Setmelanotide

How it works

It activates the MC4 receptor, restoring downstream signalling in the hypothalamic pathway that regulates appetite and energy balance in patients with defined upstream genetic deficiencies.

Prescribing in practice

• Treatment is restricted to patients with a confirmed genetic diagnosis in the leptin-melanocortin pathway, and should be discontinued if an adequate weight response is not achieved within the defined assessment period.
• Skin hyperpigmentation and darkening of naevi can occur because of effects on melanocortin-1 receptors, so skin and pigmented lesions should be examined before and during treatment.
• Injection-site reactions and disturbances of sexual function, including prolonged erections, have been reported and warrant counselling.

Monitoring

Monitor weight response against predefined targets and perform periodic skin and pigmented-lesion examination during treatment.

Counselling the patient

• Skin and moles may darken; report any new or changing pigmented spots.
• Rotate injection sites and report troublesome site reactions.
• Seek advice if a prolonged or painful erection occurs.

Evidence & guidelines

Setmelanotide is approved for defined monogenic obesity syndromes, with efficacy on weight and hunger demonstrated in the supporting trials and SPC.