TIRZEPATIDE, ELAMIPRETIDE (SS-31), TESAMORELIN AND BREMELANOTIDE: MECHANISTIC FOUNDATIONS, CLINICAL EVIDENCE AND THERAPEUTIC APPLICATIONS IN METABOLIC, MITOCHONDRIAL AND NEUROENDOCRINE CONTEXTS

Modern bioactive agents, including incretin receptor agonists, mitochondria-targeting peptides, growth hormone–releasing hormone analogues, and melanocortin receptor agonists, have substantially reshaped therapeutic strategies across metabolic disorders, HIV-associated lipodystrophy, hypoactive sexual desire disorder, and primary mitochondrial diseases. Tirzepatide has demonstrated significant efficacy in glycemic control and weight reduction within the SURPASS and SURMOUNT clinical programs. Tesamorelin has shown robust evidence in reducing visceral adiposity in people living with HIV and central fat redistribution. Bremelanotide has demonstrated statistically significant improvements in sexual desire and associated distress in premenopausal women with hypoactive sexual desire disorder in phase 3 clinical trials. Elamipretide, in turn, is grounded in a mechanistic rationale focused on mitochondrial bioenergetics modulation and has been investigated in primary mitochondrial myopathy and other rare conditions. The objective of this study was to critically review mechanisms of action, pivotal clinical evidence, pharmacological differences, indications, contraindications, and safety profiles of tirzepatide, elamipretide (SS-31), tesamorelin, and bremelanotide (PT-141). A structured narrative review was conducted using indexed databases and high-impact journals, prioritizing randomized, double-blind, placebo- or active-controlled trials, recent systematic reviews, and relevant regulatory documents. The findings indicate that tirzepatide exhibits the greatest mean weight reduction among the analyzed agents, accompanied by clinically meaningful reductions in glycated hemoglobin and improvements in cardiometabolic markers, albeit associated with dose-dependent gastrointestinal adverse events and class-specific precautions. Tesamorelin reduces visceral adiposity and may decrease hepatic fat in selected HIV populations with central lipodystrophy, with relevant contraindications such as pregnancy and active malignancy. Bremelanotide acts centrally via melanocortin receptors and is administered on demand for hypoactive sexual desire disorder, with contraindications in uncontrolled hypertension and known cardiovascular disease. Elamipretide demonstrates strong mechanistic plausibility and variable clinical signals, with more consistent evidence in mitochondrial subgroups and the need for further consolidation in hard clinical endpoints. These agents occupy distinct and non-overlapping therapeutic domains. Evidence-based implementation requires strict alignment between formal indication, individual risk profile, and therapeutic objectives. Robust evidence supports tirzepatide and tesamorelin in their respective contexts, phase 3 evidence supports bremelanotide in hypoactive sexual desire disorder, and emerging evidence supports elamipretide in mitochondrial diseases.