Leptinevervanging

Leptinevervanging, or leptin replacement therapy, is a medical approach that substitutes the hormone leptin in individuals with deficient leptin signaling. Leptin is produced by fat tissue and helps regulate appetite, energy expenditure, and metabolic processes. When natural leptin levels are low or the signaling pathway is impaired, replacement therapy aims to restore normal hypothalamic regulation and improve metabolic outcomes.

Indications and scope

Leptin replacement is primarily used for conditions caused by leptin deficiency, most notably congenital leptin deficiency and certain forms of lipodystrophy, where fat tissue is unable to produce adequate leptin or where leptin signaling is disrupted. In these contexts, replacement therapy can reduce appetite, improve insulin sensitivity, and improve lipid and liver parameters. In general obesity without leptin deficiency, leptin replacement has not proven effective, because most individuals are leptin resistant rather than deficient.

Therapy and administration

The treatment uses recombinant human leptin, commonly administered as a subcutaneous injection on a daily basis. The goal is to restore physiologic leptin signaling and mitigate hyperphagia and metabolic abnormalities associated with leptin deficiency or lipodystrophy.

Effectiveness and safety

In congenital leptin deficiency, leptin replacement can markedly reduce excessive hunger and promote weight stabilization, with positive effects on metabolic markers. In lipodystrophy, reductions in triglycerides and hepatic steatosis and improvements in insulin sensitivity have been reported in many patients. Safety concerns include injection-site reactions, antibody development, and potential serious adverse events, including associations with lymphoma in some lipodystrophy patients. Long-term use requires careful monitoring by clinicians.

Regulatory and research status

Metreleptin is the principal agent used for leptin replacement in approved indications, with regulatory status varying by country. Research continues to define its full therapeutic potential, optimal dosing, and long-term safety in diverse patient groups.