This systematic review and meta-analysis highlight the potential of tirzepatide as a superior pharmacological option for weight management compared to semaglutide in overweight and obese adults. The dual GIP/GLP-1 receptor agonism mechanism of tirzepatide may offer enhanced therapeutic benefits over single GLP-1 receptor agonism, suggesting important clinical implications for healthcare providers when selecting optimal interventions, particularly in patients with obesity-related comorbidities. This evidence concerns the gene GIP and obesity due to melanocortin 4 receptor deficiency.