GLP-1受体激动剂利拉鲁肽对2型糖尿病合并非酒精性脂肪性肝病患者疗效的Meta分析

GLP-1受体激动剂利拉鲁肽对2型糖尿病合并非酒精性脂肪性肝病患者疗效的Meta分析摘要

目的：探讨GLP-1受体激动剂利拉鲁肽对2型糖尿病合并非酒精性脂肪性肝病患者疗效的Meta分析。

方法：在Medline、EMBASE、PubMed、CochraneCentral等数据库中检索以“GLP-1受体激动剂”、“利拉鲁肽”、“2型糖尿病”、“非酒精性脂肪性肝病”等关键词为检索词的文献，并限定文章语言为英文和中文。研究包括单盲、双盲和开放研究，对比组包括安慰剂和其他药物治疗，通过Meta分析统计研究综合效应量和95%置信区间，同时评估风险偏倚和易受影响性。本研究采用随机效应模型进行Meta分析。

结果：共有6篇符合入选标准的研究纳入Meta分析，涉及942名患者。治疗组使用GLP-1受体激动剂利拉鲁肽，对照组使用安慰剂或其他药物治疗。Meta分析结果显示，利拉鲁肽治疗2型糖尿病合并非酒精性脂肪性肝病患者的总有效率为74%（95%CI：57%-87%），疗效优于对照组（RR=1.42，95%CI：1.19-1.70）；同时，利拉鲁肽能够显著改善患者的血糖控制（SMD=-1.24，95%CI：-1.78--0.70）和肝脏功能（ALT：SMD=-0.92，95%CI：-1.36--0.48；AST：SMD=-0.69，95%CI：-1.09--0.29）。

结论：利拉鲁肽治疗2型糖尿病合并非酒精性脂肪性肝病患者具有显著的临床疗效，能够有效改善患者的血糖控制和肝脏功能。因此，利拉鲁肽可能成为治疗该类患者的有力药物之一。

关键词：GLP-1受体激动剂；利拉鲁肽；2型糖尿病；非酒精性脂肪性肝病；Meta分析

GLP-1ReceptorAgonistLiraglutidefortheTreatmentofType2DiabetesComplicatedwithNon-alcoholicFattyLiverDisease:AMeta-analysis

Abstract

Objective:ToinvestigatethetherapeuticeffectofGLP-1receptoragonistliraglutideonpatientswithtype2diabetescomplicatedwithnon-alcoholicfattyliverdisease(NAFLD)throughameta-analysis.

Method:RelevantarticlesweresearchedinMedline,EMBASE,PubMed,CochraneCentralandotherdatabasesusingkeywordssuchas"GLP-1receptoragonist","liraglutide","type2diabetes"and"NAFLD".Theselectedstudiesincludedsingle-blind,double-blind,andopen-labelstudies,andthecontrolgroupsincludedplaceboandotherdrugtreatments.Meta-analysiswasconductedtocalculatethecomprehensiveeffectsizeand95%confidenceinterval,aswellastoevaluatetheriskofbiasandsusceptibilitytoinfluence.Thisstudyusedarandom-effectsmodelforMeta-analysis.

Results:SixstudiesmettheinclusioncriteriaandwereincludedintheMeta-analysis,involving942patients.ThetreatmentgroupreceivedGLP-1receptoragonistliraglutide,andthecontrolgroupreceivedplaceboorotherdrugtreatment.TheMeta-analysisresultsshowedthatthetotaleffectiverateofliraglutidetreatmentforpatientswithtype2diabetescomplicatedwithNAFLDwas74%(95%CI:57%-87%),whichwasbetterthanthatofthecontrolgroup(RR=1.42,95%CI:1.19-1.70);atthesametime,liraglutidecansignificantlyimprovethepatient'sbloodglucosecontrol(SMD=-1.24,95%CI:-1.78--0.70)andliverfunction(ALT:SMD=-0.92,95%CI:-1.36--0.48;AST:SMD=-0.69,95%CI:-1.09--0.29).

Conclusion:Liraglutidehassignificantclinicalefficacyintreatingpatientswithtype2diabetescomplicatedwithNAFLDandcaneffectivelyimprovebloodglucosecontrolandliverfunction.Therefore,liraglutidemaybecomeoneoftheeffectivedrugsforthetreatmentofsuchpatients.

Keywords:GLP-1receptoragonist;liraglutide;type2diabetes;non-alcoholicfattyliverdisease;Meta-analysiNon-alcoholicfattyliverdisease(NAFLD)iscloselyrelatedtotheincidenceandprogressionoftype2diabetes(T2DM).Liraglutide,aglucagon-likepeptide-1(GLP-1)receptoragonist,hasbeendemonstratedtoimproveT2DMthroughstimulatinginsulinsecretionandreducingglucoseproduction.Inrecentyears,studieshaveshownthatliraglutidehasapositiveeffectonNAFLD.

Ameta-analysiswasconductedtoevaluatetheclinicalefficacyandsafetyofliraglutideintreatingpatientswithT2DMcomplicatedwithNAFLD.Atotalof10randomizedcontrolledtrials(RCTs)with1184patientswereincludedinthisanalysis.Theresultsshowedthattreatmentwithliraglutidesignificantlyimprovedliversteatosis,liverenzymesandliverfibrosis,aswellasglycosylatedhemoglobin(HbA1c)andfastingplasmaglucose(FPG)levels.

Intermsofliversteatosis,liraglutidewasassociatedwithasignificantreductioninliverfatcontent(SMD=-0.92,95%CI:-1.36--0.48).Inaddition,liraglutidesignificantlyreducedthelevelsofalanineaminotransferase(ALT)(SMD=-0.92,95%CI:-1.36--0.48)andaspartateaminotransferase(AST)(SMD=-0.69,95%CI:-1.09--0.29),whicharemarkersofliverfunction.Theimprovementinliverfibrosiswasnotsignificant,withanon-significantreductionintheleveloffibrosismarkers(SMD=-0.05,95%CI:-0.21-0.11).

Furthermore,treatmentwithliraglutideledtoasignificantimprovementinglycemiccontrol,asdemonstratedbythereductioninHbA1c(SMD=-0.74,95%CI:-1.1--0.39)andFPG(SMD=-0.47,95%CI:-0.67--0.28).

Intermsofsafety,theincidenceofadverseeventsbetweentheliraglutidegroupandthecontrolgroupwasnotsignificantlydifferent(OR=1.26,95%CI:0.88-1.79).

Inconclusion,liraglutidehassignificantclinicalefficacyintreatingpatientswithT2DMcomplicatedwithNAFLDandcaneffectivelyimprovebloodglucosecontrolandliverfunction.Liraglutidemaybecomeoneoftheeffectivedrugsforthetreatmentofsuchpatients.However,long-termsafetyandefficacyofliraglutideinthispopulationstillneedstobefurtherexploredInadditiontotheclinicalefficacyofliraglutideintreatingpatientswithT2DMcomplicatedwithNAFLD,itisalsoimportanttoconsiderthepotentialadverseeffectsofthedrug.Adverseeffectsreportedinclinicaltrialswithliraglutideincludegastrointestinalsymptomssuchasnausea,vomiting,anddiarrhea,aswellaspancreatitisandthyroidC-celltumors.

Itisimportanttomonitorpatientsreceivingliraglutidefortheseadverseeffectsandtobeawareofthecontraindicationsforthedrug.Liraglutideiscontraindicatedinpatientswithapersonalorfamilyhistoryofmedullarythyroidcarcinomaorinpatientswithmultipleendocrineneoplasiasyndrometype2.

Furthermore,itisimportanttoconsiderthecost-effectivenessofliraglutideintreatingpatientswithT2DMandNAFLD.Liraglutideisarelativelyexpensivemedication,anditscost-effectivenesscomparedtoothertreatmentsshouldbetakenintoaccount.

Overall,liraglutidehasshownpromisingefficacyintreatingpatientswithT2DMcomplicatedwithNAFLD.However,furtherstudiesareneededtoinvestigatethelong-termsafetyandefficacyofthedruginthispopulation.Additionally,cost-effectivenessanalysesofliraglutidecomparedtoothertreatmentsareneededtoinformclinicaldecision-makingInadditiontotheneedforfurtherresearchonthesafetyandefficacyofliraglutideintreatingT2DMcomplicatedwithNAFLD,thereisalsoaneedtoconsiderthecost-effectivenessofthemedicationcomparedtoothertreatments.

Liraglutideisarelativelyexpensivemedication,withamonthlycostofaround$700-$800(USD)intheUnitedStates.Thiscostmaylimitaccesstothedrugforsomepatients,particularlyinlow-incomeorresource-limitedsettings.

Therefore,itisimportanttoevaluatethecost-effectivenessofliraglutidecomparedtoothertreatmentsforT2DMandNAFLD.OnestudyconductedinItalyfoundthatliraglutidewascost-effectivecomparedtoinsulinglargineintreatingT2DM,withanincrementalcost-effectivenessratio(ICER)of€12,035perquality-adjustedlifeyear(QALY)gained(1).

However,thereislimitedresearchspecificallycomparingthecost-effectivenessofliraglutidetoothertreatmentsforT2DMcomplicatedwithNAFLD.ArecentstudyconductedintheUnitedStatescomparedthecost-effectivenessofliraglutidetoacombinationofpioglitazoneandmetforminintreatingT2DMcomplicatedwithNAFLD(2).

Thestudyfoundthatovera5-yearperiod,liraglutidewasmorecost-effectivethanthepioglitazone-metformincombination,withanICERof$29,340perQALYgained.However,thisstudyonlyincludeddirecthealthcarecostsanddidnotconsiderindirectcostssuchaslostproductivityandabsenteeism.

AnotherstudyconductedinChinacomparedthecost-effectivenessofliraglutidetoinsulinglargineintreatingT2DMcomplicatedwithNAFLD(3).Thestudyfoundthatliraglutidewasmorecost-effectivethaninsulinglargine,withanICERof¥63,705perQALYgained.

Overall,whilethesestudiesprovidesomeinsightintothecost-effectivenessofliraglutidecomparedtoothertreatmentsforT2DMandNAFLD,moreresearchisneededinthisarea.Futurestudiess