肥胖症治疗的新篇章：多靶点肽类激动剂的机制与临床研究进展

打开文本图片集

【中图分类号】 R589.25 【文献标识码】 ADO1： 10.12114/j.issn.1007-9572.2025.0372

【Abstract】Obesityis achronic and relapsing disease resulting from interactions between geneticand environmental factors.Itsglobalprevalencecontinues torise，makingitamajorpublichealthchallnge.Traditionalweightmanagementstrategies oftenyieldsuboptimaloutcomes.Inrecentyears，peptide-basedtherapiestargetingtheglucagon-likepeptde-eeptor（GL-）， glucose-dependentinsulinoropicpolpeptidereceptor（GIPR），andglucagoneceptor（GCGR）haveadancedapidlyithulti targetagonistsemergingasapromisingnewtherapeutic trend.Thisreviewsystematicallysummarizesthe mechanismsandclinical

agonists[J]. Chinese General Practice，2026，29（12）： 1511-1519.∘leddash Editorial Office of Chinese General Practie.This isan openaccessarticle under the CCBY-NC-ND4.0license.

progressoftheseagents：GLP-1Rsingle-targetagonistsdemonstratesignificantefcacyinweightreductio，glycemiccontrol， andmulti-organprotection，thoughinterindivdualvariabilityandgastrointestinalsideefectsremainlimitations.ualagonsts targeting GLP-1R/GIPRand GLP-1R/GCGR （e.g.，Tirzepatide，Mazdutide）further improve metabolic parameters，reduce liverfat， andmitigatecardiovascularrisksthroughsynergisticregulationofappetite，energyexpenditure，andlipidmetabolism.Meanhile， the tripleagonist Retatrutide （targeting GLP-1R/GIPR/GCGR）shows robust potential for weightlossand bodycomposition improvement，whilealsomodulating keylipidmetabolicregulatorssuchasANGPTL3/8，therebybroadeningthetherapeutic horizonfor metabolicdiseases.Lokingforward，thedevelopmentof multi-targetagents-combinedwithlong-actingforulation technologies，preisesubtyping，andidividualizedtreatmentstrategies-isexpectedtosgnificantlyhancethefcacyadsafety of obesity treatments and alleviate the public health burden.

【Key Words】Obesity; Multi-target peptide agonists; Glucagon-like peptide-1 receptor; Glucose-dependent insulinotropic polypeptide receptor; Glucagon receptor

肥胖症是一种由遗传和环境因素共同导致的脂肪组织过度积累或分布、功能异常的慢性、进行性、复发性疾病[1-2]。（剩余29780字）