Mini-CAT #1

Clinical Question:

A 25-year-old woman presents to your OB/GYN clinic and she mentions that she feels upset that her PCOS is making her gain weight. She has tried lifestyle modifications, but it has not been working as well as she had hoped. She has seen commercials and has heard a lot of people talking about Ozempic and Metformin for weight loss alternatives. She asks you if either of those medications can be helpful in her goal of losing more weight.

Search Question: Clearly state the question (including outcomes or criteria to be tracked)

In women with polycystic ovarian syndrome (PCOS), does a GLP-1 RA (like Liraglutide or Semaglutide) compared to Metformin lead to better weight loss?

PICO Question:

Women with PCOSGLP-1 RAMetforminWeight reduction
PCOSLiraglutide Weight loss

Search Strategy:


  • PCOS AND Glp-1 RA AND Metformin -> 58
    • Filters: last 10 years
  • PCOS AND Liraglutide AND Metformin -> 27
    • Filters: last 10 years

TRIP Database

  • (PCOS) (GLP-1 RA) (Metformin) -> 40 articles
    • Filter: last 10 years

Google Scholar

  • PCOS glp-1 metformin —> 6,170
    • Filter: 2014-2024
  • PCOS liraglutide metformin —> 3,650
    • Filter: 2014-2024

For the article selection of my Mini-CAT I wanted to find articles that were of the highest level of evidence available, which were either a systematic review or a meta-analysis. I looked for studies that were within that last 10 years. Since the introduction of GLP-1 RA’s into the medical world was a fairly recent one, I was happy to see that many of the studies I was looking through were very recent. Unfortunately for me as well, many randomized control trials are still on-going and that data was not unavailable for me.

I searched through 3 different databases and I ended up choosing my five articles from PubMed and Google Scholar. I included three systematic reviews/meta-analysis, a single center study, as well as a randomized pilot study in my Mini-CAT. I believe having 5 articles gives my Mini-CAT enough of a variation of different types of articles. Other studies that I found compared the effectiveness between Liraglutide and a placebo and how GLP-1 RA’s compared to a combination of metformin and oral contraception in response to weight loss.

Articles Chosen (4 or more) for Inclusion (please copy and paste the abstract with link):

Please pay attention to whether the articles actually address your question and whether they are the highest level of evidence available.  If you cannot find high quality articles, be prepared to explain the extensiveness of your search and why there are not any better sources available. 

1) Han, Y., Li, Y., & He, B. (2019). GLP-1 receptor agonists versus metformin in PCOS: a systematic review and meta-analysis. Reproductive biomedicine online, 39(2), 332–342.


This meta-analysis aimed to evaluate the efficacy and safety of glucagon-like peptide 1 (GLP-1) receptor agonists for women with polycystic ovary syndrome (PCOS) by comparing their effect with that of metformin. Electronic databases (PubMed, EMBASE, Cochrane Library, WanFang Database, CNKI) dating from their establishment to June 2018 were searched to find all randomized controlled trials (RCTs) reporting the efficacy of GLP-1 receptor agonists versus metformin for patients with PCOS. Therapeutic variables included menstrual cycle, sex hormone and clinical manifestations, glucose metabolism and other metabolic indexes. Eight RCTs among 462 related articles were included in the meta-analysis. Compared with metformin, GLP-1 receptor agonists were more effective in improving insulin sensitivity (standard mean difference [SMD] -0.40, 95% confidence interval [CI] -0.74 to -0.06, P = 0.02) and reducing body mass index (SMD -1.02, 95% CI -1.85 to -0.19, P = 0.02) and abdominal girth (SMD -0.45, 95% CI -0.89 to -0.00, P = 0.05). GLP-1 receptor agonists were associated with a higher incidence of nausea and headache than metformin, but there were no significant differences in other data. Therefore, compared with metformin, GLP-1 receptor agonists might be a good choice for obese patients with PCOS, especially those with insulin resistance. The available evidence is, however, inconclusive given its moderate to low quality. More high-quality research is needed to assess the efficacy of a GLP-1 receptor agonist on women with PCOS.

Keywords:Glucagon-like peptide 1 (GLP-1) receptor agonists; Insulin resistance; Metformin; Obesity; Polycystic ovary syndrome.

2) Srinivasan, D., & Lofton, H. F. (2022). Effect of GLP-1 agonists on weight loss in patients with polycystic ovary syndrome and obesity: A single-center study. Obesity pillars, 2, 100016.



Weight loss of >5% in patients with polycystic ovary syndrome and obesity (PCOS–O) is believed to improve underlying drivers of the syndrome. Weight loss facilitated by GLP-1 agonists in patients with PCOS–O is not well characterized. In this single-center retrospective study, we determined weight loss in patients with PCOS–O with GLP-1 monotherapy versus metformin.


In this brief report, electronic records of 183 adult patients with PCOS–O were reviewed between January 2020 and April 2021. We identified 12 and 19 patients that were treated with metformin and GLP-1 monotherapy respectively. One patient in each cohort had diabetes mellitus. Weights were reviewed at baseline (prior to therapy initiation) and at six-month follow-up. We analyzed change in weight from baseline and proportion with >5% and 10% weight loss using Fisher exact t-test and chi-square test. Univariate linear regression was used to identify correlations between treatment and weight loss.


Baseline characteristics were similar between metformin (n = 12) and GLP-1 (n = 19) cohorts with the exception of mean days on medication. Following six months of treatment, mean weight loss was 4.9 kg (4.8%) and 9.1 kg (9.8%) in the metformin and GLP-1 cohorts (p = 0.13) respectively. Similar trends were seen in BMI with reductions of 1.8 kg/m2 (4.7%) and 3.5 kg/m2 (9.7%). A significantly greater proportion of patients achieved 5% and 10% weight loss with GLP-1 treatment (84.2% and 57.8%, p = 0.01 and p = 0.02) compared to metformin. Univariate linear regression analysis demonstrated a trend towards greater weight loss in patients treated with GLP-1 monotherapy (Coeff: 4.15, 95% CI: 1.3-9.7, p = 0.13) versus metformin.


Our study shows improvements in weight with GLP-1 monotherapy versus metformin as demonstrated by overall weight loss and proportion of patients achieving >5% weight loss. Further prospective randomized controlled studies are needed to establish GLP-1 weight loss efficacy in patients with PCOS–O and clinically related outcomes.

3) Lyu, X., Lyu, T., Wang, X., Zhu, H., Pan, H., Wang, L., Yang, H., & Gong, F. (2021). The Anti-obesity Effect of GLP-1 Receptor Agonists Alone or in Combination with Metformin in Overweight /Obese Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis. International journal of endocrinology, 2021, 6616693.


Objectives. Both glucagon-like peptide-1 receptor agonists (GLP-1RAs) and metformin (MET) have markedly anti-obesity effects in overweight/obese polycystic ovary syndrome (PCOS) patients. However, there was no literature to compare the anti-obesity effects of these two medicines. Therefore, a systematic review and meta-analysis were conducted in our present study to evaluate the anti-obesity effects of GLP-1RAs either as monotherapy or combined with MET in comparison with MET alone in overweight/obese PCOS patients.

Methods. All randomized controlled trials (RCTs) which reported the efficacy of GLP-1RAs and MET in overweight/obese PCOS patients in Medline (from Pubmed), Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases were independently searched by two reviewers. The random-effect model was used to pool data extracted from the included literature. The weighted mean difference (WMD) and 95% confidence interval (CI) were used to present the meta-analysis results (PROSPERO registration number: CRD42020173199).

Results. A total of eight eligible RCTs were finally enrolled in our meta-analysis from the 587 retrieved literature. The results showed that GLP-1RAs alone or combined with MET was associated with a greater weight loss (N = 318, WMD = −2.61, 95% CI: −3.51 to −1.72, , I2 = 77.5%), more obvious reduction of waist circumference (N = 276, WMD = −3.46, 95% CI: −4.36 to −2.56, , I2 = 0.0%), and body mass index (BMI) (N = 318, WMD = −0.93, 95% CI: −1.60 to −0.26, , I2 = 84.9%) in overweight/obese PCOS patients when compared with MET alone. Further sensitivity analysis demonstrated that the meta-analysis results of the efficacy differences in terms of body weight, waist circumference, and BMI were relatively stable and reliable.

Conclusion. Our meta-analysis demonstrated that the anti-obesity effect of GLP-1RAs alone or combined with MET was superior to MET alone in terms of weight loss, the reduction of waist circumference, and BMI. More large-scale, high-quality RCTs are needed to further confirm these results in PCOS patients.

4) Ma, Ruilin MD; Ding, Xuesong MD; Wang, Yanfang MD; Deng, Yan MD; Sun, Aijun MD. The therapeutic effects of glucagon-like peptide-1 receptor agonists and metformin on polycystic ovary syndrome: A protocol for systematic review and meta-analysis. Medicine 100(23):p e26295, June 11, 2021. | DOI: 10.1097/MD.0000000000026295



Obesity and insulin resistance (IR) are common in polycystic ovary syndrome (PCOS), which contribute to reproductive and metabolic abnormalities. Metformin increases insulin sensitivity, but it is associated with unsatisfied benefits of weight loss. Recent studies have reported that glucagon-like peptide 1 (GLP-1) receptor agonists improve IR and reduce weight in women with PCOS. We conducted a systematic review and meta-analysis to compare the effects between GLP-1 receptor agonists and metformin, and between GLP-1 receptor agonist-metformin combination and GLP-1 receptor agonists in overweight/obese women with PCOS on anthropometric, metabolic, reproductive outcomes.


Databases including PubMed, EMBASE, Web of Science, and Cochrane Library were selected to search for randomized controlled trials (RCTs) published in English up to March 2020. Eligible studies were identified according to the inclusion criteria. The primary outcomes included menstrual frequency, body mass index (BMI), total testosterone, and the homeostatic model assessment of insulin resistance. GRADE criteria were implemented to assess the quality of evidence for primary outcomes.


Seven RCTs were selected for analysis, comprising 464 overweight/obese women with PCOS. In the low-quality evidence, a meta-analysis demonstrated that GLP-1 receptor agonists showed better effects relative to metformin on the reduction of body mass index (mean difference − 1.72; 95% confidence interval −2.46 to −0.99, P < .001) and homeostatic model assessment of insulin resistance (standard mean difference −0.37; 95% confidence interval − 0.60,− 0.15, P = .001). Moreover, the combination therapy exhibited similar effects on primary outcomes relative to GLP-1 receptor agonist alone. GLP-1 receptor agonists were also found to be associated with lower abdominal girth compared to metformin. A meta-analysis of gastrointestinal discomfort showed no significant difference between GLP-1 receptor agonist and metformin therapies, and between the combination therapy and GLP-1 receptor agonist alone.


GLP-1 receptor agonists appear to be more beneficial for weight loss and IR improvement compared to metformin for overweight/obese women with PCOS. However, the combination treatment displays comparable effects with GLP-1 receptor agonist alone. The incidence of gastrointestinal discomforts was similar in different groups. However, the quality of the body of evidence is “low.” Further prospective RCTs and cost-effectiveness analyses are also warranted to guide GLP-1 receptor agonists to treat women with PCOS.

Keywords: glucagon-like peptide 1 receptor agonists; insulin resistance; metformin; polycystic ovary syndrome; weight loss

Summary of the Evidence:

Author (Date)Level of EvidenceSample/Setting (# of subjects/ studies, cohort definition etc)Outcome(s) studiedKey FindingsLimitations and Biases
Han Y, Li Y, H B (2019)Systematic Review and Meta-Analysis– 8 articles with a total sample of 375 women with PCOS   – 187 women were in the testing group (using a GLP-1 RA)   – 188 women were in the control group (using Metformin)  Primary outcomes studied were   – menstrual frequency – serum total testosterone   – homeostasis model assessment of insulin resistance (HOMA-IR) scores and adverse events of nausea and headaches.   Secondary outcomes were   – sex hormone-binding globulin (SHBG) and dehydroepiandrosterone sulphate (DHEA-S) concentrations – Ferriman–Gallwey scores, androstenedione, LH, fasting blood glucose (FBG) and fasting insulin (FINS) concentrations, – body mass index (BMI) and abdominal girth – triglyceride, total cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) concentrations, -systolic blood pressure (SBP), diastolic blood pressure (DBP) and other types of adverse event.   Tool Used: – RevMan 5.3 software (Version 5.3)  – The results showed that GLP-1 receptor agonists had a greater effect in reducing body mass index (95% to 91%) and abdominal girth (95% to 53%) than Metformin did   – For the primary outcomes, there were no statistical differences between the two drugs in terms of improving menstrual frequency, triglycerides, total cholesterol, and blood pressure   – Patients who used the GLP-1 Ras had an increased incidence of nausea and headaches than those who took Metformin– Unfortunately, GLP-1 RAs have not been out for long and this study was one of the first to include a head-to-head analysis of the effect of this drug against Metformin in the usage for PCOS   – The sample size was not the largest (at 375 participants)   – The reduction of BMI from usage of the GLP-1 RAs was statistically significant but it was right on the cusp of being so
Srinivasa D., & Lofton, H. F. (2022).Single Center Retrospective Cohort Study– 183 adult patients were identified with PCOS and obesity in the NYU Weight Management Clinic between January 2020 and April 2021   – 31 patients were treated with either GLP-1 RA or Metformin monotherapy   – 12 patients were treated with Metformin monotherapy   – 19 patients were treated with GLP-1 RA monotherapy  – The primary outcome looked at the change in patient weight from their baseline to the six-month follow-up   – Secondary outcomes looked at the proportion of patients who achieved > 5% and > 10% weight loss from the patients’ baseline   Statistical analysis was preformed using STATA software  – Following 6 months of treatment, mean weight loss was 9.1kg (9.8%) in the GLP-1 RA cohorts, while mean weight loss was 4.9kg (4.8%) in the Metformin cohort   – 84.2% of participants in the GLP-1 RA cohort lost weight versus 57.8% of participants in the Metformin cohort– The biggest limitation from this study was that it was a single-center study with a small sample size   – The GLP-1 RA cohort had participants who were either on semaglutide or liraglutide for the 6-months of treatment, so it’s difficult to reflect which drug was more efficacious  
Lyu, X., Lyu, T., Wang, X., Zhu, H., Pan, H., Wang, L., Yang, H., & Gong, F. (2021).Systematic Review and Meta-Analysis– 6 studies (that encompassed eight RCTs) that compared the efficacy between GLP-1 RAs and Metformin were chosen from Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases   – The patients chosen had PCOS and were also overweight   – The test group were treated with exenatide or liraglutide alone or in combination with Metformin   – The control group was treated only with Metformin   – There was a total of 318 patients amongst the eight RCTs   – 5 RCTs compared the efficacy of GLP-1 RAs alone and Metformin alone (with 131 patients in the treatment group, and 121 patients in the control group)   – 3 RCTs compared the efficacy of GLP-1 RAs with Metformin versus using Metformin alone (with 38 patients in the treatment group, and 28 patients in the control group)  – The primary outcome was looking at weight loss   – Secondary outcomes looked at the reduction of waist circumference and BMI   – Statistical analysis was preformed using the STATA 15.1 software– All eight RCTs showed more weight loss with the GLP-1 RAs alone or with Metformin over using Metformin by itself   – Patients who were on monotherapy of GLP-1 RAs saw a moderate amount of weight loss than patients on Metformin monotherapy, while patients who were on the dual therapy of GLP-1 RA/Metformin saw a more substantial amount of weight loss than patients on Metformin monotherapy   – Similar effects were seen with patients’ waist circumference. Patients on either monotherapy of GLP-1 RAs or dual therapy with Metformin saw more reduction on their waist circumference than patients who were taking Metformin alone    – The number of RCTs that were used in this study was small   – The different RCTs that were used had different categorizations of what overweight and obese was, that variable might have an impact in future results
Ma, R; Ding, X; Wang, Y; Deng, Y; Sun, A (2021)Systematic Review and Meta-Analysis– Seven RCTs were chosen from different databases including PubMed, EMBASE, Web of Science, and Cochrane Library that comprised of 464 patients who were overweight/obese with PCOS   – The RCTs chosen were US based as well as from China and Slovenia– The primary outcomes included menstrual frequency (MFR), BMI, total testosterone (TT), and the homeostatic model assessment of insulin resistance (HOMA-IR).   – The secondary outcomes included abdominal girth (AG), sex hormone-binding globulin, free androgen index (FAI), androstenedione, dehydroepiandrosterone sulphate (DHEAS), fasting blood glucose, fasting insulin, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein (hsCRP).   – Statistical analysis was performed using Review Manager version 5.3 (Cochrane Collaboration, Software Update)  – Three of the RCTs looked at the weight loss efficacy between usage of GLP-1 RAs versus Metformin. Usage of GLP-1 RAs monotherapy showed more weight loss than monotherapy with Metformin.   – Three of the RCTs showed that dual therapy with GLP-1 RAs + Metformin showed a substantial amount of weight loss than with Metformin alone.   – One of the studies looked at usage of GLP-1 RAs with lifestyle modification exhibited better effects on reducing BMI and weight loss than with Metformin and lifestyle modification alone   – There was no significant difference in adverse events like GI discomfort, nausea, diarrhea, stomach-ache and constipation between the testing and control groups.  – One RCT that was used described an unspecific randomization procedure which had an unclear risk of bias   – Another RCT had a higher risk of attrition because of incomplete outcome data, where the rate of lost follow-up was over 20%   – The study itself had a small sample size  


Article 1 concluded by saying GLP-1 RAs were more effective in reducing weight and improving insulin sensitivity than Metformin was. However, there were no significant differences in terms of menstrual frequency and decreasing serum testosterone between either drug.

Article 2 concluded by saying GLP-1 RA monotherapy showed more meaningful improvements in weight loss for women with PCOS than taking Metformin by itself. GLP-1 RA monotherapy also helped patients achieve greater than 5% weight loss.

Article 3 concluded by saying dual therapy with GLP-1 RA and Metformin or GLP-1 RA monotherapy showed more anti-obesity effects and was more superior to patients taking Metformin alone.

Article 4 concluded by saying taking GLP-1 receptor agonists either by themselves or with Metformin showed more benefits to patients in weight loss and combating insulin resistance than Metformin did by itself.

My overall conclusion based off these 4 studies is that usage of GLP-1 RAs by themselves or by dual therapy with Metformin is far superior in weight loss and waist circumference than by using Metformin alone. Women with PCOS and obesity challenges can benefit greatly from using GLP-1 RAs to combat gaining weight and actively keeping it off

Clinical Bottom Line:

I will weigh my studies in the following order: Article 3, Article 2, Article 1, and lastly Article 4.

I weighed article 3 the highest of all my articles. Many of the other studies I chose had primary and secondary outcomes that looked at other factors that encompass PCOS, but this one just focused on weight loss, and reduction in BMI and waist circumference. The article focused on eight randomized control trials with a total of 318 participants. The trials showed that GLP-1 RA monotherapy or dual therapy with Metformin was superior in weight loss for patients than Metformin did by itself. I liked the way the article broke down how each grouping of RCTs showed how more superior GLP-1 RAs were than Metformin. Even though the definition of obesity/overweight was a little varied between the RCTs, I still think the study did a great job in stating which treatment helped patients with PCOS more with their weight loss.

I weighed article 2 the next highest because it was more intimate with its patients. Even though there were only 31 patients that were studied, the study went on for 6 months to see how much weight was lost and if any changes needed to be implemented. This study was also the only one that gave us exact number of how much weight each cohort lost following the six months of treatment (mean weight loss of 4.9 kg [metformin] and 9.1 kg [GLP-1 RA]). The biggest limitation to the study was the very small sample size, but I think looking at one singular location gave us a lot of information about what two drugs going head-to-head can do for a patient.

Next for me is article 1. The primary outcomes of this study were not related to weight loss or BMI reduction, but rather menstrual frequency, serum total testosterone and free androgen index, homeostasis model assessment of insulin resistance scores and adverse events of nausea and headaches. Secondary outcomes were related to weight loss, and the authors of this study showed us that GLP-1 RAs had a greater efficacy in weight loss and reducing BMI versus using Metformin alone. Although the reduction of BMI and weight loss from usage of the GLP-1 RAs was statistically significant; it was right on the cusp of being so (GLP-1 RAs 95% to Metformin’s 91%).

Lastly for me is article 4. Like article 1, this study had many different primary and secondary outcomes that encompassed weight loss and many other variables into the mix. GLP-1 RAs did show success in weight reduction for patients with PCOS and obesity. Unfortunately, there may have been a randomization bias in one RCT and attrition bias in another RCT that may have risked the entire article being unusable.

Clinical significance (not just statistical significance)

GLP-1 RAs are relatively new to the market, but I believe that GLP-1 RAs would be very useful in women with PCOS who were looking to lose weight and reduce their BMIs. Every single one of the studies I have used mentioned that GLP-1 RAs are far superior to Metformin monotherapy, which is currently the FDA approved drug for weight loss and BMI reduction in women with PCOS and obesity.

Any other considerations important in weighing this evidence to guide practice 

Many, if not every single one, of my articles, mentioned that further investigation was needed into GLP-1 RAs monotherapy or dual therapy for usage to combat weight gain in patients with PCOS. I also think longer randomized control studies (like the one in article 2) that took longer than 6 months to complete to get the full effect of GLP-1 RAs are needed.

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