二甲双胍与二甲双胍+替西帕肽对PCOS患者减重效果的比较

OBJECTIVE

目的

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.

PCOS和肥胖患者的体重减轻被认为可以改善该综合征的潜在驱动因素，包括降低雄激素水平，改善生育能力和代谢健康。二甲双胍（MET）等药物通常与改变生活方式相结合来治疗PCOS患者，并可诱导适度的体重减轻。目前，胰高血糖素样肽-1（GLP-1）激动剂被用于治疗2型糖尿病和肥胖症，但其对同时接受MET治疗和未接受MET治疗的PCOS患者的减重效果尚未明确。我们的目标是比较接受MET单独治疗和接受MET和替西帕肽（一种双重GLP-1和葡萄糖依赖性胰岛素促肽（GIP）受体激动剂）联合治疗的PCOS患者的减重情况。

MATERIALS AND METHODS

材料和方法

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.

在这项单中心回顾性研究中，我们检索了我们生育诊所评估的143名多囊卵巢综合征超重/肥胖患者的电子病历。其中，我们确定了46名接受MET单药治疗（n=46）和30名接受MET和替西帕肽（COMBO）联合治疗（n=30）的非糖尿病患者，时间范围为2022年4月至2023年4月。在此期间的第一次就诊和随后的随访就诊（范围：1—6次）中，我们回顾了体重（kg）和身体质量指数[BMI（kg/m2）]。研究患者在纳入期间至少需要记录两次总就诊次数，并且对于那些怀孕的患者，数据收集在确认怀孕前的最后一次就诊时停止。使用SAS（v9.4）的Cox比例风险回归模型分析了COMBO组和MET组的治疗天数对体重、BMI和起始体重百分比的变化。估计的回归系数和标准误差转换为具有95%置信区间（CI）的风险比[HRs]。p值<0.05被认为具有显著性意义。

RESULTS

结果

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)].

我们发现，与MET单药治疗相比，COMBO对PCOS患者的总体减重、BMI变化和失去的初始体重百分比有显著影响。我们发现，在比较MET单药治疗与COMBO治疗时，药物使用对PCOS患者的总体重减轻、BMI变化和初始体重减轻百分比（%）有显著影响。MET组的体重、BMI和减重百分比的平均变化（SD）分别为-1.09（2.4）、-0.024（0.09）和-1.13（2.56），而COMBO组的变化分别为-8.65（6.9）、-0.078（0.05）和-8.07（6.21）。在服用MET的参与者中，26人（56.5%）达到了减肥效果，20人（43.5%）没有达到减肥效果。在COMBO组中，27例（90%）达到了减肥效果，而3例（10%）没有达到减肥效果[风险比 1.82 （置信区间 1.02-3.25）（p=0.04）]。

CONCLUSIONS

结论

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.

在我们的研究中，与单用MET相比，采用MET和GLP-1/GIP受体激动剂联合治疗的PCOS患者体重减轻的风险比高出近2倍。

IMPACT STATEMENT

影响声明

Our study shows improvement in weight loss over time in PCOS patients receiving combined treatment with MET and tirzepatide compared to MET alone. Further prospective randomized controlled studies are needed to validate our findings and assess clinically related metabolic and fertility outcomes.

我们的研究显示，与单独使用MET相比，接受MET和替尔齐帕肽联合治疗的PCOS患者随着时间的推移，体重减轻方面有所改善。需要进一步的前瞻性随机对照研究来验证我们的发现，并评估临床相关的代谢和生育结果。

参考文献：

EFFECTS OF METFORMIN ALONE VERSUS METFORMIN AND TIRZEPATIDE ON WEIGHT LOSS IN PATIENTS WITH POLYCYSTIC OVARIAN SYNDROME (PCOS)Sassin, Alexa M. et al.Fertility and Sterility, Volume 120, Issue 4, e222