总体考虑要点
尽管在传统上,药物治疗仅限于胰岛素,但最新证据提示,当代产科实践广泛使用口服降糖药。[75]Camelo Castillo W, Boggess K, Stürmer T, et al. Trends in glyburide compared with insulin use for gestational diabetes treatment in the United States, 2000-2011. Obstet Gynecol. 2014 Jun;123(6):1177-84. 多项研究提示,这些药物(例如二甲双胍、格列本脲)在治疗剂量使用时,是安全有效的,当饮食不能控制血糖时,可以作为下一个治疗序列使用,而非直接采用胰岛素。[76]Waugh N, Royle P, Clar C, et al. Screening for hyperglycaemia in pregnancy: a rapid update for the National Screening Committee. Health Technol Assess. 2010 Sep;14(45):1-183.https://www.journalslibrary.nihr.ac.uk/hta/hta14450#/abstract[77]Dhulkotia JS, Ola B, Fraser R, et al. Oral hypoglycemic agents vs insulin in management of gestational diabetes: a systematic review and metaanalysis. Am J Obstet Gynecol. 2010 Nov;203(5):457.e1-9.[78]Petry CJ. Gestational diabetes: risk factors and recent advances in its genetics and treatment. Br J Nutr. 2010 Sep;104(6):775-87.[79]Coustan DR. Pharmacological management of gestational diabetes: an overview. Diabetes Care. 2007 Jul;30 Suppl 2:S206-8. [Erratum in: Diabetes Care. 2007 Dec;30(12):3154.]http://care.diabetesjournals.org/content/30/Supplement_2/S206.full 关于阿卡波糖、噻唑烷二酮类药物或计算机辅助的胰岛素输注方案的安全性和有效性,临床试验数据有限,所以这些治疗仍是实验性质,不建议用于常规临床治疗。美国糖尿病协会强调,胰岛素是妊娠期间的首选治疗。[2]American Diabetes Association. Standards of medical care in diabetes - 2018. Diabetes Care. 2018 Jan 1;41 Suppl 1:S1-159.http://care.diabetesjournals.org/content/41/Supplement_1
格列本脲
格列本脲不能大量穿过胎盘,一项有关妊娠糖尿病的随机研究将其与胰岛素治疗比较;这项研究有 404 例患者,结果显示两种治疗的结局相当。[80]Langer O, Conway DL, Berkus MD, et al. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med. 2000 Oct 19;343(16):1134-8.http://www.nejm.org/doi/full/10.1056/NEJM200010193431601#t=article 一项系统评估比较了接受口服降糖药与胰岛素治疗的妊娠糖尿病结局,结果发现格列本脲与胰岛素治疗的结局相似。[81]Nicholson W, Bolen S, Witkop CT, et al. Benefits and risks of oral diabetes agents compared with insulin in women with gestational diabetes: a systematic review. Obstet Gynecol. 2009 Jan;113(1):193-205. 然而,另一项系统评估发现,与胰岛素相比,格列本脲组中,新生儿出生体重高出 93 g,但没有统计学意义。[82]Nicholson WK, Wilson LM, Witkop CT, et al. Therapeutic management, delivery, and postpartum risk assessment and screening in gestational diabetes. Evid Rep Technol Assess (Full Rep). 2008 Mar;(162):1-96.http://www.ncbi.nlm.nih.gov/books/NBK27011/ 一项随机临床试验比较了格列本脲和二甲双胍作为妊娠期糖尿病孕妇饮食和体育运动的辅助治疗对围产儿的影响,结果发现格列本脲治疗组的新生儿血糖水平较低,而二甲双胍组的新生儿体重和重量指数(出生体重/身高³×100)较低。[83]Silva JC, Fachin DR, Coral ML, et al. Perinatal impact of the use of metformin and glyburide for the treatment of gestational diabetes mellitus. J Perinat Med. 2012 Jan 10;40(3):225-8. 一项回顾性分析使用了保险索赔数据,结果提示,与接受胰岛素治疗的女性相比,在接受格列本脲治疗的女性中,不良结局风险增加,与其相关的危害包括入住新生儿重症监护室、呼吸窘迫、低血糖、大于胎龄儿和产伤。[84]Camelo Castillo W, Boggess K, Stürmer T, et al. Association of adverse pregnancy outcomes with glyburide vs insulin in women with gestational diabetes. JAMA Pediatr. 2015 May;169(5):452-8. 没有开展研究评估格列本脲用药对后代结局的长期影响。
二甲双胍
关于二甲双胍治疗妊娠期高血糖症的数据有限。 [
]How does metformin compare with insulin in pregnant women with type 2 diabetes?显示答案 二甲双胍可以自由穿过胎盘,在脐带血中达到可测量的浓度。[85]Hellmuth E, Damm P, Molsted-Pedersen L. Oral hypoglycaemic agents in 118 diabetic pregnancies. Diabet Med. 2000 Jul;17(7):507-11. 尽管如此,有限的随访数据提示,在后代中没有不良发育作用,总体身体构成也没有差异。[86]Rowan JA, Rush EC, Obolonkin V, et al. Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition at 2 years of age. Diabetes Care. 2011 Oct;34(10):2279-84.http://care.diabetesjournals.org/content/34/10/2279.long[87]Ijäs H, Vääräsmäki M, Saarela T, et al. A follow-up of a randomised study of metformin and insulin in gestational diabetes mellitus: growth and development of the children at the age of 18 months. BJOG. 2015 Jun;122(7):994-1000. 在一项小型研究中,将二甲双胍用于需要胰岛素的妊娠糖尿病,发现围产期死亡率与胰岛素治疗相似,但新生儿黄疸水平较高。其他研究报道,妊娠期间使用二甲双胍与子痫前期和围产期死亡率增加相关。[85]Hellmuth E, Damm P, Molsted-Pedersen L. Oral hypoglycaemic agents in 118 diabetic pregnancies. Diabet Med. 2000 Jul;17(7):507-11.[88]Coetzee EJ, Jackson WP. Metformin in management of pregnant insulin-independent diabetics. Diabetologia. 1979 Apr;16(4):241-5. 一些研究报告,胰岛素与二甲双胍治疗的结局相似。[89]Mesdaghinia E, Samimi M, Homaei Z, et al. Comparison of newborn outcomes in women with gestational diabetes mellitus treated with metformin or insulin: a randomised blinded trial. Int J Prev Med. 2013 Mar;4(3):327-33.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634172/[90]Tertti K, Ekblad U, Koskinen P, et al. Metformin vs. insulin in gestational diabetes. A randomized study characterizing metformin patients needing additional insulin. Diabetes Obes Metab. 2013 Mar;15(3):246-51. 在一项临床试验中,二甲双胍组中 50% 的女性需要补充胰岛素才能维持血糖控制,尤其是空腹高血糖患者,并且几乎所有女性均需要最大剂量的二甲双胍。[91]Rowan JA, Hague WM, Gao W, et al; MiG Trial Investigators. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med. 2008 May 8;358(19):2003-15.http://www.nejm.org/doi/full/10.1056/NEJMoa0707193#t=article 一项系统评估比较了接受口服降糖药与胰岛素治疗的妊娠糖尿病结局,结果发现二甲双胍与胰岛素治疗的结局相似。[81]Nicholson W, Bolen S, Witkop CT, et al. Benefits and risks of oral diabetes agents compared with insulin in women with gestational diabetes: a systematic review. Obstet Gynecol. 2009 Jan;113(1):193-205. 另一份比较二甲双胍与胰岛素的试验综述发现,二甲双胍对妊娠没有短期不良作用,在新生儿阶段可能有益处(降低新生儿低血糖和大于胎龄儿的风险,母亲妊娠期总体重增加值较低),但长期随访数据有限。作者建议对宫内暴露于二甲双胍的后代开展进一步随访研究。[92]Butalia S, Gutierrez L, Lodha A, et al. Short- and long-term outcomes of metformin compared with insulin alone in pregnancy: a systematic review and meta-analysis. Diabet Med. 2017 Jan;34(1):27-36. 二甲双胍与格列本脲的比较数据有限。