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Structure-function analysis of time-resolved immunological phases in metabolic dysfunction-associated fatty liver disease (MASH) comparing the NIF mouse model to human MASH.

October 3, 2024

Sci Rep

Abstract Metabolic dysfunction-associated steatohepatitis (MASH) is a common but frequently unrecognized complication of obesity and type 2 diabetes. The association between these conditions is multifaceted and involves complex interactions between metabolic, inflammatory, and genetic factors. Here we assess the underlying structural and molecular processes focusing on the immunological phase of MASH in the nonobese inflammation […]

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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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OXM-104, a potential candidate for the treatment of obesity, NASH and type 2 diabetes.

January 5, 2024

Eur J Pharmacol

Abstract OBJECTIVE Dual glucagon-like peptide-1 (GLP-1) and glucagon receptor agonists are therapeutic agents with an interesting liver-specific mode of action suitable for metabolic complications. In this study, dual GLP-1 and glucagon receptor agonist OXM-104 is compared head-to-head with the once-daily dual GLP-1 and glucagon receptor agonist cotadutide and GLP-1 receptor agonist semaglutide to explore the […]

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Dual amylin and calcitonin receptor agonist treatment reduces biomarkers associated with kidney fibrosis in diabetic rats.

November 1, 2023

Am J Physiol Endocrinol Metab

Abstract Dual amylin and calcitonin receptor agonists (DACRAs) are effective treatments for obesity and type 2 diabetes (T2D). They provide beneficial effects on body weight, glucose control, and insulin action. However, whether DACRAs protect against diabetes-related kidney damage remains unknown. We characterize the potential of long-acting DACRAs (KBP-A, Key Bioscience Peptide-A) as a treatment for […]

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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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The Effects of Dual GLP-1/Glucagon Receptor Agonists with Different Receptor Selectivity in Mouse Models of Obesity and Nonalcoholic Steatohepatitis.

March 1, 2023

J Pharmacol Exp Ther

Abstract There is an unmet need for nonalcoholic steatohepatitis (NASH) therapeutics, considering the increase in global obesity. Dual GLP-1/glucagon (GCG) receptor agonists have shown beneficial effects in circumventing the pathophysiology linked to NASH. However, dual GLP-1/GCG receptor agonists as a treatment of metabolic diseases need delicate optimization to maximize metabolism effects. The impacts of increased […]

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Improved metabolic efficacy of a dual amylin and calcitonin receptor agonist when combined with semaglutide or empagliflozin.

January 5, 2023

Eur J Pharmacol

Abstract Pharmacotherapies for obesity and type 2 diabetes (T2D) are thought to bridge the gap between lifestyle modification and the weight loss obtained with bariatric surgery. Although the effect of monotherapies, namely amylin and glucagon-like peptide-1 receptor (GLP-1R) agonists, has shown great potential, combination therapy is now becoming a strategy to optimize efficacy for weight […]

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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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Associations of Body Mass Index With Pain and the Mediating Role of Inflammatory Biomarkers in People With Hand Osteoarthritis.

May 1, 2022

Arthritis Rheumatol

Abstract OBJECTIVE To examine the association of body mass index (BMI) with pain in people with hand osteoarthritis (OA), and explore whether this association, if causal, is mediated by systemic inflammatory biomarkers. METHODS In 281 Nor-Hand study participants, we estimated associations between BMI and hand pain, as measured by the Australian/Canadian Osteoarthritis Hand Index (AUSCAN; […]

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