This study compared the use of glibenclamide/metformin combination versus insulin for managing diabetes during pregnancy. 43 pregnant women with gestational or type 2 diabetes were randomly assigned to receive either the oral hypoglycemic combination or insulin therapy. Both groups achieved similar levels of glycemic control and resulted in equivalent maternal and neonatal outcomes, including birth weight, rates of cesarean section, and neonatal complications. The study concluded that treatment of diabetes in pregnancy with either the oral hypoglycemic combination or insulin alone was found to be equally effective and safe for mothers and newborns. However, larger studies were recommended to confirm these findings.

1. 1
A COMPARISON OF
GLIBENCLAMIDE/METFORMIN
COMBINATION AND INSULIN
FOR THE MANAGEMENT OF
DIABETES MELLITUS DURING
SINGLETON PREGNANCY.
Moustafa A. Abdel-lah*, Adel A. Alsayed**,
Magdy A. Mohamad***
Prof. OB./GYN*, Prof. Int. Med.*,
Ass. Lecturer OB./GYN***.

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INTRODUCTION

3. 3
INTRODUCTION
 Very tight glycemic control is the main
requirement for improvement of pregnancy
outcome in diabetic women (Reece et al, 2002).
 Till now, Insulin is the only approved
pharmacological therapy to control
hyperglycemia during pregnancy (Reece et al, 2002).
 To achieve tight glycemic control required during
pregnancy by the use of insulin, the pregnant lady
has to receive multiple insulin injections or
insulin pump (Hollander et al, 2004 ).

4. 4
 In developing countries; the lack of both
affordability, education and compliance are
the main barriers to achieve this level of
tight glycemic control by insulin use.
 The use of oral therapy to control glycemia
during pregnancy; if possible; would be an
excellent alternative to overcome these
barriers.
INTRODUCTION

5. 5
 Problems with the use of oral treatment for
DM with pregnancy result from the ability
of many antidiabetic oral agents to cross the
placental barrier and cause fetal
hyperinsulinemia (Nanovskaya et al, 2006 ).
 The fear of the possible teratogenic effects
of oral antidiabetic drugs is another obstacle
to their use during pregnancy (Wyatt et al,
2005).
INTRODUCTION

6. 6
 In 1991 Elliott et al., demonstrated experimentally
that minimal glyburide was detectable crossing
the placenta in an in vitro placental perfusion
model.
 In 2000 Langer et al., published the results of
their controlled randomized clinical trial where
glyburide was compared to insulin in treatment of
diabetes mellitus. Re-analysis of the results of this
study revealed that the use of large dose of
Glyburide >10 mgm was accompanied with a
trend to increased neonatal size.
INTRODUCTION

7. 7
 Metformin on the other hand, in spite
of its significant ability to cross the
placenta, does not cause
hyperinsulinemia and was reported to
be effective and safe in several clinical
studies (Kann et al, 2006 ).
 However, most of the published
studies are small and retrospective.
INTRODUCTION

8. 8
AIM OF THE STUDY
To compare :
 Glibenclamide/Metformin combination
with
 insulin
in treatment of diabetes mellitus during
pregnancy.

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PATIENTS AND
METHODS

10. 10
Study setting
This study conducted on women attending
outpatient clinic of Ob/Gyn. department, Sohag
university hospital.
After approval from the local ethical committee
PATIENTS AND METHODS
Study design
Randomized controlled clinical trial.

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Inclusion criteria
Gestational diabetes (GDM):
the diagnosis was according to WHO
recommendation by using oral glucose
tolerance test (OGTT) that consists of a
glucose load of 75 g and a blood sample 2 hrs.
later . The diagnosis of GDM was established
if plasma glucose level more than 140 mg/dL.
type 2 diabetes:
the beginning of the recruitment was before
pregnancy.
PATIENTS AND METHODS

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Exclusion criteria
 Preexisting type 1 DM or diabetic ketoacidosis.
 Multiple pregnancy.
 Hypersensitivity to the used medications.
 Underlying vascular disease or medical condition
known to affect fetal growth or drug clearance.
 Fetal anomalies identified on ultrasound prior to
initiation of therapy.
 Diagnosis of GDM made after 32 weeks gestation
 Patient refusal.
PATIENTS AND METHODS

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 all women who agree to participate in the
study were randomized into two equal
groups ( in both groups we classified
patients into gestational and planned
pregnancy subgroups).
 The 1st group received
Glibenclamide/Metformin combination, the
beginning dose was 2.5 mg Glibenclamide
& 500 mg Metformin orally with the
morning meal.
PATIENTS AND METHODS

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 The dosage was increased gradually
according to blood glucose level to a
maximum daily dose of 10 mg
Glibenclamide & 2 gm Metformin .
 If maximum daily dose of this combination
did not result in reaching the target values
for two weeks, the patient was shifted to
insulin.
PATIENTS AND METHODS

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 The second group received standard insulin
therapy.
 Dosing was based upon subcutaneous two
shots combined dose with intermediate
acting and short acting insulin given prior to
breakfast and dinner.
 The starting dose was 0.7 IU/Kg body
weight at admission and increased weekly
as necessary.
PATIENTS AND METHODS

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 All women were provided with standard
nutritional instructions for 3 daily meals.
Adherence to the dietary regimen was
evaluated and reinforced at weekly visits to
the clinic.
 The diets were designed to provide 25
cal/kg body weight for the obese women
and 35 cal/kg for the non-obese women,
with 40 to 45 percent of the calories from
carbohydrates.
PATIENTS AND METHODS

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Depending on the 4 point profile determination, the
goal of treatment was the achievement of:
 a mean blood glucose concentration = 90 - 105
mg/dl,
 a fasting blood glucose concentration = 60 - 90
mg/dl,
 a pre-prandial blood glucose concentration = 80 -
95 mg/dl,
 a postprandial blood glucose concentration > 120
mg/dl
 Hg-A1c levels < 6.0%.
PATIENTS AND METHODS

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After establishment of optimum dose in
both groups, the patients were followed up
for:
 Weekly fasting and 2-hrs blood glucose level
 Development of polyhydramnios.
 Development of PET.
 Assessment of fetal well-being.
PATIENTS AND METHODS

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Upon admission for delivery both groups were compared
as regard to:
Gestational age at delivery
Mode of delivery
Serum Hg-A1C.
Birth weight.
Fetal umbilical cord blood glucose level.
Neonatal hyperbillirubinemia.
Admission to Neonatal intensive care unit ( NICU ) & duration of
the admission.
Neonatal outcome.
PATIENTS AND METHODS

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RESULTS

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oral hypoglycemic–
treated group
(N=43)
insulin-treated group
(N=43)
Pt. age 29.2 ± 1.2 28.9 ± 1.9*
Parity:-Pgda
-Mgda
-Gmgda
7
30
6
6*
30*
7*
BMI 31.9 ± 1.1 32.2 ± 1.4*
DM:- GDM
- Type 2 DM
34
9
33*
10*
Clinical characters of both groups (*=NS)

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oral hypoglycemic–
treated group
(N=43)
insulin-treated group
(N=43)
Mean blood
glucose levels
125.9 ± 3.2 124.7 ± 3.9*
AF I 12.2 ± 1.2 12.5 ± 1.7*
Gestational age at
delivery
35.9 ± 3.1 35.2 ± 3.4*
Mode of delivery :
- Vaginal
- CS
24/43 (55.81%)
19/43 (44.19%)
23/43 (53.49%)*
20/43 (46.51%)*
Maternal outcome of both groups (*=NS)

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oral hypoglycemic–
treated group
(N=43)
insulin-treated group
(N=43)
Perinatal mortality 3/43 (6.9%) 2/43 (4.7%)*
Congenital
anomalies
2/43 (4.7%) 4/43 (9.5%)*
Fetal birth weight 3670.9±33.1 3680.2±39.4*
Neonatal
Hypoglycemia
5/43 (11.6%) 6/43 (13.9%)*
admission to
NICU
22/43 (51.2%) 24/43 (55.8%)*
Duration of
admission
12.9±5.3 13.1±5.9*
Fetal outcome of both groups (*=NS)

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CONCLUSIONS

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The treatment of gestational diabetes & type
2 diabetes during pregnancy with
 glibenclamide/metformin combination
OR
 insulin
was found to be equivalent for both
 women & newborns
CONCLUSIONS

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RECOMMENDATIONS

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However more extension of the study is
recommended to reach sound results.
RECOMMENDATIONS

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Sohag Medical School Initiative to
participate in the Global Solution
of DM.

29. Sohag Medical
School

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Sohag Medical School Initiative to participate in the
Global Solution of DM.
 The 7th Conference, yet no official benefits
 Politics of (Barriers against) activities
through 6 decades.
 25th of January = Destruction of Barriers.
 Proud of being belonging to :
- Egypt.
- A medical school including this High Dam.

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Sohag Medical School Initiative to participate in the
Global Solution of DM.
 Referring to his “Memorial Lecture”:
Facing a global problem = global Solution.
 Under the Umbrella of “Initiatives to solve
the problem”: today we launch
Sohag Medical School Initiative to participate
in the Global Solution of DM.

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Sohag Medical School Initiative to participate in the
Global Solution of DM.
 Development of postgraduate educational
program to graduate diabetologist.
 Invite everybody to joint our initiative:
Answer the Questionnaire, which is the 1st
step in the:
Protocol of cooperation between UEDA &
Sohag Medical School.

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THANK
YOU