Most patients notice increased satiety within the first 1–2 weeks after starting GLP-1 receptor agonists such as semaglutide or tirzepatide, even at the initial low doses used during dose escalation. This early effect is due to central appetite suppression and delayed gastric emptying, which are pharmacodynamic actions of these agents and are consistently observed in clinical trials and mechanistic studies. The American Diabetes Association notes that these medications are titrated gradually over several weeks to minimize gastrointestinal side effects, but appetite reduction typically precedes significant weight loss and is often reported soon after the first few injections.[1-6]
Changes in metabolic rate are not a primary or immediate effect of GLP-1 receptor agonists. The primary mechanism for weight loss is reduced caloric intake due to increased satiety and decreased hunger, rather than a direct increase in resting energy expenditure. While some studies have explored potential effects on substrate utilization and energy expenditure, these changes are modest and not the main driver of weight loss with these agents.[1][3]
Clinically meaningful weight loss, reflecting the cumulative effect of reduced appetite and caloric intake, generally becomes apparent within 4–8 weeks, with the most rapid weight reduction occurring in the first 3–6 months of therapy.[7][5-6] The American College of Lifestyle Medicine, the Obesity Society, and the American Diabetes Association all emphasize that the early satiety effect is a reliable predictor of subsequent weight loss, provided the medication is continued and lifestyle modifications are maintained.[7]