GLP-1 physiology informs the pharmacotherapy of obesity.
Study Goal
The researchers aimed to evaluate the physiological mechanisms and therapeutic potential of GLP-1 receptor agonists (GLP1RA) for obesity treatment, comparing their efficacy to bariatric surgery.
Results Summary
The study found that GLP1RA effectively reduce food intake and body weight in obese animals and humans, with mechanisms conserved across age groups. The safety and efficacy of GLP1RA, supported by extensive preclinical and clinical data, suggest they may soon rival bariatric surgery for obesity treatment.
Population
Obese animals and humans (adolescents and adults)
Effective Dosage
Liraglutide 3 mg daily, semaglutide 2.4 mg once weekly
Duration
Not specified
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
Glucagon-like peptide-1 receptor agonists (GLP1RA) | increase | glucose-dependent insulin release | - | - | augment | #1 |
Glucagon-like peptide-1 receptor agonists (GLP1RA) | decrease | glucagon secretion | - | - | reduce | #2 |
Glucagon-like peptide-1 receptor agonists (GLP1RA) | decrease | gastric emptying | - | - | reduce | #3 |
Glucagon-like peptide-1 receptor agonists (GLP1RA) | decrease | food intake | - | - | inhibit | #4 |
Glucagon-like peptide-1 receptor agonists (GLP1RA) | decrease | body weight | - | - | reduce | #5 |
liraglutide | neutral | obesity | - | 3 mg daily | therapy | #6 |
semaglutide | neutral | obesity | - | 2.4 mg once weekly | therapy | #7 |
GLP-1 | decrease | food intake | obese animals and humans, in both adolescents and adults | - | reduce | #8 |
GLP-1 | decrease | body weight | obese animals and humans, in both adolescents and adults | - | reduce | #9 |
GLP1RA | neutral | cardiovascular disease | conditions associated with obesity | - | effective | #10 |
GLP1RA | neutral | non-alcoholic steatohepatitis (NASH) | conditions associated with obesity | - | effective | #11 |
GLP-1-based therapies | neutral | bariatric surgery | treatment of obesity and its complications | - | rival | #12 |
BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP1RA) augment glucose-dependent insulin release and reduce glucagon secretion and gastric emptying, enabling their successful development for the treatment of type 2 diabetes (T2D). These agents also inhibit food intake and reduce body weight, fostering investigation of GLP1RA for the treatment of obesity. SCOPE OF REVIEW: Here I discuss the physiology of Glucagon-like peptide-1 (GLP-1) action in the control of food intake in animals and humans, highlighting the importance of gut vs. brain-derived GLP-1 for the control of feeding and body weight. The widespread distribution and function of multiple GLP-1 receptor (GLP1R) populations in the central and autonomic nervous system are outlined, and the importance of pathways controlling energy expenditure in preclinical studies vs. reduction of food intake in both animals and humans is highlighted. The relative contributions of vagal afferent pathways vs. GLP1R+ populations in the central nervous system for the physiological reduction of food intake and the anorectic response to GLP1RA are compared and reviewed. Key data enabling the development of two GLP1RA for obesity therapy (liraglutide 3 mg daily and semaglutide 2.4 mg once weekly) are discussed. Finally, emerging data potentially supporting the combination of GLP-1 with additional peptide epitopes in unimolecular multi-agonists, as well as in fixed-dose combination therapies, are highlighted. MAJOR CONCLUSIONS: The actions of GLP-1 to reduce food intake and body weight are highly conserved in obese animals and humans, in both adolescents and adults. The well-defined mechanisms of GLP-1 action through a single G protein-coupled receptor, together with the extensive safety database of GLP1RA in people with T2D, provide reassurance surrounding the long-term use of these agents in people with obesity and multiple co-morbidities. GLP1RA may also be effective in conditions associated with obesity, such as cardiovascular disease and non-alcoholic steatohepatitis (NASH). Progressive improvements in the efficacy of GLP1RA suggest that GLP-1-based therapies may soon rival bariatric surgery as viable options for the treatment of obesity and its complications.