Effectiveness of the dual GIP/GLP1-agonist Tirzepatide in two cases of Alström syndrome, a rare obesity syndrome.

Abstract

Background: Tirzepatide, a dual GIP/GLP-1 receptor agonist was recently approved for type 2 diabetes and weight management. Alström syndrome (AS) is a rare, genetic, multi-systemic disorder, characterized by cone-rod dystrophy, progressive hearing loss, obesity and diabetes with profound insulin resistance due to marked hyperphagia. Here we highlight the potential of tirzepatide as novel therapeutic option for improving glycemic outcomes, metabolic associated steatotic liver disease (MASLD) and effectively reducing body weight in individuals with AS.

Methods: We present the first two reported cases of people living with AS treated with tirzepatide.

Results: Two individuals with AS, previously treated with semaglutide received tirzepatide in our clinic. The first, a 23-year-old male with 18 months on treatment, experienced weight loss of -28 kg (113.6 kg to 83 kg, -26.9%); HbA1c 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 MRI. The second, a 20-year-old male 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 ∼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.