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Mechanism-Level Comparison GLP-1 receptor agonists (e.g., semaglutide, tirzepatide) • Central appetite suppression • Delayed gastric emptying • Limitations include GI adverse events and lean mass loss during rapid weight reduction CagriSema (cagrilintide + semaglutide) • Dual amylin and GLP-1 receptor activation • Strong efficacy through mechanistic synergy • Tolerability remains partially constrained by GLP-1 exposure Retatrutide (GLP-1 / GIP / glucagon triple agonist) • Appetite reduction combined with increased energy expenditure • Exceptional weight-loss potential • Long-term safety, metabolic intensity, and adherence remain under evaluation Petrelintide (long-acting amylin analog) • Satiety enhancement without heavy reliance on appetite suppression • Leptin sensitization • Early data suggest competitive efficacy with improved tolerability • Potential for better lean mass preservation • Convenient once-weekly dosing A Formulation Advantage Petrelintide has been designed for chemical and physical stability, including no fibrillation at near-neutral pH—a non-trivial advantage for peptide development