From the Guidelines
GLP-1 medications promote weight loss primarily by affecting appetite regulation in the brain and slowing stomach emptying, leading to reduced calorie intake and increased feelings of fullness. These medications, such as semaglutide and liraglutide, mimic the natural hormone glucagon-like peptide-1 that is released after eating, binding to GLP-1 receptors in the hypothalamus, the brain's appetite control center 1. This mechanism of action increases feelings of fullness and reduces hunger signals, resulting in reduced calorie intake as patients naturally eat smaller portions and experience fewer cravings. Additionally, GLP-1 medications slow gastric emptying, keeping food in the stomach longer and prolonging the sensation of fullness after meals 1.
The effects of GLP-1 medications on weight loss are significant, with most patients using these medications expecting to lose 10-15% of their body weight over several months, as seen in the STEP trials with semaglutide 1. Some newer medications like tirzepatide may potentially produce even greater weight loss of up to 20% 1. However, it's essential to note that these effects continue as long as the medication is used, and weight regain is common if the medication is discontinued, highlighting the need for long-term use and lifestyle modifications to maintain weight loss 1.
Key points about the mechanism of weight loss with GLP-1 medications include:
- Binding to GLP-1 receptors in the hypothalamus to increase feelings of fullness and reduce hunger signals
- Slowing gastric emptying to prolong the sensation of fullness after meals
- Improving insulin sensitivity and reducing inflammation, which may contribute to weight loss
- Potential for significant weight loss, with most patients expecting to lose 10-15% of their body weight over several months
- Need for long-term use and lifestyle modifications to maintain weight loss, as weight regain is common if the medication is discontinued 1.
From the FDA Drug Label
Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. Semaglutide lowers fasting and postprandial blood glucose and reduces body weight.
The mechanism of weight loss with Glucagon-like peptide-1 (GLP-1) is not explicitly stated in the provided text, but it can be inferred that GLP-1 receptor agonists like semaglutide and liraglutide may contribute to weight loss through their effects on:
- Glucose-dependent insulin secretion: stimulating insulin secretion when blood glucose is high
- Glucagon secretion: lowering glucagon secretion when blood glucose is high
- Gastric emptying: causing a delay in gastric emptying, which may lead to reduced food intake and weight loss However, the exact mechanism of weight loss is not directly addressed in the provided text. 2 3
From the Research
Mechanism of Weight Loss with GLP-1
The mechanism of weight loss with Glucagon-like peptide-1 (GLP-1) involves several key factors, including:
- Delayed gastric emptying, which slows down the digestion and absorption of food 4
- Reduced postprandial insulin response, which helps to regulate blood sugar levels 4
- Suppression of appetite, which leads to a reduction in food intake 4, 5
- Activation of GLP-1 receptors in the brain, which reduces food intake and body weight through various neural pathways 6
Neural Pathways Involved in GLP-1 Mediated Weight Loss
The neural pathways involved in GLP-1 mediated weight loss include:
- Hypothalamic nuclei, such as the arcuate nucleus of the hypothalamus, periventricular hypothalamus, and lateral hypothalamic area 6
- Hindbrain nuclei, such as the parabrachial nucleus and medial nucleus tractus solitarius 6
- Hippocampus, specifically the ventral subregion 6
- Nuclei embedded within the mesolimbic reward circuitry, such as the ventral tegmental area and nucleus accumbens 6
Effects of GLP-1 on Weight Loss
The effects of GLP-1 on weight loss have been studied in several clinical trials, with results showing: