anuglipron与Orforglipron治疗2型糖尿病疗效及安全性的Meta分析

BackgroundCurrentlythere are several glucagon-like peptide-1 receptor agonistsGLP-1RAs used for the treatment of type 2 diabetesT2DMbut most are administered by subcutaneous injectionwhich reduces patient compliance.Danuglipron and Orforglipron are novel oral small molecule GLP-1RAswhich may become a strong choice for hypoglycemic drugs in the future. ObjectiveTo systematically evaluate the efficacy and safety of Danuglipron and Orforglipron in the treatment of type 2 diabetes mellitus. MethodsA computerized search was performed on several authoritative databasesincluding PubMedEmbaseCochrane LibraryWeb of ScienceSinoMedCNKIWanfangand VIP databases. Randomized controlled trialsRCTscomparing the efficacy and safety of Danuglipron or Orforgliprontest groupand placebo control groupfor the treatment of T2DM were collectedand the time frame for searching were all from the inception of the databases to May 2024. Screening was conducted based on pre-defined inclusion and exclusion criteriaand the quality of the screened literature was evaluatedthe data were meta-analyzed using RevMan 5.4 software . ResultsA total of 6 studies were included in the analysis. The results indicated that in terms of efficacycompared to the placebo groupthe Danuglipron/ Orforglipron group showed a reduction in glycosylated hemoglobinHbA1cMD=-1.0495%CI=-1.36~-0.73P<0.001levels fasting plasma glucoseFPGMD=-1.8895%CI=-2.53~-1.23P<0.01levelsand an increase in fasting plasma insulin FPIMD=4.6895%CI=2.42~6.95P<0.01levels. Howeverthere was no statistically significant difference between the two groups in terms of weight reductionMD=-4.0095%CI=-10.14~2.15P=0.20. Regarding safetycompared to the placebo groupthe Danuglipron/Orforglipron group had increased rates of nauseaOR=7.8595%CI=4.25~14.50P<0.01 vomiting OR=9.4595%CI=4.19~21.31P<0.01diarrheaOR=1.9695%CI=1.13~3.39P=0.02decreased appetite OR=4.5695%CI=1.75~11.91P<0.01indigestionOR=3.3595%CI=1.54~7.32P<0.01belching OR=4.79 95%CI=1.13~20.23P=0.03constipationOR=3.4595%CI=1.24~9.56P=0.02and overall gastrointestinal adverse reactionsOR=5.3795%CI=3.32~8.69P<0.01. And there was no statistically significant difference in the occurrence rates of bloatingOR=2.6795%CI=0.72~9.86P=0.14and headacheOR=0.7395%CI=0.37~1.42P=0.35symptoms. ConclusionsOral administration of GLP-1 RAs Danuglipron and Orforglipron can effectively reduce the levels of HbA1c and FPGalso increase the levels of FPI and the incidence of nauseavomitingdiarrheadecreased appetitedyspepsia belchingconstipation and total gastrointestinal adverse reactionsbut have no effect on the incidence of abdominal distension and headache.