European Journal of Obstetrics & Gynecology and Reproductive Biology 260 (2021) 42–47

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European Journal of Obstetrics & Gynecology and

Reproductive Biology
journal homepage: www.elsevier.com/locate/ejogrb

Full length article

Efficacy of myoinositol in treatment of gestational diabetes mellitus

in Asian Indian women: A pilot randomized clinical trial
Vidushi Kulshrestha, Shrey Balani* , Garima Kachhawa, P. Vanamail, Rajesh Kumari,
J.B. Sharma, Neerja Bhatla
Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi, India

A R T I C L E I N F O A B S T R A C T

Article history: Objective: To compare efficacy of myoinositol as an adjuvant to dietary modification for treatment of
Received 9 July 2020 gestational diabetes mellitus in Asian Indian women compared to controls.
Received in revised form 3 February 2021 Study Design: Setting: This pilot randomized open label trial was conducted in a single antenatal clinic in
Accepted 17 February 2021
India. Subjects: One hundred women with singleton pregnancy and gestational diabetes diagnosed
between 14–28 weeks’ gestation were included. Overt diabetes, twin pregnancy, pre-existing renal
Keywords: disease, heart disease and other chronic medical disorders were exclusions. Intervention: Participants
Gestational diabetes
were randomized in two groups (1:1 ratio) by opaque envelope method. Individualized nutrition
Myoinositol
Treatment
counseling with dietary modification and routine antenatal care was provided to all. Fifty women
Glycemic control received myoinositol 1000 mg twice daily; 50 controls did not receive myoinositol. Fasting and
postprandial glucose levels were assessed after two weeks. Women not achieving glycemic targets
(fasting glucose <95 and postprandial glucose <120 mg/dL) were given pharmacologic therapy.
Contributory factors in women requiring additional pharmacologic therapy, maternal and fetal outcomes
were noted. Statistical analysis: Between group comparisons reported relative risk and mean difference.
To assess predictive factors for need for pharmacologic therapy, univariate and multivariable logistic
regression analysis were used.
Results: Baseline characteristics were comparable in both groups. Except one woman in the myoinositol
group, all women provided glycaemia data throughout their pregnancy. Glycemic control was achieved in
44/ 49 (89.8 %) women in myoinositol group which was significantly higher than 34/50 (68 %) in the
controls ((relative risk 0.31, 95 % confidence interval 0.13 to 0.80, p = 0.008). Mean duration of myoinositol
treatment was 17.6 weeks (standard deviation 5.3). Additional treatment with metformin/insulin was
needed in all women failing to achieve glycaemic control. The mean (range) dose of insulin was 25.3 units
in myoinositol group compared to 14.27 units in controls (p = 0.058). Secondary outcomes were similar in
two groups except baby weight which was higher in controls (p = 0.018).
Conclusions: Oral supplementation with myoinositol in dose of 1 gm twice-daily, when started soon after
the diagnosis of GDM, is effective in achieving glycemic control and decreasing the need for additional
pharmacological therapy in Asian Indian women.
© 2021 Elsevier B.V. All rights reserved.

Introduction

Gestational diabetes mellitus (GDM) is glucose intolerance

* Corresponding author at: 3082 A, 3rd Floor, Teaching Block, Department of
Obstetrics and Gynaecology, All India Institute of Medical Sciences, Ansari Nagar,
New Delhi, 110029, India.
E-mail addresses: drvidushi.kul@gmail.com (V. Kulshrestha),
shreybalani@gmail.com (S. Balani), garimakachhawa2012@gmail.com
(G. Kachhawa), pvanamail@gmail.com (P. Vanamail), drrajeshkumari@yahoo.com
(R. Kumari), jbsharma2000@gmail.com (J.B. Sharma), neerja.bhatla07@gmail.com
(N. Bhatla).
diagnosed during pregnancy that is not clearly overt diabetes [1].
The International Diabetes Federation estimated globally 15.8 % of
women with live births in 2019 had hyperglycemia in pregnancy;
of which 83.6 % were due to GDM [2]. GDM is associated with
increased maternal and perinatal morbidity and also the long-term
consequences, including type-2 diabetes and cardiovascular
complications in mothers, and obesity and adult onset diabetes
in children born to these mothers [3]. A continuous linear
relationship between maternal hyperglycemia and complications

https://doi.org/10.1016/j.ejogrb.2021.02.017
0301-2115/© 2021 Elsevier B.V. All rights reserved.
V. Kulshrestha, S. Balani, G. Kachhawa et al.
(primary cesarean delivery, neonatal hypoglycemia, premature
delivery, shoulder dystocia or birth injury, intensive neonatal care,
hyperbilirubinemia, and preeclampsia) was demonstrated in
HAPO trial involving a large ethnically diverse cohort, signifying
importance of achieving normoglycemia while managing GDM [4].
Treating GDM reduces both short term and long term adverse
consequences affecting two generations.
Dietary changes with lifestyle modifications achieve normo-
glycemia in over 80 % women with GDM [5]. When pharmacologic
treatment is indicated, insulin is the preferred treatment though
oral hypoglycemics, mainly metformin, have been increasingly
used due to lower costs, easy administration and greater
acceptability. Long-term impacts of intrauterine exposure are
uncertain but a concern.
Myoinositol, a dietary supplement affecting glucose homeosta-
sis, is emerging as a novel preventive as well as therapeutic option
for GDM. Myoinositol is one of the nine inositol isomers found
naturally in cereals, legumes, nuts etc. and also synthesized in liver
and kidneys [6]. This nutritional supplement acts on the
intracellular secondary messengers of insulin pathway. Owing to
its role in decreasing insulin resistance, myoinositol has been
therapeutically used in polycystic ovarian syndrome (PCOS) [7],
and metabolic syndrome [8]. This potential to improve insulin
sensitivity paved way for its use in GDM. Initial studies focused on
GDM prevention; in women having high risk factors for developing
GDM such as PCOS [9], obesity [10] and family history of type-2 DM
[11]. Subsequently, a pilot case-control study by Lubin et al.
suggested myoinositol as a safe first-line treatment for GDM that
remained uncontrolled despite lifestyle changes, also reducing the
need for insulin therapy [12].
Fig. 1. CONSORT Flow Diagram.
43
European Journal of Obstetrics & Gynecology and Reproductive Biology 260 (2021) 42–47
In this pilot study, we hypothesized that for treatment of GDM,
2 gm/day myoinositol as an adjuvant to dietary modification may
improve glycemic control and reduce the need for pharmacological
intervention in Asian Indian women. Secondary objectives were to
evaluate contributory factors in women requiring additional
pharmacologic therapy and compare maternal and fetal outcomes.
Materials and methods
This open label randomized clinical trial (RCT) was conducted
after obtaining ethical clearance from the institute’s ethics
committee and registering with Clinical Trial Registry of India
(CTRI2018/05/013937). One hundred pregnant women presenting
at the antenatal outpatient department with GDM diagnosed
between 14–28 weeks’ period of gestation were recruited between
May 2018 to August 2019. For diagnosing GDM, the International
Association of Diabetes and Pregnancy Study Groups and World
Health Organization-2013 recommendations were followed. GDM
was diagnosed if at least one threshold for plasma glucose
concentration was exceeded at any time during pregnancy. The
thresholds used were  92, 180, 153 mg/dL for fasting, 1 h and 2 h
respectively, after a 75 g oral glucose tolerance test, using capillary
blood samples [13,14]. Women with overt diabetes, multiple
gestation, pre-existing renal disease, heart disease or other chronic
medical disorders and fetus with congenital anomalies were
excluded. Written informed consent was obtained from all
participants. The study was conceived as an external pilot study
and a feasible random sample size of 100 was chosen.
Participants were randomized into two groups in 1:1 ratio
according to computer generated randomization table generated
V. Kulshrestha, S. Balani, G. Kachhawa et al. European Journal of Obstetrics & Gynecology and Reproductive Biology 260 (2021) 42–47

by a biostatistician and using sequentially numbered, opaque
envelopes to allocate participants to the respective groups once
recruited to the study. Obstetric history, including details of
previous pregnancies, pregnancy outcomes, family history, dietary
history and personal history was obtained. Body mass index (BMI)
was calculated using the pre-pregnancy weight. Baseline routine
antenatal investigations including fasting and postprandial plasma
glucose along with glycosylated hemoglobin (HbA1c) were done.
All recruited women were counselled regarding individualized
nutrition plan. They were given routine antenatal care and iron,
calcium, folic acid, and vitamin D supplementation. Fifty women
additionally received oral myoinositol 1gm twice daily (myoinosi-
tol group) whereas the control group received no myoinositol
treatment.
Women were required to have their blood glucose assessed
after 2 weeks of diagnosis, in fasting state and 2 h after breakfast,
lunch and dinner, the glycemic target being fasting glucose <95
mg/dL and postprandial glucose <120 mg/dL. They were followed
up in antenatal clinic every 2 weeks from enrolment to 34 weeks,
weekly from 34 weeks and more frequently if clinically required.
Their glucose profile was evaluated and compliance to treatment
was assessed verbally in these visits. Additional pharmacological
treatment was initiated in either group if glycemic target was not
achieved after 2 weeks of recruitment or later during the course of
pregnancy. Metformin was started if fasting glucose was 95 99
mg/dL and post-prandial glucose was 120 160 mg/dL and insulin
was started for higher glucose levels or if metformin failed to
control hyperglycemia. HbA1c was repeated after 3 months. Fetal
growth parameters were estimated at 32–34 weeks. Weekly fetal
surveillance with non-stress test and biophysical profile was
started from 32 weeks or earlier if indicated.
Primary outcome was glycemic control, defined as achieving
glycemic targets. Secondary outcomes noted were the need for
additional pharmacological therapy, the occurrence of preeclamp-
sia, gestational hypertension, intrahepatic cholestasis of pregnan-
cy, preterm delivery, gestation at delivery, mode of delivery,
postpartum complications and fetal outcomes including birth-
weight, large/appropriate/small for gestational age babies (large
defined as >90th centile and small as <10th centile of birth weight),
Apgar score at 1 and 5 min, neonatal hypoglycemia (plasma
glucose<40 mg/dL), hyperbilirubinemia (need for phototherapy in
absence of another cause of jaundice), neonatal intensive care unit
(NICU) admission and respiratory distress.
Statistical analyses
Data-analysis was carried out using SPSS version-24.0 (Armonk,
NY: IBM Corp). Continuous variables were tested for normality
assumption using Kolmogorov-Smirnov test. Descriptive statistics
such as mean, standard deviation and range values were calculated
for normally distributed data and median and interquartile range
(IQR) were calculated for skewed/non-normal data. Category
variables were presented as frequencies and percentages. Stu-
dent’s t-test was used to compare mean values between groups;
non-parametric Mann-Whitney U-test for median comparison and
Chi-square test/Fischer’s exact test for categorical data. To assess
risk factors for insulin/metformin therapy, univariate and multi-
variable logistic regression analysis were used. Crude and adjusted
odds ratio (OR) with 95 % confidence interval (CI) was calculated
and p < 0.05 was considered statistically significant.
Results
A total of 100 women with GDM were randomized into two
groups of 50 each (Fig. 1; Consort flow diagram). One woman in
myoinositol group miscarried soon after recruitment and was
excluded from analysis, otherwise the analysis was by intention to
treat. All baseline characteristics were comparable in both groups
(Table 1). High risk factors for developing GDM including obesity,
PCOS, previous pregnancy with GDM or macrosomia and family
history of diabetes were present in 32/49(65.3 %) and 36/50(72.0 %)
women in myoinositol group and controls respectively (p = 0.47).
Significantly more women achieved glycemic control with
myoinositol, 89.8 %(44/49) compared to 68 %(34/50) in controls
(relative risk of achieving glycemic control 0.31, 95 % confidence
interval 0.13 to 0.80, p = 0.008). The remaining five women

Table 1
Baseline characteristics of patients in the two groups.

Parameters Myoinositol given (n = 49)* Myoinositol not given (n = 50)

Age (years) Mean  SD 29.7  4.4 31.3  3.3
Pre-pregnancy weight (kg) Mean  SD 60.9  9.7 61.4  9.6
BMI (Kg/m2) Mean  SD 25.5  4.0 26.3  4.4
BMI Category ** n (%)
Underweight 1(2 %) 1(2 %)
Normal weight 13(26.5 %) 11(22 %)
Overweight 11(22.4 %) 9(18 %)
Obese 24(48.9 %) 29(58 %)
Parity status n (%)
Primigravida 19(38.8 %) 10(20 %)
Multipara 30(61.2 %) 40(80 %)
Mode of conception n (%)
Natural 43(87.8 %) 42(84 %)
Ovulation Induction 3(6.1 %) 6(12 %)
In vitro fertilization 3(6.1 %) 2(4 %)
Fasting plasma glucose (mg/dL) (Mean  SD) 91.4  10.3 92.8  10.6
Postprandial plasma glucose (mg/dL) Mean  SD 123.2  23.1 122.6  27.6
GTT- Fasting value (mg/dL) Mean  SD 95.4  10.4 94.3  9.4
GTT-1 h (mg/dL) Mean  SD 161.4  32.0 166.8  34.7
GTT-2 h (mg/dL) Mean  SD 132.0  32.5 133.6  24.8
Baseline HbA1c (in %) Mean  SD 5.2  0.45 5.2  0.45
Gestation at GDM diagnosis (in weeks) Mean  SD 20.1  5.1 21.9  4.5

<18.5 kg/m2 -Underweight; 18.5–22.9 kg/m2 -Normal weight; 23–24.9 kg/m2 -Overweight, >25 kg/m2 -Obese.
GTT - glucose tolerance test using 75 g oral glucose at the time of diagnosis of gestational diabetes mellitus.
*
One patient miscarried after recruitment.
**
Body Mass Index (BMI) Category as per WHO Asian BMI Cut-offs:

44
V. Kulshrestha, S. Balani, G. Kachhawa et al. European Journal of Obstetrics & Gynecology and Reproductive Biology 260 (2021) 42–47

Table 2
Details of patients requiring additional treatment in the two groups.

Parameters Myoinositol given Myoinositol not given Mean Difference P value

(n = 5) (n = 16) (95 % CI: LL, UL)
Gestational at GDM Diagnosis (in weeks) 3.0
Mean  SD 16.6  3.85 19.6  5.7 (-8.8, 2.7) 0.297
Gestation at start of additional treatment (in weeks) 2.7
Mean  SD 27.2  1.9 29.9  4.37 (-6.9, 1.5) 0.204
Baseline HbA1c (in %) 0.3
Mean  SD 6.0  0.1 5.7  0.3 (-0.05, 0.6) 0.230
Insulin Dose 25.3  13.6 14.3  6.4 11.0 0.058
Mean  SD (-0.01, 20.0)

receiving myoinositol and 16 controls required additional phar-
macological treatment (Table 2). In the myoinositol group, insulin
was started in three and metformin in two women; these five
women had one or more high risk factors. Among the 19 controls,
nine women were given insulin, five needed metformin and two
women were started on metformin but further required insulin to
achieve normoglycemia. Fewer women receiving myoinositol
needed insulin compared to controls (6.1 % vs. 22.0 %, p = 0.02).
Mean duration of therapy with myoinositol was 17.6 weeks
(standard deviation 5.3, range 4.1–26.3 weeks).
Among secondary outcomes (Table 3), the maternal outcomes
were comparable in both groups. HbA1c repeated three months
after recruitment was similar to baseline HbA1c in both groups,
(p > 0.05). One woman among controls underwent forceps delivery
for fetal bradycardia in second stage of labour. Neonatal outcomes
were also similar except birth weight which was higher in controls
(p = 0.018). Apgar score at 5 min was >7 for all the babies and there
were no instances of birth asphyxia in either group. Four babies
in each group had birthweight >97th centiles, however none
developed any neonatal complication. Among neonates with
birthweight between 90th-97th centiles, two in control group
had neonatal complications: hyperbilirubinemia occurred in one
and another neonate whose mother was adequately controlled on
dietary modification, developed neonatal hypoglycaemia six hours
after birth due to poor feeding efforts. Three babies were small for
gestational age and all were in myoinositol group; the mothers of
these babies had chronic hypertension, preeclampsia and placental
insufficiency (absent end-diastolic flow). The latter baby had
respiratory distress, was admitted to NICU, was later diagnosed as
Klippel-Feil syndrome and died on day-12 of life due to respiratory
complications.
There was no intervention related adverse outcome during the
study. Klippel-Feil syndrome being a rare genetic disorder is
unlikely to be due to any intervention.
To assess risk factors for pharmacological therapy, univariate
logistic regression analysis was carried out by considering the
baseline characteristics including age, parity, BMI, family history,
presence of high risk factors, fasting and postprandial plasma
glucose at first visit, GTT fasting, 1 h and 2 h values, HbA1c and
gestation at diagnosis of GDM. Four factors among these, i.e. fasting
plasma glucose, GTT-1 h value, baseline HbA1c and gestation at
diagnosis showed a statistically significant association (Table 4). In
multivariable logistic regression using these four significant
variables, only HbA1c emerged as a significant independent risk
factor for predicting need for additional treatment. (p < 0.001),
(Table 4).
Discussion
Approximately 90 % (44/49) women with GDM achieved
normoglycemia on taking oral myoinositol with dietary advice,
with only 10 % requiring pharmacological treatment. This was
significant when compared to controls, who were prescribed only
dietary advice, which is the mainstay of GDM management. The
mean duration for which myoinositol was given was approxi-
mately four months. No effect was observed for secondary
outcomes, either maternal or perinatal, except baby weight which
was higher in controls.

Table 3
Comparison of secondary outcomes (Maternal and Neonatal) in the two groups.

S No. Parameter Myoinositol given Myoinositol not given Risk Ratio/Mean difference P value
(n = 49) (n = 50) (95 % CI: LL, UL)
Maternal Weight gain in pregnancy (In kg) 9.5  1.6 10.1  2.0 0.6 (-1.3, 0.1) 0.860
No. of women with Gestational Hypertension 7(14.2 %) 3(6.0 %) 2.4 (0.6, 8.7) 0.300
No. of women with Pre-eclampsia 3(6.1 %) 1(2.0 %) 3.1 (0.3, 28.4) 0.602
No. of women with Intrahepatic Cholestasis of Pregnancy 7(14.2 %) 9(18.0 %) 0.8 (0.3, 2.0) 0.610
Cesarean rate, n (%) 26(53.1 %) 31(62.0 %) 0.8 (0.6, 1.2) 0.360
Gestational age at delivery (weeks) 37.7  1.6 37.9  0.9 0.2 (-0.7, 0.3) 0.530
Preterm delivery 7(14.2 %) 3(6.0 %) 2.4 (0.6, 8.7) 0.300
Postpartum Complications
Fever 1(2.0 %) 3(6.0 %) 0.3 (0.03, 3.1) 0.617
Stich line complications 0(0 %) 3(6 %) Not Applicable 0.242
Urinary tract infection 0(0 %) 1(2.0 %) Not Applicable 0.995
Neonatal Baby weight (gm) 2820.3  490.8 3036.9  398.6 216.6 (-394.8, -38.4) 0.018
Large for Gestational Age Babies 8(16.3 %) 13(26.0 %) 0.6 (0.3, 1.4) 0.240
Small for Gestational Age Babies 3(6.1 %) 0(0.0 %) Not Applicable 0.117
Hypoglycemia 0(0.0 %) 1 (2.0 %) Not Applicable 0.995
Respiratory Distress 2(4.1 %) 1(2.0 %) 2.0 (0.2, 21.8) 0.540
Hyperbilirubinemia 4(8.2 %) 5(10.0 %) 0.8 (0.2, 2.9) 0.750
NICU Stay 4(8.16 %) 1(2.0 %) 4.1 (0.5, 35.2) 0.340
Hospital stay (days) 4.6  4.7 4.2  2.8 0.4 (-1.1, 1.9) 0.560

Apgar score at 5 min was >7 for all the babies.

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V. Kulshrestha, S. Balani, G. Kachhawa et al. European Journal of Obstetrics & Gynecology and Reproductive Biology 260 (2021) 42–47
Table 4
Odds ratio (OR) with 95 % Confidence Level (CI) by Univariate and Multivariate analysis for additional pharmacological therapy.
Univariate analysis
Variable Crude OR (95 % CI)
Age 1.13 (0.99 1.28)
BMI 1.06 (0.95 1.18)
Parity 1.42 (0.46.33)
Overweight 1.83 (0.60 5.54)
Obesity 1.5 (0.58 4.14)
Baseline Fasting plasma glucose 1.07 (1.02 1.13)
Baseline Postprandial plasma glucose 1.00 (0.98 1.02)
GTT (75 gm) - Fasting value 1.04 (0.98 1.10)
GTT-1 h 1.02 (1.00 1.03)
GTT-2 h 0.99 (0.97 1.01)
Family history 0.96 (0.84 1.11)
High risk factors 1.6 (0.52 4.85)
Baseline Glycosylated hemoglobin (in %) (HbA1c) 70.8 (10.28 488.50)
Gestational age at diagnosis 0.88 (0.80 0.98)
*
For every 1 unit increase in HBA1C, OR will be increased 32.56 respectively.
GDM is a state of physiological insulin resistance and
myoinositol acts as insulin-sensitizer [6]. Efficacy of myoinositol
in lowering blood glucose is well documented [15]. There is ample
literature supporting antenatal myoinositol for primary prevention
of GDM with Cochrane reporting 57 % reduction in GDM [16],
which is further substantiated in other studies [17–19].
The rationale for myoinositol in the treatment of GDM is that it
improves insulin sensitivity and potentiates endogenous insulin by
affecting insulin-signal pathway [6]. It not only lowers mean
glucose levels but also reduces glucose variability [20]. Myoinositol
for treating GDM was first reported in a small RCT where insulin
resistance reduced by 50 % in eight weeks [21]. Later Lubin
suggested myoinositol as alternative first-line treatment if GDM
remains uncontrolled on diet, however his controls were
retrospective [12].
Studies that have focussed on myoinositol as treatment rather
than prevention, are limited. A Cochrane review [22] on 142
women and infants evaluated myoinositol for treating GDM and
included two placebo-controlled studies, both conducted in Italy
with an unclear risk of bias: Corrado’s study [21] which looked at
insulin resistance with myoinositol and Matarelli’s study [15]
which evaluated its preventive role in women with elevated fasting
blood glucose. GDM was diagnosed at 12–13 weeks’ gestation in
one study and at 26 weeks in the other. The findings suggested that
myoinositol can reduce fasting blood glucose levels, though the
need for additional pharmacotherapy was not different between
myoinositol and the control groups; in contrast to the present
study.
Lubin in his study on 32 women demonstrated glycemic control
in 75 % women receiving myoinositol with only 25 % women
requiring insulin [12]. The better response seen in our study might
be attributed to early start of myoinositol as soon as GDM was
diagnosed; unlike Lubin’s study where myoinositol was given only
when diet failed to achieve normoglycemia. Reported need for
insulin was 25.3 % vs. 34.2 % in Di Biases’ study and 45 % vs. 50 % in
Fraticelli’s study which evaluated D-Chiro inositol, myoinositol and
their combination compared to controls [23,24]. The above
Cochrane review, however, concluded inadequacy of evidence
for myoinositol as treatment [22] and suggested to further
investigate and explore myoinositol for optimal dose, frequency
and timing of supplementation.
Though significantly fewer women receiving myoinositol
required insulin, the time to start of treatment was earlier than
in controls in our study, in contrast to the reported delay in the
median time of starting insulin in other studies [23,24]. Also the
required dose in our study was higher compared to controls. These
46
Multivariate analysis
p value Adjusted OR (95 % CI) p value
0.056
0.280
0.535
0.280
0.380
0.007 1.03 (0.96 1.10) 0.290
0.460
0.117
0.014 1.01 (0.99 1.03) 0.120
0.580
0.660
0.406
0.005 32.56* (4.50 235.43) 0.001
0.020* 0.94 (0.83 1.07) 0.4
can be attributed to the higher baseline HbA1c in these women as
shown in multivariate analysis; indicating a higher degree of
glucose intolerance, other factors being comparable. Other studies
have also reported a higher HbA1c as an independent predictor for
needing pharmacological therapy [23,25]. Besides, myoinositol as
an adjuvant might have treated the milder disease and the cases
requiring insulin were actually the most deranged metabolically,
explaining the higher insulin dose for their control.
Most studies did not find differences in secondary outcomes
[17,26] other than birth weight which had variable effect [12,18]. In
the present study birth weight was significantly lesser in
myoinositol group than controls. A meta-analysis (n = 513)
reported significant reduction in birth weight, neonatal hypogly-
cemia; marginal reduction in respiratory distress syndrome,
shoulder dystocia, preterm delivery; and insignificant reduction
in macrosomia and polyhydramnios with myoinositol [27].
Another recent meta-analysis evaluated maternal health outcomes
(OGTT values, weight gain, hypertensive disorders, lipid profile);
delivery outcomes (caesarean rates, preterm delivery, shoulder
dystocia and third degree perineal tear); feto-neonatal health
outcomes (gestational age at birth, birth weight, macrosomia,
NICU admission, polyhydramnios and fetal biometry) and side
effects with myoinositol given for prevention of GDM and reported
effects only on GTT values and preterm delivery [19]. In present
study also, secondary neonatal outcomes were similar in the two
groups, although the study was not necessarily powered to detect
meaningful differences. Neonatal hypoglycaemia occurred in one
baby born to a woman in the control group, but that was due to
feeding issues. Three neonates in myoinositol group were small for
gestational age, which could be explained by coexisting chronic
hypertension, preeclampsia and placental insufficiency.
There was no intervention related adverse outcome and
myoinositol was well-tolerated without side effects. None of the
RCTs and meta-analyses has reported any serious adverse event
[9,10,15,19,26]. Inositols are defined as generally-recognized-as-
safe by US Food and Drugs Administration and safety of
myoinositol in peri-conceptional and early gestation is well-
documented [9]. Nausea, diarrhea and flatulence are reported with
higher doses >12 g [28], and not with the supplementation doses.
There is need for larger studies in different ethnicities and with
different risk factors for GDM to evaluate long-term maternal and
fetal safety of inositols [29].
Currently, there are no recommendations regarding dose.
Variable daily doses ranging from 1200 to 4000 mg alone or in
chimeric-combination have been evaluated starting from 12 to 13
weeks for prevention of GDM. For treatment, myoinositol has been
V. Kulshrestha, S. Balani, G. Kachhawa et al.
given either since the time of diagnosis [21,24] or when glycemic
targets were not achieved [12]. Minimum dose shown to be effective
was 1200 mg/day in Lubin’s study [12]. Hence it was decided to give
2000 mg daily dose in this study as myoinositol is available as 1000
mg tablets. When this trial was conceived, only Lubin’s study was
published involving 32 cases and 28 historical controls; other
inositol related evidence for treatment came later [23,24].
Limitation of this study is small sample size. Based on the primary
outcome (glycemic control) achieved in myoinositol group (89.8 %)
versus controls (68 %), the post-hoc power of our study was 68 %. To
detect statistical significant difference between primary outcome
based on this study; the required sample size for 80 % power at 5%
level of significance would be 65 per group. Hence, further trials with
adequate sample-size of desired power are suggested to establish
and validate adjuvant role of myoinositol on glycemic control and
secondary outcomes as well. Despite this limitation, the number of
recruited patients was higher than other reported studies. Another
strength is the lower dose used than mostly reported. The results
suggest that myoinositol; a naturally occurring supplement that is
administered orally and has good safety profile in pregnancy; is a
feasible option for treating GDM and can bridge the gap between
non-pharmacological and pharmacological treatment.
Conclusion
Oral supplementation with myoinositol as an adjuvant to
dietary modification, in dose of 1000 mg twice daily, when started
soon after the diagnosis of GDM, is effective in achieving glycemic
control and decreasing the need for additional pharmacological
therapy as compared to controls in Asian Indian women. Baseline
HbA1c is an independent risk factor to predict the need for insulin.
Author contributions
The study was conceptualized and designed by VK and PV. All
authors contributed in the patient management and follow-up. SB
was responsible for acquisition of clinical data and obtaining
informed consent. PV and VK analyzed and interpreted the data. VK
drafted the manuscript. VK, GK, and NB were responsible for
manuscript’s critical editing.
Funding information
There were no funds or grants involved.
Declaration of Competing Interest
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
Appendix A. Supplementary data
Supplementary material related to this article can be found, in the
online version, at doi:https://doi.org/10.1016/j.ejogrb.2021.02.017.
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