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DACRA induces profound weight loss, satiety control, and increased mitochondrial respiratory capacity in adipose tissue.

October 1, 2024

Int J Obes (Lond)

Abstract BACKGROUND AND OBJECTIVES Dual amylin and calcitonin receptor agonists (DACRAs) are therapeutic candidates in the treatment of obesity with beneficial effects on weight loss superior to suppression of food intake. Hence, suggesting effects on energy expenditure by possibly targeting mitochondria in metabolically active tissue. METHODS Male rats with HFD-induced obesity received a DACRA, KBP-336, […]

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The enduring metabolic improvement of combining dual amylin and calcitonin receptor agonist and semaglutide treatments in a rat model of obesity and diabetes.

August 1, 2024

Am J Physiol Endocrinol Metab

Abstract Long-acting dual amylin and calcitonin receptor agonists (DACRAs) are novel candidates for the treatment of type 2 diabetes and obesity due to their beneficial effects on body weight, glucose control, and insulin action. However, how the metabolic benefits are maintained after long-lasting treatment is unknown. This study investigates the long-term anti-obesity and anti-diabetic treatment […]

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The dual amylin and calcitonin receptor agonist KBP-336 elicits a unique combination of weight loss, antinociception and bone protection – a novel disease-modifying osteoarthritis drug.

July 12, 2024

Arthritis Res Ther

Abstract BACKGROUND Despite the extensive research to provide a disease-modifying osteoarthritis drug (DMOAD), there is still no approved DMOAD. Dual amylin and calcitonin receptor agonists (DACRA) can provide metabolic benefits along with antinociceptive and potential structural preserving effects. In these studies, we tested a DACRA named KBP-336 on a metabolic model of OA in meniscectomised […]

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Serum levels of fibrogenesis biomarkers reveal distinct endotypes predictive of response to weight loss in advanced nonalcoholic fatty liver disease.

October 1, 2023

Hepatol Commun

Abstract BACKGROUND NAFLD is associated with activation of fibroblasts and hepatic fibrosis. Substantial patient heterogeneity exists, so it remains challenging to risk-stratify patients. We hypothesized that the amount of fibroblast activity, as assessed by circulating biomarkers of collagen formation, can define a “high-risk, high-fibrogenesis” patient endotype that exhibits greater fibroblast activity and potentially more progressive […]

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Treatment sequencing using the dual amylin and calcitonin receptor agonist KBP-336 and semaglutide results in durable weight loss.

September 5, 2023

Eur J Pharmacol

Abstract OBJECTIVE Long-acting dual amylin and calcitonin receptor agonists (DACRAs) hold great promise as potential treatments for obesity and its associated comorbidities. These agents have demonstrated beneficial effects on body weight, glucose control, and insulin action mirroring the effects observed with glucagon-like peptide-1 (GLP-1) agonist treatment. Strategies aimed at enhancing and prolonging treatment efficacy include […]

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Dual amylin and calcitonin receptor agonist treatment improves insulin sensitivity and increases muscle-specific glucose uptake independent of weight loss.

August 1, 2023

Biomed Pharmacother

Abstract Dual amylin and calcitonin receptor agonists (DACRAs) are known to induce significant weight loss as well as improve glucose tolerance, glucose control, and insulin action in rats. However, to what extent DACRAs affect insulin sensitivity beyond that induced by weight loss and if DACRAs affect glucose turnover including tissue-specific glucose uptake is still unknown. […]

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Does receptor balance matter? – Comparing the efficacies of the dual amylin and calcitonin receptor agonists cagrilintide and KBP-336 on metabolic parameters in preclinical models.

December 1, 2022

Biomed Pharmacother

Abstract Cagrilintide is a novel long-acting amylin receptor agonist, which has shown a potent induction of weight loss. Interestingly, cagrilintide is a Dual Amylin and Calcitonin Receptor Agonist (DACRA) derived from an amylin backbone. Another class of long-acting DACRAs exists, namely the KBPs. These are salmon calcitonin-based and have shown preclinical potential; however, how and […]

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KBP-066A, a long-acting dual amylin and calcitonin receptor agonist, induces weight loss and improves glycemic control in obese and diabetic rats.

November 1, 2021

Mol Metab

Abstract OBJECTIVE Dual amylin and calcitonin receptor agonists (DACRAs) are novel therapeutic agents that not only improve insulin sensitivity but also work as an adjunct to established T2DM therapies. DACRAs are currently administered once daily, though it is unknown whether DACRAs with increased plasma half-life can be developed as a once-weekly therapy. METHODS The in vitro […]

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Mono and dual agonists of the amylin, calcitonin, and CGRP receptors and their potential in metabolic diseases.

April 1, 2021

Mol Metab

Abstract BACKGROUND Therapies for metabolic diseases are numerous, yet improving insulin sensitivity beyond that induced by weight loss remains challenging. Therefore, search continues for novel treatment candidates that can stimulate insulin sensitivity and increase weight loss efficacy in combination with current treatment options. Calcitonin gene-related peptide (CGRP) and amylin belong to the same peptide family […]

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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.

January 7, 2021

BMC Endocr Disord

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 […]

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