Carmina, E., & Longo, R. A. (2023). Semaglutide Treatment of Excessive Body Weight in Obese PCOS Patients Unresponsive to Lifestyle Programs. Journal of clinical medicine, 12(18). https://doi.org/10.3390/jcm12185921
Carmina E, Longo RA. Semaglutide Treatment of Excessive Body Weight in Obese PCOS Patients Unresponsive to Lifestyle Programs. Journal of clinical medicine. 2023;12(18). doi:10.3390/jcm12185921
Carmina, E., and R. A. Longo. "Semaglutide Treatment of Excessive Body Weight in Obese PCOS Patients Unresponsive to Lifestyle Programs." Journal of clinical medicine, vol. 12, no. 18, 2023.
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In spite of the widespread use of lifestyle modifications programs, many patients with PCOS are obese and prevalence of obesity in PCOS remains high. In this study, we present the data on the use of semaglutide, an incretin mimetic drug, in obese PCOS patients who were unresponsive to a lifestyle modification program. Twenty-seven obese patients with a diagnosis of PCOS, who did not reduce their body weight by a lifestyle modification program, were included in this study and treated by semaglutide, 0.5 mg subcutaneously once a week. After three months of treatment, an improvement in body weight with a mean decrease in body weight of 7.6 kg and a mean BMI loss of 3.1 was observed, while very few side effects were reported. Almost 80% of the studied obese PCOS patients obtained at least a 5% decrease in their body weight. Only a few patients (22%) obtained a decrease in body weight lower than 5% and were considered non-responsive to semaglutide, at least at the used doses. These patients presented a more severe obesity than responsive patients. Independently of results on body weight, and in patients who did not obtain a 5% decrease in their body weight, insulin basal values decreased, and HOMA-IR improved. Fasting blood glucose normalized in 80% of semaglutide-treated IFG PCOS women. In patients who were responsive to semaglutide (weight loss > 5%), the treatment was continued for additional three months. Weight loss slowed but continued and, at the end of the six months of therapy, the mean body weight loss was 11.5 kg and mean BMI reduced from 34.4 to 29.4. A total of 80% of responsive patients normalized menstrual cycles. In conclusion, treatment with semaglutide, at low doses, significantly reduces body weight in almost 80% of obese PCOS patients who were unresponsive to a previous lifestyle plan. It is often associated with the normalization of menstrual cycles, and these important results are obtained with very few side effects.
Carmina E et al., 2026·Journal of clinical medicine·Free full text on PubMed Central
Irregular menses and chronic anovulation are key components of Polyendocrine Metabolic Ovarian Syndrome (PMOS), but available treatments generally only mask the clinical problem, which presents itself again when the drugs are stopped. Because reduction of body weight in these patients is often associated with improvement of menstrual cycles, we evaluated the effects of treatment with semaglutide, a GLP-1 agonist that has emerged as an effective treatment for obesity. A total of 96 women with PMOS and body mass index (BMI) > 25 kg/m2 completed a six-month treatment protocol with semaglutide using an individualized dose-escalation regimen. Body weight, fasting glucose, insulin levels, insulin resistance (HOMA-IR), and ovulatory function were assessed before and after treatment. After six months of treatment, mean body weight decreased significantly (-11.3 ± 5%, p < 0.01). Before treatment, 83% of PMOS patients presented with oligomenorrhea and anovulatory cycles. Following treatment, ovulatory cycles were observed in 52.5% of previously anovulatory women. The results were particularly good in overweight patients, with almost 95% of these PMOS patients achieving menstrual cycle normalization and ovulation, but also in patients with mild obesity. Results were less favorable in PMOS patients with moderate or severe obesity, but 25% of these patients achieved menstrual ovulatory cycle normalization when treated with semaglutide. This study represents an important therapeutic advancement, suggesting that women with PMOS and excessive body weight should be considered for treatment with GLP-1 receptor agonists before proceeding to therapies specifically aimed at inducing normal cycles and ovulation.
To determine the prevalence of polycystic ovary syndrome (PCOS) among hyperandrogenic women who report normal menses. Prospective observational study. Academic practice in reproductive endocrinology. PATIENT(S): Fifty-eight consecutively seen new patients with hyperandrogenism who reported normal menses. INTERVENTION(S): Ovulatory status was assessed with timed serum progesterone measurements. The following tests also were carried out: vaginal ultrasound examination; measurement of the ovarian response of 17-hydroxyprogesterone (17-OHP) after the administration of leuprolide acetate, 1 mg SC; and determination of fasting serum LH, FSH, E2, 17-OHP, insulin, and androgen levels. MAIN OUTCOME MEASURE(S): Determination of ovulatory status, polycystic appearance of ovaries, and increased response of 17-OHP to leuprolide acetate. RESULT(S): Twelve (20.7%) of the hyperandrogenic women were anovulatory and met the usual criteria for the diagnosis of PCOS. The ovulatory patients had lower serum total and unbound testosterone levels. Thirty-one (53.4%) of the ovulatory women had polycystic ovaries on ultrasound examination and/or an increased 17-OHP response to leuprolide acetate, suggesting the diagnosis of PCOS despite the presence of ovulation. Considering both the anovulatory and ovulatory patients, 74% of the hyperandrogenic women studied could have PCOS. CONCLUSION(S): The data suggest that most (74%) hyperandrogenic women who report normal menses have evidence for the diagnosis of PCOS.
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Metabolic and Endocrine Agents · GLP-1 Receptor Agonists
McCrimmon RJ et al., 2020·Diabetologia·Free full text on PubMed Central
Intra-abdominal or visceral obesity is associated with insulin resistance and an increased risk for cardiovascular disease. This study aimed to compare the effects of semaglutide 1.0 mg and canagliflozin 300 mg on body composition in a subset of participants from the SUSTAIN 8 Phase IIIB, randomised double-blind trial who underwent whole-body dual-energy x-ray absorptiometry (DXA) scanning. Adults (age >=18 years) with type 2 diabetes, HbA1c 53-91 mmol/mol (7.0-10.5%), on a stable daily dose of metformin (>=1500 mg or maximum tolerated dose) and with an eGFR >=60 ml/min/1.73m2 were randomised 1:1 to semaglutide 1.0 mg once weekly and canagliflozin placebo once daily, or canagliflozin 300 mg once daily and semaglutide placebo once weekly. Body composition was assessed using whole-body DXA scans. Change from baseline to week 52 in total fat mass (kg) was the confirmatory efficacy endpoint. A subset of 178 participants (semaglutide, n = 88; canagliflozin, n = 90) underwent DXA scanning at screening and were randomised into the substudy. Of these, 114 (semaglutide, n = 53; canagliflozin, n = 61) participants had observed end-of-treatment data included in the confirmatory efficacy analysis. Numerical improvements in body composition (including fat mass, lean mass and visceral fat mass) were observed after 52 weeks with both treatments. Total fat mass (baseline 33.2 kg) was reduced by 3.4 kg and 2.6 kg with semaglutide and canagliflozin, respectively (estimated treatment difference: -0.79 [95% CI -2.10, 0.51]). Total lean mass (baseline 51.3 kg) was also reduced by 2.3 kg and 1.5 kg with semaglutide and canagliflozin, respectively (estimated treatment difference: -0.78 [-1.61, 0.04]), though the proportion of lean mass (baseline 59.4%) increased by 1.2- and 1.1-percentage points, respectively. Changes in visceral fat mass and overall changes in body composition (fat to lean mass ratio) were comparable between treatment groups. In individuals with uncontrolled type 2 diabetes on stable-dose metformin therapy, the changes in body composition with semaglutide and canagliflozin were not significantly different; there was no placebo arm, so the specific impact of either treatment on body composition is speculative.
Metabolic and Endocrine Agents · GLP-1 Receptor Agonists
Weight loss remains one of the most important arms in obese patients with polycystic ovary syndrome (PCOS). Further studies are needed to identify the best treatment. To evaluate the effects of exenatide (EXE) on reproductive and metabolic function in overweight/obese (OW/OB) PCOS. This is a 24-week open-label prospective, randomized, clinical study. This study randomized 176 OW/OB women diagnosed with PCOS to receive either EXE 10 μg BID (n = 88) or metformin (MET) 1000 mg BID (n = 88) for the first 12 weeks. Then all patients were treated with MET alone during the second 12 weeks. We observed metabolic parameters at 0 and 12 weeks, and then tracked the rate of pregnancy during the second 12 weeks. After the first 12 weeks of intervention, compared with MET, subjects who received EXE had significantly decreased weight (4.29 ± 1.29 kg vs 2.28 ± 0.55 kg, P < .001) and total fat% (4.67 ± 0.09% vs 1.11 ± 0.32%, P < .001), improved the homeostasis model of assessment for insulin resistance (1.30 ± 0.58 vs 0.59 ± 0.12, P < .001) and increased the menstrual frequency ratio (0.62 ± 0.12 vs 0.37 ± 0.01, P < .001). During the second 12 weeks, the rate of natural pregnancy of EXE-treated patients was significantly higher than MET-treated patients (43.60% vs 18.70%, P < .05). Short-term EXE therapy was linked to significant weight loss and central adiposity reduction, which may further explain the improvements in insulin resistance, inflammatory marker and menstrual cycle, which may contribute to increasing pregnancy rates in OW/OB women with PCOS.
Metabolic and Endocrine Agents · GLP-1 Receptor Agonists
Becker AS et al., 2026·JBRA assisted reproduction·Free full text on PubMed Central
GLP-1 receptor agonists (GLP-1RAs) have gained attention as a potential adjunct in preconception care for women with polycystic ovary syndrome (PCOS) and infertility. This narrative literature review (June 2025) searched PubMed, SciELO, and LILACS using the descriptors "weight loss medication," "GLP-1 receptor agonists," "liraglutide," "semaglutide," "fertility," "PCOS," and "reproductive outcomes," including studies published between 2014 and 2025, yielding 47 relevant articles. Overall, GLP-1RAs show consistent metabolic benefits and emerging evidence of improved reproductive outcomes in PCOS, with clinical trials reporting increased menstrual regularity, ovulation, and pregnancy rates-particularly when combined with metformin. Liraglutide (1.2-3.0 mg/day) and exenatide (10 µg twice daily) have been associated with improved follicular development and endometrial receptivity. Mechanistically, GLP-1 receptors are expressed in reproductive tissues, and these agents may exert anti-inflammatory, antifibrotic, and androgen-lowering effects; liraglutide has also been reported to restore granulosa-oocyte communication via suppression of CXCL10. In one randomized trial, pregnancy rates were higher with liraglutide plus metformin (69.2%) than with metformin alone (35.4%; p<0.05). Ovulation rates up to 86% have been described with exenatide plus metformin, exceeding those observed with monotherapy. Despite these signals of benefit, GLP-1RAs remain contraindicated during pregnancy due to limited human data and fetal risks observed in animal studies; semaglutide and tirzepatide require an 8-10 week washout period prior to conception, and tirzepatide may reduce oral contraceptive effectiveness because of delayed gastric emptying. In summary, GLP-1RAs are a promising strategy for preconception management in women with PCOS and obesity-related infertility, especially in combination with metformin, but they should be avoided during pregnancy and lactation, and individualized counseling is essential to align therapy with reproductive goals.
Metabolic and Endocrine Agents · Insulin Sensitizing Agents
The long-term effects of metformin in women with polycystic ovarian syndrome (PCOS) are inadequately studied. The effects of metformin on women with PCOS during 24 months with respect to menses, hormones, and metabolic profiles are assessed. Prospective cohort. A reproductive endocrinology clinic in a university-affiliated medical center. One hundred nineteen women with PCOS, defined by the Rotterdam criteria, were enrolled. Metformin was given daily for 24 months. The primary outcome was the proportion of patients with regular menstruation during treatment. Changes in anthropometric, hormonal, and metabolic parameters were also assessed. Analyses were performed using segmented regression analysis with a generalized estimating equation methodology. Outcomes are expressed as magnitude of change from the baseline. Both overweight (OW) and normal-weight (NW) women with PCOS had increased menstrual frequency and decreased body mass index (BMI), testosterone, and luteinizing hormone levels in the first 6 months. Further stratification showed that NW women exhibiting elevated testosterone at baseline had the largest magnitude of improvement at 6 months [odds ratio (OR), 7.21; 95% confidence interval (CI), 2.35 to 22.17], whereas OW patients with normal testosterone were most likely to achieve normal menses at 12 months (OR, 0.63; 95% CI, 0.47 to 0.77). Metformin was associated with improvements in the menstrual cycle and most hormonal profiles in OW and NW women with PCOS during 24 months of treatment. Most parameters reached maximal response and steady-state after 6 months. Phenotypic differences in baseline BMI and testosterone level can be used as patient selection criteria or treatment prognostics.
Therapeutics › Metabolic and Endocrine Agents › GLP-1 Receptor Agonists
PMID 37762862 37762862 DOI 10.3390/jcm12185921 10.3390/jcm12185921 Carmina et al. 2023, Carmina 2023
Cite this article
Carmina, E., & Longo, R. A. (2023). Semaglutide Treatment of Excessive Body Weight in Obese PCOS Patients Unresponsive to Lifestyle Programs. Journal of clinical medicine, 12(18). https://doi.org/10.3390/jcm12185921
Carmina E, Longo RA. Semaglutide Treatment of Excessive Body Weight in Obese PCOS Patients Unresponsive to Lifestyle Programs. Journal of clinical medicine. 2023;12(18). doi:10.3390/jcm12185921
Carmina, E., and R. A. Longo. "Semaglutide Treatment of Excessive Body Weight in Obese PCOS Patients Unresponsive to Lifestyle Programs." Journal of clinical medicine, vol. 12, no. 18, 2023.
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