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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Emerging hormonal-based combination pharmacotherapies for the treatment of metabolic diseases.
Nat. Rev. Endocrinol. 15, 90-104 (2019)
Obesity and its comorbidities, such as type 2 diabetes mellitus and cardiovascular disease, constitute growing challenges for public health and economies globally. The available treatment options for these metabolic disorders cannot reverse the disease in most individuals and have not substantially reduced disease prevalence, which underscores the unmet need for more efficacious interventions. Neurobiological resilience to energy homeostatic perturbations, combined with the heterogeneous pathophysiology of human metabolic disorders, has limited the sustainability and efficacy of current pharmacological options. Emerging insights into the molecular origins of eating behaviour, energy expenditure, dyslipidaemia and insulin resistance suggest that coordinated targeting of multiple signalling pathways is probably necessary for sizeable improvements to reverse the progression of these diseases. Accordingly, a broad set of combinatorial approaches targeting feeding circuits, energy expenditure and glucose metabolism in concert are currently being explored and developed. Notably, several classes of peptide-based multi-agonists and peptide-small molecule conjugates with superior preclinical efficacy have emerged and are currently undergoing clinical evaluation. Here, we summarize advances over the past decade in combination pharmacotherapy for the management of obesity and type 2 diabetes mellitus, exclusively focusing on large-molecule formats (notably enteroendocrine peptides and proteins) and discuss the associated therapeutic opportunities and challenges.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Review
Schlagwörter
Glucagon-like Peptide-1; Calcitonin-receptor Agonist; Dependent Insulinotropic Polypeptide; Glp-1-gastrin Dual Agonist; Gastric-inhibitory Polypeptide; Brown Adipose-tissue; Body-weight Loss; Food-intake; Cardiovascular Outcomes; Leptin Responsiveness
ISSN (print) / ISBN
1759-5029
e-ISSN
1759-5037
Zeitschrift
Nature Reviews - Endocrinology
Quellenangaben
Band: 15,
Heft: 2,
Seiten: 90-104
Verlag
Nature Publishing Group
Verlagsort
New York, NY
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed