GDM: Pharmacological Therapy for Treatment of GDM 2006
Click here to see the explanation of recommendation ratings (Strong, Fair, Weak, Consensus, Insufficient Evidence) and labels (Imperative or Conditional). To see more detail on the evidence from which the following recommendations were drawn, use the hyperlinks in the Supporting Evidence Section below.
GDM: Pharmacological Therapy for Treatment of GDM
When optimal blood glucose levels have not been maintained with medical nutrition therapy (MNT) and/or the rate of fetal growth is excessive, the Registered Dietitian (RD) should recommend the initiation of pharmacological therapy for treatment of women with gestational diabetes mellitus (GDM). Research indicates that pharmacological therapy, such as the use of insulin, insulin analogs and glyburide, improves glycemic control and reduces the incidence of poor maternal and neonatal outcomes.
Risks/Harms of Implementing This Recommendation
- Use of pharmacological therapy to control blood glucose levels may result in hypoglycemia
- All medications taken in pregnancy should be reviewed for FDA-approved Pregnancy classification
Conditions of Application
- This recommendation applies to women with gestational diabetes mellitus when optimal blood glucose levels have not been maintained with medical nutrition therapy (MNT) and/or the rate of fetal growth is excessive.
- Not all healthcare professionals recommend the use of oral antidiabetes agents in pregnancy.
Recommended target blood glucose levels vary among organizations:
Fasting 1-hour 2-hour American Diabetes Association
American College of Obstetrics and Gynecology
<130 - 140 mg/dL
<7.2 - 7.8 mmol/L
Fifth International Workshop-Conference on GDM
90 - 99 mg/dL
5.0 - 5.5 mmol/L
<6.7 - 7.0 mmol/L
Potential Costs Associated with Application
- Although costs of MNT sessions and reimbursement vary, medical nutrition therapy sessions are essential for improved outcomes.
- Additional costs of medication, blood glucose monitoring and fetal monitoring
Twenty-four studies were evaluated to investigate the use of pharmacological therapy for women with gestational diabetes mellitus.
- In conjunction with nutrition therapy, pharmacological therapy is indicated in women with gestational diabetes mellitus when optimal blood glucose levels have not been maintained and/or when the rate of fetal growth is excessive (Rossi et al, 2000; Simpson and Kast, 2000; Kjos et al, 2001; Svare et al, 2001; Bonomo et al, 2004; Schaefer-Graf et al, 2004).
- Insulin therapy has been shown to be safe and effective in maintaining optimal blood glucose levels and reducing incidence of macrosomia, fetal morbidity and mortality. Five studies regarding the use of insulin analogs reported that lispro or aspart as rapid acting insulins may improve glycemic control and reduce the incidence of macrosomia in neonates (Franz et al, 1994; Bhattacharyya et al, 2001; Simmons et al, 2001; American Diabetes Association, 2002; Poyhonen-Alho et al, 2002; Pettitt et al, 2003; Leipold et al, 2005).
- Research on glargine is limited (Price et al, 2007).
- Eight studies reported that glyburide therapy is effective in maintaining glycemic control in conjunction with nutrition therapy, especially in women with less severe disease (Langer et al, 2000; Chmait et al, 2004; Conway et al, 2004; Kremer and Duff, 2004; Yogev et al, 2004; Bertini et al, 2005; Jacobson et al, 2005; Langer et al, 2005).
- Research on metformin is limited (Hellmuth et al, 2000; Charles et al, 2006).
- Further research on other antidiabetes agents in women with gestational diabetes mellitus is needed..
Recommendation Strength Rationale
- Conclusion Statement was given Grade II
- Risks/Harms of Implementing This Recommendation
The recommendations were created from the evidence analysis on the following questions. To see detail of the evidence analysis, click the blue hyperlinks below (recommendations rated consensus will not have supporting evidence linked).
American Diabetes Association. Gestational diabetes mellitus. Diabetes Care 2002:25(1); S94-S96.
Bertini AM, Silva JC, Taborda W, Becker F, Bebber FRL, Viesi JMZ, Aquim G, Ribeiro TE. Perinatal outcomes and the use of oral hypoglycemic agents. J Perinat Med 2005;33:519-523.
Bhattacharyya A, Brown S, Hughes S, Vice PA. Insulin lispro and regular insulin in pregnancy. QJ Med 2001;94:255-260.
Bonomo M, Cetin I, Pisoni MP, Faden D, Mion E, Taricco E, Nobile de Santis M, Radaelli T, Motta G, Costa M, Solerte L, Morabito A. Flexible treatment of Gestational Diabetes modulated on ultrasound evaluation of intrauterine growth: a controlled randomized clinical trial. Diabetes Metab 2004, 30,237-43.
Charles B, Norris R, Xiao X, Hague W. Population Pharmacokinetics of Metformin in Late Pregnancy. Ther Drug Monit 2006;28:67-72.
Chmait R, Dinise T, Moore T. Prospective Observational study to establish predictors of glyburide success in women with gestational diabetes mellitus. Journal of Perinatology 2004;24:617-622.
Conway DL, Gonzales O, Skiver D. Use of glyburide for the treatment of gestational diabetes: the San Antonio experience. J Matern Fetal Neonatal Med 2004 Jan;15(1):51-5.
Franz MJ, Horton ES, Bantle JP, Beebe CA, Brunzell JD, Coulston AM, Henry RR, Hoogwerf BJ, Stacpoole PW. Nutrition principles for the management of diabetes and related complications. Diabetes Care 1994; 17:490-518.
Hellmuth E, Damm P, Molsted-Pedersen L. Oral hypoglycaemic agents in 118 diabetic pregnancies. Diabetic Medicine 2000;17:507-511.
Jacobson GF, Ramos GA, Ching JY, Kirby RS, Ferrara A, Field DR. Comparison of glyburide and insulin for the management of gestational diabetes in a large managed care organization. American Journal of Obstetrics and Gynecology 2005:193:118-24.
Kjos S, Schaefer-Graf U, Sardesi S, Peters R, Buley A, Xiang A, Byrne J, Sutherland C, Montoro M, Buchanan T. A randomized controlled trial using glycemic plus fetal ultrasound parameters versus glycemic parameters to determine insulin therapy in gestational diabetes with fasting hyperglycemia. Diabetes Care 2001;24:1904-1910.
Kremer C, Duff P. Glyburide for the treatment of gestational diabetes. Am J Obstet Gynecol 2004;190(5):1438-9.
Langer O, Conway DL, Berkus MD, Xenakis EMJ, Gonzalez O. A comparision of glyburide and insulin in women with gestational diabetes mellitus. New Engl J Med 2000;343:1134-8.
Langer O, Yogev Y, Xenakis EMJ, Rosenn B. Insulin and glyburide therapy: Dosage, severity level of gestational diabetes, and pregnancy outcome. Am J of Obstet Gynec 2005;192:134-9.
Leipold H, Worda C, Gruber CJ, Kautzky-Willer A, Husslein PW, Bancher-Todesca D. Large-for-gestational-age newborns in women with insulin-treated gestational diabetes under strict metabolic control. Wien Klin Wochenschr 2005;117/15-16:521-525.
Pettitt DJ, Ospina P, Kolaczynski JW, Jovanovic L. Comparison of an insulin analog, insulin aspart and regular human insulin with no insulin in gestational diabetes mellitus. Diabetes Care 2003;26:183-186.
Poyhonen-Alho M, Teramo K, Kaaja R. Treatment of gestational diabetes with short-or long-acting insulin and neonatal outcome: a pilot study. Acta Obstet Gynecol Scand 2002;81:258-259.
Price N, Bartlett C, Gillmer MD. Use of insulin glargine during pregnancy: a case-control pilot study. BJOG 2007;114(4):453-7.
Rossi G, Somigliana E, Moschetta M, Bottani B, Barbieri M, Vignali M. Adequate timing of fetal ultrasound to quide metabolic therapy in mild gestational diabetes melliutus. Acta Obstet Gynecol Scand 2000;79:649-654.
Schaefer-Graf UM, Kjos SL, Fauzan OH, Buhling KJ, Siebert G, Buhrer C, Ladendorf B, Dudenhausen JW, Vetter K. A randomized trial evaluating a predominately fetal growth-based strategy to guide management of gestational diabetes in Caucasian women. Diabetes Care 2004; 27(2):297-302.
Simmons D, Thompson CF, Conroy C, Scott DJ. Use of insulin pumps in pregnancies complicated by Type 2 diabetes and gestational diabetes in a multiethnic community. Diabetes Care 2001;24(12):2078-2082.
Simpson RW, Kast SJ. Management of gestational diabetes with a conservative insulin protocol. Med J Aust 2000;172:537-540.
Svare JA, Hansen BB, Molsted-Pedersen L. Perinatal complications in women with gestational diabetes mellitus. Acta Obstet Gynecol Scand 2001;80(10):899-904.
Yogev Y, Ben-Haroush A, Chen R, Rosenn B, Hod M, Langer O. Undiagnosed asymptomatic hypoglycemia: diet, insulin and glyburide for gestational diabetic pregnancy. Obstet Gynecol 2004;104:88-93.
References not graded in Academy of Nutrition and Dietetics Evidence Analysis Process
American Diabetes Association. Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association. Diabetes Care 2007;30 Suppl 1:S48-65.
Clinical Management Guidelines for Obstetrician-Gynecologists. ACOG Practice Guidelines Number 30, 2001;98(3):525-538.
Jovanovic L, Ilic S, Pettitt DJ, Hugo K, Gutierrez M, Bowsher RR, Bastyr EJ. The metabolic and immunologic effects of insulin lispro in gestational diabetes. Diabetes Care 1999;22:1422-1426.
Metzger BE, Buchanan TA, Coustan DR, de Leiva A, Dunger DB, Hadden DR, Hod M, Kitzmiller JL, Kjos SL, Oats JN, Pettitt DJ, Sacks DA, Zoupas C. Summary and recommendations of the Fifth International Workshop Conference on Gestational Diabetes Mellitus. Diabetes Care 2007;30 Suppl 2:S251-60.
Rowan JA, Hague WM, Gao W, Battin MR, Moore MP, for the MiG Trial Investigators. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med 2008;358:2003-15.