The certainty of evidence for weight loss from GLP-1 receptor agonist and incretin-based therapies combined with lifestyle interventions is rated as low due to high heterogeneity across trials and risk-of-bias concerns, and the average 10 kg weight loss cannot be assumed to apply uniformly across all populations or treatment contexts.

GLP-1 receptor agonists activate brain regions that signal fullness and slow stomach emptying, causing people to eat less. This creates a calorie deficit that forces the body to burn fat for energy. At the same time, the body shifts from using sugar to burning fat and producing ketones, which helps preserve muscle and reduces the slowdown in metabolism that usually happens during weight loss.