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Clemmensen, C. ; Finan, B.* ; Müller, T.D. ; DiMarchi, R.D.* ; Tschöp, M.H. ; Hofmann, S.M.

Emerging hormonal-based combination pharmacotherapies for the treatment of metabolic diseases.

Nat. Rev. Endocrinol. 15, 90-104 (2019)
Verlagsversion DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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
Quellenangaben Band: 15, Heft: 2, Seiten: 90-104 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York, NY
Begutachtungsstatus Peer reviewed