超重和肥胖女性中艾塞那肽早期高应答者的减肥效果：一项随机、安慰剂对照研究。

Weight Loss Outcomes Among Early High Responders to Exenatide Treatment: A Randomized, Placebo Controlled Study in Overweight and Obese Women.

机构信息

Beth Israel Deaconess Medical Center, Boston, MA, United States.

出版信息

Front Endocrinol (Lausanne). 2021 Nov 17;12:742873. doi: 10.3389/fendo.2021.742873. eCollection 2021.

OBJECTIVE

As there is significant heterogeneity in the weight loss response to pharmacotherapy, one of the most important clinical questions in obesity medicine is how to predict an individual's response to pharmacotherapy. The present study examines patterns of weight loss among overweight and obese women who demonstrated early robust response to twice daily exenatide treatment compared to those treated with hypocaloric diet and matched placebo injections.

METHODS

We randomized 182 women (BMI 25-48 kg/m2) to treatment with exenatide alone or matched placebo injections plus hypocaloric diet. In both treatment groups, women who demonstrated ≥ 5% weight loss at 12 weeks were characterized as high responders and those who lost ≥10% of body weight were classified as super responders. Our primary outcome was long-term change in body weight among early high responders to either treatment. An exploratory metabolomic analysis was also performed.

RESULTS

We observed individual variability in weight loss with both exenatide and hypocaloric diet plus placebo injections. There was a trend toward a higher percentage of subjects who achieved ≥ 5% weight loss with exenatide compared to diet (56% of those treated with exenatide, 76% of those treated with diet, p = 0.05) but no significant difference in those who achieved ≥ 10% weight loss (23% of individuals treated with exenatide and 36% of those treated with diet, p = 0.55). In both treatment groups, higher weight loss at 3 months of treatment predicted super responder status (diet p=0.0098, exenatide p=0.0080). Both treatment groups also demonstrated similar peak weight loss during the study period. We observed lower cysteine concentrations in the exenatide responder group (0.81 0.48 p < 0.0001) and a trend toward higher levels of serotonin, aminoisobutyric acid, anandamide, and sarcosine in the exenatide super responder group.

CONCLUSION

In a population of early high responders, longer term weight loss with exenatide treatment is similar to that achieved with a hypocaloric diet.

CLINICAL TRIAL REGISTRATION

www.clinicaltrialsgov, identifier NCT01590433.

目的

由于药物治疗对体重减轻的反应存在显著异质性，肥胖医学中最重要的临床问题之一是如何预测个体对药物治疗的反应。本研究检查了与接受低热量饮食和匹配安慰剂注射相比，超重和肥胖女性中对每日两次 exenatide 治疗表现出早期显著反应的人群的体重减轻模式。

方法

我们将 182 名体重指数（BMI）为 25-48kg/m2 的女性随机分为 exenatide 单药治疗或匹配的安慰剂注射加低热量饮食治疗组。在两组治疗中，12 周时体重减轻≥5%的女性被定义为高反应者，体重减轻≥10%的女性被归类为超级反应者。我们的主要结局是两种治疗中早期高反应者的长期体重变化。还进行了探索性代谢组学分析。

结果

我们观察到 exenatide 和低热量饮食加安慰剂注射治疗中个体的体重减轻存在差异。与饮食相比，exenatide 治疗组中达到≥5%体重减轻的患者比例呈上升趋势（exenatide 治疗组为 56%，饮食治疗组为 76%，p=0.05），但达到≥10%体重减轻的患者比例无显著差异（exenatide 治疗组为 23%，饮食治疗组为 36%，p=0.55）。在两组治疗中，治疗 3 个月时体重减轻更多预示着超级反应者状态（饮食 p=0.0098，exenatide p=0.0080）。两组治疗在研究期间也表现出相似的最大体重减轻。我们观察到 exenatide 反应者组中的半胱氨酸浓度较低（0.81±0.48，p<0.0001），exenatide 超级反应者组中血清素、氨基异丁酸、大麻素和肌氨酸水平呈上升趋势。