ArticlePDF Available

The Effect of Liraglutide on Weight Loss in Women with Polycystic Ovary Syndrome: An Observational Study

Authors:
  • Copenhagen Fertility Center

Abstract and Figures

Objective: The aim of the present study was to evaluate the effect of the glucagon-like peptide-1 analog liraglutide on weight loss in overweight and obese women with polycystic ovary syndrome (PCOS). Methods: In an observational study, 84 overweight or obese women with PCOS were treated with liraglutide. Baseline characteristics and weight changes at clinical follow-up were recorded. Main outcome measures were absolute and relative weight loss. Results: In overweight or obese women with PCOS treated with liraglutide for a minimum of 4 weeks, a mean weight loss of 9.0 kg (95% CI: 7.8–10.1, p < 0.0001) and a mean decrease in BMI of 3.2 kg/m2 (95% CI: 2.8–3.6, p < 0.0001) were found. A weight loss of more than 5 and 10% of baseline weight was seen in 81.7 and 32.9% of patients, respectively. The mean duration of treatment with liraglutide was 27.8 weeks (SD 19.2). Conclusion: Treatment with liraglutide in combination with metformin and lifestyle intervention resulted in a significant weight loss in overweight and obese women with PCOS, indicating that liraglutide may be an effective alternative for weight loss in this group of patients. However, larger placebo-controlled studies are needed to confirm this.
Content may be subject to copyright.
CLINICAL CASE STUDY
published: 27 August 2014
doi: 10.3389/fendo.2014.00140
The effect of liraglutide on weight loss in women with
polycystic ovary syndrome: an observational study
Christina B. Rasmussen* and Svend Lindenberg
Copenhagen Fertility Center, Copenhagen, Denmark
Edited by:
Chun Peng,York University, Canada
Reviewed by:
Qinghua Wang, University ofToronto,
Canada
Yung-Hsi Kao, National Central
University,Taiwan
*Correspondence:
Christina B. Rasmussen, Copenhagen
Fertility Center, Lygten 2C,
Copenhagen DK-2400, Denmark
e-mail: bording@dadlnet.dk
Objective: The aim of the present study was to evaluate the effect of the glucagon-like
peptide-1 analog liraglutide on weight loss in overweight and obese women with polycystic
ovary syndrome (PCOS).
Methods: In an observational study, 84 overweight or obese women with PCOS were
treated with liraglutide. Baseline characteristics and weight changes at clinical follow-up
were recorded. Main outcome measures were absolute and relative weight loss.
Results: In overweight or obese women with PCOS treated with liraglutide for a mini-
mum of 4 weeks, a mean weight loss of 9.0 kg (95% CI: 7.8–10.1, p<0.0001) and a mean
decrease in BMI of 3.2 kg/m2(95% CI: 2.8–3.6, p<0.0001) were found. A weight loss
of more than 5 and 10% of baseline weight was seen in 81.7 and 32.9% of patients,
respectively. The mean duration of treatment with liraglutide was 27.8 weeks (SD 19.2).
Conclusion: Treatment with liraglutide in combination with metformin and lifestyle inter-
vention resulted in a significant weight loss in over weight and obese women with PCOS,
indicating that liraglutide may be an effective alternative for weight loss in this group of
patients. However, larger placebo-controlled studies are needed to confirm this.
Keywords: polycystic ovary syndrome, weight loss, obesity, liraglutide, GLP-1 analogs
INTRODUCTION
Polycystic ovary syndrome (PCOS) is the most commonendocrine
disorder in women of reproductive age, with a reported preva-
lence of 6–15% depending on the population studied and the
diagnostic criteria used (13). According to the Rotterdam cri-
teria introduced in 2003, PCOS is defined by at least two of
the following: oligo-amenorrhea, clinical or biochemical hyper-
androgenism and polycystic ovaries on ultrasound (4). A large
proportion of women with PCOS are overweight or obese, in
particular with abdominal obesity (5). They often have insulin
resistance, compensatory hyperinsulinemia, impaired glucose tol-
erance, and a higher risk of type 2 diabetes (68). PCOS is therefore
considered as a prediabetic state. Although PCOS and obesity
are strongly related, the underlying mechanism linking the two
involves a complex pathophysiology. Obesity may play a patho-
genic role in the development of PCOS in susceptible individuals.
Obesity-related insulin resistance and resulting hyperinsulinemia
may cause a decreased sex-hormone binding globulin production
and an increased ovarian androgen production,b oth of which con-
tribute to the hyperandrogenism. However, this may form a vicious
circle as hyperandrogenism may also contribute to the insulin
resistance by increasing free fatty acid flux to the liver and muscle
through visceral lipolysis and, in addition, byaltering muscle struc-
ture toward less insulin-sensitive muscle fibers (5). In addition,
PCOS is associated with dyslipidemia and endothelial dysfunction
Abbreviations: BMI, body mass index; CI,confidence interval; GLP-1, glucagon-like
peptide-1; PCOS, polycystic ovary syndrome; SD, standard deviation.
(9,10). The most pronounced metabolic abnormalities are seen
in women with hyperandrogenism and obesity, especially central
obesity (8,11).
Even a modest weight loss in overweight or obese women with
PCOS reduces insulin resistance, hyperinsulinemia, and hyperan-
drogenism and increases sex-hormone binding globulin produc-
tion (1214), thereby improving hirsutism, menstrual cyclicity,
ovulation rates, and fertility. Especially, loss of intra-abdominal
fat is associated with resumption of ovulation (15). Furthermore,
weight loss has beneficial effects on cardiovascular risk factors
such as dyslipidemia and blood pressure (12). Therefore, weight
reduction is essential in overweight and obese women with PCOS.
Liraglutide, a glucagon-like peptide-1 (GLP-1) analog w ith 97%
structural homology to human GLP-1 is used in the treatment of
type 2 diabetes. GLP-1 is a gut hormone of the incretin family that
enhances glucose-stimulated insulin secretion, inhibits glucagon
secretion, delays gastric emptying, and reduces food intake and
appetite. In type 2 diabetes, liraglutide significantly lowers HbA1c
and, in addition, reduces body weight (16). A recent meta-analysis
concluded that GLP-1 receptor agonists not only had a significant
effect on weight loss in overweight type 2 diabetic patients but also
in non-diabetic overweight persons (17). Only one smaller study
has investigated the effect of liraglutide in PCOS patients reporting
a significantly greater weight loss with liraglutide in combination
with metformin than metformin alone (18). Furthermore, a ben-
eficial effect on blood pressure and cholesterol levels has been
observed with GLP-1 analogs (16,17).
Given that PCOS is a frequent condition and weight loss is
essential but difficult to achieve, it is important to study if the effect
www.frontiersin.org August 2014 |Volume 5 | Article 140 | 1
Rasmussen and Lindenberg Liraglutide for weight loss in PCOS
on body weight reported in other studies can be confirmed in a
selected population of PCOS patients, especially since liraglutide
is not currently approved for weight reduction. In this study, we
therefore investigated the effect of liraglutide on weight reduction
in a larger cohort of PCOS patients.
MATERIALS AND METHODS
The study population comprises all overweight or obese women
starting treatment with liraglutide in the period August 2010 to
January 2012 in a private gynecology and fertility clinic. The fol-
lowing variables were recorded: date of first prescription, age,body
weight at start of treatment, height, weight loss at clinical follow-
up, and dose of liraglutide. Patients were all diagnosed with PCOS
according to the Rotterdam criteria, were overweight or obese,
and had failed to lose any weight after 6 months with metformin
and life style intervention. The intervention consisted of a low-
glycemic diet with no caloric restriction, guidance by a dietitian,
and a recommendation of 45 min of moderate exercise for a min-
imum of three times per week. Treatment with metformin was
given due to insulin resistance and was therefore continued after
start of liraglutide. The procedures of the study were in accordance
with the Helsinki Declaration, and all patients were informed of
the off-label use of liraglutide and gave written informed consent.
Duration of treatment was calculated in full weeks from date
of prescription to discontinuation of treatment or date of last reg-
istered weight loss for patients still being treated. Body weight
and weight loss were self-reported. In patients who temporarily
stopped treatment and gained weight in the pause, weight loss was
calculated as net weight loss over the entire period. Starting dose
was 0.6 mg given as a subcutaneous injection once daily. Dose was
increased if no effect on weight (i.e., weight loss 0 kg) and no side
effects, initially to 1.2 mg and later to 1.8 mg.
Descriptive characteristics are reported as mean and standard
deviation (SD). Mean value with corresponding 95% confidence
interval for changes in body weight and BMI was estimated using
Student’s paired t-test. Level of statistical significance was set
at p<0.05 and all p-values were two-sided. Data analysis was
conducted in SAS, version 9.1 (SAS Institute, Cary, NC, USA).
RESULTS
A total of 105 overweight or obese women with PCOS had a pre-
scription of liraglutide. We excluded four patients who never used
the prescription. Of the 101 patients starting on liraglutide, four
patients (4.0%) were excluded because of discontinuation of treat-
ment due to side effects after less than 4 weeks, eight patients
(7.9%) were excluded because of missing data, and finally five
patients (5.0%) were lost to follow-up after <4weeks and were
excluded, leaving 84 patients for analysis (Figure 1).
Mean age at start of treatment was 35.5 years (SD 7.9). The
patients had a mean body weight at baseline of 98.9 kg (SD 17.0)
(Table 1). For two patients, no data on baseline weight could be
obtained, thus BMI could not be calculated. Of the remaining
82 women, 67 (81.7%) were obese defined as BMI30 and 15
(18.3%) were overweight with BMI between 25 and 30. Mean BMI
at baseline was 35.0 kg/m2(SD 6.0). Mean duration of treatment
was 27.8 weeks (SD 19.2). Twenty women (23.8%) were trying to
lose weight prior to fertility treatment and six women (7.1%) had
FIGURE 1 | Overview of women included in the study.
previously been treated for infertility. Two patients (2.4%) were
diagnosed with diabetes.
Overall, we observed a significant weight loss in women with
PCOS after treatment with liraglutide, the mean weight loss being
9.0 kg (95% CI: 7.8–10.1, p<0.0001). Likewise, a significant mean
decrease in BMI of 3.2 kg/m2(95% CI: 2.8–3.6, p<0.0001) was
found (Table 1). Two patients lost no weight, but no patients expe-
rienced a net weight gain. In all, 67 women (81.7%) lost more than
5% and 27 women (32.9%) lost more than 10% of their baseline
weight. The mean relative weight loss was 9.4% (95% CI: 8.2–10.6,
p<0.0001) of baseline weight.
A dose of 1.8 mg was reached at some point during treatment in
52/84 (61.9%) patients. As interval to increase in dose differed sub-
stantially among patients and some patients had multiple increases
and decreases, no comparisons between dose groups have been
made.
A total of 50/84 patients (59.5%) were treated for a mini-
mum of 20 weeks. When restricting analysis to patients treated
for 20 weeks or more, mean weight loss was 10.9 kg (95% CI:
9.4–12.5, p<0.0001) and mean decrease in BMI was 3.9 kg/m2
(95% CI: 3.3–4.4, p<0.0001) after a mean duration of 39.1 weeks
(SD 17.0). Figure 2 shows weight loss in relation to duration of
treatment.
Treatment with liraglutide was terminated for the following rea-
sons: achieving the desired weight loss in 10 women (11.9%), side
effects in four women (4.8%), start of fertility treatment or preg-
nancy in five women (6.0%), no further effect of liraglutide in 11
women (13.1%), moving or traveling in two women (2.4%), and in
one woman (1.2%) no reason was given. Six women (7.1%) were
Frontiers in Endocrinology | Experimental Endocrinology August 2014 | Volume 5 | Article 140 | 2
Rasmussen and Lindenberg Liraglutide for weight loss in PCOS
Table 1 | Changes in body weight and BMI after treatment with liraglutide in overweight and obese women with PCOS.
Baseline After treatment
with liraglutide
Decrease 95% CI p
Body weight (kg) 98.9 (17.0) 89.8 (17.8) 9.0 (5.3) 7.8–10.1 <0.0001
BMI (kg/m2) 35.0 (6.0) 31.8 (6.2) 3.2 (1.9) 2.8–3.6 <0.0001
Values are mean (SD). Student’s paired t-test was used to estimate mean difference from baseline with corresponding 95% confidence intervals (CI) and p-values.
BMI, body mass index.
FIGURE 2 | Scatterplot of the relation between duration of treatment with liraglutide and weight loss with best fitted right line and 95% confidence
interval.
lost to follow after more than 4 weeks of treatment. These women
were included in the analysis with data from their last clinical visit.
The remaining 45 women (53.6%) were still being treated with
liraglutide when conducting the present study.
A total of 19 women (22.6%) reported side effects. Nausea was
reported by six (7.1%), vomiting by one (1.2%), diarrhea by four
(4.8%), constipation by one (1.2%), abdominal pain/discomfort
by six (7.1%), itching by two (2.4%), and discomfort by four
(4.8%). In another four women (4.8%), side effect was not spec-
ified. Dose was reduced in nine women (10.7%) due to side
effects.
DISCUSSION
The prevalence of obesity is increasing worldwide. Due to its
weight reducing effect, the potential role of liraglutide in the treat-
ment of obesity is currently being debated including its role in
PCOS-related obesity (19,20). In the present study, treatment
with liraglutide in 84 overweight and obese women with PCOS
resulted in a significant weight loss of 9.0 kg. Only one smaller
study has evaluated the effect of liraglutide in PCOS and, in agree-
ment with our findings, showed a beneficial effect on body weight
(18). In a 12-week open-label study of 36 obese women with PCOS,
mean weight losses of 6.5, 3.8, and 1.2 kg with liraglutide 1.2 mg
plus metformin, liraglutide 1.2 mg alone, and metformin alone,
respectively, were reported. Weight loss with combination therapy
was significantly greater than with metformin alone. However,
there were only 11 patients in each of the two groups treated with
liraglutide. A meta-analysis of GLP-1 receptor agonists in type 2
diabetes and obesity, including eight trials using liraglutide, also
demonstrated a positive effect on weight loss (17). In type 2 dia-
betes, mean weight losses of 2.05, 2.45, and 2.8kg after 52 weeks
of liraglutide 1.2, 1.8, and 26 weeks of liraglutide 1.8 mg in com-
bination with metformin, respectively, have been reported (16,21,
22). In obese non-diabetic subjects, liraglutide in doses of 1.2, 1.8,
2.4, and 3.0 mg resulted in mean weight losses of 4.8, 5.5, 6.3, and
7.2 kg, respectively, after 20 weeks (23).
In our study, 81.7% of patients lost more than 5% of baseline
weight. In comparison, a 20-week randomized study of liraglutide
www.frontiersin.org August 2014 |Volume 5 | Article 140 | 3
Rasmussen and Lindenberg Liraglutide for weight loss in PCOS
in obese non-diabetic subjects demonstrated a relative weight loss
of 5% or more in 61% of individuals treated with liraglutide in
doses of 1.2–3.0 mg, with a higher proportion achieving this in the
highest dose group (23). In an extension of that trial, 64% of sub-
jects on liraglutide lost >5% of body weight after 1 year and 85%
of these maintained that weight loss after 2 years of treatment (24).
Differences in the magnitude of the effect of liraglutide on
weight loss between studies may be due to differences in study
populations and design. The population in our study is not com-
parable to most trials on liraglutide, which have been done on a
more diverse population with greater mean age and also includ-
ing men. Although, similar weight losses with liraglutide have
been observed in men and women (24), and none of the stud-
ies have reported weight loss in relation to age. All women in
our study were taking metformin simultaneously. Slightly, higher
mean weight reductions have been reported in trials of liraglutide
in combination with metformin than trials of liraglutide alone (21,
22), but no larger studies with direct comparison of liraglutide
monotherapy versus combination therapy with metformin could
be identified. Except for metformin, most antidiabetic drugs are
associated with weight gain potentially augmenting the effect of
liraglutide in studies in diabetic populations. Only two patients in
our study had diabetes. Furthermore, some women in the present
study were referred for infertility and could be more motivated to
make favorable changes in lifestyle in order to improve chance of
pregnancy and possibly also be willing to accept side effects to a
greater extent compared to type 2 diabetics or obese non-diabetics.
Additionally, we excluded patients dropping out before four full
weeks of treatment, whereas most of the above mentioned trials
have been based on analyses of the intention-to-treat population.
Finally, weight loss on liraglutide is dose-dependent with greater
loss with increasing dose (23,25), and 61.9% of patients in the
present study received a dose of 1.8 mg.
Our results are also in agreement with a study evaluating the
effect of another GLP-1 receptor agonist in PCOS.A 24-week ran-
domized study of exenatide demonstrated a mean weight loss of
3.2, 6.0, and 1.6kg with monotherapy, combination therapy with
metformin, and metformin alone, respectively, and in both exe-
natide arms was the difference from metformin alone statistically
significant (26). Liraglutide has been shown to decrease HbA1c
more than exenatide,but no difference in weight loss was observed
(25). However, the exenatide study had only 20 patients in each of
the 3 arms and thus had limitations of small sample size and also
a high drop-out rate of 30%.
A large proportion of women with PCOS are overweight or
obese and infertility due to anovulation is common. Significant
improvements in insulin resistance, hyperinsulinemia, dyslipide-
memia, menstrual cyclicity, ovulation rates, and fertility have been
shown with a modest relative weight loss of 5–10% in PCOS
(1215,27,28). Therefore, weight reduction is essential in the
management of PCOS. As 81.7 and 32.9% of patients in the present
study lost more than 5 and 10% of baseline weight, respectively, it
is possible that improvements in these parameters have occurred.
However, we had no information on metabolic and reproduc-
tive changes, and were thus unable to investigate any potential
effect of weight loss in this aspect. Exenatide combined with
metformin in PCOS significantly improved ovulation rates and
metabolic parameters (decreased free androgen index, total cho-
lesterol and trigyceride, increased insulin sensitivity measures) and
reduced abdominal girth compared with metformin alone (26). In
obese non-diabetic subjects, liraglutide has been shown to reduce
the prevalence of prediabetes with 84–96% and the proportion
of patients with metabolic syndrome by more than 60% (23).
Although no significant effect on menstrual frequency and most
metabolic and hormonal parameters were observed in women
with PCOS using liraglutide for 12 weeks, this is possibly due to
the short duration of that study (18).
Gastrointestinal side effects such as diarrhea, vomiting and, in
particular, nausea are common with liraglutide treatment. Nausea
has been reported by 11–48% and vomiting by 4–15% of sub-
jects taking liraglutide, and like the weight reduction it occurs in
a dose-dependent manner (2125). It could therefore be specu-
lated whether the weight reducing effect of liraglutide could be
ascribed to these side effects. However, nausea mostly occurred
in the first 4–6 weeks of treatment, was transient, and of mild
to moderate intensity (2125). In the present study, frequency
of side effects was generally low when compared to other stud-
ies of liraglutide. Reasons for this could include a slower dose
titration, but also our exclusion of patients who did not com-
plete 4 weeks of treatment, among these four women with side
effects. Additionally, some women lost to follow-up could have
dropped out because of side effects. Garber et al. found no differ-
ence in weight loss between patients with and without persistent
nausea (defined as 7 days) with liraglutide 1.2 and 1.8 mg (21).
Similar results were found in a post hoc analysis of the study by
Astrup et al. where the difference in weight loss between individ-
uals with and without nausea or vomiting was significant only
for the group on liraglutide 3.0 mg (29). Furthermore, the dose-
dependent weight reduction with increasing doses of liraglutide
was maintained both for participants with and without nausea
or vomiting. Finally, weight loss among patients without nau-
sea or vomiting was still significantly greater with liraglutide
than with placebo or orlistat (24). Thus, nausea may increase
weight loss some in high doses of liraglutide, but does not seem
to be a major contributor for the weight reduction seen with
liraglutide.
All patients in our study were taking metformin simultaneously.
Gastrointestinal side effects are also frequent with metformin.
It is therefore noteworthy that studies investigating combina-
tion therapy of liraglutide and metformin did not report higher
frequencies of nausea or vomiting than studies of liraglutide
monotherapy (21,22).
A limitation of our study is the lack of a placebo group.
Secondly, weight loss was self-reported, potentially reducing the
accuracy of the effect. Furthermore, weight loss from our study
is difficult to compare with studies of a fixed duration because of
great variations in duration of treatment among women in our
study. Treatment duration ranged from 4 to 76 weeks and weight
loss tended to increase with increasing duration of treatment with
liraglutide, probably contributing to the differences in weight loss
between subjects. Most studies have evaluated effect after at least
20 weeks of treatment. We tried to compensate for this by con-
ducting a subgroup analysis restricting duration to 20 weeks or
more, resulting in a slightly higher mean weight loss. In addition,
Frontiers in Endocrinology | Experimental Endocrinology August 2014 | Volume 5 | Article 140 | 4
Rasmussen and Lindenberg Liraglutide for weight loss in PCOS
all women had initially been treated with metformin and lifestyle
intervention with a low-glycemic diet and exercise for 6months,
and only women who did not lose any weight on this regimen
were prescribed liraglutide. After starting liraglutide, women were
encouraged to continue the lifestyle intervention. We cannot rule
out that this has contributed to the weight loss or that adher-
ence to lifestyle intervention might have changed. However, we do
not believe this to be the primary explanation for the weight loss.
Finally, the lack of information on improvements in reproductive
and metabolic dysfunction limits assessment of the clinical effect
of weight loss. This should be addressed in future studies.
In summary, the results of this study indicate that liraglutide in
combination with metformin and lifestyle intervention may be an
effective alternative for weight loss in women with PCOS who fail
to lose weight on diet, exercise, and metformin. However, larger
prospective placebo-controlled intervention studies in overweight
and obese women with PCOS are needed to establish the effect on
weight loss. The clinical effect of weight loss on reproductive and
metabolic parameters should be investigated. Finally, studies on
sustainability of the achieved weight loss are needed.
REFERENCES
1. Fauser BC, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, et al. Con-
sensus on women’s health aspects of polycystic ovary syndrome (PCOS): the
Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group.
Fertil Steril (2012) 97:28–38. doi:10.1016/j.fertnstert.2011.09.024
2. March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, Davies MJ. The
prevalence of polycystic ovary syndrome in a community sample assessed under
contrasting diagnostic criteria. Hum Reprod (2010) 25:544–51. doi:10.1093/
humrep/dep399
3. Broekmans FJ, Knauff EA, Valkenburg O, Laven JS, Eijkemans MJ, Fauser BC.
PCOS according to the Rotterdam consensus criteria: change in prevalence
among WHO-II anovulation and association with metabolic factors. BJOG
(2006) 113:1210–7. doi:10.1111/j.1471-0528.2006.01008.x
4. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group.
Revised 2003 consensus on diagnostic criteria and long-term health risks
related to polycystic ovary syndrome (PCOS). Hum Reprod (2004) 19:41–7.
doi:10.1093/humrep/deh098
5. Gambineri A, Pelusi C, Vicennati V, Pagotto U, Pasquali R. Obesity and the
polycystic ovary syndrome. Int J Obes Relat Metab Disord (2002) 26:883–96.
doi:10.1038/sj.ijo/0801994
6. Salley KE, Wickham EP, Cheang KI, Essah PA, Karjane NW, Nestler JE. Glu-
cose intolerance in polycystic ovary syndrome – a position statement of
the androgen excess society. J Clin Endocrinol Metab (2007) 92:4546–56.
doi:10.1210/jc.2007-1549
7. Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of
risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic
ovary syndrome: a prospective, controlled study in 254 affected women. J Clin
Endocrinol Metab (1999) 84:165–9. doi:10.1210/jc.84.1.165
8. DeUgarte CM, Bartolucci AA, Azziz R. Prevalence of insulin resistance in the
polycystic ovary syndrome using the homeostasis model assessment. Fertil Steril
(2005) 83:1454–60. doi:10.1016/j.fertnstert.2004.11.070
9. Norman RJ,Dewailly D, Legro RS, Hickey TE. Polycystic ovary syndrome. Lancet
(2007) 370:685–97. doi:10.1016/S0140-6736(07)61345-2
10. Glueck CJ, Papanna R, Wang P, Goldenberg N, Sieve-Smith L. Incidence and
treatment of metabolic syndrome in newly referred women with confirmed
polycystic ovarian syndrome. Metabolism (2003)52:908–15. doi:10.1016/S0026-
0495(03)00104-5
11. Goverde AJ, van Koert AJ, Eijkemans MJ, Knauff EA, Westerveld HE,Fauser BC,
et al. Indicators for metabolic disturbances in anovulatory women with polycys-
tic ovary syndrome diagnosed according to the Rotterdam consensus criteria.
Hum Reprod (2009) 24:710–7. doi:10.1093/humrep/den433
12. Thomson RL, Buckley JD,Noakes M, Clifton PM,Norman RJ, Brinkworth GD.
The effect of a hypocaloric diet with and without exercise training on body
composition, cardiometabolic risk profile, and reproductive function in over-
weight and obese women with polycystic ovary syndrome. J Clin Endocrinol
Metab (2008) 93:3373–80. doi:10.1210/jc.2008-0751
13. Stamets K, Taylor DS, Kunselman A, Demers LM, Pelkman CL, Legro RS. A
randomized trial of the effects of two types of short-term hypocaloric diets
on weight loss in women with polycystic ovary syndrome. Fertil Steril (2004)
81:630–7. doi:10.1016/j.fertnstert.2003.08.023
14. Tolino A, Gambardella V, Caccavale C, D’Ettore A, Giannotti F, D’Antò V,
et al. Evaluation of ovarian functionality after a dietary treatment in obese
women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol (2005)
119:87–93. doi:10.1016/j.ejogrb.2004.06.043
15. KuchenbeckerWK, Groen H, van Asselt SJ, Bolster JH, Zwerver J, Slart RH, et al.
In women with polycystic ovary syndrome and obesity, loss of intra-abdominal
fat is associated with resumption of ovulation. Hum Reprod (2011) 26:2505–12.
doi:10.1093/humrep/der229
16. Bode B. An overview of the pharmacokinetics, efficacy and safety of liraglutide.
Diabetes Res Clin Pract (2012) 97:27–42. doi:10.1016/j.diabres.2011.12.015
17. Vilsboll T, Christensen M, Junker AE, Knop FK, Gluud LL. Effects of glucagon-
like peptide-1 receptor agonists on weight loss: systematic review and meta-
analyses of randomised controlled trials. BMJ (2012) 344:d7771. doi:10.1136/
bmj.d7771
18. Jensterle SM, Kocjan T, Pfeifer M, Kravos NA, Janez A. Short-term combined
treatment with liraglutide and metformin leads to significant weight loss in
obese women with polycystic ovary syndrome and previous poor response to
metformin. Eur J Endocrinol (2014) 170:451–9. doi:10.1530/EJE-13-0797
19. Torekov SS, Madsbad S, Holst JJ. Obesity – an indication for GLP-1 treat-
ment? Obesity pathophysiology and GLP-1 treatment potential. Obes Rev (2011)
12:593–601. doi:10.1111/j.1467-789X.2011.00860.x
20. Kahal H, Atkin SL, Sathyapalan T. Pharmacological treatment of obesity in
patients with polycystic ovary syndrome. J Obes (2011) 2011:402052. doi:10.
1155/2011/402052
21. Garber A,Henr y R,Ratner R, Garcia-Hernandez PA,Rodriguez-Pattzi H, Olvera-
Alvarez I, et al. Liraglutide versus glimepiride monotherapy for type 2 diabetes
(LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-
treatment trial. Lancet (2009) 373:473–81. doi:10.1016/S0140-6736(08)61246- 5
22. Nauck M, Frid A, Hermansen K, Shah NS, Tankova T, Mitha IH, et al. Efficacy
and safety comparison of liraglutide, glimepiride, and placebo, all in combina-
tion with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action
in diabetes)-2 study. Diabetes Care (2009) 32:84–90. doi:10.2337/dc08-1355
23. Astrup A, Rössner S, Van Gaal L, Rissanen A, Niskanen L, Al Hakim M,
et al. Effects of liraglutide in the treatment of obesity: a randomised, double-
blind, placebo-controlled study. Lancet (2009) 374:1606–16. doi:10.1016/
S0140-6736(09)61375- 1
24. Astrup A, Carraro R, Finer N, Harper A, Kunesova M, Lean ME, et al. Safety, tol-
erability and sustained weight loss over 2 years with the once-daily human GLP-1
analog, liraglutide. Int J Obes (Lond) (2011) 36:843–54. doi:10.1038/ijo.2011.158
25. Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, et al. Liraglu-
tide once a day versus exenatide twice a day for type 2 diabetes: a 26-week
randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet
(2009) 374:39–47. doi:10.1016/S0140-6736(09)60659- 0
26. Elkind-Hirsch K, Marrioneaux O, Bhushan M, Vernor D, Bhushan R. Compari-
son of single and combined treatment with exenatide and metformin on men-
strual cyclicity in overweight women with polycystic ovary syndrome. J Clin
Endocrinol Metab (2008) 93:2670–8. doi:10.1210/jc.2008-0115
27. Crosignani PG, Colombo M, Vegetti W, Somigliana E, Gessati A, Ragni G. Over-
weight and obese anovulatory patients with polycystic ovaries: parallel improve-
ments in anthropometric indices, ovarian physiology and fertility rate induced
by diet. Hum Reprod (2003) 18:1928–32. doi:10.1093/humrep/deg367
28. Huber-Buchholz MM, Carey DG, Norman RJ. Restoration of reproductive
potential by lifestyle modification in obese polycystic ovary syndrome: role of
insulin sensitivity and luteinizing hormone. J Clin Endocrinol Metab (1999)
84:1470–4. doi:10.1210/jc.84.4.1470
29. Astrup A, Rossner S, van Gaal L, Rasmussen MF. Liraglutide for weight loss in
obese people. Lancet (2010) 375:552–3. doi:10.1016/S0140-6736(10)60227- 9
Conflict of Interest Statement: The authors declare that the researchwas conducted
in the absence of any commercial or financial relationships that could be construed
as a potential conflict of interest.
www.frontiersin.org August 2014 |Volume 5 | Article 140 | 5
Rasmussen and Lindenberg Liraglutide for weight loss in PCOS
Received: 26 May 2014; accepted: 12 August 2014; published online: 27 August 2014.
Citation: Rasmussen CB and Lindenberg S (2014) The effect of liraglutide on weight loss
in women with polycystic ovary syndrome: an observational study. Front. Endocrinol.
5:140. doi: 10.3389/fendo.2014.00140
This article was submitted to Experimental Endocrinology, a section of the journal
Frontiers in Endocrinology.
Copyright © 2014 Rasmussen and Lindenberg . This is an open-access article distr ibuted
under the terms of the Creative Commons Attribution License (CC BY). The use, dis-
tribution or reproduction in other forums is permitted, provided the original author(s)
or licensor are credited and that the original publication in this journal is cited, in
accordance with accepted academic practice. No use, distribution or reproduction is
permitted which does not comply with these terms.
Frontiers in Endocrinology | Experimental Endocrinology August 2014 | Volume 5 | Article 140 | 6
... Weight loss has beneficial effects on hirsutism, ovulation rates, fertility, BP, IR and cholesterol levels in women with PCOS [83]. Clinical Data: Combined LIRA and metformin (MET) treatment resulted in significant weight loss and decrease in WC in obese women with PCOS [84,85]. LIRA 1.2 mg was found to be more effective in decreasing BW than MET in subjects with severe obesity and PCOS [86]. ...
Article
Full-text available
Background: Obesity is a chronic disease associated with increased morbidity and mortality due to its complications. The aims of obesity treatment are primarily to accomplish weight loss, and prevention or treatment of its complications. Lifestyle changes along with behavioral therapy constitute the first line treatment of obesity followed by pharmacotherapy. Glucagon-like peptide receptor analogs (GLP-1 RA's) are among the approved pharmacotherapy options. Their central effect on suppressing appetite results in considerable weight loss. However their effect on the complications of obesity have not been very well recognized. This review aims to analyze the effects of GLP-RA's on the complications of obesity, as diabetes mellitus, hypertension, nonalcoholic steatohepatitis (NASH), cardiovascular diseases, polycystic ovary syndrome, infertility, obstructive sleep apnea (OSA) and central nervous system problems. Summary: Data from preclinical studies and clinical trials have been thoroughly evaluated. Effects regarding the complications as far as the scope of this review has covered can be summarized as blood glucose lowering, blood pressure lowering, resolution of NASH, improving major cardiovascular events, improving fertility and sex hormone levels, improvement in OSA symptoms and in cognitive scores. Although the mechanisms are not fully elucidated, it is clear that the effects are not solely due to weight loss, but some pleiotropic effects like decreased inflammation, oxidative stress and fibrosis also play role in some of the complications. Key messages: Treating obesity is not only enabling weight loss but ameliorating complications related with obesity. Thus any anti-obesity medication has to have some favorable effects on the complications. As far as the GLP-RA's analogs are concerned, there seem to be improvement in many of the complications regardless of the weight loss effect of these medications.
... The potential mechanism could be the utilization of GLP-1RA in gestational diabetes mellitus, a disease only harms women. Studies have indicated a potential beneficial [27][28][29]. Physiologically, GLP-1RA modulates mammalian hypothalamus, pituitary, gonads, ovaries, and has an anti-inflammatory and anti-fibrotic function. In the aspect of age, older adults had a higher chance of being prescribed SGLT2i. ...
Article
Full-text available
Backgrounds Robust evidence have demonstrated the beneficial effect of Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) in T2D patients with cardiovascular diseases and chronic kidney disease. Multiple studies analyzed patterns and predictors of SGLT2i and GLP-1RA in the US, Europe and worldwide. However, there is no study about the utilization of these two classes of drugs in real-world in China. Method A total of 181743 prescriptions of SGLT2i and 59720 GLP-1RA were retrospectively pooled from Hospital Prescription Analysis Cooperation Project from 2018 to 2021. The social-economic characteristics of patients and prescribers, including age, gender, residency, hospital level, insurance type, department visited, and payment amount, were collected and analyzed to study trends and risk factors associated with preference among two antidiabetics. Results Annual number of prescriptions of SGLT2i significantly increased to approximately 140 folds, while GLP-1RA increased to about 6.5 folds. After adjustment for socio-economic information, several patients or physician characteristics were positively associated with the preference of GLP-1RA, including female gender (OR 1.581, 95% CI 1.528-1.635), residents in second-tier cities (OR 1.194, 95% CI 1.148-1.142), visiting primary or secondary hospital level (OR 2.387, 95% CI 2.268-2.512); while other factors were associated with the preference of SGLT2i, including older adults (OR 0.713, 95% CI 0.688-0.739), uncovered by insurance (OR 0.310, 95% CI 0.293-0.329), visiting other departments compared with endocrinology. In addition, the share of SGLT2i and GLP-1RA was low but in an increasing tendency. Conclusions SGLT2i and GLP-1RA prescription significantly increased from 2018 to 2021. The socio-economic risk factors in choosing SGLT2i or GLP-1RA highlight an effort required to reduce disparities and improve health outcomes.
... Liraglutid ist ein GLP-1-Analogon mit Zulassung zur Gewichtsreduktion. Studien konnten zeigen, dass eine Behandlung mit Liraglutid in Kombination mit Metformin und Lebensstilveränderung zu einem signifikanten Gewichtsverlust bei übergewichtigen Patientinnen mit PCOS geführt hat [19]. ...
Article
Full-text available
Zusammenfassung In der vorliegenden Arbeit werden die funktionelle Androgenisierung der Frau und ihre Einteilung dargestellt. Bei der funktionellen Androgenisierung handelt es sich um eine Gruppe komplexer endokriner Störungen, zu denen das polyzystische Ovarsyndrom (PCOS) und das „late onset“ adrenogenitale Syndrom (AGS) gehören. Man unterscheidet die funktionelle kutane Androgenisierung vom funktionell androgenisierenden Syndrom. Die Darstellung der verschiedenen Formen der funktionellen Androgenisierung kann Hilfestellung bei der Diagnostik und Therapie der heterogenen und komplexen Erkrankungsbilder leisten. Insbesondere in der Behandlung des PCOS kann hiermit gezielter auf die verschiedenen Symptombereiche eingegangen werden.
... Significant reductions in BMI, abdominal circumference and body weight were reported when LIRA was administered, both as a monotherapy and together with metformin (MET), in overweight or obese women with PCOS. [37][38][39][40][41][42][43][44][45] Sex hormone-binding globulin (SHBG) levels were significantly increased and free testosterone (T) levels were significantly reduced in several of these studies. 38,41,43,44 A preprint version of the SAXAPCOS study (NCT03480022), in which 82 women with PCOS were randomly assigned to LIRA group (3 mg, n = 55) or placebo group (n = 27) for 32 weeks, stated that LIRA decreased the free androgen index (FAI), while it increased SHBG levels compared to placebo (p < 0.049 and p < 0.006, respectively). ...
Article
Full-text available
Polycystic ovary syndrome (PCOS) is a disorder that involves several organ systems and cellular pathways. It is strongly influenced by environmental and epigenetic factors. The principal goal of all therapeutic approaches to individuals with reproductive abnormalities is the treatment of subfertility or the regulation of menstruation when pregnancy is not desired. Obesity is closely related to insulin resistance (IR) and subsequent hyperinsulinemia, which aggravate hyperandrogenism and impair early follicle development. Weight loss is of vital importance for overweight/obese individuals with anovulatory infertility. The GLP-1R agonists have achieved remarkable weight reduction and abdominal fat loss in patients with type 2 diabetes (T2D), as well as in overweight/obese individuals and individuals with prediabetes. They have also been shown to promote lower fasting insulin levels and insulin resistance markers. These beneficial effects have been suggested to be particularly helpful in women with PCOS, while their possible role in the hypothalamic-pituitary-gonadal axis is under intense research. This review analyzes the current evidence for GLP-1R agonists, focusing on their effects on ovarian morphology, menstrual dysfunction and fertility outcomes. It also discusses their future role in achieving targeted therapeutic approaches.
... Therefore, new medication such as GLP-1 agonist [8] has been very efficient. This in combination with metformin might even be better in the obese PCO patient [9] having manifest insulin resistance. Bearing in mind the very high number of patients gaining weight after treatment, low dose treatment for a longer time might ...
Article
Full-text available
The aim of this study is to scan different doses of Liraglutid on the neural tube in a chick embryo model, which is similar to first month development in mammals. 100 eggs of 61 ± 5 gr, specific pathogen-free 0 day white fertilized chicken eggs were used. Incubation of 28 hours was maintained at a constant temperature of 37.5 ± 0.5°C, humidity in the range of 60-68%. They were divided into 4 groups of 25 eggs each. Liraglutid was administered subblastodermically with a Hamilton micro-injector in 3 different doses. The control group was injected with 0.9% sterile saline, and the experimental groups were injected with liraglutide at doses of 1.5, 7.5 and 15 µg/egg. After the injection, the windows were closed with sterile drape and left for incubation. At the end of 48 hours of incubation, all eggs were hatched and evaluated on the basis of Hamburger-Hamilton scale. In the study, neural tube patency, somite numbers, and Hamburger-Hamilton stages were examined, it was determined that the dose-related difference between the control and experimental groups was not statistically significant (p>0.05). It was determined that the difference between the high dose group and the other groups in terms of fore-aft lengths was statistically significant (P<0.05). As a result, there was no significant relationship between the doses of Liraglutide and neural tube patency and somite counts, but differences were found between fore-aft measurements. Further research is recommended for a clearer understanding of the effects of liraglutide on embryo development. ÖZ Bu çalıĢmada tip 2 diyabet ve obezite tedavisinde kullanılan inkretin bazlı glukagon benzeri peptid-1 (GLP-1) reseptör agonistlerinden liraglutid'in tavuk embriyo modelinde nöral tüp üzerine etkilerinin incelenmesi amaçlandı. ÇalıĢmada 100 adet 61 ± 5 gr ağırlıkta, spesifik patojen içermeyen fertil yumurta 37.5 ± 0.5°C'de ve % 60-68 nem ortamında 28 saat inkübe edildi. Bu süre sonunda pencereleme tekniği ile açılan yumurtalar 4 gruba (n=25) ayrılarak subblastodermik olarak uygulama yapıldı. Kontrol grubuna % 0.9 steril serum fizyolojik, deney gruplarına ise 1.5, 7.5 ve 15 µg/yumurta dozda liraglutid enjekte edildi. Enjeksiyon sonrası pencereler steril drape ile kapatılarak inkübasyona bırakıldı. 48 saat inkübasyon sonunda tüm yumurtalar açılıp Hamburger-Hamilton skalası temel alınarak değerlendirildi. ÇalıĢmada nöral tüp açıklığı, somit sayıları, Hamburger Hamilton skalasına göre geliĢim evreleri incelendiğinde kontrol grubu ile deney grupları arasındaki doza bağlı farkın istatistiksel olarak anlamlı olmadığı tespit edildi (p>0.05). BaĢ-kıç uzunlukları bakımından yüksek doz grubu ile diğer gruplar arasındaki farkın istatistiksel olarak anlamlı olduğu tespit edildi (P<0.05). Sonuç olarak Liraglutid'in dozları ile nöral tüp açıklığı ve somit sayıları arasında anlamlı bir iliĢki saptanmazken baĢ-kıç ölçümleri arasında farklılıklar saptandı. Liraglutid'in embriyo geliĢimi üzerine etkilerinin daha net anlaĢılması için ileri araĢtırmalar önerilmektedir. Anahtar Kelimeler: tavuk embriyo modeli, inkretinler, liraglutid, nöral tüp, obezite.
Article
Currently, gastrointestinal hormone glucagon like peptide-1 (GLP-1) has received significant attention in maintaining glucose homeostasis through mechanisms involving augmentation of insulin, inhibition of glucagon secretion and regulation of gut motility. Therefore, GLP-1 receptor agonist (GLP-1RA) turns to be one of the most promising hypoglycemic agents for the treatment of type 2 diabetes mellitus (T2DM) and obesity. However, the benefits of GLP-1 and GLP-1RAs are not limited to glucose control and weight loss. Here, we provide a concise overview of the roles of GLP-1 and GLP-1RAs in autoimmune disease, cardiovascular disease (CVD), diabetic kidney disease (DKD), diabetic foot ulcer (DFU), polycystic ovary syndrome (PCOS), and Alzheimer's disease (AD) as well as future challenges in this regard.
Article
Full-text available
Despite the continuous effort to understand the pathophysiology and determine potential therapeutic targets, PCOS treatment largely depends on lifestyle intervention and symptomatic management of individual signs and symptoms. International guidelines recognize the importance of weight reduction as a cornerstone for the achievement of better metabolic, reproductive, and car-diovascular outcomes in PCOS women who are overweight or obese. With its profound weight loss potential in patients with or without diabetes, the administration of GLP-1 receptor agonists has been investigated in overweight/obese women with PCOS in several single-center randomized control trials with considerable variation in the dosing regimen, follow-up duration, and outcome measurements over recent years. Most trials reported superior weight loss effects of GLP-1 receptor agonists compared to lifestyle changes or metformin, with additional metabolic, reproductive, and cardiovascular benefits in this population. However, their use is currently not widely accepted by the clinical community that treats this population. The major concern is how to balance the reproductive and metabolic treatment strategies since the use of GLP-1 receptor agonists requires effective contraception while on therapy and a washout period before pregnancy. Both approaches are not mutually exclusive, yet the best choice requires a careful assessment of the clinical context. Knowing a patient's individual circumstances, precise clinical sub-phenotyping, and regular monitoring are crucial components for the safe and effective use of these new tools. In the present narrative review, we explore the current clinical evidence and provide the future perspectives and challenges for their implementation in PCOS management.
Article
Full-text available
Bu çalışmada tip 2 diyabet ve obezite tedavisinde kullanılan inkretin bazlı glukagon benzeri peptid-1 (GLP-1) reseptör agonistlerinden liraglutid’in civciv embriyo modelinde nöral tüp üzerine etkilerinin incelenmesi amaçlandı. Çalışmada 100 adet 61 ± 5 gr ağırlıkta, spesifik patojen içermeyen yumurta 37.5 ± 0.5°C’de ve % 60 - 68 nem ortamında 28 saat inkübe edildi. Bu süre sonunda pencerleme tekniği ile açılan yumurtalar 4 gruba (n=25) ayrılarak subblastodermik olarak uygulama yapıldı. Kontrol grubuna % 0.9 steril serum fizyolojik, deney gruplarına ise 1.5 µg, 7.5 µg ve 15 µg dozda liraglutid enjekte edildi. Enjeksiyon sonrası pencereler steril drape ile kapatılarak inkübasyona bırakıldı. 48 saat inkübasyon sonunda tüm yumurtalar açılıp Hamburger-Hamilton skalası temel alınarak değerlendirildi. Çalışmada nöral tüp açıklığı, somit sayıları, Hamburger Hamilton evreleri incelenmesinde kontrol grubu ile deney grupları arasındaki doza bağlı farkın istatistiksel olarak anlamlı olmadığı tespit edildi (p>0.05). Baş-kıç uzunlukları bakımından yüksek doz grubu ile diğer gruplar arasındaki farkın istatistiksel olarak anlamlı olduğu tespit edildi (P
Chapter
Polycystic ovary syndrome (PCOS) is one of the most common reproductive health problems of women, causing irregular periods and potential infertility amongst other challenging symptoms. Effective treatment remains a significant challenge and is largely achieved through hormonal medication and lifestyle changes. This third edition covers the aetiology, pathology, impact on fertility and effective medical and surgical management. The content has been thoroughly revised in line with updated guidelines and research developments in the field. A new chapter on the patient's perspective has been included, bringing valuable insight into the lived experience of the condition. Mood disorders and the psychological aspects of PCOS are also covered for the first time. This is a key reference for all clinicians involved in the care of patients with PCOS, including gynaecologists, IVF specialists and reproductive endocrinologists.
Article
Full-text available
Since the 1990 NIH‐sponsored conference on polycystic ovary syndrome (PCOS), it has become appreciated that the syndrome encompasses a broader spectrum of signs and symptoms of ovarian dysfunction than those defined by the original diagnostic criteria. The 2003 Rotterdam consensus workshop concluded that PCOS is a syndrome of ovarian dysfunction along with the cardinal features hyperandrogenism and polycystic ovary (PCO) morphology. PCOS remains a syndrome and, as such, no single diagnostic criterion (such as hyperandrogenism or PCO) is sufficient for clinical diagnosis. Its clinical manifestations may include: menstrual irregularities, signs of androgen excess, and obesity. Insulin resistance and elevated serum LH levels are also common features in PCOS. PCOS is associated with an increased risk of type 2 diabetes and cardiovascular events.
Article
Full-text available
OBJECTIVETHE EFFECT OF METFORMIN ON WEIGHT REDUCTION IN POLYCYSTIC OVARY SYNDROME (PCOS) IS OFTEN UNSATISFACTORY. WE INVESTIGATED THE POTENTIAL ADD-ON EFFECT OF TREATMENT WITH THE GLUCAGON-LIKE PEPTIDE 1 RECEPTOR AGONIST LIRAGLUTIDE ON WEIGHT LOSS IN OBESE NON-DIABETIC WOMEN WITH PCOS WHO HAD LOST LESS THAN 5% BODY WEIGHT DURING PRE-TREATMENT WITH METFORMIN.METHODS40 OBESE WOMEN WITH PCOS WHO HAD BEEN PRE-TREATED WITH METFORMIN FOR AT LEAST 6 MONTHS, PARTICIPATED IN A 12-WEEK OPEN, PROSPECTIVE STUDY. metformin arm (MET) 1000 mg BID, liraglutide arm (LIRA) 1.2 mg QD sc or combined - MET 1000 mg BID and LIRA 1.2 mg QD sc (COMBI). The primary outcome was change in body weight. RESULTS36 PATIENTS (AGED 31.3 7.1 YEARS, BMI 37.1 4.6 KG/M2) COMPLETED THE STUDY: 14 on MET, 11 on LIRA and 11 on combined treatment. COMBI therapy was superior to LIRA and MET monotherapy in reducing weight, BMI and waist circumference. Subjects treated with COMBI lost on average 6.5 ± 2.8 kg compared with a 3.8 ± 3.7 kg loss in LIRA group and a 1.2±1.4 kg loss in MET group (p<0.001). BMI decreased for 2.4±1.0 in COMBI arm compared to 1.3±1.3 in LIRA and 0.5±0.5 in MET arm (p<0.001). Waist circumference also decreased for 5.5±3.8 cm in COMBI arm compared to 3.2±2.9 cm in LIRA and 1.6±2.9 cm in MET arm (p=0.029). Subjects treated with liraglutide experienced more nausea than those treated with metformin, but severity of nausea decreased over time and did not correlate with weight loss.Conclusions Short-term combined treatment with liraglutide and metformin was associated with significant weight loss and decrease in waist circumference in obese women with PCOS who had been previously poor responders regarding weight reduction on metformin monotherapy.
Article
Full-text available
To determine whether treatment with agonists of glucagon-like peptide-1 receptor (GLP-1R) result in weight loss in overweight or obese patients with or without type 2 diabetes mellitus. Systematic review with meta-analyses. Electronic searches (Cochrane Library, Medline, Embase, and Web of Science) and manual searches (up to May 2011). Review methods Randomised controlled trials of adult participants with a body mass index of 25 or higher; with or without type 2 diabetes mellitus; and who received exenatide twice daily, exenatide once weekly, or liraglutide once daily at clinically relevant doses for at least 20 weeks. Control interventions assessed were placebo, oral antidiabetic drugs, or insulin. Three authors independently extracted data. We used random effects models for the primary meta-analyses. We also did subgroup, sensitivity, regression, and sequential analyses to evaluate sources of intertrial heterogeneity, bias, and the robustness of results after adjusting for multiple testing and random errors. 25 trials were included in the analysis. GLP-1R agonist groups achieved a greater weight loss than control groups (weighted mean difference -2.9 kg, 95% confidence interval -3.6 to -2.2; 21 trials, 6411 participants). We found evidence of intertrial heterogeneity, but no evidence of bias or small study effects in regression analyses. The results were confirmed in sequential analyses. We recorded weight loss in the GLP-1R agonist groups for patients without diabetes (-3.2 kg, -4.3 to -2.1; three trials) as well as patients with diabetes (-2.8 kg, -3.4 to -2.3; 18 trials). In the overall analysis, GLP-1R agonists had beneficial effects on systolic and diastolic blood pressure, plasma concentrations of cholesterol, and glycaemic control, but did not have a significant effect on plasma concentrations of liver enzymes. GLP-1R agonists were associated with nausea, diarrhoea, and vomiting, but not with hypoglycaemia. The present review provides evidence that treatment with GLP-1R agonists leads to weight loss in overweight or obese patients with or without type 2 diabetes mellitus.
Article
Full-text available
Having demonstrated short-term weight loss with liraglutide in this group of obese adults, we now evaluate safety/tolerability (primary outcome) and long-term efficacy for sustaining weight loss (secondary outcome) over 2 years. A randomized, double-blind, placebo-controlled 20-week study with 2-year extension (sponsor unblinded at 20 weeks, participants/investigators at 1 year) in 19 European clinical research centers. A total of 564 adults (n=90-98 per group; body mass index 30-40 kg m(-2)) enrolled, 398 entered the extension and 268 completed the 2-year trial. Participants received diet (500 kcal deficit per day) and exercise counseling during 2-week run-in, before being randomly assigned (with a telephone or web-based system) to once-daily subcutaneous liraglutide (1.2, 1.8, 2.4 or 3.0 mg, n=90-95), placebo (n=98) or open-label orlistat (120 mg × 3, n=95). After 1 year, liraglutide/placebo recipients switched to liraglutide 2.4 mg, then 3.0 mg (based on 20-week and 1-year results, respectively). The trial ran from January 2007-April 2009 and is registered with Clinicaltrials.gov, number NCT00480909. From randomization to year 1, liraglutide 3.0 mg recipients lost 5.8 kg (95% confidence interval 3.7-8.0) more weight than those on placebo and 3.8 kg (1.6-6.0) more than those on orlistat (P0.0001; intention-to-treat, last-observation-carried-forward). At year 2, participants on liraglutide 2.4/3.0 mg for the full 2 years (pooled group, n=184) lost 3.0 kg (1.3-4.7) more weight than those on orlistat (n=95; P<0.001). Completers on liraglutide 2.4/3.0 mg (n=92) maintained a 2-year weight loss of 7.8 kg from screening. With liraglutide 3.0 mg, 20-week body fat decreased by 15.4% and lean tissue by 2.0%. The most frequent drug-related side effects were mild to moderate, transient nausea and vomiting. With liraglutide 2.4/3.0 mg, the 2-year prevalence of prediabetes and metabolic syndrome decreased by 52 and 59%, with improvements in blood pressure and lipids. Liraglutide is well tolerated, sustains weight loss over 2 years and improves cardiovascular risk factors.
Article
Full-text available
It is not clear why some anovulatory women with polycystic ovary syndrome (PCOS) and obesity resume ovulation and others remain anovulatory after weight loss. The objective of this study was to compare the changes in body fat distribution and specifically intra-abdominal fat (IAF) and subcutaneous abdominal fat (SAF) between a group of anovulatory women with PCOS and obesity who resume ovulation (RO+) to those who remain anovulatory (RO-) during a lifestyle program. In a prospective pilot cohort study, anovulatory women with PCOS underwent a 6 month lifestyle program in a tertiary fertility clinic. Body fat distribution was assessed by anthropometrics, dual-energy X-ray absorptiometry (DEXA) and single slice abdominal CT scan at intake, after 3 months and after 6 months. Baseline-corrected changes over time were analysed using generalized estimating equations longitudinal regression analysis. In 32 anovulatory women with PCOS (age, 28 ± 4 years; BMI, 37.5 ± 5.0 kg/m²), there were no significant baseline differences in anthropometrics and biochemical assessment between 14 RO+ participants and 18 RO- participants. RO+ women lost more weight (6.3 versus 3.0%) and abdominal fat on DEXA (15.0 versus 4.3%) compared with RO- women. Resumption of ovulation was associated with early and consistent loss of IAF (12.4 versus 5.0% at 3 months and 18.5 versus 8.6% at 6 months). Loss of SAF between the RO+ women and the RO- women was similar at 3 months (6.2 versus 6.1%) but did not change any further in RO- women (6.1%) as it did in RO+ women (11.4%) at 6 months. In anovulatory women with PCOS and obesity undergoing a lifestyle program, RO+ women lose more body weight and abdominal fat on DEXA than RO- women. In addition, this study shows that early and consistent loss of IAF is associated with resumption of ovulation. Future studies should address the mechanisms behind these changes and should assess interventions aimed at loss of IAF to facilitate resumption of ovulation.
Article
Incretin-based therapies, including glucagon-like peptide 1 (GLP-1) receptor agonists, are the latest addition to the range of available medications for the management of patients with type 2 diabetes. The GLP-1 analog liraglutide has been approved for use in Europe and the US for over a year and has undergone evaluation in several pharmacokinetic/pharmacodynamics studies and in an extensive phase 3 clinical program. The aim of this review is to assess the pharmacokinetics, efficacy and safety of the phase 3 data. Data are presented from the pharmacokinetics/pharmacodynamics studies of liraglutide and from nine published phase 3 studies, including the six Liraglutide Effect and Action in Diabetes (LEAD) studies. Liraglutide is effective at improving indices of glycemic control, and has a good tolerability and safety profile. Beneficial effects on weight (mean reduction of 1-3.4 kg) and blood pressure (systolic blood pressure decreased by 2.1-6.7 mmHg) are also observed. Liraglutide is an effective and well tolerated option for the treatment of type 2 diabetes.
Article
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in females, with a high prevalence. The etiology of this heterogeneous condition remains obscure, and its phenotype expression varies. Two widely cited previous ESHRE/ASRM sponsored PCOS consensus workshops focused on diagnosis (published in 2004) and infertility management (published in 2008), respectively. The present third PCOS consensus report summarizes current knowledge and identifies knowledge gaps regarding various women's health aspects of PCOS. Relevant topics addressed-all dealt with in a systematic fashion-include adolescence, hirsutism and acne, contraception, menstrual cycle abnormalities, quality of life, ethnicity, pregnancy complications, long-term metabolic and cardiovascular health, and finally cancer risk. Additional, comprehensive background information is provided separately in an extended online publication.
Article
Obesity is common and associated with a high rate of morbidity and mortality; therefore, treatment is of great interest. At present, bariatric surgery is the only truly successful treatment of severe obesity. Mimicking one of the effects of bariatric surgery, namely the increased secretion of glucagon-like peptide (GLP)-1, by artificially increasing the levels of GLP-1 might prove successful as obesity treatment. Recent studies have shown that GLP-1 is a physiological regulator of appetite and food intake. The effect on food intake and satiety is preserved in obese subjects and GLP-1 may therefore have a therapeutic potential. The GLP-1 analogues result in a moderate average weight loss, which is clinically relevant in relation to reducing the risk of type 2 diabetes and cardiovascular disease. Inspired by the hormone profile after gastric bypass, a future strategy in obesity drug development could be to combine several hormones, and thereby produce a superior appetite suppressing hormone profile that may result in a weight loss exceeding that seen in single-agent trials. In conclusion, with the GLP-1 analogues combining a moderate weight loss with beneficial effects on metabolic and cardiovascular risk factors, it seems that we are on the right track for future treatment of obesity.