Effects of metformin alone versus metformin and tirzepatide on weight loss in patients with polycystic ovarian syndrome (pcos)

Weight loss in patients with PCOS and obesity is thought to improve the underlying drivers of the syndrome, including reducing androgen levels and improving fertility and metabolic health. Medications like metformin (MET) are commonly used in combination with lifestyle modification to treat individuals with PCOS and can induce modest weight loss. The effects of glucagon-like peptide-1 (GLP-1) agonists, which are currently indicated for the treatment of type 2 diabetes mellitus and obesity, on weight loss in PCOS patients both with and without concurrent MET therapy are not well characterized. Our objective was to compare weight loss in PCOS patients receiving MET monotherapy versus those receiving a combination of MET and tirzepatide, a dual GLP-1 and glucose-dependent insulinotropic peptide (GIP) receptor agonist. In this single-center retrospective study, electronic medical records of 143 overweight/obese patients with PCOS evaluated at our fertility clinic were identified. Of these, we identified 46 and 30 non-diabetic patients that were treated with MET monotherapy (n=46) and both MET and tirzepatide (COMBO)(n=30) respectively between April 2022 and April 2023. Weight (kg) and body mass index [BMI (kg/m2)] were reviewed at the first visit during this time frame and subsequent follow-up visits (range: 1-6 visits). Study patients needed at least two total visits recorded during the inclusion period, and for those who conceived, data collection stopped at the last visit prior to confirmation of the pregnancy. Changes in weight, BMI, and percentage of starting weight were analyzed by the Cox proportional hazards regression model with the number of days on treatment for both the COMBO and MET groups in SAS (v9.4). The estimated regression coefficients and standard errors were converted to hazard ratios [HRs] with 95% confidence intervals (CIs). A p-value <0.05 was considered significant. We found that medication usage had a significant influence on PCOS patients’ total weight loss, change in BMI, and percent of the initial weight that was lost (%) when comparing MET monotherapy versus COMBO treatment. The mean (SD) change in weight, BMI, and % of weight loss for the MET group was -1.09(2.4), -0.024(0.09), and -1.13(2.56) respectively compared to -8.65(6.9), -0.078(0.05) and -8.07(6.21) in the COMBO group. Of the participants taking MET, 26 (56.5%) achieved weight loss while 20 (43.5%) achieved no weight loss. In the COMBO group, 27 (90%) achieved weight loss while 3 (10%) achieved no weight loss [HR 1.82 (CI 1.02-3.25) (p=0.04)]. In our study, the hazard ratio of weight loss is nearly 2 times higher in patients with PCOS taking COMBO treatment with MET and a GLP-1/GIP receptor agonist compared to MET alone.