This study aimed to determine if dulaglutide combined with CRD could further reduce VAT and clinical symptoms in overweight PCOS-affected women.

Polycystic ovary syndrome (PCOS) is a combination of reproductive endocrine and metabolic disorders affecting 6-20% of reproductive-age women. Approximately 60–70% of women suffering from PCOS are overweight or obese. 

PCOS has been associated with an increased abdominal fat distribution phenotype in normal-weight and overweight/obese women, forming vicious circles with insulin resistance and hyperandrogenic states.

Compared with subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) secretes more metabolically harmful adipokines and inflammation factors. VAT can aggravate IR, and hyperandrogenism and oligo/anovulation can be worsened. Therefore, it is crucial to reduce visceral adiposity in PCOS patients, particularly overweight or obese women.

Weight management in PCOS patients is best achieved through calorie-restricted diets (CRDs). Although there is limited data on how the CRD regimen affects visceral adiposity in PCOS-affected women, it is believed that it could reduce body weight, improve metabolic and reproductive parameters, and increase conception probability.

Enteroendocrine cells release glucagon-like peptide 1 (GLP-1), a hormone that lowers body weight and improves glucose homeostasis. Several GLP-1 analogs coupled with receptor agonists (RAs) have been studied to treat PCOS. They have significantly improved insulin sensitivity, reproductive function, weight reduction, and VAT reduction in PCOS patients.

As a once-weekly GLP-1 RA, dulaglutide has a higher adherence rate than other GLP-1 RAs that require daily injections. Still, there is no clear evidence that combining once-weekly GLP-1 RAs with a CRD regimen reduces VAT and improves metabolic risk factors more than the CRD regimen alone.

As a result, the researchers conducted a randomized clinical trial to determine if a CRD regimen with or without dulaglutide induced modest and equivalent weight loss in overweight and obese PCOS patients. In addition, they evaluated changes in fat distribution, the androgenic state, and metabolic profiles.

Results of The Study

As part of this single-center, randomized, controlled, open-label clinical trial, 243 PCOS patients were screened. 68 overweight or obese individuals were randomly assigned to receive dulaglutide in combination with CRD treatment or CRD alone.

It was determined how long it would take to lose 7% of body weight from baseline, which was limited to 6 months. The difference in VAT area reduction between groups was the primary endpoint. 

In addition, changes in menstrual frequency, metabolic profiles, hormonal parameters, liver fat, and body composition were secondary endpoints.

With dulaglutide + CRD, 7% weight loss was achieved considerably faster than with CRD alone. Area changes in VAT reduction did not differ significantly between groups. Dulaglutide + CRD showed significant advantages in reducing glycated hemoglobin A1c and postprandial plasma glucose levels compared to CRD alone.

The analyses showed no significant differences in menstruation frequency, metabolic profiles, hormonal markers, liver fat, or body composition between the two groups. Dulaglutide was the primary adverse event associated with nausea, vomiting, constipation, and loss of appetite.

As a result, PCOS-affected women should be treated with dietary interventions as a first line of defense. At the same time, glucagon-like peptide 1 receptor agonist therapy is an effective, well-tolerated adjuvant therapy that helps overweight/obese PCOS-affected women reach their weight targets by using dietary therapy.

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