBasal mean CT concentrations were at the low end of normal range in all treatment groups and remained low throughout the trials. At 2 yr, estimated geometric mean values were no greater than 1.0 ng/liter, well below upper normal ranges for males and females. Proportions of subjects whose CT levels increased above a clinically relevant cutoff of 20 ng/liter were very low in all groups. There was no consistent dose or time-dependent relationship and no consistent difference between treatment groups.

conclusionsThese data do not support an effect of GLP-1 receptor activation on serum CT levels in humans and suggest that findings previously reported in rodents may not apply to humans. However, the long-term consequences of GLP-1 receptor agonist treatment are a subject of further studies.

Indexed as

AdultCalcitoninDiabetes ComplicationsDiabetes Mellitus, Type 2Dose-Response Relationship, DrugFemaleGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorHumansHypoglycemic AgentsLiraglutideMaleMiddle AgedObesityReceptors, GlucagonCalcitoninGLP1R protein, humanGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorHypoglycemic AgentsLiraglutideReceptors, Glucagon

Identifiers

PMID21209033
OpenAlexW2118710260

What Socratic holds

Texttitle and abstract
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.