司美格鲁肽联合非诺贝特治疗2型糖尿病合并非酒精性脂肪性肝病患者疗效初步研究*

doi:10.3969/j.issn.1672-5069.2025.06.010

摘要/Abstract

摘要： 目的探讨司美格鲁肽联合非诺贝特治疗2型糖尿病(T2DM)合并非酒精性脂肪性肝病(NAFLD)患者的短期疗效。方法 2022年1月～2024年1月我院接受治疗的102例T2DM合并NAFLD患者,被随机分为对照组和观察组,每组51例。对照组在常规降糖治疗的基础上联合非诺贝特治疗,而观察组则在对照组治疗的基础上应用司美格鲁肽治疗,两组均治疗6个月。常规检测空腹血糖(FBG)、餐后2 h血糖(2hPBG)和糖化血红蛋白(HbA1c),采用ELISA法检测血清白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平,使用日本欧姆龙 HDs-2000型内脏脂肪测量装置测定腹部脐水平层面内脏脂肪面积和皮下脂肪面积。结果在治疗6个月结束时,观察组体质指数、FBG、2hPBG和HbA1c水平分别为(24.6±2.1)kg/m²、(6.0±1.3)mmol/L、(7.0±0.8)mmol/L和(6.3±0.8)%,均显著低于对照组【分别为(27.8±5.7)kg/m²、(7.8±1.3)mmol/L、(8.5±1.0)mmol/L和(6.9±1.0)%,P＜0.05】;观察组血清总胆固醇、甘油三酯和低密度脂蛋白水平分别为(4.9±0.4)mmol/L、(1.9±0.3)mmol/L和(2.4±0.4)mmol/L,均显著低于对照组【分别为(5.6±0.9)mmol/L、(3.2±0.4)mmol/L和(3.6±0.5)mmol/L,P＜0.05】,而血清高密度脂蛋白水平为(1.2±0.5)mmol/L,显著高于对照组【(1.0±0.3)mmol/L,P＜0.05】;观察组内脏和皮下脂肪面积分别为(135.11±14.0)cm²和(202.3±18.4)cm²,均显著低于对照组【分别为(164.9±18.7)cm²和(240.7±23.3)cm²,P＜0.05】,血清IL-6和TNF-α水平分别为(5.7±2.4)pg/mL和(18.9±4.7)pg/mL,均显著低于对照组【分别为(19.2±3.0)pg/mL和(46.1±5.5)pg/mL,P＜0.05】。结论在降糖治疗的基础上,联合应用司美格鲁肽和非诺贝特治疗T2DM合并NAFLD患者短期降低体质量效果明显,改善糖脂代谢,其远期疗效还需要观察。

关键词: 非酒精性脂肪性肝病, 2型糖尿病, 司美格鲁肽, 非诺贝特, 治疗

Abstract: Objective The aim of this clinical trial was to investigate semaglutide in combination with fenofibrate in the treatment of patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Methods A total of 102 patients with T2DM and NAFLD were encountered in our hospital between January 2022 and January 2024, and were randomly assigned to receive fenofibrate at base of metformin in 51 cases in control, or receive semaglutide at base of treatment as mentioned in the control in another 51 cases in the observation for six months. Fasting blood glucose (FBG), 2-hour postprandial blood glucose (2hPBG) and Hemoglobin A1c (HbA1c) levels were routinely detected, and serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were assayed by ELISA. Visceral and subcutaneous fat areas were obtained by special equipment. Results By end of six-month treatment, body mass index, FBG, 2hPBG and HbA1c levels in the observation group were (24.6±2.1)kg/m², (6.0±1.3)mmol/L, (7.0±0.8)mmol/L and (6.3±0.8)%, all significantly lower than [(27.8±5.7)kg/m², (7.8±1.3)mmol/L, (8.5±1.0)mmol/L and (6.9±1.0)%, respectively, P＜0.05] in the control; serum TC, TG and LDL levels were (4.9±0.4)mmol/L, (1.9±0.3)mmol/L and (2.4±0.4)mmol/L, all much lower than [(5.6±0.9)mmol/L, (3.2±0.4)mmol/L and (3.6±0.5)mmol/L, respectively, P＜0.05], while serum HDL level was (1.2±0.5)mmol/L, much higher than [(1.0±0.3)mmol/L, P＜0.05] in the control group; visceral and subcutaneous fat areas were (135.11±14.0)cm² and (202.3±18.4)cm², both significantly lower than [(164.9±18.7)cm² and (240.7±23.3)cm², respectively, P＜0.05], and serum IL-6 and TNF-α levels were (5.7±2.4)pg/mL and (18.9±4.7)pg/mL, both significantly lower than [(19.2±3.0)pg/mL and (46.1±5.5)pg/mL, respectively, P＜0.05] in the control group. Conclusion The regimen with semaglutide, fenofibrate and metformin at base of diet control and exercise in dealing with patients with T2DM and concomitant NAFLD could have a short-term efficacy of weight loss, and needs further clinical investigation.

Key words: Non-alcoholic fatty liver disease, Type 2 diabetes mellitus, Semaglutide, Fenofibrate, Therapy

王美玲, 李洁, 刘娟, 孙婷婷. 司美格鲁肽联合非诺贝特治疗2型糖尿病合并非酒精性脂肪性肝病患者疗效初步研究^*[J]. 实用肝脏病杂志, 2025, 28(6): 838-841.

Wang Meiling, Li Jie, Liu Juan, et al. Semaglutide in combination with fenofibrate in the treatment of patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease[J]. Journal of Practical Hepatology, 2025, 28(6): 838-841.

参考文献

[1] 吴彬彬,李丹丹,王子铭. 非酒精性脂肪性肝病合并2型糖尿病患者尿微量白蛋白及血清糖化血红蛋白和甲状腺激素水平变化. 实用肝脏病杂志,2025,28(2):210-213.
[2] Soltanieh S, Salavatizadeh M, Poustchi H,et al. The association of dietary inflammatory index (DII) and central obesity with non-alcoholic fatty liver disease (NAFLD) in people with diabetes (T2DM). Heliyon, 2023 , 9(3):e13983.
[3] Miceli DD, Vidal VP, Blatter MFC, et al. Fenofibrate treatment for severe hypertriglyceridemia in dogs. Domest Anim Endocrinol, 2021, 74:106578.
[4] Helmstädter J, Keppeler K, Küster L,et al. Glucagon-like peptide-1 (GLP-1) receptor agonists and their cardiovascular benefits-The role of the GLP-1 receptor. Br J Pharmacol, 2022, 179(4):659-676.
[5] 中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2017年版). 中国实用内科杂志,2018,38(4):292-344.
[6] 中华医学会肝病学分会脂肪肝和酒精性肝病学组,中国医师协会脂肪性肝病专家委员会.非酒精性脂肪性肝病防治指南(2018年更新版). 实用肝脏病杂志,2018,21(2):177-186.
[7] Hu C, Zhuang X, Zhang J, et al. Serum metabolomics in patients with coexisting NAFLD and T2DM using liquid chromatography-mass spectrometry. Lab Med, 2022, 53(4):360-368.
[8] Ahmad R, Haque M. Metformin: beyond type 2 diabetes mellitus. Cureus, 2024 , 16(10):e71730.
[9] El-Fayoumi S, Mansour R, Mahmoud A, et al. Pioglitazone enhances β-arrestin2 signaling and ameliorates insulin resistance in classical insulin target tissues. Pharmacology, 2021, 106(7-8):409-417.
[10] Seminotti B, Grings M, Glänzel NM, et al. Peroxisome proliferator-activated receptor (PPAR) agonists as a potential therapy for inherited metabolic disorders. Biochem Pharmacol, 2023, 209:115433.
[11] Farahani RA, Egan AM, Welch AA,et al. The effect of glucagon-like peptide 1 receptor blockade on glucagon-induced stimulation of insulin secretion. Diabetes, 2023, 72(4):449-454.
[12] Li H, Zhou Y, Cai C,et al. Fenofibrate induces liver enlargement in aging mice via activating the PPARα-YAP signaling pathway. Chem Biol Interact, 2025, 405:111286.
[13] Zhang D, Ma Y, Liu J,et al. Fenofibrate improves hepatic steatosis, insulin resistance, and shapes the gut microbiome via TFEB-autophagy in NAFLD mice. Eur J Pharmacol, 2023, 960:176159.
[14] Mann JFE, Buse JB, Idorn T,et al. Potential kidney protection with liraglutide and semaglutide: Exploratory mediation analysis. Diabetes Obes Metab, 2021, 23(9):2058-2066.
[15] Patel JP, Hardaswani D, Patel J,et al. Comparative effectiveness of semaglutide, liraglutide, orlistat, and phentermine for weight loss in obese individuals: a systematic review. Cureus, 2025, 17(3):e80321.
[16] 马明梅,马晓春,马生花,等. 司美格鲁肽注射液治疗不同体质量指数2型糖尿病对糖脂代谢和脂肪因子的影响. 实用医学杂志,2025,41(9):1394-1400.
[17] Varra FN, Varras M, Varra VK,et al. Molecular and pathophysiological relationship between obesity and chronic inflammation in the manifestation of metabolic dysfunctions and their inflammation-mediating treatment options (Review). Mol Med Rep, 2024 , 29(6):95.
[18] Zhu S, Zhang M, Qu Z,et al. Moscatilin alleviates oxidative stress and inflammatory response of Müller cells in diabetic retinopathy through suppressing the p38 mitogen-activated protein kinase/c-Jun N-terminal kinase and nuclear factor kappa-B signaling pathways. J Cell Commun Signal, 2025, 19(1):e12059.
[19] Wrońska A, Kieżun J, Kmieć Z. High-dose fenofibrate stimulates multiple cellular stress pathways in the kidney of old rats. Int J Mol Sci, 2024,25(5):3038.
[20] Moiz A, Filion KB, Tsoukas MA,et al. Mechanisms of GLP-1 receptor agonist-induced weight loss: a review of central and peripheral pathways in appetite and energy regulation. Am J Med, 2025, 138(6):934-940.

司美格鲁肽联合非诺贝特治疗2型糖尿病合并非酒精性脂肪性肝病患者疗效初步研究^*

Semaglutide in combination with fenofibrate in the treatment of patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease

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