二甲双胍联合GLP-1受体激动剂对多囊卵巢综合征患者代谢特征影响的Meta分析
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摘要
目的:探讨二甲双胍联合GLP-1受体激动剂对多囊卵巢综合征(PCOS)患者代谢特征的影响。方法:通过计算机检索PubMed数据库、Cochrane图书馆、EMbase数据库、中国期刊全文数据库(CNKI)、万方数据库、维普数据库,并进一步对纳入文献的参考文献进行扩大检索。对符合纳入标准的随机对照研究(RCT)按Cochrane系统评价的方法,独立进行资料提取、质量评价并交叉核对后,采用Stata12.0软件进行Meta分析。结果:共纳入4篇临床试验文献,试验组(二甲双胍联合GLP-1受体激动剂)61例,对照组(GLP-1受体激动剂)60例。Meta分析结果显示,试验组相较于对照组在改善PCOS患者代谢方面仅在腰围改变上差异有统计学意义(SMD=0.39,95%CI=0.03～0.75,P=0.035),而在BMI(SMD=-0.13,95%CI=-0.48～0.23,P=0.492)、体质量(SMD=-0.19,95%CI=-0.54～0.17,P=0.311)、胰岛素抵抗指数(SMD=-0.68,95%CI=-2.23～0.86,P=0.386)、空腹胰岛素水平(SMD=0.19,95%CI=-0.28～0.66,P=0.426)、性激素结合球蛋白(SMD=0.72,95%CI=-0.55～2.00,P=0.266)、血清总睾酮(SMD=-0.70,95%CI=-1.98～0.57,P=0.279)方面差异无统计学意义。结论:二甲双胍联合GLP-1受体激动剂仅在改善PCOS患者腰围方面的疗效优于GLP-1受体激动剂单用,而在BMI、体质量、胰岛素抵抗指数、空腹胰岛素水平、性激素结合球蛋白、血清总睾酮方面二甲双胍并不增加GLP-1受体激动剂的治疗效果。
Objective: Meta-analysis was performed to assess the efficacy of metformin in combination with GLP-1 agonist on the Metabolic syndrome of women with polycystic ovary syndrome(PCOS). Methods: The randomized controlled trials(RCT) were retrieved from Pubmed, Cochrane library, EMbase, CNKI,WanFang and VIP database and references listed in all studies. RCTs meeting inclusive studies were included the data extracted, the quality was evaluated and cross-checked by two reviews independently according to Cochrane Handbook for Systematic Reviews of Interventions and then Meta-analysis was conducted using Stata12.0 software. Results: A total of 4 studies were included, of which 61 were in test group(metformin combined with GLP-1 agonist) and 60 were in control group(GLP-1 agonist). The results of Meta-analysis showed that test group had a significant difference in waist circumference change compared with control group(SMD=0.39, 95%CI: 0.03-0.75, P=0.035), the rest in BMI(SMD=-0.13, 95%CI:-0.48-0.23, P=0.492), body mass(SMD=-0.19, 95%CI:-0.54-0.17, P=0.311), insulin resistance index(SMD=-0.68, 95%CI:-2.23-0.86,P=0.386), fasting insulin level(SMD=0.19, 95%CI:-0.28-0.66, P=0.426), sex hormone binding globulin(SMD=0.72, 95%CI:-0.55-2.00, P=0.266), serum total testosterone(SMD=-0.70, 95%CI:-1.98-0.57, P=0.279), there were no significant difference. Conclusion: Metformin combined with GLP-1 agonist is superior to GLP-1 agonist alone in improving the waist circumference of patients with PCOS. In contrast, metformin does not increase the therapeutic effect of GLP-1 agonists in BMI, body mass, insulin resistance index, fasting insulin level, sex hormone binding globulin, serum total testosterone.
Objective: Meta-analysis was performed to assess the efficacy of metformin in combination with GLP-1 agonist on the Metabolic syndrome of women with polycystic ovary syndrome(PCOS). Methods: The randomized controlled trials(RCT) were retrieved from Pubmed, Cochrane library, EMbase, CNKI,WanFang and VIP database and references listed in all studies. RCTs meeting inclusive studies were included the data extracted, the quality was evaluated and cross-checked by two reviews independently according to Cochrane Handbook for Systematic Reviews of Interventions and then Meta-analysis was conducted using Stata12.0 software. Results: A total of 4 studies were included, of which 61 were in test group(metformin combined with GLP-1 agonist) and 60 were in control group(GLP-1 agonist). The results of Meta-analysis showed that test group had a significant difference in waist circumference change compared with control group(SMD=0.39, 95%CI: 0.03-0.75, P=0.035), the rest in BMI(SMD=-0.13, 95%CI:-0.48-0.23, P=0.492), body mass(SMD=-0.19, 95%CI:-0.54-0.17, P=0.311), insulin resistance index(SMD=-0.68, 95%CI:-2.23-0.86,P=0.386), fasting insulin level(SMD=0.19, 95%CI:-0.28-0.66, P=0.426), sex hormone binding globulin(SMD=0.72, 95%CI:-0.55-2.00, P=0.266), serum total testosterone(SMD=-0.70, 95%CI:-1.98-0.57, P=0.279), there were no significant difference. Conclusion: Metformin combined with GLP-1 agonist is superior to GLP-1 agonist alone in improving the waist circumference of patients with PCOS. In contrast, metformin does not increase the therapeutic effect of GLP-1 agonists in BMI, body mass, insulin resistance index, fasting insulin level, sex hormone binding globulin, serum total testosterone.
引文
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[2]黄晓燕,吕红,吴春香,等.多囊卵巢综合征患者的体质量指数和脂代谢水平对促性腺激素释放激素拮抗剂方案妊娠结局的影响[J].中华生殖与避孕杂志,2018,38(12):969-975.
[3]侯宇婕.艾塞那肽联合二甲双胍在伴胰岛素抵抗的肥胖型PCOS患者中的临床疗效及安全性分析[J].川北医学院学报,2018,33(5):731-733.
[4]NIAFAR M,NADER N D.Adiponectin as serum biomarker of insulin resistance in patients with polycystic ovarian syndrome[J].Gynecol Endocrinol,2015,31(6):473-476.
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[7]MIETLICKI-BAASE E G,ORTINSKI P I,REINER D J,et al.Glucagon-like peptide-1 receptor activation in the nucleus accumbens core suppresses feeding by increasing glutamatergic AMPA/kainate signaling[J].J Neurosci,2014,34(20):6985-6992.
[8]曾利文,张萍.胰高血糖素样肽-1类似物对减重影响[J].中国实用内科杂志,2017,37(1):17-20.
[9]史薇,朱鸿秋,肖雪,等.达英-35联合中医治疗PCOS疗效的Meta分析[J].中国中医药现代远程教育,2018,16(21):156-158.
[10]马捷,刘莹,钟来平,等.Jadad量表与Cochrane偏倚风险评估工具在随机对照试验质量评价中的应用与比较[J].中国口腔颌面外科杂志,2012,10(5):417-422.
[11]ELKIND-HIRSCH K,MARRIONEAUX O,BHUSHAN M,et al.Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome[J].J Clin Endocrinol Metab,2008,93(7):2670-2678.
[12]JENSTERLE M,GORICAR K,JANEZ A.Metformin as an initial adjunct to low-dose liraglutide enhances the weightdecreasing potential of liraglutide in obese polycystic ovary syndrome:Randomized control study[J].Exp Ther Med,2016,11(4):1194-1200.
[13]JENSTERLE SEVER M,KOCJAN T,PFEIFER M,et al.Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin[J].Eur J Endocrinol,2014,170(3):451-459.
[14]JENSTERLE M,KRAVOS N A,GORI?AR K,et al.Shortterm effectiveness of low dose liraglutide in combination with metformin versus high dose liraglutide alone in treatment of obese PCOS:randomized trial[J].BMC Endocr Disord,2017,17(1):5.
[15]高芳,杜海燕,段彪,等.多囊卵巢综合征代谢异常的相关机制的论述[J].世界最新医学信息文摘,2017,17(95):50-52,55.
[16]ASTRUP A,ROSSNER S,VAN GAAL L,et al.Effects of liraglutide in the treatment of obesity:a randomised,doubleblind,placebo-controlled study[J].Lancet,2009,374(9701):1606-1616.
[17]张新霞,童南伟.胰高血糖素样肽-1受体激动剂在多囊卵巢综合征的临床应用[J].华西医学,2018,33(5):611-615.
[18]冯惠芳,杜巧梅,黄翠萍.百令胶囊联合二甲双胍治疗对多囊卵巢综合征患者代谢指标及性激素的影响[J].新中医,2018,50(12):137-139.
[19]MONAMI M,DICEMBRINI I,MARCHIONNI N,et al.Effects of glucagon-like peptide-1 receptor agonists on body weight:a Meta-analysis[J].Exp Diabetes Res,2012,2012:672658.
[20]VILSBOLL T,CHRISTENSEN M,JUNKER A E,et al.Effects of glucagon-like peptide-1 receptor agonists on weight loss:systematic review and Meta-analyses of randomised controlled trials[J].BMJ,2012,344:d7771.
[21]NIAFAR M,POURAFKARI L,PORHOMAYON J,et al.Asystematic review of GLP-1 agonists on the Metabolic syndrome in women with polycystic ovaries[J].Arch Gynecol Obstet,2016,293(3):509-515.
[2]黄晓燕,吕红,吴春香,等.多囊卵巢综合征患者的体质量指数和脂代谢水平对促性腺激素释放激素拮抗剂方案妊娠结局的影响[J].中华生殖与避孕杂志,2018,38(12):969-975.
[3]侯宇婕.艾塞那肽联合二甲双胍在伴胰岛素抵抗的肥胖型PCOS患者中的临床疗效及安全性分析[J].川北医学院学报,2018,33(5):731-733.
[4]NIAFAR M,NADER N D.Adiponectin as serum biomarker of insulin resistance in patients with polycystic ovarian syndrome[J].Gynecol Endocrinol,2015,31(6):473-476.
[5]DIAMANTI-KANDARAKIS E,DUNAIF A.Insulin resistance and the polycystic ovary syndrome revisited:an update on mechanisms and implications[J].Endocr Rev,2012,33(6):981-1030.
[6]BILLA E,KAPOLLA N,NICOPOULOU S C,et al.Metformin administration was associated with a modification of LH,prolactin and insulin secretion dynamics in women with polycystic ovarian syndrome[J].Gynecol Endocrinol,2009,25(7):427-434.
[7]MIETLICKI-BAASE E G,ORTINSKI P I,REINER D J,et al.Glucagon-like peptide-1 receptor activation in the nucleus accumbens core suppresses feeding by increasing glutamatergic AMPA/kainate signaling[J].J Neurosci,2014,34(20):6985-6992.
[8]曾利文,张萍.胰高血糖素样肽-1类似物对减重影响[J].中国实用内科杂志,2017,37(1):17-20.
[9]史薇,朱鸿秋,肖雪,等.达英-35联合中医治疗PCOS疗效的Meta分析[J].中国中医药现代远程教育,2018,16(21):156-158.
[10]马捷,刘莹,钟来平,等.Jadad量表与Cochrane偏倚风险评估工具在随机对照试验质量评价中的应用与比较[J].中国口腔颌面外科杂志,2012,10(5):417-422.
[11]ELKIND-HIRSCH K,MARRIONEAUX O,BHUSHAN M,et al.Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome[J].J Clin Endocrinol Metab,2008,93(7):2670-2678.
[12]JENSTERLE M,GORICAR K,JANEZ A.Metformin as an initial adjunct to low-dose liraglutide enhances the weightdecreasing potential of liraglutide in obese polycystic ovary syndrome:Randomized control study[J].Exp Ther Med,2016,11(4):1194-1200.
[13]JENSTERLE SEVER M,KOCJAN T,PFEIFER M,et al.Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin[J].Eur J Endocrinol,2014,170(3):451-459.
[14]JENSTERLE M,KRAVOS N A,GORI?AR K,et al.Shortterm effectiveness of low dose liraglutide in combination with metformin versus high dose liraglutide alone in treatment of obese PCOS:randomized trial[J].BMC Endocr Disord,2017,17(1):5.
[15]高芳,杜海燕,段彪,等.多囊卵巢综合征代谢异常的相关机制的论述[J].世界最新医学信息文摘,2017,17(95):50-52,55.
[16]ASTRUP A,ROSSNER S,VAN GAAL L,et al.Effects of liraglutide in the treatment of obesity:a randomised,doubleblind,placebo-controlled study[J].Lancet,2009,374(9701):1606-1616.
[17]张新霞,童南伟.胰高血糖素样肽-1受体激动剂在多囊卵巢综合征的临床应用[J].华西医学,2018,33(5):611-615.
[18]冯惠芳,杜巧梅,黄翠萍.百令胶囊联合二甲双胍治疗对多囊卵巢综合征患者代谢指标及性激素的影响[J].新中医,2018,50(12):137-139.
[19]MONAMI M,DICEMBRINI I,MARCHIONNI N,et al.Effects of glucagon-like peptide-1 receptor agonists on body weight:a Meta-analysis[J].Exp Diabetes Res,2012,2012:672658.
[20]VILSBOLL T,CHRISTENSEN M,JUNKER A E,et al.Effects of glucagon-like peptide-1 receptor agonists on weight loss:systematic review and Meta-analyses of randomised controlled trials[J].BMJ,2012,344:d7771.
[21]NIAFAR M,POURAFKARI L,PORHOMAYON J,et al.Asystematic review of GLP-1 agonists on the Metabolic syndrome in women with polycystic ovaries[J].Arch Gynecol Obstet,2016,293(3):509-515.