Novel NPY2R agonist BI 1820237 provides synergistic anti-obesity efficacy when combined with the GCGR/GLP-1R dual agonist survodutide
Summary: Objective: Nutrient-stimulated gut hormone peptide YY3–36 (PYY3–36) selectively activates the neuropeptide Y2 receptor (NPY2R) and reduces energy intake in humans. We describe the discovery and pharmacology of the long-acting NPY2R agonist BI 1820237 and its potential bodyweight-lowering e...
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Elsevier
2025-09-01
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| Series: | Molecular Metabolism |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877825001127 |
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| author | Robert Augustin Anouk Oldenburger Tamara Baader-Pagler Tina Zimmermann Jens Borghardt Jacob Hecksher-Sørensen Angela Baljuls Wolfgang Reindl Bartlomiej Krawczyk Eric Martel Albert Brennauer Stefan Peters Achim Grube Lise Biehl Rudkjaer Peter Haebel |
| author_facet | Robert Augustin Anouk Oldenburger Tamara Baader-Pagler Tina Zimmermann Jens Borghardt Jacob Hecksher-Sørensen Angela Baljuls Wolfgang Reindl Bartlomiej Krawczyk Eric Martel Albert Brennauer Stefan Peters Achim Grube Lise Biehl Rudkjaer Peter Haebel |
| author_sort | Robert Augustin |
| collection | DOAJ |
| description | Summary: Objective: Nutrient-stimulated gut hormone peptide YY3–36 (PYY3–36) selectively activates the neuropeptide Y2 receptor (NPY2R) and reduces energy intake in humans. We describe the discovery and pharmacology of the long-acting NPY2R agonist BI 1820237 and its potential bodyweight-lowering efficacy alone and in combination with the glucagon receptor (GCGR)/glucagon-like peptide-1 receptor (GLP-1R) dual agonist survodutide. Methods & Results: BI 1820237 dose-dependently reduced food intake and gastric emptying in lean mice. Significant bodyweight reductions were not observed with BI 1820237 alone in diet-induced obese mice, however combination with survodutide led to bodyweight reduction of 22% which was significantly (p < 0.01) greater than the 17% bodyweight reduction with survodutide alone. Regression-based interaction analysis demonstrated that BI 1820237 increased the efficacy of survodutide by 265% at an ED50 of 11.7 nmol/kg over a range of dose combinations. Conclusion: Synergistic NPY2R and GCGR/GLP-1R agonism provides an attractive mode of action for clinically relevant weight loss in patients with obesity. |
| format | Article |
| id | doaj-art-afccfa8cf8c444efb0ab8acb57a8ef02 |
| institution | Matheson Library |
| issn | 2212-8778 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj-art-afccfa8cf8c444efb0ab8acb57a8ef022025-07-26T05:23:05ZengElsevierMolecular Metabolism2212-87782025-09-0199102205Novel NPY2R agonist BI 1820237 provides synergistic anti-obesity efficacy when combined with the GCGR/GLP-1R dual agonist survodutideRobert Augustin0Anouk Oldenburger1Tamara Baader-Pagler2Tina Zimmermann3Jens Borghardt4Jacob Hecksher-Sørensen5Angela Baljuls6Wolfgang Reindl7Bartlomiej Krawczyk8Eric Martel9Albert Brennauer10Stefan Peters11Achim Grube12Lise Biehl Rudkjaer13Peter Haebel14Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397, Biberach an der Riβ, Germany; Corresponding author. Boehringer Ingelheim International GmbH, Birkendorfer Str. 65, 88397, Biberach an der Riβ, Germany.Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397, Biberach an der Riβ, GermanyBoehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397, Biberach an der Riβ, GermanyBoehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397, Biberach an der Riβ, GermanyBoehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397, Biberach an der Riβ, GermanyGubra A/S, Hørsholm Kongevej 11B, 2970, Hørsholm, DenmarkBoehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397, Biberach an der Riβ, GermanyBoehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397, Biberach an der Riβ, GermanyBoehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397, Biberach an der Riβ, GermanyBoehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397, Biberach an der Riβ, GermanyBoehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397, Biberach an der Riβ, GermanyBoehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397, Biberach an der Riβ, GermanyBoehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397, Biberach an der Riβ, GermanyGubra A/S, Hørsholm Kongevej 11B, 2970, Hørsholm, DenmarkBoehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397, Biberach an der Riβ, GermanySummary: Objective: Nutrient-stimulated gut hormone peptide YY3–36 (PYY3–36) selectively activates the neuropeptide Y2 receptor (NPY2R) and reduces energy intake in humans. We describe the discovery and pharmacology of the long-acting NPY2R agonist BI 1820237 and its potential bodyweight-lowering efficacy alone and in combination with the glucagon receptor (GCGR)/glucagon-like peptide-1 receptor (GLP-1R) dual agonist survodutide. Methods & Results: BI 1820237 dose-dependently reduced food intake and gastric emptying in lean mice. Significant bodyweight reductions were not observed with BI 1820237 alone in diet-induced obese mice, however combination with survodutide led to bodyweight reduction of 22% which was significantly (p < 0.01) greater than the 17% bodyweight reduction with survodutide alone. Regression-based interaction analysis demonstrated that BI 1820237 increased the efficacy of survodutide by 265% at an ED50 of 11.7 nmol/kg over a range of dose combinations. Conclusion: Synergistic NPY2R and GCGR/GLP-1R agonism provides an attractive mode of action for clinically relevant weight loss in patients with obesity.http://www.sciencedirect.com/science/article/pii/S2212877825001127PYY3–36NPYNPY2RBI 1820237SurvodutideObesity |
| spellingShingle | Robert Augustin Anouk Oldenburger Tamara Baader-Pagler Tina Zimmermann Jens Borghardt Jacob Hecksher-Sørensen Angela Baljuls Wolfgang Reindl Bartlomiej Krawczyk Eric Martel Albert Brennauer Stefan Peters Achim Grube Lise Biehl Rudkjaer Peter Haebel Novel NPY2R agonist BI 1820237 provides synergistic anti-obesity efficacy when combined with the GCGR/GLP-1R dual agonist survodutide Molecular Metabolism PYY3–36 NPY NPY2R BI 1820237 Survodutide Obesity |
| title | Novel NPY2R agonist BI 1820237 provides synergistic anti-obesity efficacy when combined with the GCGR/GLP-1R dual agonist survodutide |
| title_full | Novel NPY2R agonist BI 1820237 provides synergistic anti-obesity efficacy when combined with the GCGR/GLP-1R dual agonist survodutide |
| title_fullStr | Novel NPY2R agonist BI 1820237 provides synergistic anti-obesity efficacy when combined with the GCGR/GLP-1R dual agonist survodutide |
| title_full_unstemmed | Novel NPY2R agonist BI 1820237 provides synergistic anti-obesity efficacy when combined with the GCGR/GLP-1R dual agonist survodutide |
| title_short | Novel NPY2R agonist BI 1820237 provides synergistic anti-obesity efficacy when combined with the GCGR/GLP-1R dual agonist survodutide |
| title_sort | novel npy2r agonist bi 1820237 provides synergistic anti obesity efficacy when combined with the gcgr glp 1r dual agonist survodutide |
| topic | PYY3–36 NPY NPY2R BI 1820237 Survodutide Obesity |
| url | http://www.sciencedirect.com/science/article/pii/S2212877825001127 |
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