Diabetes Obes Metab:利拉鲁肽治疗1型糖尿病的疗效和安全性

2021-11-13 从医路漫漫 MedSci原创

尽管引入了新的胰岛素类似物和血糖监测系统,但对于大多数1型糖尿病患者来说,实现和保持严格的血糖控制仍是困难的。

尽管引入了新的胰岛素类似物和血糖监测系统,但对于大多数1型糖尿病患者来说,实现和保持严格的血糖控制仍是困难的。使用胰岛素与低血糖和体重增加的风险有关。在世界工业化地区,患有1型糖尿病的成年人经常超重或肥胖,使得血糖控制和心血管并发症的风险更加复杂化,这在1型糖尿病患者中明显增加。此外,有证据表明,高体重指数(Bmi)可能促进1型糖尿病的标志性病理生理特征,即免疫介导的β细胞破坏。除了胰岛素之外,治疗1型糖尿病的安全有效的药物仍然是迫切需要的。虽然钠-葡萄糖共转运蛋白-2抑制剂已经显示出明显的潜力,但它们还没有在美国被批准用于1型糖尿病,它们在欧洲的用途也不清楚。这是1型糖尿病缺乏重大治疗进展的一个缩影。同时,在过去的十年中,随着胰高血糖素样肽-1受体激动剂(GLP-1RAS)的引入,2型糖尿病的治疗模式发生了转变。GLP-1RAS显著降低糖化血红蛋白(HbA1c)、外源性胰岛素需求、低血糖风险和体重,同时还有其他已证实的益处,如对心血管风险的益处。可注射的GLP-1RA利拉鲁肽治疗1型糖尿病已经在小规模、开放标签的临床研究和两个3期试验中进行了评估:ADJUNCT ONE和ADJUNCT TWO。ADJUNCT 试验证实,作为胰岛素的辅助药物,利拉鲁肽可以改善血糖控制,降低体重和外源性胰岛素需求量。然而,这些益处伴随着低血糖风险的增加,并且很少出现伴有酮症但没有糖尿病酮症酸中毒(DKA)的高血糖。这些发现已得到多项研究的证实和扩展。在ADJUNCT试验中,与没有β细胞功能(以C肽水平衡量)的参与者相比,发现利拉鲁肽对糖化血红蛋白(HbA1c)有更明显的安慰剂调整效应,并降低了低血糖的风险。残余β细胞功能是该病的一个临床基础变量,到目前为止仍然是唯一被证实对利拉鲁肽治疗1型糖尿病的疗效有显著影响的人体测量学指标。本研究的目的的评价利拉鲁肽治疗1型糖尿病(T1D)26周的疗效。

方法:ADJUNCT 试验为随机、安慰剂对照、双盲、平行组、3期试验。在为期52周的ADJUNCT ONE试验中(17个国家的177个中心;1398名参与者;NCT01836523),胰岛素中加入了每天一次的利拉鲁肽皮下注射,该注射继续进行,并在治疗的基础上进行测定。在为期26周的ADJUNCT TWO试验(12个国家的59个中心;835名参与者;NCT02098395)中,皮下利拉鲁肽被用作胰岛素的辅助药物,每个参与者的皮下利拉鲁肽上限为前7天平均每日总剂量。关在这两个试验中,利拉鲁肽起始剂量为0.6毫克,然后根据需要每隔一周递增一次,直到达到目标剂量(每天0.6、1.2或1.8毫克);此后,剂量不减少。安慰剂注射遵循相同的方案。在随机化(第0周),试验前每日胰岛素总剂量减少25%,并在每个剂量递增日至少24小时内进一步减少10%。这项事后分析根据分组评估了治疗效果:糖化血红蛋白(<或≥8.5%)、体重指数(≥;<或BMI 27 kg/m2)和胰岛素方案(基础剂量或持续皮下注射胰岛素)。

结果:在第26周的两个试验中,糖化血红蛋白(HbA1c)、体重和每日胰岛素剂量的降低与基线糖化血红蛋白(HbA1c)或体重指数(BMI)没有显著差异(P>0.05)。临床显着低血糖或高血糖伴酮症的风险无显著差异(P>0.05)。0 5)基础糖化血红蛋白(HbA1c)、体重指数(BMI)或胰岛素方案。在ADJUNCT ONE的第26周,这些风险在治疗组之间没有差异(P>0.05)。安慰剂调整后的糖化血红蛋白(HbA1c)、体重和胰岛素剂量(利拉鲁肽1.8 mg,分别为0.30%、5.0 kg和12%)显著降低(P<0.05),大于第52周,与ADJUNCT TWO试(分别为0.35%、4.8 kg和10%,利拉鲁肽1.8 mg)相似。

图1 糖化血红蛋白和胰岛素使用:第26周。在第26周,ADJUNCT ONE(图左)和ADJUNCT TWO(图右)的数据是从基线(条)到安慰剂(95%置信区间)的估计的平均变化和估计的治疗差异。HbA1c(A-D组)和每日胰岛素总剂量(E-H组)按基线糖化血红蛋白水平(HbA1c<或≥8.5%[69 mmol/m ol])和基线体重指数(<或≥27 kg/m2)分组估计。以治疗、亚组、分层、访问和国家为固定因素,基线值为固定协变量的重复测量的混合模型得出估计值;该模型还包括亚组和治疗组之间的交互作用,以及每个模型项和访问之间的交互作用,并根据观察到的每个亚组中的基线分布来调整组平均估计值。基线后的治疗数据(在治疗的第一天或之后以及不晚于治疗的最后一天的次日收集的数据)包括在分析中。除非注明(*),否则在所有利拉鲁肽剂量水平的亚组中,估计的安慰剂调整后的治疗效果在统计学上没有显著差异(治疗和组之间相互作用的所有测试都没有统计学意义)。*表明对治疗和小组之间的相互作用进行了具有统计学意义的测试。BMI,体重指数;N,参与者数量

图2 体重:第26周。在第26周,ADJUNCT ONE(图左)和ADJUNCT TWO(图右)的数据是从基线(条)到安慰剂(95%置信区间)的估计的平均变化和估计的治疗差异。小组A-D显示了体重变化的估计值,按亚组、基线糖化血红蛋白水平(<或≥8.5%[69 mmol/m ol])和基线体重指数(<或≥27 kg/m2)显示。以治疗、亚组、分层、访问和国家为固定因素,基线值为固定协变量的重复测量的混合模型得出估计值;该模型还包括亚组和治疗组之间的交互作用,以及每个模型项和访问之间的交互作用,并根据观察到的每个亚组中的基线分布来调整组平均估计值。基线后的治疗数据(在治疗的第一天或之后以及不晚于治疗的最后一天的次日收集的数据)包括在分析中。在所有利拉鲁肽剂量水平的亚组内,估计的安慰剂调整后的治疗效果在统计学上没有显著差异(治疗组和亚组之间相互作用的所有测试都没有统计学意义)。BMI,体重指数;N,参与者数量

图3 高血糖伴酮症和低血糖(临床意义):第26周。数据是ADJUNCT ONE(图左)和ADJUNCT TWO(图右)在第26周与安慰剂的平均比率,95%的可信区间。对伴酮症的高血糖发作(血糖>16.7 mmol/L和血酮>1.5 mmol/L的发作)(A-F组)和临床上有意义的低血糖发作(根据美国糖尿病协会诺和诺德定义为严重的症状性低血糖发作,且血糖值<3.1 mmol/L[<56 mg/dL],症状与低血糖相一致)(G-L组),按分组,按基线H值显示(G-L组),显示为酮症的高血糖发作(小组A-F),以及临床上显著的低血糖发作(根据美国糖尿病协会,诺和诺德定义为严重的症状性低血糖发作,且血糖值<3.1 mmol/L[<56 mg/dL],症状与低血糖相一致)(小组G-L)。以及基线时使用的胰岛素治疗类型(基础推注或CSII)。发作是紧急治疗的(在治疗的第一天或之后并且不晚于治疗的最后一天的次日起病)。估计值来自负二项回归模型,该模型以对数链接、治疗、亚组、国家、分层因素、治疗与亚组之间的交互作用为因素,以基线HbA1c为协变量,以暴露时间的对数为偏移量。除非注明(*),否则在所有利拉鲁肽剂量水平的亚组内,发病率比率在统计学上没有显著差异。*表明对治疗和小组之间的相互作用进行了具有统计学意义的测试。体重指数(BMI),体重指数(BMI);CSII,持续皮下胰岛素输注(CSII)

结论:在ADJUNCT ONE和ADJUNCT TWO中,利拉鲁肽的疗效和血糖安全性并不依赖于分组,残留的β细胞功能是T1D中唯一确定的影响胰高血糖素样肽-1受体激动剂(GLP-1 RAs)效果的变量。这些发现支持GLP-1 RAs在T1D中作为胰岛素辅助物的作用,值得进一步研究。

原文出处:

Dejgaard TF,  von Scholten BJ,  Christiansen E,et al.Efficacy and Safety of Liraglutide in Type 1 Diabetes by Baseline Characteristics in the ADJUNCT ONE and ADJUNCT TWO Randomized Clinical Trials.Diabetes Obes Metab 2021 Aug 31

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    2022-10-07 ms1000000251410274

    就是1型也可以用?

    0

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    2022-10-14 一闲
  3. [GetPortalCommentsPageByObjectIdResponse(id=2092256, encodeId=8f932092256a0, content=就是1型也可以用?, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5f1f5633705, createdName=ms1000000251410274, createdTime=Fri Oct 07 11:59:04 CST 2022, time=2022-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1896942, encodeId=db011896942a7, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Fri Oct 14 13:18:21 CST 2022, time=2022-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1721109, encodeId=1ffc1e2110996, content=<a href='/topic/show?id=634ee040179' target=_blank style='color:#2F92EE;'>#疗效和安全性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70401, encryptionId=634ee040179, topicName=疗效和安全性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=16ef32982072, createdName=经常头晕, createdTime=Tue Aug 30 20:18:21 CST 2022, time=2022-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1902669, encodeId=e8b71902669b8, content=<a href='/topic/show?id=c097591ed5' target=_blank style='color:#2F92EE;'>#Diabetes#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5917, encryptionId=c097591ed5, topicName=Diabetes)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0045169, createdName=木头人513, createdTime=Sun Apr 17 15:18:21 CST 2022, time=2022-04-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1761760, encodeId=b0211e61760a6, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Sun Oct 16 14:18:21 CST 2022, time=2022-10-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1888384, encodeId=6d6a18883843d, content=<a href='/topic/show?id=d56611584ec' target=_blank style='color:#2F92EE;'>#Meta#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11584, encryptionId=d56611584ec, topicName=Meta)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8f4110, createdName=guojianrong, createdTime=Sun Mar 06 13:18:21 CST 2022, time=2022-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1639957, encodeId=7f43163995e3a, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5916, encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Sat Oct 22 02:18:21 CST 2022, time=2022-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1070932, encodeId=8b3c10e09326f, content=2型可以用吗?, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c4a44885671, createdName=419040982, createdTime=Tue Nov 16 22:44:45 CST 2021, time=2021-11-16, status=1, ipAttribution=)]
  4. [GetPortalCommentsPageByObjectIdResponse(id=2092256, encodeId=8f932092256a0, content=就是1型也可以用?, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5f1f5633705, createdName=ms1000000251410274, createdTime=Fri Oct 07 11:59:04 CST 2022, time=2022-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1896942, encodeId=db011896942a7, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Fri Oct 14 13:18:21 CST 2022, time=2022-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1721109, encodeId=1ffc1e2110996, content=<a href='/topic/show?id=634ee040179' target=_blank style='color:#2F92EE;'>#疗效和安全性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70401, encryptionId=634ee040179, topicName=疗效和安全性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=16ef32982072, createdName=经常头晕, createdTime=Tue Aug 30 20:18:21 CST 2022, time=2022-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1902669, encodeId=e8b71902669b8, content=<a href='/topic/show?id=c097591ed5' target=_blank style='color:#2F92EE;'>#Diabetes#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5917, encryptionId=c097591ed5, topicName=Diabetes)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0045169, createdName=木头人513, createdTime=Sun Apr 17 15:18:21 CST 2022, time=2022-04-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1761760, encodeId=b0211e61760a6, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Sun Oct 16 14:18:21 CST 2022, time=2022-10-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1888384, encodeId=6d6a18883843d, content=<a href='/topic/show?id=d56611584ec' target=_blank style='color:#2F92EE;'>#Meta#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11584, encryptionId=d56611584ec, topicName=Meta)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8f4110, createdName=guojianrong, createdTime=Sun Mar 06 13:18:21 CST 2022, time=2022-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1639957, encodeId=7f43163995e3a, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5916, encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Sat Oct 22 02:18:21 CST 2022, time=2022-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1070932, encodeId=8b3c10e09326f, content=2型可以用吗?, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c4a44885671, createdName=419040982, createdTime=Tue Nov 16 22:44:45 CST 2021, time=2021-11-16, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=2092256, encodeId=8f932092256a0, content=就是1型也可以用?, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5f1f5633705, createdName=ms1000000251410274, createdTime=Fri Oct 07 11:59:04 CST 2022, time=2022-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1896942, encodeId=db011896942a7, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Fri Oct 14 13:18:21 CST 2022, time=2022-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1721109, encodeId=1ffc1e2110996, content=<a href='/topic/show?id=634ee040179' target=_blank style='color:#2F92EE;'>#疗效和安全性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70401, encryptionId=634ee040179, topicName=疗效和安全性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=16ef32982072, createdName=经常头晕, createdTime=Tue Aug 30 20:18:21 CST 2022, time=2022-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1902669, encodeId=e8b71902669b8, content=<a href='/topic/show?id=c097591ed5' target=_blank style='color:#2F92EE;'>#Diabetes#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5917, encryptionId=c097591ed5, topicName=Diabetes)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0045169, createdName=木头人513, createdTime=Sun Apr 17 15:18:21 CST 2022, time=2022-04-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1761760, encodeId=b0211e61760a6, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Sun Oct 16 14:18:21 CST 2022, time=2022-10-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1888384, encodeId=6d6a18883843d, content=<a href='/topic/show?id=d56611584ec' target=_blank style='color:#2F92EE;'>#Meta#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11584, encryptionId=d56611584ec, topicName=Meta)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8f4110, createdName=guojianrong, createdTime=Sun Mar 06 13:18:21 CST 2022, time=2022-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1639957, encodeId=7f43163995e3a, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5916, encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Sat Oct 22 02:18:21 CST 2022, time=2022-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1070932, encodeId=8b3c10e09326f, content=2型可以用吗?, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c4a44885671, createdName=419040982, createdTime=Tue Nov 16 22:44:45 CST 2021, time=2021-11-16, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=2092256, encodeId=8f932092256a0, content=就是1型也可以用?, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5f1f5633705, createdName=ms1000000251410274, createdTime=Fri Oct 07 11:59:04 CST 2022, time=2022-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1896942, encodeId=db011896942a7, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Fri Oct 14 13:18:21 CST 2022, time=2022-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1721109, encodeId=1ffc1e2110996, content=<a href='/topic/show?id=634ee040179' target=_blank style='color:#2F92EE;'>#疗效和安全性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70401, encryptionId=634ee040179, topicName=疗效和安全性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=16ef32982072, createdName=经常头晕, createdTime=Tue Aug 30 20:18:21 CST 2022, time=2022-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1902669, encodeId=e8b71902669b8, content=<a href='/topic/show?id=c097591ed5' target=_blank style='color:#2F92EE;'>#Diabetes#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5917, encryptionId=c097591ed5, topicName=Diabetes)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0045169, createdName=木头人513, createdTime=Sun Apr 17 15:18:21 CST 2022, time=2022-04-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1761760, encodeId=b0211e61760a6, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Sun Oct 16 14:18:21 CST 2022, time=2022-10-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1888384, encodeId=6d6a18883843d, content=<a href='/topic/show?id=d56611584ec' target=_blank style='color:#2F92EE;'>#Meta#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11584, encryptionId=d56611584ec, topicName=Meta)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8f4110, createdName=guojianrong, createdTime=Sun Mar 06 13:18:21 CST 2022, time=2022-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1639957, encodeId=7f43163995e3a, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5916, encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Sat Oct 22 02:18:21 CST 2022, time=2022-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1070932, encodeId=8b3c10e09326f, content=2型可以用吗?, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c4a44885671, createdName=419040982, createdTime=Tue Nov 16 22:44:45 CST 2021, time=2021-11-16, status=1, ipAttribution=)]
    2022-03-06 guojianrong
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    2021-11-16 419040982

    2型可以用吗?

    0

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