Meral Rasimcan, Celik Guler Merve, Kaba Diarratou, Prativadi Jeevitha, Frontera Eric D, Foss-Freitas Maria Cristina, Nachawi Noura, Broome David T, Lightbourne Marissa, Brown Rebecca J, Taylor Simeon I, Oral Elif A
medRxiv. 2024 Sep 27:2024.09.25.24313345. doi: 10.1101/2024.09.25.24313345.
Lipodystrophy encompasses a group of rare disorders associated with severe metabolic disease. These disorders are defined by abnormal fat distribution, with near-total (generalized lipodystrophy, GL) or partial (partial lipodystrophy, PL; i.e. familial partial lipodystrophy, FPLD) absence of adipocyte mass leading to a decreased ability to store lipids safely. Excess lipids are more likely to be stored in non-adipose tissues, which leads to the metabolic manifestations. We have recently shown that glucagon-like peptide-1 agonists are associated with metabolic improvements in FPLD. We hypothesized that tirzepatide, a dual incretin, may also lead to metabolic improvement in patients with lipodystrophy.
Observational cohort of patients with PL or GL who received tirzepatide clinically were tracked in the context of ongoing natural history studies.
Seventeen patients received tirzepatide, 14 with FPLD (ages within 30-74 years; 12 female 2 male). After a median 8.7 months of follow-up, BMI (medianΔ -1.7; range -5.9 to 0.9 kg/m ; =0.008), HbA1c (medianΔ -1.1%; range -6.3 to -0.1%; <0.001), triglycerides [medianΔ - 65 mg/dL (-0.73 mmol/L); range -3820 to 43 mg/dL (-43.2 to 0.49 mmol/L); =0.003] and total daily insulin requirements (medianΔ -109; range -315 to 0 units/day; =0.002) were significantly reduced. Three patients with acquired GL (Ages within 35-64 years; all female) also demonstrated a robust response to tirzepatide with reduced BMI (22.2->20.9; 26.2->25.4; 19.5->17.6 kg/m ), HbA1c (8.5%->7.0%; 10.2%->7.8%; 9.1%->6.5%), triglycerides (91->80; 641->293; 1238->100 mg/dL or 1.03->0.90; 7.24->3.31; 14.0->1.13 mmol/L), and total daily insulin requirement (85->0; 0->0; 1000->750 units/day). Three patients did not tolerate dose escalation due to gastroesophageal reflux.
Tirzepatide may be an effective treatment for patients with lipodystrophy.
脂肪营养不良是一组与严重代谢性疾病相关的罕见病症。这些病症的定义是脂肪分布异常，脂肪细胞数量几乎完全缺失（全身性脂肪营养不良，GL）或部分缺失（部分性脂肪营养不良，PL；即家族性部分性脂肪营养不良，FPLD），导致安全储存脂质的能力下降。多余的脂质更有可能储存在非脂肪组织中，从而导致代谢表现。我们最近发现，胰高血糖素样肽-1激动剂与FPLD的代谢改善有关。我们假设，双重肠促胰岛素替尔泊肽可能也会使脂肪营养不良患者的代谢得到改善。
在正在进行的自然病史研究中，对临床上接受替尔泊肽治疗的PL或GL患者的观察性队列进行了跟踪。
17名患者接受了替尔泊肽治疗，其中14例为FPLD（年龄在30 - 74岁之间；12名女性，2名男性）。经过中位8.7个月的随访，体重指数（中位变化值 -1.7；范围 -5.9至0.9 kg/m²；P = 0.008）、糖化血红蛋白（中位变化值 -1.1%；范围 -6.3至 -0.1%；P < 0.001）、甘油三酯[中位变化值 - 65 mg/dL（-0.73 mmol/L）；范围 -382至43 mg/dL（-4.32至0.49 mmol/L）；P = 0.003]和每日胰岛素总需求量（中位变化值 -109；范围 -315至0单位/天；P = 0.002）均显著降低。3例获得性GL患者（年龄在35 - 64岁之间；均为女性）对替尔泊肽也表现出明显反应，体重指数降低（22.2 -> 20.9；26.2 -> 25.4；19.5 -> 17.6 kg/m²）、糖化血红蛋白降低（8.5% -> 7.0%；10.2% -> 7.8%；9.1% -> 6.5%）、甘油三酯降低（91 -> 80；641 -> 293；1238 -> 100 mg/dL或1.03 -> 0.90；7.24 -> 3.31；14.0 -> 1.13 mmol/L），以及每日胰岛素总需求量降低（85 -> 0；0 -> 0；1000 -> 750单位/天）。3例患者因胃食管反流不耐受剂量增加。
替尔泊肽可能是治疗脂肪营养不良患者的有效药物。
