Metformin and appetite
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Metformin and Appetite Suppression: Key Mechanisms
Metformin, a widely used medication for type 2 diabetes, is also recognized for its ability to reduce appetite and promote modest weight loss in both diabetic and non-diabetic individuals 1510. The appetite-suppressing effects of metformin are driven by several interconnected biological mechanisms.
GDF15 Pathway and Appetite Regulation
A major mechanism involves the increase of growth differentiation factor 15 (GDF15), a hormone that acts on the brain to reduce appetite. Metformin stimulates the production and release of GDF15, which then signals through the GFRAL receptor in the brainstem to suppress food intake and promote weight loss 369. Studies in both animals and humans show that the appetite and weight-reducing effects of metformin are closely linked to this GDF15 pathway, and blocking GDF15 or its receptor can eliminate these benefits 39.
Lac-Phe: A Newly Identified Appetite-Suppressing Metabolite
Recent research has identified N-lactoyl-phenylalanine (Lac-Phe) as another key player. Metformin significantly increases Lac-Phe levels in the blood, both after acute administration and following meals 28. Lac-Phe is now recognized as a critical mediator of metformin’s effects on reducing food intake and body weight, with genetic studies in mice confirming that the absence of Lac-Phe production blunts metformin’s appetite-suppressing action .
Effects on Hypothalamic Appetite Centers and Hormonal Sensitivity
Metformin also acts directly on the hypothalamus, the brain region responsible for hunger regulation. It improves the sensitivity of appetite-regulating hormones such as leptin and insulin, which helps decrease food intake 1510. By reducing insulin resistance in specific hypothalamic neurons, metformin further contributes to reduced hunger and increased satiety .
Gastrointestinal and Microbiome Changes
The drug enhances satiety by stimulating the release of gut hormones like glucagon-like peptide 1 (GLP-1) and induces favorable changes in the gut microbiome, both of which support appetite reduction and improved metabolism 1510.
Appetite Suppression in Special Populations
Metformin’s appetite-suppressing effects have been observed in various settings, including in patients experiencing excessive hunger due to hypothalamic dysfunction, where it has been associated with substantial appetite reduction . Additionally, metformin can reduce feelings of hunger even during episodes of low blood sugar, although this does not always translate to reduced food intake immediately after such episodes .
Conclusion
Metformin reduces appetite through multiple mechanisms, including the elevation of GDF15 and Lac-Phe, modulation of hypothalamic appetite centers, and changes in gut hormones and microbiota. These effects collectively contribute to its modest but durable weight loss benefits, making metformin a valuable tool for managing appetite and body weight, especially in individuals at risk for or living with type 2 diabetes 123568910.
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