Emerging hormonal-based combination pharmacotherapies for the treatment of metabolic diseases.
Animals
Body Mass Index
Diabetes Mellitus, Type 2
/ diagnosis
Drug Administration Schedule
Drug Therapy, Combination
Female
Gastrins
/ therapeutic use
Gastrointestinal Hormones
/ therapeutic use
Glucagon-Like Peptide 1
/ therapeutic use
Humans
Male
Metabolic Diseases
/ diagnosis
Metformin
/ therapeutic use
Mice
Molecular Targeted Therapy
/ methods
Obesity
/ diagnosis
Prognosis
Risk Assessment
Sodium-Glucose Transporter 2 Inhibitors
/ therapeutic use
Treatment Outcome
Journal
Nature reviews. Endocrinology
ISSN: 1759-5037
Titre abrégé: Nat Rev Endocrinol
Pays: England
ID NLM: 101500078
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
pubmed:
18
11
2018
medline:
18
7
2019
entrez:
18
11
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30446744
doi: 10.1038/s41574-018-0118-x
pii: 10.1038/s41574-018-0118-x
doi:
Substances chimiques
Gastrins
0
Gastrointestinal Hormones
0
Sodium-Glucose Transporter 2 Inhibitors
0
Glucagon-Like Peptide 1
89750-14-1
Metformin
9100L32L2N
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
90-104Références
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