Case Report: Efficacy and safety of SGLT2 inhibitors in patients with Alström syndrome: a follow-up report of two siblings from the same family.

BACKGROUND: Ertugliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, is approved for the glycemic management of patients with type 2 diabetes. Alström syndrome (AS) is a rare autosomal recessive disorder caused by mutations in the ALMS1 gene, leading to ciliary dysfunction and multisystem involvement. AS is characterized by progressive neurosensory decline and metabolic disturbances, with symptoms such as retinal degeneration, which begins in childhood, sensorineural hearing loss, obesity, and cardiomyopathy. The 2020 European Alström Syndrome Clinical Management Guidelines, developed by experts from various medical fields, offer evidence-based recommendations for managing these symptoms and improving the quality of life of affected individuals. Severe insulin resistance, type 2 diabetes, non-alcoholic fatty liver disease, and renal failure significantly affect the quality of life and lifespan of patients with AS. OBJECTIVE: To investigate the efficacy and safety of ertugliflozin in improving glycemic control, lipid metabolism, and insulin sensitivity in patients with AS. METHODS: We retrospectively analyzed the clinical data of two sibling with AS treated at the Department of Endocrinology in our hospital. Follow-up data were collected and analyzed to evaluate the efficacy and safety of ertugliflozin in patients with AS. RESULTS: During an 11-month observation period, ertugliflozin treatment exerted favorable effects on multiple metabolic parameters in the two patients. Glycemic control improved in both patients, as evidenced by significant reductions in HbA1c levels observed at 2 months. The homeostatic model assessment of insulin resistance (HOMA-IR) showed marked improvement in Patient 1. Patient 2 showed significant early improvement in HOMA-IR, but a rebound trend was observed later, potentially related to the inherent, rapidly progressive, severe insulin resistance characteristic of puberty in this patient. Further comprehensive evaluation is required to distinguish the long-term effects of SGLT2 inhibitors, such as ertugliflozin, from the progression of type 2 diabetes. Additionally, ertugliflozin demonstrated significant regulatory effects on lipid metabolism, and no adverse events occurred during the treatment period, indicating good safety. CONCLUSION: Consistent with current clinical management guidelines for Alström syndrome, ertugliflozin demonstrated clinically meaningful reductions in fasting and postprandial glucose concentrations in two patients with AS, as documented in this longitudinal case report. Modest improvements in total cholesterol levels were also observed; however, the isolated effect of ertugliflozin on triglycerides could not be ascertained in one patient due to concurrent fibrate therapy. Early enhancements in insulin sensitivity-assessed via HOMA-IR and dynamic glucose tolerance testing-were observed during the initial treatment phase; however, this effect waned over time in Patient 2, the younger patient. The agent was generally well tolerated, with no serious adverse events reported. Owing to the inherent limitations of this analysis-including a small sample size (n = 2), absence of a control group, and lack of histopathological or mechanistic biomarker data-these observations remain preliminary and warrant validation in adequately powered, prospective, controlled clinical trials.