metformin4

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PCOS

Metformin versus acarbose therapy in patients with polycystic ovary

syndrome (PCOS): a prospective randomised double-blind study

AIDA HANJALIC-BECK 1, BORIS GABRIEL 1, WOLFGANG SCHAEFER 1,

HANS-PETER ZAHRADNIK 1, MARCUS SCHORIES2, CLEMENS TEMPFER 3,

CHRISTOPH KECK 4, & DOMINIK DENSCHLAG1

1Department of Obstetrics and Gynecology, University of Freiburg, Freiburg, Germany,

2Clinic for hormonal disease and

diabetes, Basel, Switzerland,3

Department of Obstetrics and Gynecology, Vienna General Hospital, Vienna, Austria, and 4

Pan Institut for Endocrinology and Reproductive Medicine, Cologne, Germany

(Received 15 October 2009; accepted 8 February 2010)

AbstractThe objective of this study was to investigate the effect of metformin versus acarbose in terms of ovulation rate, their impacton hormonal and metabolic status and tolerability of both drugs in patients with polycystic ovary syndrome (PCOS).

Seventy-five patients with PCOS were included in this prospective randomised controlled double-blinded clinical study.According to randomisation, patients were allocated to receive either metformin 2550 mg/day (n¼37) or acarbose 300 mg/ day (n¼38) for 12 weeks. Primary study outcomes were ovulation rate, restoration of a regular menstrual cycle and theincidence of side effects. Secondary outcomes included treatment-related hormonal and metabolic changes.

Comparable high rates of regular menstrual cycles as well as ovulation could be achieved in both groups (70% and 73% formetformin vs. 78% and 59% for acarbose, p¼0.330 and p¼0.185, respectively). In contrast, only in patients treated withmetformin a statistically significant decrease in fasting insulin and cholesterol levels as well as BMI was observed. However,comparing both groups at the end of treatment, no significant differences in metabolic and/or hormonal parameters could bedetected. Regarding side effects, the rate of flatulence and/or diarrhoea was significantly lower for acarbose compared to

metformin (38% vs. 80%, p50.001).

Keywords: Polycystic ovary syndrome, insulin resistance, ovulation induction

Introduction

Polycystic ovary syndrome (PCOS) as a common

endocrine disorder affecting 5–10% of the population

[1], is a clinically heterogeneous disorder charac-

terised by a dysregulation between the central nervous

system, the pituitary and adrenal glands, and most

important the ovaries. Furthermore, in a large

proportion of affected individuals, PCOS is alsoassociated with insulin resistance, obesity and dis-

orders of lipid metabolism as well as infertility [2].

A link between PCOS and disturbed insulin action

has been reported by several authors, promoting that

insulin resistance is an integral feature of PCOS [3,4].

The associated hyperinsulinemia might cause an

increased ovarian androgen secretion leading to

an abnormal ovarian follicular development and

therefore dysfunctional menstrual activity [5,6]. Im-

proved understanding of those pathophysiological

mechanisms and the recognition of the important

role of hyperinsulinemia have provided the rationale

for trials evaluating the therapeutic value of insulin-

sensitising agents, with metformin being the most

intensively studied drug [7]. Although effective as

shown by numerous studies [7,8], metformin has

important side-effects, like nausea, diarrhoea orthough rare severe lactic acidosis, which often limit

its use [9]. The a-glucosidase inhibitors like acarbose

act by slowing the absorption of carbohydrates from

the intestines, so minimising the post-prandial rise

of blood glucose concentration [10]. Minor gastro-

intestinal side-effects may require gradual dosage

increments over weeks after therapy is initiated, but

serious adverse reactions are extremely rare.

Correspondence: Dr. Aida Hanjalic-Beck, Department of Obstetrics and Gynecology, University of Freiburg, Freiburg, Germany.

E-mail: [email protected]

Gynecological Endocrinology , September 2010; 26(9): 690–697

ISSN 0951-3590 print/ISSN 1473-0766 online ª 2010 Informa UK Ltd.

DOI: 10.3109/09513591003686379



Since Geisthovel et al. [11] were able to demon-

strate in a pilot study, that hyperinsulinemia and

hyperandrogenism can be substantially decreased by

acarbose treatment, this observation was confirmed

by two randomised controlled trials [12,13].

Moreover, in order to compare metformin

treatment with acarbose with a main focus on

ovulation rates in patients with PCOS, Sonmez

et al. published a small randomised controlled

trial including only 30 patients, with inconsistent

results showing only a significant higher ovulation

rate in the second month of metformin treatment,

in contrast to the first and third month, where no

significant difference between the groups was

observed [14].

The aim of this study was to compare the efficacy of

metformin and acarbose therapy in patients with

PCOS with respect to ovarian function, meta-

bolic parameters and the incidence of side effects in

a larger cohort.

Methods

Eighty-four women with PCOS aged 18–43 years

were enrolled in the study between September 2002

and November 2004. Due to the trial opening in

2002 before the new Rotterdam criteria were

published [15], the recruitment of patients was based

on the criteria of the National Institute of Health

and Child Health from 1990 requiring the following

three conditions for the diagnosis of PCOS: (i)

oligomenorrhea (cycles 435 days) or amenorrhea

(lack of menstruation for 6 months), (ii) clinicaland/or biochemical hyperandrogenemia i.e. total

serum testosterone 40.8 ng/ml and (iii) exclusion

of other endocrinological disorders. In addition, for

inclusion anovulatory cycles had to be confirmed in

all patients by serum concentrations of progesterone

less than 3.5 ng/ml on two occasions 4 weeks apart

within 1 month before randomisation.

After performing appropriate blood tests and

taking the patients’ medical history, patients were

screened for hyperprolactinemia, thyroid disease,

congenital adrenal hyperplasia or liver, kidney and

bowel disease, since these disorders were defined

as exclusion criteria (Figure 1). Prior to study enrolment patients were requested not to take any

hormones (oral contraception, ovulation induction

agents, cortisone, etc.), antidiabetic drugs and not to

go on any specific diet for at least 6 weeks.

The study was approved by the Ethics Committee

of the University of Freiburg, and all patients gave

their written informed consent prior to entering the

study.

At screening during early follicular phase (cycle

day 2–5) after spontaneous or progestin-induced

bleeding the following measures were performed:

body mass index calculation (BMI¼weight (kg)/

[height (m)]2), oral glucose tolerance test (OGTT)

with 75 g glucose after an overnight fasting includ-

ing: fasting insulin, fasting glucose (mg/dl) to fasting

insulin (mU/ml) ratio with cut-off point 54.5 as a

parameter for insulin resistance according to Legro

et al. [16], hormone assays (FSH, LH, progesterone,

testosterone, androstendione, dehydroepiandroster-

one-sulfate (DHEAS), sex hormone-binding globu-

lin (SHBG), 17-hydroxy-progesterone (17-OH-P),

cortisole) and metabolic assays (cholesterol and

triglyceride). Hormones and metabolic parameters

were measured with following intra-assay and inter-

assay coefficients of variation, respectively: 2% and

53% for follicle-stimulating hormone (FSH), 52%

and 54% for luteinizing hormone (LH), 53% and

54% for progesterone,55% and54% for testos-

terone,53% and 55% for SHBG, 52% and 53%

for insulin (automated Elecsys Immunoanalyser,

Roche Diagnostics, Mannheim, Germany), 510%

and 510% for DHEAS,59% and59% for corti-sole (IMMULITE analyzer, Siemens Medical Solu-

tion Diagnostics, Bad Nauheim, Germany),56%

and 510% for androstenedione, 510% and 513%

for 17-OH-P (Multi-Kristall Gamma-counter LB

2111, Berthold, Bad Wildbad, Germany), 51% and

53% for cholesterol, 52% and 53% for triglycer-

ide, 52% and 52% for glucose (P-Modull, Roche

Diagnostics, Mannheim, Germany).

Furthermore, individual menstrual cycle pattern

was assessed by interviewing the patients.

The patients were randomised in two groups –

metformin (group I) and acarbose (group II) – using

a computer generated code. The randomisation listwas kept in the examination room. According to the

randomisation, the patients received consecutively

numbered sealed envelopes including either metfor-

min (group I, Glucophage 500 mg/850 mg MERCK

Pharma, Darmstadt, Germany) or acarbose (group

II, Glucobay 50 mg/100 mg BAYER Vital, Leverku-

sen, Germany) in a neutral white tablet form. The

envelops were prepared by a nurse, who was not

involved in the study. The investigators and the

patients were blinded to their assignments.

The treatment lasted for 12 weeks in both

groups. The patients in group I were treated with

metformin starting with 500 mg/day for the firstweek, followed by 850 mg/day in the second week,

1700 mg/day in the third week (850 mg twice

daily) and for the next 9 weeks the patients were

asked to increase the dose up to 2550 mg, if no

side effects had occurred. Patients in group II

received acarbose 50 mg/day in the first week,

100 mg/day in the second week, 200 mg/day in the

third week (100 mg twice daily) and finally

300 mg/day for the next 9 weeks. During the last

9 weeks patients in both groups were advised to

take the maximum dose.

Antidiabetic drugs in PCOS 691



The primary endpoint was ovulation rate, and re-

establishment of a regular menstrual cycle. Thus,

during the treatment period serum progesterone (P4)

concentration was measured every 2 weeks in order

to evaluate for ovulary cycles as considered if a serum

level of P443.5 ng/ml was detected. In addition, all

patients were asked to record their menstrual

bleeding pattern in order to evaluate for re-establish-ment of a regular menstrual cycle as defined by a

cycle length between 21 and 35 days.

Secondary endpoints included differences in hor-

monal and metabolic parameters, including insulin

resistance, differences in BMI as well as the inci-

dence of side effects during metformin and acarbose

therapy. Thus, at the end of treatment the follow-

ing measures were repeated: BMI, OGTT includ-

ing fasting insulin and fasting glucose (mg/dl) to

fasting insulin (mU/ml) ratio as a parameter for

insulin resistance, hormone assays (FSH, LH,

testosterone, androstendione, DHEAS, SHBG,

17-OH-P, cortisole) and metabolic assays (cholester-

ol and triglyceride). Furthermore, individual side

effects were rated by subjective scoring.

Statistical analysis

Statistical Package for the Social sciences, version 13(SPSS Inc Chicago, IL.) was used for statistical

analyses. All data are shown as means (+SD). For

categorical variables Fisher’s exact test was used. For

continuous variables, between-group differences

were assessed by the non-parametric Mann–Whitney

U-test for unpaired samples. Continuous variables

within each group were assessed for differences using

Student’s t-test for paired samples. p value50.05

was considered statistically significant.

Based on the available literature we assumed an

ovulation rate of 50% in patients with PCOS. In

Figure 1. Flow chart for metformin versus acarbose treatment in patients with PCOS.

692 A. Hanjalic-Beck et al.



order to detect a clinically meaningful difference of

25% as minimally detectable effect size with a power

of 80% (a¼ 0.10) using a 1 to 1 randomisation, a

sample size of n¼ 33 in each group was needed.

Results

Overall 84 women were screened for the study, of

whom nine patients did not meet the inclusion

criteria (Figure 1). Thus, 75 patients were eligible for

intention-to-treat analysis (n¼ 37 in group I and

n¼ 38 in group II, Table I). Overall, 13 women had

to discontinue the study medication (7 in group I

and 6 in group II, n.s.) due to side effects and

were therefore excluded for the treated-per-protocol

analysis (n¼ 30 in group I and n¼ 32 in group II,

Table II).

The mean age was 28 years in both groups. At

baseline, there was no difference between both

groups regarding metabolic or hormonal parameters

(Table III). Thirty-five per cent of the patients in the

metformin group and 18% of the patients in the

acarbose group showed a fasting glucose to fasting

insulin ratio54.5 as a parameter for insulin resis-

tance ( p¼ 0.053).

The rate of ovulation, regular menstrual cycles and

pregnancies did not differ significantly between both

treatment groups as shown in Table I. However, with

respect to the most commonly reported side effects,

the rate of flatulence, diarrhoea and nausea was

significantly higher in group I (metformin) compared

to group II (acarbose).

After 12 weeks of treatment an improvement of the

metabolic situation was observed in group I (de-

crease of BMI, decrease of fasting insulin, increase of

fasting glucose/insulin ratio and reduction of choles-

terol levels) (Table III), whereas this trend was not

seen in group II.There were no treatment-related changes in

hormonal parameters in both groups (FSH, LH, T,

cortisol, androstendion, 17-OH-P, SHBG) with the

exception of DHEAS showing a slight increase

(group I) and decrease (group II) after treatment,

which was considered not being clinically relevant,

since all values were within normal range. Patients

who became pregnant during the therapy (three

patients in each group) were excluded from analysis

due to pregnancy-induced alterations of hormones

and metabolic values.

Although significant differences in terms of insulin

resistance and cholesterol levels before and after thetreatment were observed in group I, the overall

comparison between both groups at the end of

treatment did not reveal any significant difference

in metabolic or hormonal parameters (Table III).

Table I. Rate of ovulation, regular menstrual cycle, pregnancies

and most commonly reported side effects according to treatment

(intention to treat analysis).

Group I Group II p

Ovulation 59% (22/37) 55% (21/38) n.s.

Regular menstrual cycle 62% (23/37) 68% (26/38) n.s.

Pregnancy 8% (3/37) 8% (3/38) n.s.

Nausea 30% (11/37) 15% (6/38) n.s.

Flatulence/diarrhoea 76% (28/37) 39% (15/38) 0.001

n.s. ¼ not significant with p value 4 0.05.

Table II. Rate of ovulation, regular menstrual cycle and

pregnancies according to treatment (treated per protocol analysis).

Group I Group II p

Ovulation 73% (22/30) 59% (19/32) n.s.Regular menstrual cycle 70% (21/30) 78% (25/32) n.s.

Pregnancy 10% (3/30) 9% (3/32) n.s.

Nausea 23% (7/30) 6% (2/32) 0.049

Flatulence/diarrhoea 80% (24/30) 38% (12/32) 50.001

Table III. Changes in hormonal and metabolic parameters before and after 12 weeks of treatment (treated per protocol analysis); pregnant

patients excluded.

Group I (metformin); n¼ 27 Group II (acarbose); n¼29Group I vs. II after 12 weeks

Before After p1 Before After p

1 p2

FSH (U/l) 4.25+1.88 4.40+1.51 n.s. 4.38+2.11 5.02+2.14 n.s. n.s.

LH (U/l) 5.65+3.03 7.41+5.58 n.s. 6.05+3.76 6.97+7.37 n.s. n.s.

Testosterone (ng/ml) 1.08+0.36 1.04+0.31 n.s. 1.12+0.32 1.09+0.32 n.s. n.s.

C or tis ole (ng/ml) 168.6+64.2 147.3+44.3 n.s. 183.0+36.8 172.1+57.0 n.s. n.s.

DHEAS (ng/ml) 2171+824 2362+919 0.045 2350+955 2178+837 0.046 n.s.

Androstendione (ng/ml) 3.32+1.47 3.29+1.68 n.s. 3.31+1.13 3.62+1.77 n.s. n.s.

17-OH-P (ng/ml) 2.40+1.72 1.86+1.13 n.s. 2.28+1.12 2.02+1.03 n.s. n.s.

SHBG (nmol/l) 68.5+59.3 52.7+41.8 n.s. 48.0+24.6 48.4+32.3 n.s. n.s.

BMI (kg/m2) 31.6+7.77 30.6+7.39 0.000 29.0+7.52 28.4+6.91 n.s. n.s.

Cholesterol (mg/dl) 191.4+35.1 181.6+27.8 0.023 195.4+41.7 197.6+38.0 n.s. n.s.

Triglyceride (mg/dl) 134.7+75.4 116.3+55.0 0.056 123.9+93.4 129.3+78.9 n.s. n.s.

Fasting insulin (mU/ml) 19.5+17.7 14.3+9.8 0.013 13.0+10.2 14.2+13.7 n.s. n.s.

Fasting glucose/insulin 7.28+5.03 8.65+5.86 0.028 9.86+5.44 9.70+7.10 n.s. n.s.

Results are shown as mean+SD; n.s.: not significant; p1 value for Student’s t -test; p2 value for Mann–Whitney U test.




Since BMI was not a criterion for the recruitment

of patients in our study (BMI range 17–46),

we performed subsequently a subgroup analysis

considering in particular patients with

BMI425 kg/m2 (group I, n¼ 19; group II, n¼ 18)

which revealed additionally decreased triglyceride

levels (group I, p¼ 0.026) and increased FSH levels

(group II, p¼ 0.038) after therapy. Again, there was

no difference in these parameters between both

groups at the end of treatment. DHEAS, BMI and

fasting insulin levels were the only parameters

showing significant changes after metformin therapy

both for the entire group I and for the subgroup of

women with BMI425 kg/m2 (Table IV).

Discussion

The first-line treatment for patients with PCOS with

anovulatory infertility is clomiphene citrate (CC)

[17]. With CC ovulation rates of up to 80% and

pregnancy rates of 30–50% [18] can be achieved.However, approximately 15–40% of patients with

PCOS show a so called clomiphene resistance

[18,19]. There is no consensus on the definition of

clomiphene resistance, but most clinicians would

classify it as a failure to ovulate after three treatment

cycles with gradually increasing doses of CC.

Especially, patients with PCOS with obesity and

severe insulin resistance are more likely to fail to

respond to CC [20] contrary to non-obese patients

with PCOS, who are able to achieve ovulation rates

of up to 67% with CC treatment [21]. Nevertheless

the risk of poor response, lower pregnancy rates

and potentially higher abortion rates after treatmentwith CC [21] led to a search for alternatives to this

drug.

Over the past years, oral antidiabetics like metfor-

min, troglitazone, rosiglitazone or acarbose were

increasingly used for the treatment of insulin

resistance in patients with PCOS. Metformin is an

oral biguanid antihyperglycemic drug and has been

widely investigated in patients with PCOS. Various

studies have been able to show positive effects of

metformin in terms of reducing hyperinsulinemia

and optimising the metabolic situation, [7,22]. Be-

side these metabolic effects, metformin seems to have

a significant impact on ovulation rates in anovulatory

obese as well as lean patients with PCOS [7,8,21,23–

25]. Although, according to a recently published

large randomised controlled trial [26], metformin

seems to be less effective regarding live birth rate

compared to CC in patients with PCOS, a restora-

tion of regular menstrual cycles could be achieved in

up to 50–91% of the patients [22,27,28]. This

positive effect on menstrual cyclicity and ovulation

can occur without additional metabolic changes like

weight reduction [23,25]. Although the results of

previous studies regarding the improvement of

hyperandrogenemia under metformin treatment are

controversial [7], it appears to be consensus that

metformin possesses ‘antiandrogenic properties’[22,27,28]. Side effects of metformin include ab-

dominal bloating, flatulence, diarrhoea, nausea and

vomiting [29,30]. These side effects can be reduced

by initially starting the treatment at a low dose, with

further slowly increasing the dose according to side

effects, and taking the drug after meals. In some

patients side effects improve spontaneously. Further-

more, lactic acidosis, as a potentially life-threatening

complication of metformin treatment occurs in

1:30,000 patients with diabetes, but has not been

reported as a complication in women with PCOS [7].

Acarbose is an antidiabetic drug which reversibly

inhibits a-glucosidase activity in the intestinal muco-sa decreasing disaccharide digestion, thus delaying

glucose entry into the blood stream. It has been

widely used for treatment of type 2 diabetes mellitus,

as well as for prevention of type 2 diabetes in patients

with impaired glucose tolerance [31]. To the best of

our knowledge, only five small trials have been

Table IV. Changes in hormonal and metabolic parameters for patients with BMI 425 (treated per protocol analysis).

Group I (metformin, n¼19) Group II (acarbose, n¼18)Group I vs. II after 12 weeks

Before After p1 Before After p1 p2

FSH (U/l) 4.09+2.03 4.25+1.72 n.s. 4.21+2.12 5.46+1.92 0.038 n.s.

LH (U/l) 5.73+2.91 6.39+4.05 n.s. 5.24+3.23 5.67+3.45 n.s. n.s.

Testosterone (ng/ml) 1.12+0.36 1.11+0.29 n.s. 1.13+0.36 1.14+0.35 n.s. n.s.

Cortisole (ng/ml) 162.4+58.1 146.9+46.0 n.s. 182.0+41. 4 175.2+52.7 n.s. n.s.

DHEAS (ng/ml) 2107+806 2396+946 0.017 2307+900 2221+798 n.s. n.s.

Androstendione (ng/ml) 3.30+1.52 2.95+0.87 n.s. 3.13+0.98 3.46+1.84 n.s. n.s.

17-OH-P (ng/ml) 2.41+1.82 1.90+1.27 n.s. 2.12+1.06 1.65+0.76 n.s. n.s.

SHBG (nmol/l) 45.00+39.3 32.3+15.1 n.s. 41.1+19.6 37.1+19.7 n.s. n.s.

BMI (kg/m2) 35.5+5.62 33.99+5.51 0.000 33.5+5.50 32.5+5.00 n.s. n.s.

Cholesterol (mg/dl) 191.1+37.7 182.9+29.1 n.s. 197.9+37. 0 202.0+33.1 n.s. n.s.

Triglyceride (mg/dl) 159.7+74.0 131.2+58.6 0.026 145.0+102.2 146.4+88.3 n.s. n.s.

Fasting insulin (mU/ml) 25.6+18.5 18.4+9.4 0.016 16.9+11.5 18.5+16.3 n.s. n.s.

Fasting glucose/insuline 4.75+2.94 5.80+3.43 n.s. 7.58+4.07 6.91+3.46 n.s. n.s.

Results are shown as mean+SD; n.s.: not significant; p1 value for Student’s t-test; p2 value for Mann–Whitney U -test.




published so far, investigating the effects of acarbose

in patients with PCOS [11–14,32]. Positive effects in

terms of decreased insulin resistance and hyperan-

drogenemia, as well as improvement of ovulation

rates and menstrual cyclicity were observed.

In our study, we observed comparable ovulation

rates for metformin and acarbose treatment after 12

weeks of therapy in patients with PCOS. These

results should clarify the data previously obtained

from a small randomised controlled trial, which

revealed inconsistent results showing only a signifi-

cantly higher ovulation rate in the second month of

metformin treatment compared to acarbose, in

contrast to the first and third months, where no

significant difference between the groups could be

observed [14]. However, both studies showed an

improvement of ovulation under metformin and

acarbose treatment compared to the ovulation rate

in patients with PCOS treated with placebo being in

a range of 4–24% [7,8]. Furthermore, in both trials

the number of patients with regular menstrual cycleswas significantly increased due to metformin (62–

80%) as well as acarbose treatment (68–69%), with

no statistically significant difference between both

treatment arms. These results regarding restoration

of a regular menstrual cycle are in accordance with

results of earlier published data on metformin

[22,27,28,33], as well as acarbose in obese [13]

and/or non-obese hyperinsulinemic patients with

PCOS [12].

With respect to metabolic changes, in our study we

were not able to demonstrate a significant difference

between metformin and acarbose after 12 weeks of

therapy. Analysing the metabolic effects of bothtreatment arms separately, we found a statistically

significant decrease in fasting insulin and cholesterol

levels as well as BMI after 12 weeks of metformin

treatment, which was confirmed for fasting insulin

and BMI in a subgroup analysis including only

patients with a BMI of more than 25 kg/m2. These

positive effects of metformin on insulin resistance

and dyslipidemia are in accordance to earlier results

[7,28]. In contrast, in patients with acarbose treat-

ment, no significant metabolic changes were ob-

served after 12 weeks of therapy in comparison to

baseline. Other investigators have been able to

demonstrate positive metabolic effects for acarbosein patients with PCOS in terms of an improved

insulin resistance [11,12,14,32] or a decreased BMI

[13,14].

It is of note that a direct comparison seems to be

difficult in light of the fact that in those studies

different definitions, criteria and/or functional tests

were used in order to diagnose hyperinsulinaemia. In

addition, it is important to mention, that despite

randomisation a borderline significantly higher num-

ber of patients with insulin resistance at baseline

in the metformin group (35%) compared to the

acarbose group (18%) was observed. This could

partly explain why the positive metabolic effects were

only detected in the metformin group.

Rather speculative is that metformin might have a

stronger metabolic impact in patients with PCOS

compared to acarbose, since metformin interacts on

different levels of insulin physiology by decreasing

intestinal absorption of glucose, increasing peripheral

glucose utilisation, inhibiting hepatic gluconeogen-

esis and enhancing insulin sensitivity of hepatic and

peripheral tissue [34], whereas acarbose only acts

locally by slowing down the absorption of carbohy-

drates from the intestine, hence only reducing insulin

levels indirectly [10,34].

The effects of metformin and/or acarbose treat-

ment in terms of hyperandrogenemia and/or hirsut-

ism are varying. Whereas some investigators have

reported decreased testosterone levels and/or im-

proved hirsutism after acarbose [11–14,32] as well as

metformin treatment [8,22,28], those effects were

not confirmed by other trials [7,25]. According tothese variable data, and the results of our study, in

which we were not able to demonstrate significantly

decreased androgen levels neither after metformin

nor after acarbose treatment, those drugs can not

generally be recommended for treatment of hyper-

androgenemia and/or hirsutism in patients with

PCOS [35].

Typical side effects of metformin include abdom-

inal discomfort and diarrhoea, which occurs in

20–30% of the patients, and up to 5% have to

discontinue the medication due to the severity of the

side effects [34]. In addition, the use of metformin is

limited to patients without renal or hepatic disease,respiratory insufficiency, severe infections and hy-

poxemic conditions due to an increased risk of fatal

lactic acidosis. Gastrointestinal side effects like

abdominal disturbance, flatulence and diarrhoea in

up to 30% of the patients have also been reported

for acarbose treatment [10]. In addition, a transient

elevation of serum transaminase concentrations can

occur at maximal dose and is completely reversible

after discontinuation of treatment [10]. However, in

contrast to metformin serious adverse reactions like

fatal hypoglycemia or lactic acidosis have not been

reported.

In general, the dosage of both drugs should beincreased gradually in order to reduce the described

side effects. Furthermore, those side effects tend to

improve spontaneously after several weeks of treat-

ment [34]. In our study treatment with acarbose was

associated with significantly less side effects like

flatulence, diarrhoea and nausea compared with

metformin treatment. However, no differences regar-

ding drop-out rate due to side effects was observed.

With respect to the safety during pregnancy,

metformin has been documented in several trials

to be safe for use in pregnancy, and in fact, even




beneficial in terms of decreasing the incidence of

early pregnancy loss and the development of gesta-

tional diabetes, reducing insulin levels and insulin

resistance and preventing androgen excess in women

with PCOS [36].

The use of acarbose in pregnancy seems to be a

good option because it primarily acts in the gut by

delaying carbohydrate absorption and is not ab-

sorbed, thereby having no systemic effects. However,

this drug has not yet been studied well in pregnancy.

In a small study by Zarate et al. [37], six pregnant

women with moderately elevated levels of fasting and

postprandial blood glucose were treated with acar-

bose, after which, the fasting and postprandial

glucose levels normalised. The pregnancies were

uneventful and the newborn babies were normal

[37]. Although this study shows promising results, it

is still a very early and small study on acarbose use in

pregnancy, and therefore, no plausible and definitive

conclusions can be drawn.

In conclusion, we were able to demonstrate acomparable high ovulation rate and improvement

regarding regular menstrual cycles for both metfor-

min and acarbose treatment. No significant differ-

ences in terms of metabolic and/or hormonal

parameters could be observed between both groups

at the end of treatment. Nevertheless this result could

be due to short treatment period and heterogeneity of

patients in our study. Since acarbose was better

tolerated than metformin, we suggest acarbose as an

effective alternative to metformin in patients with

anovulatory PCOS.

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