ueda2012 comparison of glibenclamide and mtaformin_d.ma_mostafa abdel khalek.

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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