Effectiveness of the Dual GIP/GLP1-Agonist Tirzepatide in 2 Cases of Alström Syndrome, a Rare Obesity Syndrome.

CONTEXT: Tirzepatide, a dual glucose-dependent insulinotropic peptide/glucagon-like peptide 1 (GIP/GLP1) receptor agonist, was recently approved for type 2 diabetes and weight management. Alström syndrome (AS) is a rare, genetic, multisystemic disorder, characterized by cone-rod dystrophy, progressive hearing loss, obesity, and diabetes with profound insulin resistance due to marked hyperphagia. OBJECTIVE: Here we highlight the potential of tirzepatide as a novel therapeutic option for improving glycemic outcomes, metabolic dysfunction-associated steatotic liver disease (MASLD), and effectively reducing body weight in individuals with AS. METHODS: We present the first 2 reported cases of people living with AS treated with tirzepatide. RESULTS: Two individuals with AS, previously treated with semaglutide, received tirzepatide at our clinic. The first, a 23-year-old man with 18 months of treatment, experienced a weight loss of -28 kg (113.6 to 83 kg, -26.9%); glycated hemoglobin A1c decreased by -0.4% (6.7% to 6.3%), with considerable reductions in daily insulin doses of -96 IU/day (-83%; 58 to 20 IU insulin glargine and 58 to 0 IU prandial insulin), while maintaining oral antidiabetics. Hepatic steatosis, with a previous fat fraction of 20%, resolved as confirmed by magnetic resonance imaging (MRI). The second, a 20-year-old man with previously well-controlled diabetes, was followed up for 9 months and showed a weight reduction of -9.5 kg (132 kg to 122.5 kg; -7.2%) with a reduction of hepatic lipid content from 21% at the latest MRI to 11% after approximately 3 months of therapy. CONCLUSION: Tirzepatide shows great effectiveness with regard to body weight, MASLD, and insulin resistance in AS. Follow-up studies with larger cohorts have to be performed to confirm these findings.