ORIGINAL ARTICLE

Efficacy of Metformin Versus Insulin in the Management

of Pregnancy with Diabetes
Seema Waheed, Farhat Perveen Malik and Syeda Batool Mazhar

ABSTRACT

Objective: To compare the efficacy of metformin with insulin in the management of pregnancy with diabetes.
Study Design: Randomized clinical trial.
Place and Duration of Study: Department of Obstetrics and Gynaecology, Maternal and Child Health Centre (MCH),
Pakistan Institute of Medical Sciences, Islamabad, from May 2010 to January 2011.
Methodology: A total of 68 pregnant patients with diabetes were included in this study. Patients were randomly divided
in to two groups of each 34 patients based on table of random numbers. One was labelled as group-A and other was
labelled as group-B. Group-A received insulin and group-B received metformin for the management of diabetes.
Results: The mean age was 29.82 4.58 and 29.35 4.97 years in groups-A and B respectively. Fasting blood sugar
level after 1 month was controlled in 22 (64.7%) patients in group-A and in 27 (79.4%) in group-B (p > 0.05). Fasting blood
sugar level at term, remained controlled in 30 (88.2%) patients in group-A and 27 (79.4%) in group-B (p > 0.05).
Comparison of random blood sugar levels within normal limits after 1 month in 25 (73.5%) in group-A and in 24 (70.6%)
in group-B. At term, random blood sugar level was controlled in 28 (82.4%) and 27 (79.4%) patients in group-A and B,
respectively. Comparison of post-treatment HBA1C level depicts that diabetes controlled in 27 (79.4%) patients in group-A
while in 28 (82.3%) patients of group-B. The efficacy of metformin and insulin in controlling diabetes was equal in two
groups.
Conclusion: There was no marked difference in efficacy of metformin and insulin in controlling diabetes in pregnant
patients in two groups.
Key Words: Gestational diabetes mellitus. Metformin. Insulin. Pre-gestational diabetes type-2.

INTRODUCTION

Diabetes is a group of metabolic disorders characterized

by hyperglycemia resulting from defects in insulin
secretions, action or both.1 Gestational diabetes mellitus
is defined as glucose intolerance of various degrees
that is first detected during pregnancy.2 Diabetes
mellitus accounts for over 2-5% of pregnancies3 and is
associated with increased risk of complications of
pregnancy and prenatal mortality.4 Detection and
treatment of gestational diabetes mellitus reduces and
eliminates the risks for the fetus. It also improves the
woman's health-related quality of life.5
Traditionally, treatment includes diet control and insulin
use if glycemic targets are not achieved but insulin
therapy requires patient education and is associated
with hypoglycemia and weight gain. The use of safe and
effective oral agents may offer advantages over insulin.6
Different reports suggest that metformin is effective in
controlling gestational diabetes and is not associated
Department of Obstetrics and Gynaecology, Maternal and
Child Health Centre (MCH), Pakistan Institute of Medical
Sciences, Islamabad.

Correspondence: Dr. Seema Waheed, c/o Dr. Dildar Hussain

Surgery Department, Level 5 West, Dubai Hospital, P.O. Box.
7272, Dubai, United Arab Emirates.
E-mail: w_seema@hotmail.com
Received: August 13, 2012; Accepted: June 13, 2013.
866

with a higher risk of maternal or neonatal complications

compared with insulin.6 Metformin improves insulin
sensitivity, probably by activating AMP kinase, and is not
associated with weight gain or hypoglycemia.7 However,
local trails and data on the same is scarce.

The objective of the current study was to compare the

efficacy of metformin with insulin in the management of
pregnancy with diabetes.

METHODOLOGY

It was a randomized clinical trial, carried out at the

Department of Obstetrics and Gynaecology, Maternal
and Child Health Centre (MCH), Pakistan Institute of
Medical Sciences, Islamabad, from May 2010 to
January 2011.

The sample size was assessed by using WHO SS

calculation, with level of significance 5% and power of
test 80%. A non-probability consecutive sampling
technique was used. A total of 68 patients were included
in this study, 34 patients in each group. All pregnant
women with diabetes, having fasting blood sugar (FBS)
> 100 mg and random blood sugar (RBS) > 140 mg,
beyond 14 weeks of gestation were included in the
study. Patients with renal and hepatic impairment, and
patients having type-1 diabetes were excluded.
The data was collected prospectively after taking
permission from the hospital ethical committee and

Journal of the College of Physicians and Surgeons Pakistan 2013, Vol. 23 (12): 866-869

Efficacy of metformin versus insulin in the management of pregnancy with diabetes

informed consent from the patients. History was taken,

and patients were examined and demographic data was
collected. Baseline liver function test and renal function
tests were done to rule out hepatic and renal
impairment.

Patients were randomly divided in to two groups of each

34 patients based on table of random numbers. Group-A
received insulin and group-B received metformin for the
management of diabetes.
A 6-hourly glycemic profile i.e. fasting (FG), 2 hours
post-breakfast (PB), pre-luch, 2 hours post-lunch (PL),
pre-dinner and 2 hours post-dinner (PD) glucose was
done prior to therapy and after starting the therapy till
desired blood sugar levels are achieved. HBA1C was
also recorded. The starting dose of metformin was 500
mg once daily and was increased to achieve glycemic
control, upto 1500 mg if needed. Glycemic profile was
repeated after one month and at term to check the
control of blood sugar level.
Efficacy was measured in terms of well-controlled
glycemic levels. It was considered efficacious to have
term fasting blood sugar between 63 100 mg/dl, RBS
below 140 mg/dl and HBAIC below 6.1%.

The data was analyzed on Statistical Package for Social

Sciences (SPSS) version 11. Mean standard deviation
was calculated for all quantitative variables. Frequency
and percentage was calculated for blood sugar level
and HBA1C. Chi-square test was used to compare
proportions efficacy of drugs between the two study
groups. A p-value of 0.05 was taken as significant.

RESULTS

A total of 68 patients were included in this study. Most of

the women in both groups were between 26 30 years.
In group-A, 13 women (38.2%) while in group-B, 16
women (47.1%) were between 31 35 years with mean
age of 29.82 4.58 and 29.35 4.97 years in group-A and
B, respectively.
Fasting blood sugar level after 1 month was controlled in
22 (64.7%) patients in group-A and 27 patients (79.4%) in
group-B (p > 0.05). Fasting blood sugar level at term was
at controlled level in 30 (88.2%) patients in group-A and
27 (79.4%) in group-B (p > 0.05, Table I).

Comparison of random blood sugar levels after 1 month

showed controlled level in 25 (73.5%) in group-A and in 24
(70.6%) in group-B. At term, random blood sugar level
was controlled in 28 (82.4%) and 27 (79.4%) patients in
group-A and B, respectively (Table II).
Comparison of post-treatment HBA1C level showed
normal levels in 27 (79.4%) patients in group-A while in 28
(82.3%) patients of group-B (Table III).

Table IV shows that there was no statistically significant

difference in efficacy of metformin and insulin in
controlling diabetes in pregnant patients between two
groups (p = 1.000).

Table I: Comparison of fasting blood sugar levels after 1 month and at

term.
Sugar level

Group-A
(Insulin)

Fasting blood sugar

level after 1 month

Group-B

p-value Chi-square

(Metformin)

Number Percent Number Percent

Controlled

22

Not Controlled

64.7

12

Total

Fasting blood sugar

level at term
Controlled

Not Controlled

79.4

34

100.0

07

34

100.0

30

88.2

27

79.4

34

100.0

34

100.0

04

Total

27

35.3

11.8

20.6

07

20.6

0.176

1.83

0.323

0.98

Table II: Comparison of random blood sugar levels after 1 month and at
term.
Sugar level

Group-A
(Insulin)

Random blood sugar

level after 1 month

Group-B

p-value Chi-square

(Metformin)

Number Percent Number Percent

Controlled

25

Not Controlled

73.5

09

Total

34

Random blood sugar

level at term
Controlled

06

Total

34

100.0

82.4

27

79.4

100.0

34

100.0

17.6

34

70.6

10

100.0

28

Not Controlled

24

26.5

29.4

07

20.6

Table III: Comparison of post-treatment HBA1C level.

HBA1C

Group-A
(Insulin)

Group-B

(Metformin)

Controlled

27

Not Controlled

79.4

07

Total

20.6

34

100.0

28

Efficacy

Total

0.757

0.10

p-value Chi-square

82.3

06

Group-A
(Insulin)

0.757

17.7

34

Group-B

(Metformin)

Number

Percent

Number

Percent

07

20.6

06

20.6

27

34

79.4

100.0

0.10

100.0

Table IV: Distribution of cases by efficacy.

No

0.07

Number Percent Number Percent

HBA1C level
(post- treatment)

Yes

0.786

27

34

DISCUSSION

79.4

p-value

1.000

100.0

Pregnancy increases requirements for insulin secretion

while increasing insulin resistance, increasing demands
on pancreatic -cells, promoting development of
gestational diabetes, particularly in women with preexisting insulin resistance. If there is impaired pancreatic
-cell compensation for insulin resistance during
pregnancy, then gestational diabetes develops. This has
maternal and neonatal implications for pregnancy

Journal of the College of Physicians and Surgeons Pakistan 2013, Vol. 23 (12): 866-869

867

Seema Waheed, Farhat Perveen Malik and Syeda Batool Mazhar

outcomes and for the later development of type-2

diabetes mellitus. In women with gestational diabetes,
14 60% will develop type-2 diabetes later in life, and
30 50% will have gestational diabetes with consecutive
pregnancies.

The incidence of diabetes in pregnancy is increasing. As

diabetes is associated with adverse pregnancy outcomes, it is important that it is recognized and appropriately managed. This study examined the pharmacological options for the management of diabetes in
pregnancy, as well as the evidence for blood glucose
monitoring, dietary and exercise therapy. The medical
management of diabetes in pregnancy is still evolving,
and recent randomized controlled trials have added
considerably to our knowledge in this area. As insulin
therapy is effective and safe, it is considered the gold
standard of pharmacotherapy for diabetes, against
which other treatments have been compared.8
When treatment targets are not achieved by dietary
means, then insulin is required. A basal-bolus regimen of
insulin gives the most effective glucose control, and
produces better fetal outcomes than a twice daily
regimen.9 Prandial fast-acting insulin is administered to
control post-prandial hyperglycemia, and bed time basal
insulin is given if there is fasting hyperglycemia. In some
cases, an additional morning injection of basal insulin
may further improve glycemic control. As the level of
insulin resistance varies from person to person, it is
common practice to commence the woman on small
doses of insulin, and then to increase the doses at
frequent intervals until target glucose levels are
attained.9 For many years, fast-acting (regular) insulin,
and intermediate-acting (isophane) insulin have been
the preferred insulin for the treatment of diabetes in
pregnancy. Human insulin does not normally cross the
placenta, though antibody bound animal insulin has
been reported to do so.10

It has been shown that it is maternal glucose control

rather than maternal anti-insulin antibody levels, which
influence birthweight.11,12 Human insulin is considered
safe in pregnancy as years of experience has not
suggested an increase in fetal complications as a
consequence of its use.

Theoretically, metformin is an alternative to insulin in

the treatment of hyperglycemia during pregnancy. It
decreases hepatic gluconeogenesis and improves
peripheral glucose uptake. It does not induce hypoglycemia and it is not associated with increased weight
gain. Evidence supporting the use of metformin in
pregnancy is available from studies in patients with
polycystic ovary syndrome. Metformin is being used
increasingly in pregnancy and recent MiG trial
concluded that children exposed to metformin had larger
measures of subcutaneous fat, but overall body fat was
same as in children whose mothers were treated with
868

insulin alone. Further follow-up is required to see

whether these findings will persist in later life or these
children will develop less visceral fat, and be more
sensitive to insulin.13 In the current study, comparison of
insulin and metformin showed that metformin and insulin
is equally effective in the management of pregnancy with
diabetes. Two studies have also concluded that
metformin is as effective as insulin for glycemic control
in gestational diabetes.14,15

However, one study, a randomised controlled trial, was

underpowered to address the effectiveness and safety
of metformin in gestational diabetes.16 In another study,
a retrospective case control one, subjects treated with
insulin had a greater degree of initial glucose
intolerance, so the comparison was of limited validity.17
Metformin reduces insulin resistance and hepatic
gluconeogenesis, which theoretically would be beneficial for the preservation of -cell function. In subjects
with type-2 diabetes, it has been demonstrated that
metformin is superior to glyburide in this regard.18,19

As there is transplacental passage of metformin,20 its

effect on fetal insulin resistance might even provide
further benefit in light of data of insulin resistance and
insulin secretory defects in offspring of diabetic
pregnancies.21 A recent study by Gandhi et al. showed,
metformin is safe and effective in the treatment of
gestational diabetes and it reduces the requirement for
supplementary insulin.22

CONCLUSION

Since there was no significant difference in efficacy of

metformin and insulin in controlling diabetes in pregnant
patients in two groups, therefore, efficacy of metformin
and insulin was found to be comparable in the
management of pregnancy with diabetes in this study.
Disclosure: This is a dissertation-based article
approved by Research Evaluation Unit (REU) of CPSP
as part of the requirement for fellowship examination.

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