PMID- 23478327
OWN - NLM
STAT- MEDLINE
DCOM- 20140116
LR  - 20211021
IS  - 1759-5037 (Electronic)
IS  - 1759-5029 (Linking)
VI  - 9
IP  - 7
DP  - 2013 Jul
TI  - Emerging combinatorial hormone therapies for the treatment of obesity and T2DM.
PG  - 425-33
LID - 10.1038/nrendo.2013.47 [doi]
AB  - Peptide hormones and proteins control body weight and glucose homeostasis by 
      engaging peripheral and central metabolic signalling pathways responsible for the 
      maintenance of body weight and euglycaemia. The development of obesity, often in 
      association with type 2 diabetes mellitus (T2DM), reflects a dysregulation of 
      metabolic, anorectic and orexigenic pathways in multiple organs. Notably, 
      therapeutic attempts to normalize body weight and glycaemia with single agents 
      alone have generally been disappointing. The success of bariatric surgery, 
      together with emerging data from preclinical studies, illustrates the rationale 
      and feasibility of using two or more agonists, or single co-agonists, for the 
      treatment of obesity and T2DM. Here, we review advances in the science of 
      co-agonist therapy, and highlight promising areas and challenges in co-agonist 
      development. We describe mechanisms of action for combinations of glucagon-like 
      peptide 1, glucagon, gastric inhibitory polypeptide, gastrin, islet amyloid 
      polypeptide and leptin, which enhance weight loss whilst preserving 
      glucoregulatory efficacy in experimental models of obesity and T2DM. Although 
      substantial progress has been achieved in preclinical studies, the putative 
      success and safety of co-agonist therapy for the treatment of patients with 
      obesity and T2DM remains uncertain and requires extensive additional clinical 
      validation.
FAU - Sadry, Sharon A
AU  - Sadry SA
AD  - Department of Medicine, Samuel Lunenfeld Research Institute, Mount Sinai 
      Hospital, 600 University Avenue TCP5-1004, Toronto M5G 1X5, ON, Canada.
FAU - Drucker, Daniel J
AU  - Drucker DJ
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20130312
PL  - England
TA  - Nat Rev Endocrinol
JT  - Nature reviews. Endocrinology
JID - 101500078
RN  - 0 (Blood Glucose)
RN  - 0 (Leptin)
RN  - 59392-49-3 (Gastric Inhibitory Polypeptide)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 9007-92-5 (Glucagon)
SB  - IM
MH  - Animals
MH  - Blood Glucose/drug effects
MH  - Body Weight/drug effects
MH  - Central Nervous System/drug effects
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Gastric Inhibitory Polypeptide/therapeutic use
MH  - Glucagon/therapeutic use
MH  - Glucagon-Like Peptide 1/therapeutic use
MH  - Humans
MH  - Leptin/therapeutic use
MH  - Obesity/*drug therapy
EDAT- 2013/03/13 06:00
MHDA- 2014/01/17 06:00
CRDT- 2013/03/13 06:00
PHST- 2013/03/13 06:00 [entrez]
PHST- 2013/03/13 06:00 [pubmed]
PHST- 2014/01/17 06:00 [medline]
AID - nrendo.2013.47 [pii]
AID - 10.1038/nrendo.2013.47 [doi]
PST - ppublish
SO  - Nat Rev Endocrinol. 2013 Jul;9(7):425-33. doi: 10.1038/nrendo.2013.47. Epub 2013 
      Mar 12.