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 trialResearch in context
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-08-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419304517 |
| _version_ | 1811285376324599808 |
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| author | Rahim Mohammad Naimi Mark Hvistendahl Nikolaj Nerup Rikard Ambrus Michael Patrick Achiam Lars Bo Svendsen Henning Grønbæk Holger Jon Møller Hendrik Vilstrup Adam Steensberg Palle Bekker Jeppesen |
| author_facet | Rahim Mohammad Naimi Mark Hvistendahl Nikolaj Nerup Rikard Ambrus Michael Patrick Achiam Lars Bo Svendsen Henning Grønbæk Holger Jon Møller Hendrik Vilstrup Adam Steensberg Palle Bekker Jeppesen |
| author_sort | Rahim Mohammad Naimi |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-04-13T02:43:15Z |
| format | Article |
| id | doaj.art-a0522ef4154c445996f51c2e5666d5cd |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-04-13T02:43:15Z |
| publishDate | 2019-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-a0522ef4154c445996f51c2e5666d5cd2022-12-22T03:06:08ZengElsevierEBioMedicine2352-39642019-08-0146444451Effects 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 trialResearch in contextRahim Mohammad Naimi0Mark Hvistendahl1Nikolaj Nerup2Rikard Ambrus3Michael Patrick Achiam4Lars Bo Svendsen5Henning Grønbæk6Holger Jon Møller7Hendrik Vilstrup8Adam Steensberg9Palle Bekker Jeppesen10Department of Medical Gastroenterology and Hepatology, Rigshospitalet, Copenhagen, Denmark; Corresponding author at: Department of Medical Gastroenterology and Hepatology, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.Department of Medical Gastroenterology and Hepatology, Rigshospitalet, Copenhagen, DenmarkDepartment of Surgical Gastroenterology, Rigshospitalet, Copenhagen, DenmarkDepartment of Surgical Gastroenterology, Rigshospitalet, Copenhagen, DenmarkDepartment of Surgical Gastroenterology, Rigshospitalet, Copenhagen, DenmarkDepartment of Surgical Gastroenterology, Rigshospitalet, Copenhagen, DenmarkDepartment of Hepatology & Gastroenterology, Aarhus University Hospital, DenmarkDepartment of Clinical Biochemistry, Aarhus University Hospital, DenmarkDepartment of Hepatology & Gastroenterology, Aarhus University Hospital, DenmarkResearch & Development, Zealand Pharma, Glostrup, DenmarkDepartment of Medical Gastroenterology and Hepatology, Rigshospitalet, Copenhagen, DenmarkBackground: 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 receptorhttp://www.sciencedirect.com/science/article/pii/S2352396419304517 |
| spellingShingle | Rahim Mohammad Naimi Mark Hvistendahl Nikolaj Nerup Rikard Ambrus Michael Patrick Achiam Lars Bo Svendsen Henning Grønbæk Holger Jon Møller Hendrik Vilstrup Adam Steensberg Palle Bekker Jeppesen 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 trialResearch in context EBioMedicine |
| title | 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 trialResearch in context |
| title_full | 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 trialResearch in context |
| title_fullStr | 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 trialResearch in context |
| title_full_unstemmed | 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 trialResearch in context |
| title_short | 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 trialResearch in context |
| title_sort | 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 trialresearch in context |
| url | http://www.sciencedirect.com/science/article/pii/S2352396419304517 |
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