Tirzepatide in Smith-Magenis syndrome

A case report published in JCEM Case Reports in June 2026 describes a 31-year-old woman with Smith-Magenis syndrome (SMS) who lost 9.4% of her body weight over 10 months on tirzepatide 5 mg weekly, with no reported adverse effects^[1]. The finding is notable less for the weight loss itself and more for the behavioural improvements: caregivers reported reduced food-seeking, lower impulsivity, and less aggression, including less hitting and hair-pulling.

What Smith-Magenis syndrome is and why weight matters

SMS is a rare genetic disorder caused by a deletion on chromosome 17p11.2 or a variant in the RAI1 gene, with an estimated incidence of roughly 1 in 25,000 births^[2]. It produces intellectual disability, sleep disruption (over 90% of affected individuals have an inverted circadian melatonin rhythm), self-injurious behaviour, and childhood-onset obesity. Over 90% of individuals with SMS exceed the 90th percentile for weight.

The obesity is driven partly by hyperphagia and a food fixation that caregivers describe as relentless: night-time food foraging, constant preoccupation with meals, and aggressive behaviour when food access is restricted^[2]. Self-injurious behaviours (self-hitting, self-biting, skin picking) affect the majority of individuals after age two, and aggression toward caregivers is common. The behavioural profile means that standard weight-management advice (eat less, move more) does not map well onto this population. Impulse-control deficits and a neurological drive to seek food make dietary restriction difficult to enforce and distressing for both patient and caregiver.

That is the clinical gap the case report addresses: whether a pharmacological intervention that reduces appetite centrally could help where behavioural strategies alone have limited reach.

What the case report found

The patient, a 31-year-old woman with a BMI of 32.0 to 32.9 at baseline, was started on tirzepatide and titrated to 5 mg weekly. Over 10 months she lost 7.3 kg (9.4% of body weight) and her fasting glucose improved^[1]. Her caregivers reported that food-seeking behaviour decreased, impulsivity dropped, and episodes of physical aggression (hitting, hair-pulling, slapping) became less frequent. The treatment was well tolerated, with no adverse events documented.

This is the second published case report of a GLP-1 class drug in SMS. In 2025, Correia and colleagues in JCEM Case Reports described a patient with SMS treated with semaglutide, reporting similar improvements in weight and behaviour on the injectable formulation. When the same patient was switched to oral semaglutide, however, violent behaviour returned, food intake increased, and weight climbed back up^[3]. Restarting injectable semaglutide reversed the relapse. The authors speculated that the difference could reflect lower bioavailability of the oral formulation or a route-of-administration effect on central appetite pathways.

Taken together the two cases suggest that injectable incretin-class drugs may address both the metabolic and behavioural components of SMS-related obesity. But the evidence base is two patients, and neither case controlled for the effects of caregiver attention, routine changes, or concurrent therapies.

What this does not tell us

Two case reports are not a trial. There is no control group, no blinding, and no way to separate the pharmacological effect of tirzepatide from caregiver expectations or natural fluctuation in behaviour. The behavioural improvements were reported by caregivers rather than measured with a validated instrument, which limits how much weight the findings can bear.

The dose used (5 mg) is the second step on tirzepatide's titration schedule; the label goes up to 15 mg for both the type-2 diabetes and the weight-management indications^[4]. Whether higher doses would produce larger effects or introduce new adverse events in this population is unknown. Tolerability in people with intellectual disability and complex behavioural needs may differ from what the general-population SURMOUNT trials established.

SMS is rare enough that a randomised controlled trial would be difficult to power. The practical path forward is likely more case reports and, eventually, a small prospective series. Until then, these two cases are the entire published evidence base for incretin-class drugs in SMS.

Where this sits for readers

If you are a caregiver or clinician working with someone who has SMS, this case report adds tirzepatide to the short list of published pharmacological options for the food-seeking and obesity phenotype. It does not establish a standard of care. Any decision about starting tirzepatide in a patient with SMS belongs with a clinician familiar with both the drug and the syndrome. For background on how tirzepatide works, see the tirzepatide overview. For country-by-country prescribing status, see tirzepatide regulation.