GLP-1: from gut hormone to therapeutic target

Glucagon-like peptide 1 (GLP-1) is an incretin hormone produced by intestinal L-cells in response to nutrient ingestion. It was originally studied for its role in glucose homeostasis — enhancing insulin secretion in a glucose-dependent manner — before its profound effects on appetite became a central focus of obesity research.

Native GLP-1 has a very short half-life (approximately 2 minutes) due to rapid degradation by dipeptidyl peptidase-4 (DPP-4). The development of GLP-1 receptor agonists — engineered to resist enzymatic degradation — transformed this transient physiological signal into a sustained pharmacological intervention, enabling continuous appetite suppression over days or weeks.

Today, molecules such as semaglutide (Ozempic®, Wegovy®), liraglutide (Saxenda®), and tirzepatide (Mounjaro®) represent one of the most significant advances in obesity pharmacotherapy — demonstrating weight reductions of 15–20% in clinical trials.

Four mechanisms, one hormonal pathway

GLP-1 receptor agonists reduce food intake through multiple interconnected mechanisms, all operating within the neuroendocrine system:

The discontinuation challenge and the role of residual pathways

One of the most clinically significant challenges with GLP-1 therapy is what happens after treatment is interrupted. Studies consistently show that appetite returns — often rapidly — after discontinuation, and weight regain is common within months.

This occurs because GLP-1 receptor agonists produce a sustained pharmacological override of the appetite system. When that override is removed, the underlying physiological drivers of appetite reassert themselves — including the mechanical signals that were being modulated indirectly through delayed gastric emptying.

In this context, the mechanical pathway becomes particularly relevant. Unlike hormonal signals, which depend on continued drug administration, mechanical signals are endogenous and immediate — they are generated every time the stomach fills, every time abdominal pressure changes. They persist regardless of pharmacological status.

Two inputs, one integrated satiety response

Rather than viewing hormonal and mechanical satiety as separate systems, contemporary physiology increasingly recognizes them as convergent inputs into a single integrated response — processed in the brainstem, modulated by higher brain centers, and expressed as the conscious perception of fullness.

This convergence model suggests that strategies addressing both pathways — whether simultaneously or sequentially — may produce a more robust and resilient satiety response than either pathway alone. This is the physiological foundation for exploring mechanical satiety modulation as a complement to GLP-1 therapies.

What this means for patient care

The physiological convergence of hormonal and mechanical satiety pathways has direct implications for how appetite regulation strategies are designed and combined in clinical practice.

If mechanical signals contribute meaningfully to the integrated satiety response — and if they can be modulated externally — then approaches targeting this pathway may provide value in several clinical contexts: as a complement during active GLP-1 therapy, as a transitional support during dose reduction, as a non-pharmacological relay after discontinuation, or as a first-line option when pharmacotherapy is contraindicated or not tolerated.

GASTER control® is designed to act precisely on this mechanical dimension — applying controlled extra-parietal compression to the epigastric region to modulate the conditions in which mechanical satiety signals are perceived. It does not interfere with hormonal pathways, carries no pharmacological interactions, and can be used alongside any existing treatment strategy.

Key literature