Currently, there are several glucagon-like peptide-1 receptor agonists (GLP-1RAs) used for the treatment of type 2 diabetes (T2DM) , but most are administered by subcutaneous injection, which reduces patient compliance.Danuglipron and Orforglipron are novel oral small molecule GLP-1RAs, which may become a strong choice for hypoglycemic drugs in the future.

To systematically evaluate the efficacy and safety of Danuglipron and Orforglipron in the treatment of T2DM.

A computerized search was performed on several authoritative databases, including PubMed, Embase, Cochrane Library, Web of Science, SinoMed, CNKI, Wanfang Data, and VIP databases. Randomized controlled trials (RCTs) comparing the efficacy and safety of Danuglipron or Orforglipron (test group) and placebo (control group) for the treatment of T2DM were collected, and 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 criteria, and the quality of the screened literature was evaluated, the data were meta-analyzed using RevMan 5.4 software .

A total of 6 studies were included in the analysis. The results indicated that in terms of efficacy, compared to the placebo group, the Danuglipron/Orforglipron group showed a reduction in glycosylated hemoglobin (HbA_1c) (MD=-1.04, 95%CI=-1.36 to -0.73, P<0.01) levels, fasting plasma glucose (FPG) (MD=-1.88, 95%CI=-2.53 to -1.23, P<0.01) levels, and an increase in fasting plasma insulin (FPI) (MD=4.68, 95%CI=2.42 to 6.95, P<0.01) levels. However, there was no statistically significant difference between the two groups in terms of weight reduction (MD=-4.00, 95%CI=-10.14 to 2.15, P=0.20) . Regarding safety, compared to the placebo group, the Danuglipron/Orforglipron group had increased rates of nausea (OR=7.85, 95%CI=4.25 to 14.50, P<0.01) , vomiting OR=9.45, 95%CI=4.19 to 21.31, P<0.01) , diarrhea (OR=1.96, 95%CI=1.13 to 3.39, P=0.02) , decreased appetite OR=4.56, 95%CI=1.75 to 11.91, P<0.01) , indigestion (OR=3.35, 95%CI=1.54 to 7.32, P<0.01) , belching OR=4.79, 95%CI=1.13 to 20.23, P=0.03) , constipation (OR=3.45, 95%CI=1.24 to 9.56, P=0.02) , and overall gastrointestinal adverse reactions (OR=5.37, 95%CI=3.32 to 8.69, P<0.01) . And there was no statistically significant difference in the occurrence rates of bloating (OR=2.67, 95%CI=0.72 to 9.86, P=0.14) and headache (OR=0.73, 95%CI=0.37 to 1.42, P=0.35) symptoms.

Oral administration of GLP-1 RAs Danuglipron and Orforglipron can effectively reduce the levels of HbA_1c and FPG, also increase the levels of FPI and the incidence of nausea, vomiting, diarrhea, decreased appetite, dyspepsia, belching, constipation and total gastrointestinal adverse reactions, but have no effect on the incidence of abdominal distension and headache.

目前已有多种胰高血糖素样肽1受体激动剂（GLP-1RAs）用于治疗２型糖尿病（T2DM），但多为皮下注射给药，其给药方式降低了患者的依从性。Danuglipron和Orforglipron为新型口服小分子GLP-1RAs，未来可能会成为降糖药物中强有力的选择。

系统评价Danuglipron与Orforglipron治疗T2DM的疗效及安全性。

计算机检索PubMed、Embase、Cochrane Library、Web of Science、中国生物医学文献数据库、中国知网、万方数据知识服务平台和维普网，收集比较Danuglipron或Orforglipron（试验组）和安慰剂（对照组）治疗T2DM疗效与安全性的随机对照试验（RCT），检索时限均从建库至2024年5月。根据预先设定的纳入及排除标准进行筛选，并对筛选出的文献进行质量评价，采用RevMan 5.4软件对数据进行Meta分析。

共纳入6篇文献。分析结果显示，在疗效方面，相较于安慰剂组，Danuglipron/Orforglipron组具有降低糖化血红蛋白（HbA_1c）（MD=-1.04，95%CI=-1.36~-0.73，P<0.01）、降低空腹血糖（FPG）（MD=-1.88，95%CI=-2.53~-1.23，P<0.01）及升高空腹血浆胰岛素（FPI）水平（MD=4.68，95%CI=2.42~6.95，P<0.01）的作用，但在降低体质量方面两组差异无统计学意义（MD=-4.00，95%CI=-10.14~2.15，P=0.20）。安全性方面，与安慰剂组相比，Danuglipron/Orforglipron组的恶心（OR=7.85，95%CI=4.25~14.50，P<0.01）、呕吐（OR=9.45，95%CI=4.19~21.31，P<0.01）、腹泻（OR=1.96，95%CI=1.13~3.39，P=0.02）、食欲下降（OR=4.56，95%CI=1.75~11.91，P<0.01）、消化不良（OR=3.35，95%CI=1.54~7.32，P<0.01）、嗳气（OR=4.79，95%CI=1.13~20.23，P=0.03）、便秘（OR=3.45，95%CI=1.24~9.56，P=0.02）症状及总胃肠道不良反应（OR=5.37，95%CI=3.32~8.69，P<0.01）发生率增加，而腹胀（OR=2.67，95%CI=0.72~9.86，P=0.14）、头痛（OR=0.73，95%CI=0.37~1.42，P=0.35）发生率比较，差异无统计学意义。

口服GLP-1RAs Danuglipron和Orforglipron能够有效降低HbA_1c和FPG水平，升高FPI水平，同时也会增加恶心、呕吐、腹泻、食欲下降、消化不良、嗳气、便秘症状及总胃肠道不良反应的发生率，但对腹胀、头痛的发生率无影响。