Hormonal
Pharmacological activation of GLP-1 and amylin receptors causes sustained weight loss in humans by overriding homeostatic defenses that normally prevent long-term reduction in body fat.
Drugs that mimic GLP-1 (like semaglutide) or amylin (like pramlintide) can help you lose weight even if your body fights back by making you hungrier. This happens because the drug doses are high enough to override your body's natural defenses. Expect some nausea at first, which often gets better over time.
The effect of chronic GLP-1r agonists to cause weight loss is not consistent with the general principle that satiation peptides are subservient to long-term regulators of energy balance... One potential explanation is that because GLP-1 can activate nonhomeostatic pathways that suppress food intake... the effects of chronic administration of GLP-1r agonists work around the homeostatic systems controlling body weight.
Why this rating
The paper cites multiple human studies showing weight loss with GLP-1 and amylin agonists, though it notes variability and side effects.
Source
Central Control of Body Weight and Appetite
Stephen C. Woods et al. · The Journal of Clinical Endocrinology & Metabolism · 2008
DOI 10.1210/jc.2008-1630
More from this paper
- Endogenous satiation signals (like CCK) are subservient to long-term adiposity signals (leptin/insulin) and cannot cause long-term weight loss in free-feeding animals because they compensate by eating more frequently.Good
- Obese individuals have attenuated postprandial secretion of satiation signals like PYY and GLP-1 compared to lean individuals, which may contribute to obesity.Good
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