ueda2012 comparison of glibenclamide and mtaformin_d.ma_mostafa abdel khalek.
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Transcript of ueda2012 comparison of glibenclamide and mtaformin_d.ma_mostafa abdel khalek.
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
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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 ).
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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
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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
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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
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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
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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
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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
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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.
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