From Research to Practice / Diabetes

In Brief
The use of oral antidiabetic drugs in pregnancy is an accepted treatment modali-
ty for women with gestational diabetes mellitus (GDM). This efficacious option

Downloaded
provides physicians more choices that, in turn, translate into more complex
decision making for the management of GDM. However, regardless of the

and
mode of therapy, whole patient care (glucose monitoring, education, diet adher-

from Pregnancy
ence, and so forth) will determine overall success in managing this disease and

http://diabetesjournals.org/spectrum/article-pdf/20/2/101/556946/101.pdf by guest on 18 May 2023

the potential to maximize the quality of perinatal outcome.

Oral Antidiabetic Drugs in Pregnancy:

The Other Alternative

In the United States, depending on the lines the management approach

diagnosis criteria used, 135,000– (intensified treatment) and describes
200,000 women annually develop ges- the use of oral antidiabetic agents
Oded Langer, MD, PhD tational diabetes mellitus (GDM), (mainly glyburide) to prevent glycemic
adding to the number of pregnant extremes (i.e., hypoglycemia and
women who already have either type hyperglycemia) in pregnant women
1 or type 2 diabetes. There has also with GDM and type 2 diabetes.
been a significant increase (~ 33%) in
the incidence of type 2 diabetes with Fundamental Structure
its presumed parallel risk for obesity1 of Intensified Therapy
in addition to the development of Intensified therapy is an approach to
adolescent obesity in the offspring of achieving established levels of glycemic
diabetic women.2 control. Two breakthrough studies in
Two main factors have contributed nonpregnant diabetic patients demon-
to the dramatic increase in pharmaco- strated the effectiveness of intensified
logical therapy: recognition that therapy: the Diabetes Control and
GDM is an early stage in the develop- Complications Trial3,4 in type 1 dia-
ment of type 2 diabetes and increased betes and the U.K. Prospective Dia-
awareness of the impact of the meta- betes Study in type 2 diabetes. 5
bolic syndrome on public health and Regardless of the type of diabetes, the
its appearance in 20–50% of women intensified approach incorporates
who have had GDM. This article out- several components:
101
Diabetes Spectrum Volume 20, Number 2, 2007
 • Memory-based self-monitoring producing outcomes comparable to regardless of treatment modality (diet
of blood glucose (SMBG). This those among the general population. or insulin). In contrast, in patients
empowers patients to take charge with a fasting plasma glucose > 95
of their glycemic control and pro- Goals of Pharmacological Treatment mg/dl, the majority of patients failed
vides feedback on the timing and Targeted levels of glycemic control to achieve the desired level of
dose of pharmacological therapy achieved with intensified therapy pre- glycemic control throughout the 4-
(insulin and/or oral agents). Previ- vent microvascular and macrovascular week period, with a resulting three-
ous approaches to evaluating the complications in nonpregnant diabetic fold higher rate of LGA infants in
level of glycemia in pregnant dia- patients. However, the thresholds for diet-treated patients. Thus, it is rea-
betic women on a weekly basis or targeted levels of glycemic control are sonable and appropriate to recom-
by measuring hemoglobin A1c at 8- higher than those used for the defini- mend that patients with a fasting plas-
to 10-week intervals failed to pro- tion of normoglycemia in nondiabetic ma glucose > 95 mg/dl be assigned to
vide the information required to pregnant women.12,13 Thus, one must pharmacological therapy, especially
optimize pregnancy outcome. distinguish between normoglycemic considering the high rate of obesity in
• Dietary regulation. For all types of levels and the thresholds recommend- patients with GDM.19
diabetes, the foundation of treat- ed to optimize outcome in pregnant Patients with a fasting plasma glu-
ment is diet adherence. The diet and nonpregnant diabetic women.14,15 cose < 95 mg/dl may be candidates for
should include a low percentage of Regardless of the treatment modal- a trial of diet therapy for a 2- to 3-
carbohydrates (~ 40%) and be ity, the primary goal is always to week period before initiation of phar-

Downloaded from http://diabetesjournals.org/spectrum/article-pdf/20/2/101/556946/101.pdf by guest on 18 May 2023

designed to help achieve and main- attain the recommended level of macological therapy. However, it
tain established maternal glucose glycemic control, thereby reducing should be noted that ~ 30% will fail to
levels.6 glycemic extremes (i.e., incidence of achieve the desired levels of glycemic
• Strict criteria for initiation of phar- hypoglycemia, hyperglycemia, and control and will require pharmacologi-
macological therapy ketosis) while maximizing perinatal cal therapy.18 The failure to introduce
• Interdisciplinary team effort outcome. In pregnancy, the criteria pharmacological therapy in a timely
used for targeted levels of glycemic fashion may lead to fetal hyperinsuline-
We demonstrated in a large control at our institution are: mia, which is central to the pathophys-
prospective study 7 that intensified • Mean blood glucose: 90–105 mg/dl iology of diabetes complications
therapy, in comparison to the conven- • Fasting blood glucose: 60–90 mg/dl in pregnancy. These complications
tional approach used for women with • Preprandial blood glucose: 80–95 include an increase in neonatal inten-
GDM, resulted in pregnancy out- mg/dl sive care unit admission; metabolic,
comes comparable to the general pop- • 2-hour postprandial blood glucose: hematological, and respiratory compli-
ulation. Independent of the particular < 115 mg/dl cations; increased rate of accelerated
treatment modality used and the type fetal growth; maternal and birth trau-
of diabetes, memory-based SMBG How do you know when diet has mas; cesarean delivery; and risk for
accurately quantifies the glucose data failed and pharmacological therapy stillbirth. In addition, there is an
that set the foundation for achieving should be initiated? There is no con- increased rate of congenital malforma-
success with intensified therapy. sensus and there are no hard data to tions in the infants of type 1 and type 2
Capillary blood glucose monitoring guide this decision. Authoritative diabetic women. Conversely, prema-
provides the feedback for suitable organizations differ on the threshold ture initiation of pharmacological ther-
adjustments to the timing and dose of of severity that necessitates pharma- apy in women who could have
insulin administration. Patients with cological intervention with glyburide achieved glycemic control with diet
all types of diabetes readily acknowl- or insulin. Some suggest as a thresh- alone leads to unnecessary drug treat-
edge and accept SMBG as an expres- old a fasting plasma glucose of _> 95 ment. When GDM is diagnosed after
sion of patient empowerment because mg/dl,15–17 which will decrease the rate 30–33 weeks’ gestation and there is
it involves them more in efforts to of macrosomic and large-for- limited time available to influence the
improve pregnancy outcome. These gestational-age (LGA) infants, where- desired level of control, pharmacologi-
performance measures are comparable as others suggest >_ 105 mg/dl.14,15 cal intervention is recommended. There
for all ethnic groups; race or ethnicity All authorities agree that drug ther- is greater flexibility when GDM is
as a predictor of enduring or success- apy should be initiated when 2-hour diagnosed early in the third trimester.
ful treatment participation is not a sig- postprandial glucose levels are > _ 120
nificant factor.8–11 mg/dl or 1-hour levels are >_ 140 Oral Antidiabetic Agents
These integrally related compo- mg/dl. Using these standards, 30–50% Different oral hypoglycemic and anti-
nents often make the difference of women with GDM require phar- hyperglycemic agents have diverse
between success and failure in dia- macological therapy when diet alone mechanisms of action to correct or
betes management. SMBG and inten- fails to reduce glucose levels. improve the pathological lesion respon-
sified therapy assist the gravida to In a study evaluating the time sible for glucose intolerance. Therefore,
achieve glycemic control and enhance required to achieve glycemic control these drugs provide an enhanced
perinatal outcome at a lower cost with diet alone during a 4-week peri- approach to the treatment of type 2
than conventional management. New od,18 70% of patients with a fasting diabetes and GDM. Furthermore, com-
pharmacological agents, such as plasma glucose < 95 mg/dl achieved bination therapies will further improve
insulin analogs (mainly lispro) and established levels of glycemic control the effect of these drugs on glucose
oral antidiabetic drugs (mainly gly- within 2 weeks with no substantial metabolism. Insulin therapy, in con-
buride), have profoundly altered the improvement thereafter. Furthermore, trast to therapy with oral agents, is
management of diabetes in pregnancy, the rate of LGA infants was similar designed to mimic the physiological
102
Diabetes Spectrum Volume 20, Number 2, 2007
secretion of endogenous insulin. in the morning. If the targeted level of neously 3 times/daily, increasing each

From Research to Practice / Diabetes

Oral agents are a pragmatic alterna- glycemia is not attained, add 2.5 mg week as necessary) for glycemic con-
tive to insulin therapy in pregnancy to the morning dose. If indicated trol. Subjects were required to measure
because they are easy to administer (after 3–7 days), add 5 mg in the their glucose values seven times daily.
and noninvasive and therefore user- evening. Thereafter, increase the dose Blood glucose profile characteris-
friendly. Since the original study in in 5-mg increments to a maximum of tics before and at the conclusion of
2000,20 many experts and authoritative 20 mg/day. If the patient does not therapy were comparable for the two
organizations in the United States (e.g., achieve targeted levels of glycemic groups. Eighty-two percent of the gly-
the Fifth International Workshop on control, add long-acting insulin to the buride- and 88% of the insulin-treat-
Gestational Diabetes and the North regimen or assign the patient to ed subjects were able to achieve tar-
American Diabetes in Pregnancy Study insulin therapy alone (Figure 1). geted levels of glycemia. However,
Group) have endorsed the use of gly- In our first randomized study in eight glyburide-treated women (4%)
buride (a sulfonylurea) as an alterna- 2000, 20 we enrolled 440 women failed to achieve the desired level of
tive pharmacological therapy to between 11 and 33 weeks’ gestation control early in the third trimester and
insulin during pregnancy.21–29 with singleton pregnancies who had were transferred to insulin therapy.
The introduction of any new drug GDM requiring treatment (failed oral None of the patients developed severe
in pregnancy will raise concerns about glucose tolerance test and fasting plas- symptoms of hypoglycemia. However,
fetal and maternal safety. The ulti- ma glucose level of 95–140 mg/dl). in the insulin-treated group, a signifi-
mate proof that a drug cannot affect Patients were randomly assigned to cantly higher rate of subjects had

Downloaded
the fetus during pregnancy is founded receive either glyburide (n = 201; ini- 1–6% of their SMBG results in the
on its inability to cross the placenta. tial dose 2.5 mg orally, increasing by 5 hypoglycemic range (< 40 mg/dl).

and
The majority of drugs used in preg- mg to a total of 20 mg) or insulin (n = The glyburide- and insulin-treated

from Pregnancy
nancy cross the placenta. Thus, even if 203; initial dose 0.7 units/kg subcuta- groups had similar rates of preeclampsia

http://diabetesjournals.org/spectrum/article-pdf/20/2/101/556946/101.pdf by guest on 18 May 2023

a new drug crosses the placenta, it
remains to be proven that it will cause
a teratogenic effect on the fetus in
utero. If there is no adverse effect on
the fetus, the drug can be used.
Glyburide does not cross the pla-
centa.30–32 Our original observations
have been reconfirmed by several stud-
ies.33–35 Glyburide has been safely used
in pregnancy without adverse effects
on the fetus. In contrast, metformin,
rosiglitazone, and pioglitazone freely
cross the placenta.36–38 We await fur-
ther evidence on safety when fetuses
are exposed to these drugs. In the case
of metformin with patients who have
polycystic ovary syndrome, data from
retrospective studies give us hope for
its safe use. The ongoing Metformin in
Gestational Diabetes study from
Australia and New Zealand is evaluat-
ing in a randomized design the efficacy
of metformin versus insulin use.
Because there is no clinical study to
date reporting on the use of thiazo-
lidinediones in pregnancy, these agents
should not be prescribed.

Attributes of Glyburide
Glyburide is the most common oral
agent used in GDM and is wholeheart-
edly endorsed by authoritative organi-
zations. The drug increases insulin
secretion and diminishes insulin resis-
tance by lowering glucose toxicity. Its
onset of action is ~ 4 hours, and its
duration of action is ~ 10 hours. Thus,
after achieving the targeted therapeutic
level, glyburide covers the basal
requirement as well as postprandial
glucose excursions.
The starting dose is 2.5 mg orally Figure 1. Decision tree for pharmacological treatment of GDM.
103
Diabetes Spectrum Volume 20, Number 2, 2007
 (6%) and cesarean section (23–24%). affect the failure rate to achieve target- have comparable psychological pro-
Neonatal outcomes did not differ sig- ed levels of control.40 Therefore, it is files in different ethnic groups.
nificantly between the two groups. not surprising that studies reported However, it is self-evident that given
Furthermore, the groups had similar similar success rates in achieving the choice of insulin injection versus
rates of LGA infants (12 and 13%, desired levels of glycemic control for tablets, patients will invariably prefer
respectively), macrosomia (7 and 4%), insulin- or glyburide-treated patients taking two tablets daily instead of at
lung complications (8 and 6%), hypo- but with unacceptable perinatal out- least three daily injections.
glycemia (9 and 6%), admission to a come in both groups (i.e., LGA or Sulfonylureas are the only oral
neonatal intensive care unit (6 and macrosomia rates of ~ 30–45%). agent group studied in women with
7%), and fetal anomalies (2 and 2%). Hellmuth et al.41 and Jacobson et GDM in randomized controlled trials.
42
Hypoglycemia is the main side al. had similar success rates to our However, other oral hypoglycemic
effect of glyburide treatment in non- study but significantly higher rates of agents may have an even greater ther-
pregnant women. However, the adverse outcome. In a randomized apeutic effect in controlling abnormal
majority of women with type 2 dia- study,43 we found comparable preg- levels of glycemia. Although the evi-
betes who used this drug in the non- nancy outcomes with either glyburide dence suggests that glyburide is as
pregnant state are older than the aver- or insulin therapy. effective as insulin in maintaining
age gravida. Thus, the severity of the Several retrospective and random- desired glycemic levels and results in
hypoglycemia can be less pronounced ized studies have evaluated the effica- comparable outcomes, it should be
in the younger age-group of women cy of oral agents during pregnancy, noted that achievement of both glu-

Downloaded from http://diabetesjournals.org/spectrum/article-pdf/20/2/101/556946/101.pdf by guest on 18 May 2023

with GDM. In our original study,20 we with an 80–85% reported success rate cose and outcome goals is conditional
found that hypoglycemic episodes in studies using glyburide treatment. on the overall successful management
were more common in insulin-treated Moreover, when insulin and glyburide of women with GDM.
patients than in those taking gly- were compared, similar success rates The use of glyburide should be
buride. Furthermore, in an additional were reported and were comparable based on evidence-based criteria. The
study,39 we used continuous glucose to insulin in glycemic control and two randomized studies and the ~ 20
monitoring and found hypoglycemic pregnancy outcome.42-48 retrospective studies provide a sound
episodes in 63% of the insulin-treated We further analyzed the association base for evaluation. To be considered
women with GDM, but only in 28% between glyburide dose, GDM severi- Level I in the U.S. Preventive Service
in those treated with glyburide. Thus, ty, and selected maternal and neonatal Task Force criteria for quality, evi-
although some laboratory hypo- factors. 49 We found that glyburide dence needs to be the result of a single
glycemic episodes (using SMBG or dose increased with GDM severity. properly designed, randomized, con-
laboratory plasma values) may be The success rate (i.e., achievement of trolled trial. Clinical experts have con-
identified during pharmacological glycemic control) decreased as disease sistently applauded and welcomed the
therapy, the rate of these episodes will severity increased. However, there was results of the glyburide study 21–29 as
be significantly lower in glyburide- no difference between glyburide- and convincing data that glyburide is a safe
versus insulin-treated women. insulin-treated patients at each level of and effective alternative therapy for use
It is customary to evaluate the suc- severity. Thus, achieving glycemic con- in women with GDM. The existing
cess rate of a new pharmacological trol—not the mode of pharmacologi- body of research should encourage us
modality that will potentially provide cal therapy—is the key to improving to rely on evidence-based knowledge
an alternative to the established treat- pregnancy outcome in GDM. When and not emotion-based misinformation
ment (insulin). In general, the success costs of insulin therapy and glyburide when considering this medication for
rate is defined as achieving targeted treatment are compared, the latter is use with diabetic pregnant women.
levels of glycemic control as a primary considerably less expensive.50
outcome. Secondarily, after achieving
established glycemic levels, the success The Road Ahead
rate will also be determined by the In the future, more pharmacological References
ability of the therapy to achieve com- alternatives will become available. 1
Mokdad AH, Serdula MK, Dietz WH, Bowman
parable perinatal outcome (i.e., levels These may include metformin and BA, Marks JS, Koplan JP: The spread of the obe-
of LGA or metabolic complications). other oral antidiabetic drugs, insulin sity epidemic in the United States. JAMA
282:1519–1522, 1999
When comparing different studies on glargine, oral insulin, and a techno-
2
the success rate of achieving glycemic logically improved insulin pump that Silverman BL, Rizzo TA, Cho NH, Metzger BE:
control, it should be noted that differ- can interact directly with blood glu- Long-term effects of the intrauterine environ-
ment. Diabetes 21 (Suppl. 2):B142–B149, 1998
ent criteria for targeted levels of cose levels. Different oral hypo-
3
glycemic control will influence study glycemic agents have different mecha- The DCCT Research Group: The effect of inten-
results. Furthermore, different popula- nisms of action. A detailed discussion sive treatment of diabetes on the development
and progression of long-term complications in
tions (ethnic and geographical groups) of the seven classes of oral agents is insulin-dependent diabetes mellitus. N Engl J
and sample size, as well as quality and beyond the scope of this review but Med 329:977–986, 1993
method of glucose testing (self-moni- can be found elsewhere.51–56 4
American Diabetes Association: Implications of
toring; postprandial, preprandial, or Insulin therapy involves daily injec- the United Kingdom Prospective Diabetes Study.
mean blood glucose) will also influ- tions, which may lead to suboptimal Diabetes Care 23 (Suppl. 2):S27–S31, 2000
ence the definition of success in a given adherence by many women. In many 5
U.K. Prospective Diabetes Study Group:
study. Finally, the physician factor in developing countries, women cannot Intensive blood-glucose control with sulfony-
patient-provider communication and afford insulin therapy. Our studies lureas or insulin compared with conventional
drug administration (doses and algo- and others8–11 have demonstrated that treatment and risk of complications in patients
rithms) was shown to significantly both diet- and insulin-treated women with type 2 diabetes. Lancet 352:837–853, 1998
104
Diabetes Spectrum Volume 20, Number 2, 2007
6 42
Dornhorst A, Frost G: Nutritional management in tional diabetes [Editorial]. N Engl J Med Jacobson GF, Ramos GA, Ching JY, Kirby RS,

From Research to Practice / Diabetes

diabetic pregnancy: a time for reason not dogma. 343:1178–1179, 2000 Ferrara A, Field DR: Comparison of glyburide
In Diabetes and Pregnancy. Hod M, Jovanovic L, 24
and insulin for the management of gestational
DiRenzo GC, deLevia A, Langer O, Eds. London, Cefalo RC: A comparison of glyburide and diabetes in a large managed care organization.
Taylor & Francis, 2003, p. 340–358 insulin in women with gestational diabetes melli- Am J Obstet Gynecol 193:118–124, 2005
tus. Obstet Gynecol Surv 56:126–127, 2001
7 43
Langer O, Rodriguez DA, Xenakis EM, 25
Fines V, Moore T, Castle S: A comparison of
Mcfarland MB, Berkus MD, Arrendondo F: Koren G: The use of glyburide in gestational glyburide and insulin treatment in gestational dia-
Intensified versus conventional management of diabetes: an ideal example of “bench to bed- betes mellitus on infant birth weight and adiposity
gestational diabetes. Am J Obstet Gynecol side.” Pediatr Res 49:734, 2001 [Abstract]. Am J Obstet Gynecol 189: S108, 2003
170:1036–1047, 1994 26
Ryan EA: Glyburide was as safe and effective as 44
Conway DL, Gonzales O, Skiver D: Use of gly-
8
Langer N: Culturally competent professionals in insulin in gestational diabetes. EBM 6:79, 2001 buride for the treatment of gestational diabetes:
therapeutic alliances enhance patient compliance. 27
Saade G: Gestational diabetes mellitus: a pill or the San Antonio experience. J Matern Fetal
J Health Care Poor Underserved 10:19–26, 1999 a shot? Obstet Gynecol 105:456–457, 2005 Neonatal Med 15:51–55, 2004
9 45
Langer N, Langer O: Gestational diabetes vs. 28
Durnwald C, Landon MB: Glyburide: the new Kremer CJ, Duff P: Glyburide for the treatment
pre-existing diabetes: comparison of pregnancy alternative for treating gestational diabetes? Am J of gestational diabetes. Am J Obstet Gynecol
mood profiles. Diabetes Educ 26:667–672, 2000 Obstet Gynecol 193:1–2, 2005 190:1438–1439, 2004
10 46
Langer O, Langer N: Is cultural diversity a fac- 29
Jovanovic L: The use of oral agents during Chmait R, Dinise T, Moore T: Prospective
tor in self-monitoring blood glucose in gestation- pregnancy to treat gestational diabetes. Curr observational study to establish predictors of
al diabetes? J Assoc Minor Phys 6:73–77, 1995 Diabetes Rep 1:69–70, 2001 glyburide success in women with gestational
diabetes mellitus. J Perinatol 24:617–622, 2004

Downloaded
11
Langer N, Langer O: Emotional adjustment to 30
Elliot BD, Langer O, Schenker S, Johnson RF: 47
diagnosis and intensified treatment of gestational Insignificant transfer of glyburide occurs across Velazquez MD, Bolnick J, Cloakey D: The use of
diabetes. Obstet Gynecol 84:329–334, 1994 the human placenta. Am J Obstet Gynecol glyburide in the management of gestational dia-

and
12 165:807–812, 1991 betes. Obstet Gynecol 101 (Suppl.):88S, 2003
Parretti E, Mecacci F, Papini M, Cioni R,

from Pregnancy
48
Carignani L, Mignosa M, LaTorre P, Mello G: 31
Elliot B, Schenker S, Langer O, Johnson R, Pendsey SP, Sharma RR, Chalkhore SS:

http://diabetesjournals.org/spectrum/article-pdf/20/2/101/556946/101.pdf by guest on 18 May 2023

Third-trimester maternal glucose levels from Prihoda T: Comparative placental transport of Repaglinide: a feasible alternative to insulin
diurnal profiles in non-diabetic pregnancies: cor- oral hypoglycemic agents: a model of human pla- in management of gestational diabetes mellitus
relation with sonographic parameters of fetal cental drug transfer. Am J Obstet Gynecol [Abstract]. Diabetes Res Clin Pract 56
growth. Diabetes Care 24:1319–1323, 2001 171:653–660, 1994 (Suppl. 1):S46, 2002
13 49
Yogev Y, Ben-Haroush A, Chen R, Rosenn B, 32
Elliot B, Langer O, Schussling F: A model of Langer O, Yogev Y, Xenakis EM, Rosenn B:
Hod M, Langer O: Diurnal glycemic profile in human placental drug transfer. Am J Obstet Insulin and glyburide therapy: dosage, severity
obese and normal weight non-diabetic pregnant Gynecol 176:527–530, 1997 level of gestational diabetes and pregnancy out-
women. Am J Obstet Gynecol 191:1655–1660, come. Am J Obstet Gynecol 192:134–139, 2005
33
2004 Koren G: Glyburide and fetal safety: transpla- 50
cental pharmacokinetic considerations. Reprod Goetzel L, Wilkins I: Glyburide compared to
14
American Diabetes Association: Gestational Toxicol 15:227–229, 2001 insulin for the treatment of gestational diabetes mel-
diabetes mellitus [Position Statement]. Diabetes litus: a cost analysis. J Perinatol 22:403–406, 2002
34
Care 27 (Suppl 1):S88–S90, 2004 Nanovskaya TN, Nekhayeva I, Hankins G, 51
Ahmed M: Effect of human serum albumin on Buxton ILO: Pharmacokinetics and pharmaco-
15
Metzger BE, Coustan DR, the Organizing transplacental transfer of glyburide. Biochem dynamics. In Goodman and Gillman’s The
Committee: Summary and recommendations of Pharmacol 72:632–639, 2006 Pharmacologic Basis of Therapeutics. 11th ed.
the Fourth International Workshop-Conference Brunton LL, Lazo JS, Parker KL, Eds. New
35
on Gestational Diabetes. Diabetes Care 21 Kraemer J, Klein J, Lubetsky A, Koren G: York, McGraw Hill, 2002
(Suppl. 2): B161–B167, 1998 Perfusion studies of glyburide transfer across the 52
human placenta: implications for fetal safety. Langer O: When diet fails: Insulin and oral
16
Langer O: Maternal glycemic criteria for insulin Am J Obstet Gynecol 195:270–274, 2006 hypoglycemic agents as alternatives for the man-
therapy in gestational diabetes mellitus. Diabetes agement of gestational diabetes. J Maternal-Fetal
36
Care 21 (Suppl. 2):B91–B98, 1998 Nanovskaya TN, Nekhayeva IA, Patrikeeva SL, Med 11:1–8, 2002
17
Hankins GD, Ahmed MS: Transfer of metformin 53
Langer O, Berkus MD, Brustman L, across the dually perfused human placental lob- Langer O: Insulin and other treatment alterna-
Anyaegbunam A, Mazze R: Rationale for insulin ule. Am J Obstet Gynecol 195:1081–1085, 2006 tives in gestational diabetes mellitus. Prenat
management in gestational diabetes mellitus. Neonat Med 3:524–549, 1998
37
Diabetes 40 (Suppl. 2):186–190, 1991 Kovo M, Haroutiunian S, Feldman N: 54
Determination of metformin transfer across the Langer O: Oral hypoglycemic agents and the
18
McFarland MB, Langer O, Conway DL, Berkus human placenta using dually perfused ex-vivo pregnant diabetic: from bench to bedside. Sem
MD: Dietary therapy for gestational diabetes: how placental cotyledon model [Abstract]. Am J Perinatol 26:196–205, 2002
long is long enough? Obstet Gynecol 93:978–982, Obstet Gynecol 193:S85, 2005 55
1999 Langer O: Management of gestational diabetes:
38
Ruano R, Aubry MC, Barthe B, Mitanchez D, pharmacologic treatment options and glycemic
19
Langer O, Yogev Y, Xenakis E, Brustman L: Dumez Y, Benachi A: Quantitative analysis of control. Endocrinol Metab Clin North Am
Overweight and obese in gestational diabetes: the fetal pulmonary vasculature by 3-dimensional 35:53–78, 2006
impact on pregnancy outcome. Am J Obstet power Doppler ultrasonography in isolated con- 56
Gynecol 192:1768–1776, 2005 Langer O (Ed.): The Diabetes in Pregnancy
genital diaphragmatic hernia. Am J Obstet Dilemma: Leading Changes With Simple
20
Langer O, Conway DL, Berkus MD, Xenakis Gynecol 195:1720–1728, 2006 Solutions. New York, University Press of
EM, Gonzalez O: A comparison of glyburide and 39
Yogev Y, Ben-Haroush A, Chen R, Rosenn B, America, 2006
insulin in women with gestational diabetes melli- Hod M, Langer O: Undiagnosed asymptomatic
tus. N Engl J Med 343:1134–1138, 2000 hypoglycemia: diet, insulin, and glyburide for
21
Reece EA, Homko C, Miodovnik M, Langer O: gestational diabetic pregnancy. Obstet Gynecol
A consensus report of the Diabetes in Pregnancy 104:88–93, 2004 Oded Langer, MD, PhD, is a profes-
Study Group of North America Conference. J 40
Langer O, Most O, Monga S: Glyburide: predic- sor and chairman of the Department
Maternal-Fetal Neonatal Med 12:362–364, 2002 tors of treatment failure in gestational diabetes of Obstetrics and Gynecology at St.
22
Gabbe SG, Graves CR: Management of dia- [Abstract]. Am J Obstet Gynecol 195:S136, 2006 Luke’s-Roosevelt Hospital Center,
betes mellitus complicating pregnancy. Obstet 41
Hellmuth E, Damm P, Molsted-Pedersen L: University Hospital of Columbia
Gynecol 102:857–868, 2003 Oral hypoglycaemic agents in 118 diabetic preg- University in New York.
23
Greene MF: Oral hypoglycemic drugs for gesta- nancies. Diabet Med 17:507–511, 200l
105
Diabetes Spectrum Volume 20, Number 2, 2007