Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Center, Vrije University Medical Center (VUmc), Amsterdam, Netherlands.
Department of Psychiatry, Amsterdam University Medical Center, Vrije University Medical Center (VUmc), Amsterdam, Netherlands.
Front Endocrinol (Lausanne). 2022 May 4;13:863592. doi: 10.3389/fendo.2022.863592. eCollection 2022.
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) induce less weight loss than expected. This may be explained by SGLT2i-induced alterations in central reward and satiety circuits, contributing to increased appetite and food intake. This hyperphagia may be specific to high-calorie foods. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are associated with lower preferences for high-calorie foods, and with decreased activation in areas regulating satiety and reward in response to high-calorie food pictures, which may reflect this lower preference for energy-dense foods. To optimize treatment, we need a better understanding of how intake is controlled, and how [(un)healthy] food choices are made. The aim of the study was to investigate the effects of dapagliflozin, exenatide, and their combination on brain activation in response to low-calorie food pictures.
We performed an exploratory analysis of a larger, 16-week, double-blind, randomized, placebo-controlled trial. Sixty-eight subjects with obesity and type 2 diabetes were randomized to dapagliflozin, exenatide, dapagliflozin plus exenatide, or double placebo. Using functional MRI, the effects of treatments on brain responses to low-calorie food pictures were assessed after 10 days and 16 weeks.
Dapagliflozin versus placebo decreased activity in response to low-calorie food pictures, in the caudate nucleus, insula, and amygdala after 10 days, and in the insula after 16 weeks. Exenatide versus placebo increased activation in the putamen in response to low-calorie food pictures after 10 days, but not after 16 weeks. Dapagliflozin plus exenatide versus placebo had no effect on brain responses, but after 10 days dapagliflozin plus exenatide versus dapagliflozin increased activity in the insula and amygdala in response to low-calorie food pictures.
Dapagliflozin decreased activation in response to low-calorie food pictures, which may reflect a specific decreased preference for low-calorie foods, in combination with the previously found increased activation in response to high-calorie foods, which may reflect a specific preference for high-calorie foods, and may hamper SGLT2i-induced weight loss. Exenatide treatment increased activation in response to low-calorie foods. Combination treatment may lead to more favorable brain responses to low-calorie food cues, as we observed that the dapagliflozin-induced decreased response to low-calorie food pictures had disappeared.
钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）引起的体重减轻低于预期。这可能是由于 SGLT2i 引起的中枢奖赏和饱腹感回路的改变，导致食欲增加和食物摄入增加。这种多食可能是特定于高热量食物的。胰高血糖素样肽-1 受体激动剂（GLP-1RA）与对高热量食物的偏好较低有关，并且在响应高热量食物图片时调节饱腹感和奖赏的区域的激活降低，这可能反映了对高能量食物的偏好较低。为了优化治疗，我们需要更好地了解摄入是如何控制的，以及[（不）健康]的食物选择是如何做出的。本研究的目的是研究达格列净、艾塞那肽及其联合用药对低热量食物图片反应的脑激活的影响。
我们对一项更大的、为期 16 周的双盲、随机、安慰剂对照试验进行了探索性分析。68 例肥胖和 2 型糖尿病患者被随机分为达格列净、艾塞那肽、达格列净加艾塞那肽或双安慰剂组。使用功能磁共振成像（fMRI），在 10 天和 16 周后评估治疗对低热量食物图片反应的脑激活的影响。
与安慰剂相比，达格列净在 10 天时降低了对低热量食物图片的反应，在纹状体、岛叶和杏仁核中，16 周时在岛叶中降低了对低热量食物图片的反应。与安慰剂相比，艾塞那肽在 10 天时增加了对低热量食物图片的纹状体反应，但在 16 周时没有增加。与安慰剂相比，达格列净加艾塞那肽对脑反应没有影响，但在 10 天时，达格列净加艾塞那肽与达格列净相比，增加了对低热量食物图片的岛叶和杏仁核反应。
达格列净降低了对低热量食物图片的反应，这可能反映了对低热量食物的特定偏好降低，结合先前发现的对高热量食物的反应增加，这可能反映了对高热量食物的特定偏好，可能会阻碍 SGLT2i 引起的体重减轻。艾塞那肽治疗增加了对低热量食物的反应。联合治疗可能会导致对低热量食物线索更有利的大脑反应，因为我们观察到达格列净诱导的对低热量食物图片的反应已经消失。
