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.
BMC Endocr Disord
; 21(1): 10, 2021 Jan 07.
Article
em En
| MEDLINE
| ID: mdl-33413317
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Redução de Peso
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Receptores da Calcitonina
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Peptídeos Semelhantes ao Glucagon
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Receptores de Polipeptídeo Amiloide de Ilhotas Pancreáticas
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Agonistas dos Receptores da Amilina
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Liraglutida
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Receptor do Peptídeo Semelhante ao Glucagon 1
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Obesidade
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article