Gestational Diabetes Calls for Quick Action
When lifestyle changes fail, medication becomes necessary to decrease chances of maternal and newborn complications.
Gestational diabetes (GD) is a common pregnancy complication (Table 11-3).
The American Diabetes Association (ADA) indicates that 70% to 85% of women have class A1 GD or diet-controlled GD. If patients need insulin, it is classified as class A2 GD.1
Treatment begins with dietary counseling, exercise, and lifestyle modifications.2 Women must avoid ketosis while restricting their carbohydrate intake and try to limit weight gain. Euglycemia is the primary treatment goal, so women should monitor their glucose levels 4 times a day initially (1 fasting glucose and 3 postprandial measurements).1,2 Continuous glucose monitoring is reserved for women who experience severe fluctuating or unstable plasma glucose levels or hypoglycemia episodes.2,3
The ADA recommends glucose target levels as follows1:
- Fasting blood glucose (FBG) less than 95 mg/dL
- Postprandial 1-hour glucose less than 140 mg/dL
- Postprandial 2-hour glucose less than 120 mg/dL
The ADA and American College of Obstetricians and Gynecologists (ACOG) indicate that if hyperglycemia persists (eg, one-third of glucose levels are above the target fasting or postprandial levels within a week), insulin is a next step. Meeting these targets is crucial. Study results show a risk of fetal macrosomia 5 times higher in women with FBG levels of 100 to 105 mg/dL than in women with levels of 75 mg/dL.4
Glycated hemoglobin A1c (HbA1c) goals tend to be lower in pregnant women than nonpregnant women.5 HbA1c levels at or exceeding 5.9% may predict adverse pregnancy outcomes.5 If hypoglycemia becomes a problem, raising the HbA1c goal to 7% is reasonable.3
About 20% of women with GD require insulin or oral antihyperglycemic agents. The ACOG and ADA prefer insulin, because it does not cross the placenta.1 The FDA has not approved oral antihyperglycemic agents for GD. The ACOG recommends metformin in 3 instances: women who are unable to afford, refuse, or would have adherence issues with insulin.2
Rapid-acting insulin analogs (insulin aspart and insulin lispro) are safe and often preferred because of minimal placental transfer and no evidence of teratogenicity. They can be administered immediately before meals, making them more convenient than regular insulin, which requires waiting for 30 to 60 minutes before eating.1 They also lower the risk of delayed postprandial hypoglycemia compared with human regular insulin.6 Insulin isophane suspension (NPH) is the intermediate/long-acting insulin used most often, but clinicians also prescribe insulin detemir and insulin glargine.7 Insulins aspart, detemir, and glargine have not been associated with pregnancy-related complications. Insulin lispro may decrease neonatal jaundice and severe maternal hypoglycemia but increase fetal macrosomia rates slightly.8
Insulin dosing depends on the patient’s hyperglycemic episodes and the gestational age.1,2 Usually, women with GD will need a combination of basal (intermediate/long acting) and bolus insulin (rapid/short) to achieve glycemic goals. Long-acting insulins are preferred because of a lower risk of hypoglycemia. Most clinicians start insulin as 0.5 to 1 unit/ kg per day with 50% basal and 50% bolus.
Oral Antihyperglycemic Agents
Obstetricians tend to use 2 oral antihyperglycemic drugs— glyburide and metformin (Table 22,9-17)—in pregnancy, with no clear benefit from either. Both cross the placenta.
In pregnant women with GD, hypoglycemia occurs when the blood glucose level falls below 70 mg/dL. Signs include confusion, dizziness, numbness in lips and tongue, shaking, sweating, and tachycardia. Consuming 15 g to 20 g of glucose from a carbohydrate source should elevate glucose levels within 20 minutes.1,2 Women should measure blood glucose again in 15 minutes and consider eating a snack with 15 g to 20 g of complex carbohydrates if their next meal is more than 30 minutes away to prevent recurring hypoglycemia.
Diagnosing GD early and managing it well decreases newborn complications and the risk of maternal preeclampsia.
Jeanette Y. Wick, MBA, RPh, FASCP, is the assistant director of the Office of Pharmacy Professional Development at the University of Connecticut School of Pharmacy in Storrs.
- American Diabetes Association. 14. Management of diabetes in pregnancy: standards of medical care in diabetes—2020. Diabetes Care. 2020;43(suppl 1):S183-S192.
- ACOG practice bulletin no. 190 gestational diabetes mellitus. Obstet Gynecol. 2018;131(2):e49-e64. doi:10.1097/AOG.0000000000002501
- National Collaborating Centre for Women’s and Children’s Health (UK). Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. February 2015. Accessed April 9, 2021. https://www.ncbi.nlm.nih.gov/books/NBK293625/[RP1]
- HAPO Study Cooperative Research Group. The hyperglycemia and adverse pregnancy outcome (HAPO) study. Int J Gynaecol Obstet. 2002;78(1):69-77.
- Hughes RCE, Moore MP, Gullam JE, Mohamed K, Rowan J. An early pregnancy HbA1c ≥5.9% (41 mmol/mol) is optimal for detecting diabetes and identifies women at increased risk of adverse pregnancy outcomes. Diabetes Care. 2014;37(11):2953-2959. doi:10.2337/dc14-1312
- 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;(162):1-96.
- Vellanki P, Umpierrez G. Detemir is non-inferior to NPH insulin in women with pregestational type 2 diabetes and gestational diabetes mellitus. Evid Based Med. 2016;21(3):104-105. doi:10.1136/ebmed-2015-110309
- Lv S, Wang J, Xu Y. Safety of insulin analogs during pregnancy: a meta-analysis. Arch Gynecol Obstet. 2015;292(4):749-756. doi:10.1007/s00404-015-3692-3
- Brown J, Martis R, Hughes B, Rowan J, Crowther CA. Oral anti-diabetic pharmacological therapies for the treatment of women with gestational diabetes. Cochrane Database Syst Rev. 2017;1(1):CD011967. doi:10.1002/14651858.CD011967.pub2
- Denno KM, Sadler TW. Effects of the biguanide class of oral hypoglycemic agents on mouse embryogenesis. Teratology. 1994;49(4):260-266. doi:10.1002/tera.1420490405
- Gilbert C, Valois M, Koren G. Pregnancy outcome after first-trimester exposure to metformin: a meta-analysis. Fertil Steril. 2006;86(3):658-663. doi:10.1016/j.fertnstert.2006.02.098
- Panchaud A, Rousson V, Vial T, et al. Pregnancy outcomes in women on metformin for diabetes or other indications among those seeking teratology information services. Br J Clin Pharmacol. 2018;84(3):568-578. doi:10.1111/bcp.13481
- Rowan JA, Rush EC, Plank LD, et al. Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition and metabolic outcomes at 7-9 years of age. BMJ Open Diabetes Res Care. 2018;6(1):e000456. doi:10.1136/bmjdrc-2017-000456
- Spaulonci CP, Bernardes LS, Trindade TC, Zugaib M, Francisco RPV. Randomized trial of metformin vs insulin in the management of gestational diabetes. Am J Obstet Gynecol. 2013;209(1):34.e1-7. doi:10.1016/j.ajog.2013.03.022
- Landi SN, Radke S, Boggess K, et al. Comparative effectiveness of metformin versus insulin for gestational diabetes in New Zealand. Pharmacoepidemiol Drug Saf. 2019;28(12):1609-1619. doi:10.1002/pds.4907
- Song R, Chen L, Chen Y, et al. Comparison of glyburide and insulin in the management of gestational diabetes: a meta-analysis. PLoS One. 2017;12(8):e0182488. doi:10.1371/journal.pone.0182488
- Harper LM, Mele L, Landon MB, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. Carpenter-Coustan compared with National Diabetes Data Group criteria for diagnosing gestational diabetes. Obstet Gynecol. 2016;127(5):893-898. doi:10.1097/AOG.0000000000001383