钠-葡萄糖协同转运蛋白2抑制剂治疗2型糖尿病合并非酒精性脂肪性肝病有效性和安全性的Meta分析

李晓静; 孙元隆; 张彬彬; 梅祖兵; 冯琴; 胡义扬

doi:10.3969/j.issn.1001-5256.2020.10.016

钠-葡萄糖协同转运蛋白2抑制剂治疗2型糖尿病合并非酒精性脂肪性肝病有效性和安全性的Meta分析

DOI: 10.3969/j.issn.1001-5256.2020.10.016

1. 上海中医药大学附属曙光医院肝病研究所
2. 上海中医药大学附属曙光医院肛肠科

基金项目:

国家自然科学基金(81673765)；

详细信息

中图分类号: R575.5;R587.2
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出版历程
- 收稿日期: 2020-04-01
- 出版日期: 2020-10-20

Efficacy and safety of sodium-glucose co-transporter 2 inhibitors in treatment of type 2 diabetes mellitus with nonalcoholic fatty liver disease: A meta-analysis

Institute of Hepatology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
Department of Coloproctology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Research funding:

摘要

摘要: 目的系统评价钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂对2型糖尿病合并非酒精性脂肪性肝病的有效性和安全性。方法检索截至2020年3月外文数据库Pub Med、Cohrane Library、Embase;中文数据库中国知网、维普、万方,检索关键词筛选符合条件的研究,根据量表评价文献质量,应用Rev Man 5.3和Stata 15.0软件对数据进行Meta分析。结果共纳入9项队列研究和5项随机对照试验,共计605例患者。主要观察指标Meta分析结果显示:SGLT2抑制剂可显著降低队列研究中的ALT（MD=-24.22,95%CI:-29.54～-18.89,P <0.001）、Hb A1c（MD=-0.53,95%CI:-0.74～-0.32,P <0.001）;随机对照试验中的ALT（MD=-12.51,95%CI:-15.61～-9.41,P <0.001）和Hb A1c（MD:-0.54,95%CI:-0.80～-0.27,P <0.001）水平,差异均具有统计学意义。次要观察指标:SGLT2抑制剂可明显改善患者BMI（P <0.001）、脂肪重量...
- 非酒精性脂肪性肝病 /
- 糖尿病,2型 /
- 钠-葡萄糖转运体2 /
- Meta分析(主题)
Abstract: Objective To systematically review the efficacy and safety of sodium-glucose co-transporter 2( SGLT2) inhibitors in the treatment of type 2 diabetes mellitus( T2 DM) with nonalcoholic fatty liver disease( NAFLD). Methods Foreign databases( PubMed,Cochrane Library,and Embase) and Chinese databases( CNKI,VIP,and Wanfang Data) were searched for articles published up to March2020. Keywords were used to screen out eligible studies,related scales were used to evaluate the quality of articles,and RevMan 5. 3 and Stata 15. 0 were used to perform the meta-analysis. Results A total of 9 cohort studies and 5 randomized controlled trials( RCTs) were included,with 605 patients in total. The meta-analysis of main observation indices showed that SGLT2 inhibitors significantly inhibited alanine aminotransferase( ALT)( mean difference [MD]=-24. 22,95% confidence interval [CI]:-29. 54 to-18. 89,P < 0. 001) and hemoglobin A1 c( Hb A1 c)( MD =-0. 53,95% CI:-0. 74 to-0. 32,P < 0. 001) in cohort studies,as well as ALT( MD =-12. 51,95% CI:-15. 61 to-9. 41,P < 0. 001) and HbA1 c( MD =-0. 54,95% CI:-0. 80 to-0. 27,P < 0. 001) in RCTs. The analysis of secondary observation indices showed that SGLT2 inhibitors significantly improved body mass index( P < 0. 001),fat mass( P < 0. 001),hepatic fat fraction( P < 0. 001),gamma-glutamyl transpeptidase( P < 0. 001),fasting blood glucose( P < 0. 001),serum ferritin( P <0. 001),and serum type Ⅳ collagen 7 S( P = 0. 02). There was a significant difference in the result of the meta-analysis of aspartate aminotransferase between RCTs( P = 0. 16) and cohort studies( P < 0. 001). After the administration of SGLT2 inhibitors,there were significant increases in the incidence rates of decreased body fluid volume( risk ratio [RR]= 7. 67,95% CI: 1. 45-40. 42,P = 0. 02),urinary tract infection( RR = 4. 27,95% CI: 1. 11-16. 43,P = 0. 03),and reproductive system infection( RR = 3. 76,95% CI: 1. 21-11. 69,P =0. 02). Conclusion Current evidence suggests that SGLT2 inhibitors can reduce body mass,blood glucose,liver enzymes,and liver fat content in patients with T2 DM and NAFLD and improve liver fibrosis to a certain degree,but they can increase the risk of fluid loss and reproductive system infection in patients. More studies are needed for further verification.
- non-alcoholic fatty liver disease /
- diabetes mellitus,type 2 /
- sodium-glucose transporter 2 /
- Meta-analysis as topic

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参考文献(26)

[1] SAPONARO C,GAGGINI M,GASTALDELLI A. Nonalcoholic fatty liver disease and type 2 diabetes:Common pathophysiologic mechanisms[J]. Curr Diab Rep,2015,15(6):607.

[2] HUMMEL CS,LU C,LOO DD,et al. Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2[J]. Am J Physiol Cell Physiol,2011,300(1):c14-c21.

[3] GAUTAM A,AGRAWAL PK,DONERIA J,et al. Effects of canagliflozin on abnormal liver function tests in patients of type2 diabetes with non-alcoholic fatty liver disease[J]. J Assoc Physicians India,2018,66(8):62-66.

[4] INOUE M,HAYASHI A,TAGUCHI T,et al. Effects of canagliflozin on body composition and hepatic fat content in type2 diabetes patients with non-alcoholic fatty liver disease[J]. J Diabetes Investig,2019,10(4):1004-1011.

[5] LAI LL,VETHAKKAN SR,NIK MUSTAPHA NR,et al. Empagliflozin for the treatment of nonalcoholic steatohepatitis in patients with type 2 diabetes mellitus[J]. Dig Dis Sci,2020,65(2):623-631.

[6] SEKO Y,NISHIKAWA T,UMEMURA A,et al. Efficacy and safety of canagliflozin in type 2 diabetes mellitus patients with biopsy-proven nonalcoholic steatohepatitis classified as stage 1-3 fibrosis[J]. Diabetes Metab Syndr Obes,2018,11:835-843.

[7] SUMIDA Y,MUROTANI K,SAITO M,et al. Effect of luseogliflozin on hepatic fat content in type 2 diabetes patients with non-alcoholic fatty liver disease:A prospective,single-arm trial(LEAD trial)[J]. Hepatol Res,2019,49(1):64-71.

[8] TOBITA H,SATO S,MIYAKE T,et al. Effects of dapagliflozin on body composition and liver tests in patients with nonalcoholic steatohepatitis associated with type 2 diabetes mellitus:A prospective,open-label,uncontrolled study[J]. Curr Ther Res Clin Exp,2017,87:13-19.

[9] ARASE Y,SHIRAISHI K,ANZAI K,et al. Effect of sodium glucose co-transporter 2 inhibitors on liver fat mass and body composition in patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus[J]. Clin Drug Investig,2019,39(7):631-641.

[10] SEKO Y,SUMIDA Y,TANAKA S,et al. Effect of sodium glucose cotransporter 2 inhibitor on liver function tests in Japanese patients with non-alcoholic fatty liver disease and type 2 diabetes mellitus[J]. Hepatol Res,2017,47(10):1072-1078.

[11] YAMASHIMA M,MIYAAKI H,MIUMA S,et al. The long-term efficacy of sodium glucose co-transporter 2 inhibitor in patients with non-alcoholic fatty liver disease[J]. Intern Med,2019,58(14):1987-1992.

[12] ASO Y,KATO K,SAKURAI S,et al. Impact of dapagliflozin,an SGLT2 inhibitor,on serum levels of soluble dipeptidyl peptidase-4 in patients with type 2 diabetes and non-alcoholic fatty liver disease[J]. Int J Clin Pract,2019,73(5):e13335.

[13] ERIKSSON JW,LUNDKVIST P,JANSSON PA,et al. Effects of dapagliflozin and n-3 carboxylic acids on non-alcoholic fatty liver disease in people with type 2 diabetes:A doubleblind randomised placebo-controlled study[J]. Diabetologia,2018,61(9):1923-1934.

[14] KUCHAY MS,KRISHAN S,MISHRA SK,et al. Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease:A Randomized Controlled Trial(E-LIFT Trial)[J]. Diabetes Care,2018,41(8):1801-1808.

[15] SHIBUYA T,FUSHIMI N,KAWAI M,et al. Luseogliflozin improves liver fat deposition compared to metformin in type 2 diabetes patients with non-alcoholic fatty liver disease:A prospective randomized controlled pilot study[J]. Diabetes Obes Metab,2018,20(2):438-442.

[16] ITO D,SHIMIZU S,INOUE K,et al. Comparison of ipragliflozin and pioglitazone effects on nonalcoholic fatty liver disease in patients with type 2 diabetes:A randomized,24-week,open-label,active-controlled trial[J]. Diabetes Care,2017,40(10):1364-1372.

[17] XUE MM,LI XP,LI Y,et al. Researches advances in sodium-glucose co-transporter 2 inhibitor in treatment of type 2 diabetes mellitus with nonalcoholic fatty liver disease[J]. J Clin Hepatol,2019,35(12):2812-2816.(in Chinese)薛苗苗，李雪萍，李亚，等．钠-葡萄糖协同转运蛋白2抑制剂治疗2型糖尿病合并非酒精性脂肪肝病的研究进展[J]．临床肝胆病杂志，2019,35(12):2812-2816.

[18] HAYASHIZAKI-SOMEYA Y,KUROSAKI E,TAKASU T,et al.Ipragliflozin,an SGLT2 inhibitor,exhibits a prophylactic effect on hepatic steatosis and fibrosis induced by choline-deficient l-amino acid-defined diet in rats[J]. Eur J Pharmacol,2015,754:19-24.

[19] QIANG S,NAKATSU Y,SENO Y,et al. Treatment with the SGLT2 inhibitor luseogliflozin improves nonalcoholic steatohepatitis in a rodent model with diabetes mellitus[J]. Diabeto Metab Syndr,2015,7(1):104.

[20] SHIMIZU M,SUZUKI K,KATO K,et al. Evaluation of the effects of dapagliflozin,a sodium-glucose co-transporter-2 inhibitor,on hepatic steatosis and fibrosis using transient elastography in patients with type 2 diabetes and non-alcoholic fatty liver disease[J]. Diabetes Obes Metab,2019,21(2):285-292.

[21] TAHRANI AA,BARNETT AH,BAILEY CJ. SGLT inhibitors in management of diabetes[J]. Lancet Diabetes Endocrinol,2013,1(2):140-151.

[22] SCHEEN AJ. Reduction in HbA1c with SGLT2 inhibitors vs.DPP-4 inhibitors as add-ons to metformin monotherapy according to baseline HbA1c:A systematic review of randomized controlled trials[J]. Diabetes Metab,2020,46(3):186-196.

[23] YU X,WANG WJ,JIN JY,et al. Linggui Zhugan Decoction combined with probiotics in the treatment of nonalcoholic fatty liver disease[J]. J Changchun Univ Chin Med,2019,35(5):891-894.(in Chinese)喻晓，王雯婕，金嘉悦，等．苓桂术甘汤联合益生菌治疗非酒精性脂肪肝[J]．长春中医药大学学报，2019,35(5):891-894.

[24] HERMANSEN K,MORTENSEN LS. Bodyweight changes associated with antihyperglycaemic agents in type 2 diabetes mellitus[J]. Drug Saf,2007,30(12):1127-1142.

[25] KOWDLEY KV,BELT P,WILSON LA,et al. Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease[J].Hepatology,2012,55(1):77-85.

[26] WANG LN,ZHOU L. Effect observation of SLGT-2 inhibitor on serum leptin level in patients with diabetic fatty liver disease[J]. Clin J Chin Med,2019,11(30):49-50.(in Chinese)王丽娜，周林．SLGT-2抑制剂在糖尿病脂肪肝患者的治疗中对血清瘦素水平的作用观察[J]．中医临床研究，2019,11(30):49-50.

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