SUN-644 Pharmacological Approaches in Lipodystrophy: Concomitant Medication and Metreleptin Therapy Use in the Participants of LD-Lync Study

Le résumé fourni par la source

Abstract Disclosure: M. Celik Guler: None. M.C. Foss de Freitas: None. M. Yosef: None. S. Khalatbari: None. M. Ashmus: None. D. Guler: None. D. Gilio: None. D. Kaba: None. A. Dill Gomes: None. C. Uwandu: None. M. Brush: None. R. Tuska: None. T. Neal: None. M. Hwang: None. B. Tracey: None. M. Okawa: None. B. Brite: None. C. Richison: None. I. Yildirim Simsir: None. B. Akinci: Chiesi Farmaceutici, Alnylam, Regeneron Pharmaceuticals, Marea Therapeutics, AstraZeneca, Novo Nordisk, Boehringer Ingelheim, Sanofi, Bilim Ilac, ARIS, Servier. R.J. Brown: Pfizer, Inc., Regeneron Pharmaceuticals, Marea Therapeutics, Chiesi Farmaceutici. E.A. Oral: Chiesi Farmaceutici, Ionis Pharmaceuticals Inc., Regeneron Pharmaceuticals, Rhythm Pharmaceuticals, Marea Therapeutics, Novo Nordisk, Rejuvenate Bio, Fractyl, Morphic Medical. Background: Lipodystrophy (LD) syndromes are rare diseases characterized by subcutaneous adipose tissue deficiency and associated metabolic disorders, often requiring specialized pharmacological management. This study investigates the utilization of metreleptin and other metabolic therapies for managing complications across different LD subtypes. Methods: Data were analyzed from an ongoing prospective, multicenter registry study (LD Lync; NCT03087253, n=266, at the end of October 2023). Demographic information and medical history were collected at baseline and annual visits. Medication usage, including metreleptin, insulin, oral antidiabetics, and lipid-lowering therapies, was evaluated for prevalence and distribution across subgroups. Results: A total of 81 patients (30.5%) received at least one dose of metreleptin, either through clinical trials, expanded access or commercial use. This included 26 patients (70.2%) with congenital generalized lipodystrophy (CGL, n=37), ten patients (62.5%) with acquired generalized lipodystrophy (AGL, n=16), 37 patients (21.4%) with familial partial lipodystrophy (FPLD, n=173), two patients (8.0%) with acquired partial lipodystrophy (APL, n=25), and six patients categorized within the unclassified subgroup (n=15). Insulin use varied across subtypes, with the highest prevalence observed in the AGL (63%, 7/11) and FPLD (59%, 79/133), compared to the CGL (44%, 11/25) and the APL (35%, 5/14) subgroups, based on available data from documented cases. Metformin was the most commonly used antidiabetic agent, particularly in FPLD (n=101), followed by CGL (n=21), APL (n=10), and AGL (n=5). Thiazolidinediones (n=48), sodium-glucose cotransporter-2 inhibitors (n=47), injectable incretin therapies (n=40), and gliptins (n=16) were other commonly used antidiabetic drugs. Fenofibrate was used by 79 patients, with the highest prevalence observed in the CGL (48%) and FPLD (35%) subgroups. Statins, primarily atorvastatin (n=57) and rosuvastatin (n=25), were the most prescribed lipid-lowering agents, and were used by 100 patients overall, including 47.9% of those in the FPLD subgroup. Their use was infrequent in the CGL subgroup (n=3). Omega-3 derivatives were used by 53 patients (19%), while niacin and cholestyramine were used by only two patients. Despite extensive metabolic therapies, current metabolic control was suboptimal, especially in FPLD (mean ± SD: HbA1c 7.3% ± 1.9, low-density lipoprotein 97 ± 39 mg/dL, and TG 542 ± 730 mg/dL). Conclusion: This study highlights the heterogeneity in pharmacological management across lipodystrophy subtypes, reflecting their diverse metabolic profiles and needs. While metreleptin remains the cornerstone therapy for generalized lipodystrophy, there is a need for novel therapeutic options to achieve improved metabolic control and optimize treatment outcomes in partial lipodystrophy. Presentation: Sunday, July 13, 2025

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.