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The British Journal of Diabetes & Vascular Disease
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Mechanisms behind GLP-1 induced weight loss

Philip J Larsen

Lilly Corporate Center, Indianapolis, IN 46285, USA, larsenph{at}lilly.com

Endogenous glucagon-like peptide-1 (GLP-1) is an incretin hormone that plays an important role in maintaining pancreatic function as well as caloric intake. Since the advent of GLP-1 receptor agonists resistant to dipeptidyl peptidase-4 (DPP-4) (degradation, it has become clear that their chronic use promotes negative energy balance. With regard to their effects on body weight, the principal action of GLP-1 agonists is mediated via their inhibition of eating. In searching for the underlying mechanism of GLP-1 receptor agonist-induced anorexic effect, scientists have discovered pathways in the central nervous system, as well as in the periphery. This review describes emerging knowledge of a peripheral endocrine GLP-1 system mediating its activity through a central ascending GLP-1 pathway and targeting hypothalamic sites involved in the regulation of energy homeostasis. Thus peripheral and central GLP-1 sensitive pathways appear to be organised to co-operatively help control food intake and body weight. Br J Diabetes Vasc Dis 2008; 8 (Suppl 2): S34—S41

Key Words: glucagon-like peptide agonists • dipeptidyl peptidase 4 • insulin resistance • obesity • type 2 diabetes • weight loss

The British Journal of Diabetes & Vascular Disease, Vol. 8, No. 2 Suppl, S34-S41 (2008)
DOI: 10.1177/1474651408100525
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