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

INTRODUCTIONDiabetes is a group of metabolic disorders characterizedby hyperglycemia resulting from defects in insulinsecretions, action or both.1 Gestational diabetes mellitusis defined as glucose intolerance of various degreesthat is first detected during pregnancy.2 Diabetesmellitus accounts for over 2-5% of pregnancies3 and isassociated with increased risk of complications ofpregnancy and prenatal mortality.4 Detection andtreatment of gestational diabetes mellitus reduces andeliminates the risks for the fetus. It also improves thewoman's health-related quality of life.5

Traditionally, treatment includes diet control and insulinuse if glycemic targets are not achieved but insulintherapy requires patient education and is associatedwith hypoglycemia and weight gain. The use of safe andeffective oral agents may offer advantages over insulin.6Different reports suggest that metformin is effective incontrolling gestational diabetes and is not associated

with a higher risk of maternal or neonatal complicationscompared with insulin.6 Metformin improves insulinsensitivity, probably by activating AMP kinase, and is notassociated 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 theefficacy of metformin with insulin in the management ofpregnancy with diabetes.

METHODOLOGYIt was a randomized clinical trial, carried out at theDepartment of Obstetrics and Gynaecology, Maternaland Child Health Centre (MCH), Pakistan Institute ofMedical Sciences, Islamabad, from May 2010 toJanuary 2011.

The sample size was assessed by using WHO SScalculation, with level of significance 5% and power oftest 80%. A non-probability consecutive samplingtechnique was used. A total of 68 patients were includedin this study, 34 patients in each group. All pregnantwomen with diabetes, having fasting blood sugar (FBS)> 100 mg and random blood sugar (RBS) > 140 mg,beyond 14 weeks of gestation were included in thestudy. Patients with renal and hepatic impairment, andpatients having type-1 diabetes were excluded.

The data was collected prospectively after takingpermission from the hospital ethical committee and

ORIGINAL ARTICLE

Efficacy of Metformin Versus Insulin in the Management of Pregnancy with Diabetes

Seema Waheed, Farhat Perveen Malik and Syeda Batool Mazhar

ABSTRACTObjective: 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 dividedin to two groups of each 34 patients based on table of random numbers. One was labelled as group-A and other waslabelled 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 sugarlevel 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 bloodsugar 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-Awhile in 28 (82.3%) patients of group-B. The efficacy of metformin and insulin in controlling diabetes was equal in twogroups.Conclusion: There was no marked difference in efficacy of metformin and insulin in controlling diabetes in pregnantpatients in two groups.

Key Words: Gestational diabetes mellitus. Metformin. Insulin. Pre-gestational diabetes type-2.

Department of Obstetrics and Gynaecology, Maternal andChild Health Centre (MCH), Pakistan Institute of MedicalSciences, Islamabad.

Correspondence: Dr. Seema Waheed, c/o Dr. Dildar HussainSurgery Department, Level 5 West, Dubai Hospital, P.O. Box.7272, Dubai, United Arab Emirates.E-mail: [email protected]

Received: August 13, 2012; Accepted: June 13, 2013.

informed consent from the patients. History was taken,and patients were examined and demographic data wascollected. Baseline liver function test and renal functiontests were done to rule out hepatic and renalimpairment.

Patients were randomly divided in to two groups of each34 patients based on table of random numbers. Group-Areceived insulin and group-B received metformin for themanagement of diabetes.

A 6-hourly glycemic profile i.e. fasting (FG), 2 hourspost-breakfast (PB), pre-luch, 2 hours post-lunch (PL),pre-dinner and 2 hours post-dinner (PD) glucose wasdone prior to therapy and after starting the therapy tilldesired blood sugar levels are achieved. HBA1C wasalso recorded. The starting dose of metformin was 500mg once daily and was increased to achieve glycemiccontrol, upto 1500 mg if needed. Glycemic profile wasrepeated after one month and at term to check thecontrol of blood sugar level.

Efficacy was measured in terms of well-controlledglycemic levels. It was considered efficacious to haveterm fasting blood sugar between 63 – 100 mg/dl, RBSbelow 140 mg/dl and HBAIC below 6.1%.

The data was analyzed on Statistical Package for SocialSciences (SPSS) version 11. Mean ± standard deviationwas calculated for all quantitative variables. Frequencyand percentage was calculated for blood sugar leveland HBA1C. Chi-square test was used to compareproportions efficacy of drugs between the two studygroups. A p-value of ≤ 0.05 was taken as significant.

RESULTSA total of 68 patients were included in this study. Most ofthe women in both groups were between 26 – 30 years.In group-A, 13 women (38.2%) while in group-B, 16women (47.1%) were between 31 – 35 years with meanage of 29.82 ± 4.58 and 29.35 ± 4.97 years in group-A andB, respectively.

Fasting blood sugar level after 1 month was controlled in22 (64.7%) patients in group-A and 27 patients (79.4%) ingroup-B (p > 0.05). Fasting blood sugar level at term wasat controlled level in 30 (88.2%) patients in group-A and27 (79.4%) in group-B (p > 0.05, Table I).

Comparison of random blood sugar levels after 1 monthshowed controlled level in 25 (73.5%) in group-A and in 24(70.6%) in group-B. At term, random blood sugar levelwas controlled in 28 (82.4%) and 27 (79.4%) patients ingroup-A and B, respectively (Table II).

Comparison of post-treatment HBA1C level showednormal 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 significantdifference in efficacy of metformin and insulin incontrolling diabetes in pregnant patients between twogroups (p = 1.000).

DISCUSSIONPregnancy increases requirements for insulin secretionwhile increasing insulin resistance, increasing demandson pancreatic β-cells, promoting development ofgestational diabetes, particularly in women with pre-existing insulin resistance. If there is impaired pancreaticβ-cell compensation for insulin resistance duringpregnancy, then gestational diabetes develops. This hasmaternal and neonatal implications for pregnancy

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

Journal of the College of Physicians and Surgeons Pakistan 2013, Vol. 23 (12): 866-869 867

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

Sugar level Group-A Group-B p-value Chi-square

(Insulin) (Metformin)

Number Percent Number Percent

Fasting blood sugarlevel after 1 month

Controlled 22 64.7 27 79.4 0.176 1.83

Not Controlled 12 35.3 07 20.6

Total 34 100.0 34 100.0

Fasting blood sugarlevel at term

Controlled 30 88.2 27 79.4 0.323 0.98


Total 34 100.0 34 100.0

Table II: Comparison of random blood sugar levels after 1 month and atterm.

Sugar level Group-A Group-B p-value Chi-square



Random blood sugarlevel after 1 month

Controlled 25 73.5 24 70.6 0.786 0.07


Total 34 100.0 34 100.0

Random blood sugarlevel at term

Controlled 28 82.4 27 79.4 0.757 0.10


Total 34 100.0 34 100.0

Table III: Comparison of post-treatment HBA1C level.

HBA1C Group-A Group-B p-value Chi-square



HBA1C level (post- treatment)

Controlled 27 79.4 28 82.3 0.757 0.10


Total 34 100.0 34 100.0

Table IV: Distribution of cases by efficacy.

Efficacy Group-A Group-B p-value



Yes 27 79.4 27 79.4 1.000

No 07 20.6 06 20.6

Total 34 100.0 34 100.0

outcomes and for the later development of type-2diabetes mellitus. In women with gestational diabetes,14 – 60% will develop type-2 diabetes later in life, and30 – 50% will have gestational diabetes with consecutivepregnancies.

The incidence of diabetes in pregnancy is increasing. Asdiabetes is associated with adverse pregnancy out-comes, it is important that it is recognized and appro-priately managed. This study examined the pharma-cological options for the management of diabetes inpregnancy, as well as the evidence for blood glucosemonitoring, dietary and exercise therapy. The medicalmanagement of diabetes in pregnancy is still evolving,and recent randomized controlled trials have addedconsiderably to our knowledge in this area. As insulintherapy is effective and safe, it is considered the goldstandard of pharmacotherapy for diabetes, againstwhich other treatments have been compared.8

When treatment targets are not achieved by dietarymeans, then insulin is required. A basal-bolus regimen ofinsulin gives the most effective glucose control, andproduces better fetal outcomes than a twice dailyregimen.9 Prandial fast-acting insulin is administered tocontrol post-prandial hyperglycemia, and bed time basalinsulin is given if there is fasting hyperglycemia. In somecases, an additional morning injection of basal insulinmay further improve glycemic control. As the level ofinsulin resistance varies from person to person, it iscommon practice to commence the woman on smalldoses of insulin, and then to increase the doses atfrequent intervals until target glucose levels areattained.9 For many years, fast-acting (regular) insulin,and intermediate-acting (isophane) insulin have beenthe preferred insulin for the treatment of diabetes inpregnancy. Human insulin does not normally cross theplacenta, though antibody bound animal insulin hasbeen reported to do so.10

It has been shown that it is maternal glucose controlrather than maternal anti-insulin antibody levels, whichinfluence birthweight.11,12 Human insulin is consideredsafe in pregnancy as years of experience has notsuggested an increase in fetal complications as aconsequence of its use.

Theoretically, metformin is an alternative to insulin inthe treatment of hyperglycemia during pregnancy. Itdecreases hepatic gluconeogenesis and improvesperipheral glucose uptake. It does not induce hypo-glycemia and it is not associated with increased weightgain. Evidence supporting the use of metformin inpregnancy is available from studies in patients withpolycystic ovary syndrome. Metformin is being usedincreasingly in pregnancy and recent MiG trialconcluded that children exposed to metformin had largermeasures of subcutaneous fat, but overall body fat wassame as in children whose mothers were treated with

insulin alone. Further follow-up is required to seewhether these findings will persist in later life or thesechildren will develop less visceral fat, and be moresensitive to insulin.13 In the current study, comparison ofinsulin and metformin showed that metformin and insulinis equally effective in the management of pregnancy withdiabetes. Two studies have also concluded thatmetformin is as effective as insulin for glycemic controlin gestational diabetes.14,15

However, one study, a randomised controlled trial, wasunderpowered to address the effectiveness and safetyof metformin in gestational diabetes.16 In another study,a retrospective case control one, subjects treated withinsulin had a greater degree of initial glucoseintolerance, so the comparison was of limited validity.17

Metformin reduces insulin resistance and hepaticgluconeogenesis, which theoretically would be bene-ficial for the preservation of β-cell function. In subjectswith type-2 diabetes, it has been demonstrated thatmetformin is superior to glyburide in this regard.18,19

As there is transplacental passage of metformin,20 itseffect on fetal insulin resistance might even providefurther benefit in light of data of insulin resistance andinsulin secretory defects in offspring of diabeticpregnancies.21 A recent study by Gandhi et al. showed,metformin is safe and effective in the treatment ofgestational diabetes and it reduces the requirement forsupplementary insulin.22

CONCLUSIONSince there was no significant difference in efficacy ofmetformin and insulin in controlling diabetes in pregnantpatients in two groups, therefore, efficacy of metforminand insulin was found to be comparable in themanagement of pregnancy with diabetes in this study.

Disclosure: This is a dissertation-based articleapproved by Research Evaluation Unit (REU) of CPSPas part of the requirement for fellowship examination.

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5. Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS,Robinson JS. Effect of treatment of gestational diabetesmellitus on pregnancy outcomes. N Engl J Med 2005; 352:2477-86. Epub 2005 Jun 12.

Seema Waheed, Farhat Perveen Malik and Syeda Batool Mazhar

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

6. Tertti K, Ekblad U, Vahlberg T, Rönnemaa T. Comparison ofmetformin and insulin in the treatment of gestational diabetes:a retrospective case-control study. Rev Diabet Stud 2008;5:95-101.

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22. Gandhi P, Bustani R, Madhuvrata P, Ferrell T. Introduction ofmetformin for gestational diabetes mellitus in clinical practice:has it an impact? Eur J Obstet Gynecol Reprod Biol 2012;160:147-50. Epub 2011 Dec 3.

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

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

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