NDLI: The dual amylin and calcitonin receptor agonist KBP-089 and the GLP-1 receptor agonist liraglutide act complimentarily on body weight reduction and metabolic profile

Content Provider	Springer Nature : BioMed Central
Author	Larsen, Anna Thorsø Gydesen, Sofie Sonne, Nina Karsdal, Morten Asser Henriksen, Kim
Abstract	Background Weight loss therapy is becoming more and more important, and two classes of molecules, namely amylin receptor and GLP-1 receptor agonists, have shown promise in this regard. Interestingly, these molecules have several overlapping pharmacological effects, such as suppression of gastric emptying, reduction of glucagon secretion and weight loss in common; however, they also have distinct effects on prandial insulin secretion. Hence, a combination of these two mechanisms is of significant interest. Methods In this study, we investigated the add-on potential of the dual amylin and calcitonin receptor agonist (DACRA) KBP-089 in combination with the GLP-1 receptor agonist liraglutide as obesity treatment in high-fat diet (HFD) fed rats. Results Increasing doses of KBP-089 and liraglutide alone and in combination were studied with respect to their effects on body weight, food intake and glucose metabolism during a 9-week intervention study conducted in HFD rats. Further, the gastric emptying rate during an oral glucose tolerance was assessed. Treatment with KBP-089 and liraglutide dose-dependently lowered body weight 15% (at 2.5 μg/kg/day) and 7% (at 400 μg/kg/day) in HFD rats, respectively, while the combination resulted in a 21% body weight reduction, which was mirrored by reduction in fat depot sizes. Gastric emptying and glucose metabolism were improved, primarily by KBP-089, although liraglutide led to a reduction in fasting plasma glucagon. Conclusion DACRAs complement GLP-1 on food intake, body weight, and glucose tolerance indicating the potential for an add-on therapy.
Related Links	https://bmcendocrdisord.biomedcentral.com/counter/pdf/10.1186/s12902-020-00678-2.pdf
Ending Page	9
Page Count	9
Starting Page	1
File Format	HTM / HTML
ISSN	14726823
DOI	10.1186/s12902-020-00678-2
Journal	BMC Endocrine Disorders
Issue Number	1
Volume Number	21
Language	English
Publisher	BioMed Central
Publisher Date	2021-01-07
Access Restriction	Open
Subject Keyword	Endocrinology Metabolic Diseases Diabetes Andrology DACRA GLP-1 Obesity Glucose tolerance
Content Type	Text
Resource Type	Article
Subject	Endocrinology, Diabetes and Metabolism
Journal Impact Factor	2.8/2023
5-Year Journal Impact Factor	3.1/2023

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