Effects of glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, on markers of liver status in patients with short bowel syndrome:findings from a randomised phase 2 trial
| Autor: | Mark Hvistendahl, Nikolaj Nerup, Palle Jeppesen, Rahim M. Naimi, Holger Jon Møller, Hendrik Vilstrup, Henning Grønbæk, A Steensberg, Lars Bo Svendsen, Michael Patrick Achiam, Rikard Ambrus |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Research paper Transient elastography LBP Lipopolysaccharide Binding Protein Denmark ICG Indocyanine Green lcsh:Medicine ALAT Alanine Transaminase HBsAg Hepatitis B Surface Antigen Gastroenterology chemistry.chemical_compound 0302 clinical medicine Glucagon-Like Peptide 2 PDR Plasma Disappearance Rate IF Intestinal Failure lcsh:R5-920 biology Soluble CD163 Short bowel syndrome General Medicine Liver/diagnostic imaging Middle Aged Glucagon-like peptide-2 Indocyanine green GLP Glucagon-Like Peptide ALP Alkaline Phosphatase Treatment Outcome Liver sCD163 Soluble CD163 030220 oncology & carcinogenesis Elasticity Imaging Techniques Female lcsh:Medicine (General) Lipopolysaccharide binding protein Short Bowel Syndrome SBS Short Bowel Syndrome medicine.medical_specialty Glucagon-Like Peptide 2/pharmacology TE Transient Elastography IFALD Intestinal Failure Associated Liver Disease Aspartate transaminase LLN Lower Limits of Normal ULN Upper Limits of Normal General Biochemistry Genetics and Molecular Biology CAP Controlled Attenuation Parameter 03 medical and health sciences II Intestinal Insufficiency Internal medicine medicine Humans PS Parenteral Support sMR Soluble Mannose Receptor ELISA Enzyme-Linked Immunosorbent Assay Aged ASAT Aspartate Transaminase Short Bowel Syndrome/diagnosis ANCOVA Analysis of Covariance business.industry lcsh:R Soluble mannose receptor medicine.disease C4 7α-Hydroxy-4-Cholesten-3-One CI Confidence Interval FXR Farnesoid X Receptor 030104 developmental biology chemistry Alanine transaminase R15 Retention Rate after 15 min biology.protein FGF Fibroblast Growth Factor Liver function business Biomarkers |
| Zdroj: | Naimi, R M, Hvistendahl, M, Nerup, N, Ambrus, R, Achiam, M P, Svendsen, L B, Grønbæk, H, Møller, H J, Vilstrup, H, Steensberg, A & Jeppesen, P B 2019, ' Effects of glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, on markers of liver status in patients with short bowel syndrome : findings from a randomised phase 2 trial ', EBioMedicine, vol. 46, pp. 444-451 . https://doi.org/10.1016/j.ebiom.2019.07.016 EBioMedicine, Vol 46, Iss, Pp 444-451 (2019) EBioMedicine |
| DOI: | 10.1016/j.ebiom.2019.07.016 |
| Popis: | Background: With the introduction of glucagon-like peptide-2 (GLP-2) in the treatment of short bowel syndrome (SBS), there is emerging evidence that GLP-2 may play a role in the restoration of the disturbed homeostatic feedback in the gut-liver axis and may ameliorate SBS-associated liver damage.We have previously presented that daily subcutaneous injections with 1 and 10 mg of glepaglutide improved intestinal function in patients with SBS. As exploratory endpoints, we here assessed the effect of glepaglutide on liver function. Methods: Liver tests, transient elastography (TE) with controlled attenuation parameter (CAP), indocyanine green (ICG) kinetics, soluble CD163 (sCD163), soluble mannose receptor (sMR), and lipopolysaccharide binding protein (LBP) were assessed in 18 patients with SBS in a randomised, cross-over, dose-finding phase 2 trial before and after three weeks of treatment with glepaglutide. This trial is completed and registered at ClinicalTrials.gov: NCT02690025. Findings: Between Feb 2016 and Jan 2017, 22 patients with SBS were screened. Of these, 18 patients were randomised and treated with glepaglutide; 16 patients completed the trial. Treatment with glepaglutide was associated with increase in TE and ICG-elimination. In the 10 mg dose group, glepaglutide increased sCD163 by 0·44 mg/mL (P = 0·0498), and alkaline phosphatase (ALP) decreased in the 1 mg dose group by 33 U/L (P = 0·032). CAP, sMR, LBP, liver transaminases, and INR were not affected. Interpretation: Glepaglutide may improve hepatic excretory function, but at the same time activate resident liver macrophages and increase liver stiffness. The excretory and the stiffness findings may to some extent relate to increased splanchnic blood flow which would not influence the marker of macrophage activation. Thus, glepaglutide exerted diverse effects on liver status that call for attention in future studies. Funding: Zealand Pharma. Keywords: Short bowel syndrome, Transient elastography, Indocyanine green, Soluble CD163, Soluble mannose receptor |
| Databáze: | OpenAIRE |
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