Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital

GLP-1 secretion is regulated by IL-6 signalling: a randomised, placebo-controlled study

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Gut microbiota profile and selected plasma metabolites in type 1 diabetes without and with stratification by albuminuria

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Major decreases in the lipidome following liraglutide treatment: 21-25 September 2020.

    Research output: Contribution to journalConference abstract in journalResearchpeer-review

  1. Preserved postprandial suppression of bone turnover markers, despite increased fasting levels, in postmenopausal women

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Plasma proteome profiles treatment efficacy of incretin dual agonism in diet-induced obese female and male mice

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. A cell-autonomous signature of dysregulated protein phosphorylation underlies muscle insulin resistance in type 2 diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Nonalcoholic Fatty Liver Disease Impairs the Liver-Alpha Cell Axis Independent of Hepatic Inflammation and Fibrosis

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

AIMS/HYPOTHESIS: IL-6 is a cytokine with various effects on metabolism. In mice, IL-6 improved beta cell function and glucose homeostasis via upregulation of glucagon-like peptide 1 (GLP-1), and IL-6 release from muscle during exercise potentiated this beneficial increase in GLP-1. This study aimed to identify whether exercise-induced IL-6 has a similar effect in humans.

METHODS: In a multicentre, double-blind clinical trial, we randomly assigned patients with type 2 diabetes or obesity to intravenous tocilizumab (an IL-6 receptor antagonist) 8 mg/kg every 4 weeks, oral sitagliptin (a dipeptidyl peptidase-4 inhibitor) 100 mg daily or double placebos (a placebo saline infusion every 4 weeks and a placebo pill once daily) during a 12 week training intervention. The primary endpoints were the difference in change of active GLP-1 response to an acute exercise bout and change in the AUC for the concentration-time curve of active GLP-1 during mixed meal tolerance tests at baseline and after the training intervention.

RESULTS: Nineteen patients were allocated to tocilizumab, 17 to sitagliptin and 16 to placebos. During the acute exercise bout active GLP-1 levels were 26% lower with tocilizumab (multiplicative effect: 0.74 [95% CI 0.56, 0.98], p = 0.034) and 53% higher with sitagliptin (1.53 [1.15, 2.03], p = 0.004) compared with placebo. After the 12 week training intervention, the active GLP-1 AUC with sitagliptin was about twofold that with placebo (2.03 [1.56, 2.62]; p < 0.001), while GLP-1 AUC values showed a small non-significant decrease of 13% at 4 weeks after the last tocilizumab infusion (0.87 [0.67, 1.12]; p = 0.261).

CONCLUSIONS/INTERPRETATION: IL-6 is implicated in the regulation of GLP-1 in humans. IL-6 receptor blockade lowered active GLP-1 levels in response to a meal and an acute exercise bout in a reversible manner, without lasting effects beyond IL-6 receptor blockade.


FUNDING: Danish National Research Foundation. Danish Council for Independent Research. Novo Nordisk Foundation. Danish Centre for Strategic Research in Type 2 Diabetes. European Foundation for the Study of Diabetes. Swiss National Research Foundation.

Original languageEnglish
Issue number2
Pages (from-to)362-373
Number of pages12
Publication statusPublished - Feb 2020

ID: 59937407