Evidence map›Paper›PMID 41738774›Full record

ArticleEndocrine connections2026

Metabolic, enterohepatic and gut microbial effects of atorvastatin in healthy men.

Martin Thomasen, Maria-Anna Misiakou, Simone S Li, Mari Cristina Rodriguez de Evgrafov, Mads B Lynggaard, Martin L Kårhus, Andreas Brønden, Jonatan Kornholt, Oscar Chávez-Talavera, Anne Tailleux and 11 more

Registry-linked trialAbstract read
In one paragraph

Article in Endocrine connections, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT03018444. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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.

NCT03018444 nacompleted

The Effect of HMG-CoA Reductase Inhibition on Postprandial GLP-1 Secretion

Ran2016Enrolled15Registered outcomes12Posted comparisons0ConditionsDiabetes Mellitus, Type 2, Hydroxymethylglutaryl-CoA Reductase InhibitorsArmsAtorvastatin, Placebo
Open the trial in the graph
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
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

21 authors.

Martin ThomasenCenter for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.
Maria-Anna MisiakouNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
Simone S LiNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
Mari Cristina Rodriguez de EvgrafovNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
Mads B LynggaardCenter for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.
Martin L KårhusCenter for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.
Andreas BrøndenDepartment of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Jonatan KornholtDepartment of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Oscar Chávez-TalaveraUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, F-59000 Lille, France.
Anne TailleuxUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, F-59000 Lille, France.
Bart StaelsUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, F-59000 Lille, France.
Amandine DescatUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, F-59000 Lille, France.
Bolette HartmannDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Nicolai J Wewer AlbrechtsenDepartment of Clinical Biochemistry, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Jens F RehfeldDepartment of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Jens J HolstDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Tina VilsbøllDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0002-0456-6787
Anne-Marie EllegaardCenter for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.ORCID 0000-0002-4389-3908
Morten O A SommerNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
David P SonneDepartment of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Filip K KnopCenter for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Objective: Statins are low-density lipoprotein cholesterol-lowering drugs that are highly effective in the prevention of cardiovascular disease and death. Evidence that statin therapy increases the risk of type 2 diabetes is accumulating, but the mechanism behind this phenomenon remains obscure. Design: A clinical, randomised, placebo-controlled, double-blind, crossover study. Methods: Here, we investigated the effect of atorvastatin on fasting and postprandial circulating concentrations of glucose, gluco-regulatory hormones, bile acid profiles as well as gut microbiota composition. Fifteen healthy men came in for a mixed meal test following 14 days of treatment with atorvastatin (40 mg once-daily during week one and 80 mg once-daily during week two) or placebo. Results: Treatment with atorvastatin did not affect postprandial plasma glucose or insulin concentrations, but basal as well as postprandial concentrations of glucagon were increased compared with placebo. Postprandial plasma concentrations of the gut-derived incretin hormones glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 were increased after atorvastatin treatment compared with placebo. Also, postprandial concentrations of taurine-conjugated primary bile acids increased, whereas glycine-conjugated secondary bile acids decreased. Microbiota composition was not affected by atorvastatin treatment. Conclusions: Atorvastatin treatment did not alter glucose or insulin concentrations, nor did it alter gut microbiota composition. However, we found that atorvastatin treatment increased fasting and postprandial glucagon concentrations, which may point to hyperglucagonaemia as a possible link between statin treatment and type 2 diabetes. Clinicaltrials.gov: NCT03018444. Significance Statement: This randomised, placebo-controlled, double-blind, crossover study reveals that short-term high-dose atorvastatin treatment increases fasting and postprandial glucagon levels and alters amino acid and bile acid profiles without affecting glucose, insulin, or gut microbiota in healthy men. These findings suggest hyperglucagonaemia as a potential mechanistic contributor to the increased risk of type 2 diabetes associated with statin therapy.

Indexed as

Amino acidsAtorvastatinBile acidsGlucagonGlucagon-like peptide 1Gut microbiomeType 2 diabetes

Identifiers

PMID41738774
PMCPMC12978631

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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 OpenQuestion graph.