Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.
Department of Clinical Research, University of Basel, Basel, Switzerland.
J Clin Invest. 2021 Oct 15;131(20). doi: 10.1172/JCI151800.
BackgroundPrimary polydipsia, characterized by excessive fluid intake, carries the risk of water intoxication and hyponatremia, but treatment options are scarce. Glucagon-like peptide 1 (GLP-1) reduces appetite and food intake. In experimental models, GLP-1 has also been shown to play a role in thirst and drinking behavior. The aim of this trial was to investigate whether GLP-1 receptor agonists reduce fluid intake in patients with primary polydipsia.MethodsIn this randomized, double-blind, placebo-controlled, 3-week crossover trial, 34 patients with primary polydipsia received weekly dulaglutide (1.5 mg, Trulicity) in one treatment segment and placebo (0.9% sodium chloride) in the other. During the last treatment week, patients attended an 8-hour evaluation visit with free access to water. The primary endpoint was total fluid intake during the evaluation visits. Treatment effects were estimated using linear mixed-effects models. In a subset of 15 patients and an additional 15 matched controls, thirst perception and neuronal activity in response to beverage pictures were assessed by functional MRI.RESULTsPatients on dulaglutide reduced their fluid intake by 490 mL (95% CI: -780, -199; P = 0.002), from 2950 mL (95% CI: 2435, 3465) on placebo to 2460 mL (95% CI: 1946, 2475) on dulaglutide (model estimates), corresponding to a relative reduction of 17%. Twenty-four-hour urinary output was reduced by -943 mL (95% CI: -1473, -413; P = 0.001). Thirst perception in response to beverage pictures was higher for patients with primary polydipsia than for controls, and lower for patients on dulaglutide versus placebo, but functional activity was similar among groups and treatments.CONCLUSIONSGLP-1 receptor agonists reduce fluid intake and thirst perception in patients with primary polydipsia and could therefore be a treatment option for these patients.Trial registrationClinicaltrials.gov NCT02770885.FundingSwiss National Science Foundation (grant 32473B_162608); University Hospital and University of Basel; Young Talents in Clinical Research grant from the Swiss Academy of Medical Sciences and the Gottfried & Julia Bangerter-Rhyner Foundation; Top-up Grant from the PhD Programme in Health Sciences, University of Basel.
背景原发性多尿症的特征是过度摄入液体，有发生水中毒和低钠血症的风险，但治疗选择有限。胰高血糖素样肽 1（GLP-1）可降低食欲和食物摄入量。在实验模型中，GLP-1 也被证明在口渴和饮水行为中发挥作用。本试验旨在研究 GLP-1 受体激动剂是否可减少原发性多尿症患者的液体摄入。
方法这是一项随机、双盲、安慰剂对照、3 周交叉试验，34 例原发性多尿症患者在一个治疗阶段接受每周 1.5 毫克度拉糖肽（Trulicity）治疗，在另一个治疗阶段接受安慰剂（0.9%氯化钠）治疗。在最后一个治疗周，患者参加了 8 小时的评估访问，可自由饮水。主要终点是评估访问期间的总液体摄入量。使用线性混合效应模型估计治疗效果。在 15 例患者和 15 例匹配对照者的亚组中，通过功能磁共振成像评估口渴感知和对饮料图片的神经元活动。
结果接受度拉糖肽治疗的患者减少了 490 毫升液体摄入（95%CI：-780，-199；P = 0.002），从安慰剂组的 2950 毫升（95%CI：2435，3465）降至度拉糖肽组的 2460 毫升（95%CI：1946，2475）（模型估计值），相对减少 17%。24 小时尿量减少了 943 毫升（95%CI：-1473，-413；P = 0.001）。原发性多尿症患者对饮料图片的口渴感知高于对照组，而接受度拉糖肽治疗的患者低于安慰剂组，但各组和各治疗组的功能活动相似。
结论 GLP-1 受体激动剂可减少原发性多尿症患者的液体摄入和口渴感知，因此可能是这些患者的一种治疗选择。
试验注册Clinicaltrials.gov NCT02770885。
资金瑞士国家科学基金会（grant 32473B_162608）；巴塞尔大学附属医院；瑞士医学科学院和 Gottfried & Julia Bangerter-Rhyner 基金会的青年临床研究人才奖；巴塞尔大学健康科学博士课程的补充拨款。
