More than 1 billion people worldwide are affected by obesity, a chronic disease linked to increased mortality.
Excess body fat is closely tied to higher energy intake.
Most effective anti-obesity medications work by reducing appetite to facilitate weight loss.
New glucagon-like peptide-1 () analogs show significant weight loss in clinical trials and initial real-world applications.
These medications primarily lower food intake by activating GLP-1 receptors in the brain.
The specific brain areas and neural pathways involved in GLP-1's effects on eating behavior are still under investigation.
Simplified
Obesity is now considered a chronic relapsing progressive disease, associated with increased all-cause mortality that scales with body weight, affecting more than 1 billion people worldwide. Excess body fat is strongly associated with excess energy intake, and most successful anti-obesity medications () counter this positive energy balance through the suppression of eating to drive weight loss. Historically, AOMs have been characterized by modest weight loss and side effects which are compliance-limiting, and in some cases life-threatening. However, the field of obesity pharmacotherapy has now entered a new era of AOMs based on analogues of the gut hormone and neuropeptide glucagon-like peptide-1 (). The latest versions of these drugs elicit unprecedented levels of weight loss in clinical trials, which are now starting to be substantiated in real-world usage. Notably, these drugs reduce weight primarily by reducing energy intake, via activation of the GLP-1 receptor on multiple sites of action primarily in the central nervous system, although the most relevant sites of action, and the neural circuits recruited remain contentious. Here we provide a targeted synthesis of recent developments in the field of GLP-1 neurobiology, highlighting studies which have advanced our understanding of how GLP-1 signaling modulates eating, and identify open questions and future challenges we believe still need to be addressed to aid the prevention and/or treatment of obesity.
Key numbers
15%
Weight Loss with Semaglutide
Percentage of body weight loss in clinical trials with semaglutide.
50% to 65%
Weight Regain After Cessation
Proportion of weight regained within a year after stopping treatment.
32%
Nonresponders to Treatment
Percentage of patients in the SELECT trial who did not achieve clinically meaningful weight loss.
Full Text
We can’t show the full text here under this license.
