CagriSema, combining semaglutide with cagrilintide, achieved 11 kilograms greater absolute weight loss than semaglutide monotherapy or placebo across 4,419 participants in four randomized trials. The dual therapy also reduced waist circumference by 9.41 cm and systolic blood pressure by 7.06 mmHg, though gastrointestinal side effects increased 32%. This represents a meaningful advance in obesity pharmacotherapy, addressing the plateau effect often seen with single-agent GLP-1 therapies. Cagrilintide, an amylin receptor agonist, appears to synergistically enhance semaglutide's weight loss effects by targeting different appetite and satiety pathways. The 11-kilogram difference translates to clinically significant health improvements, potentially reducing diabetes and cardiovascular risk more effectively than current monotherapies. However, the high heterogeneity between studies and increased adverse events signal the need for careful patient selection and monitoring protocols. While promising, this meta-analysis reflects relatively short-term data from a limited number of trials. The obesity treatment landscape increasingly favors combination approaches targeting multiple metabolic pathways, and CagriSema exemplifies this evolution toward more potent, multi-mechanism interventions.