Dilaver Ragibe Gulsah, Afsar Rengin Elsurer, Crescenzi Rachelle, Gamboa Jorge, Ikizler Talat Alp
Vanderbilt University Medical Center, Dept of Medicine, Nashville, TN, United States.
Suleyman Demirel University Hospital, Department of Nephrology, Isparta, Turkey.
medRxiv. 2025 Mar 20:2025.03.19.25324266. doi: 10.1101/2025.03.19.25324266.
Patients with chronic kidney disease (CKD) often exhibit ectopic fat accumulation, including intermuscular adipose tissue (IMAT), which is associated with metabolic and muscular dysfunctions. This study aimed to evaluate the effects of dulaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), on reducing IMAT and improving metabolic and physical functions in patients with CKD stage 3-4.
Seven patients were recruited between April 2022 and November 2023. A 12-week dulaglutide (1.5 mg/wk) intervention was conducted with pre-and post-treatment assessments, including magnetic resonance imaging (MRI) for the IMAT evaluation and systemic physical performance battery test (SPPB) for physical performance evaluation. Their body mass indexes (BMI) were calculated and blood samples were analyzed for inflammatory and metabolic markers, including high sensitive C-reactive protein (Hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), glucose, insulin resistance (IR), total cholesterol, triglyceride, adiponectin, leptin, and leptin-adiponectin ratio (LAR) before and after treatment. Paired t-tests and Mann-Whitney U tests were used for statistical analysis, with significance set at p < 0.05.
Out of 58 assessed patients with CKD stage 3-4, 7 were enrolled, with 5 completing the full 12-week dulaglutide treatment. The total 7 people had a mean age of 59 years, mean BMI of 31.4 kg/m, and baseline eGFR of 31.7 mL/min/1.73m. IMAT decreased in 4 patients and increased in 3 patients, with no statistically significant changes overall (p = 0.69). The quadriceps muscle cross-sectional area (CSA) also showed no significant difference (p = 0.73). BMI and serum leptin levels significantly decreased after treatment (p < 0.05), while other inflammatory and metabolic markers, and physical performance scores showed no significant changes. No serious adverse events were reported.
This study examined the effects of a 12-week dulaglutide treatment on IMAT accumulation in patients with CKD stage 3-4. While BMI significantly decreased, changes in IMAT were modest and not statistically significant, with potential but unproven clinical and metabolic benefits. Many metabolic and inflammatory markers improved, though not statistically significantly, and physical performance remained unchanged. Muscle CSA and function were maintained, which may alleviate concerns about potential GLP-1RA-induced muscle loss. Dulaglutide was well-tolerated, with minimal side effects. The small sample size and short duration highlight the need for further research.
慢性肾脏病（CKD）患者常出现异位脂肪堆积，包括肌间脂肪组织（IMAT），这与代谢和肌肉功能障碍有关。本研究旨在评估胰高血糖素样肽-1受体激动剂（GLP-1RA）度拉糖肽对减少3-4期CKD患者的IMAT以及改善其代谢和身体功能的影响。
在2022年4月至2023年11月期间招募了7名患者。进行了为期12周的度拉糖肽（1.5毫克/周）干预，并在治疗前后进行评估，包括用于IMAT评估的磁共振成像（MRI）和用于身体功能评估的全身身体性能综合测试（SPPB）。计算他们的体重指数（BMI），并分析治疗前后血液样本中的炎症和代谢标志物，包括高敏C反应蛋白（Hs-CRP）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、血糖、胰岛素抵抗（IR）、总胆固醇、甘油三酯、脂联素、瘦素以及瘦素-脂联素比值（LAR）。采用配对t检验和曼-惠特尼U检验进行统计分析，显著性设定为p<0.05。
在58名评估的3-4期CKD患者中，7名被纳入研究，其中5名完成了为期12周的度拉糖肽完整治疗。这7人平均年龄59岁，平均BMI为31.4千克/平方米，基线估算肾小球滤过率（eGFR）为31.7毫升/分钟/1.73平方米。4名患者的IMAT减少，3名患者的IMAT增加，总体无统计学显著变化（p=0.69）。股四头肌横截面积（CSA）也无显著差异（p=0.73）。治疗后BMI和血清瘦素水平显著降低（p<0.05），而其他炎症和代谢标志物以及身体功能评分无显著变化。未报告严重不良事件。
本研究考察了为期12周的度拉糖肽治疗对3-4期CKD患者IMAT堆积的影响。虽然BMI显著降低，但IMAT的变化较小且无统计学显著意义，具有潜在但未经证实的临床和代谢益处。许多代谢和炎症标志物有所改善，尽管无统计学显著意义，且身体功能保持不变。肌肉CSA和功能得以维持，这可能减轻了对GLP-1RA潜在导致肌肉流失的担忧。度拉糖肽耐受性良好，副作用极小。样本量小和持续时间短凸显了进一步研究的必要性。
