Analysis of 23 studies examining GLP-1 receptor agonists like semaglutide and liraglutide reveals these medications don't increase energy expenditure independent of weight loss itself. Most studies found non-significant effects on resting metabolic rate, while nearly half produced inconclusive results due to statistical limitations. However, combination therapies showed promise: GLP-1 paired with glucagon produced varied metabolic effects, while combination with GIP increased fat utilization. This finding challenges assumptions about how these blockbuster drugs work. While GLP-1 medications are highly effective for weight loss, they don't appear to provide the metabolic boost that could help prevent the typical slowdown in energy expenditure that accompanies weight reduction. This metabolic adaptation is a major factor in weight regain after loss. The lack of metabolic enhancement suggests these drugs work primarily through appetite suppression rather than metabolic acceleration. For patients using these medications, this underscores the importance of maintaining physical activity and muscle mass during weight loss to preserve metabolic rate. The emerging combination therapies warrant further investigation as potential solutions to metabolic adaptation.