Department of Materials Science & Engineering, Stanford University, Stanford, CA 94025, USA.
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Cell Rep Med. 2023 Nov 21;4(11):101292. doi: 10.1016/j.xcrm.2023.101292.
Glucagon-like peptide-1 (GLP-1) is an incretin hormone and neurotransmitter secreted from intestinal L cells in response to nutrients to stimulate insulin and block glucagon secretion in a glucose-dependent manner. Long-acting GLP-1 receptor agonists (GLP-1 RAs) have become central to treating type 2 diabetes (T2D); however, these therapies are burdensome, as they must be taken daily or weekly. Technological innovations that enable less frequent administrations would reduce patient burden and increase patient compliance. Herein, we leverage an injectable hydrogel depot technology to develop a GLP-1 RA drug product capable of months-long GLP-1 RA delivery. Using a rat model of T2D, we confirm that one injection of hydrogel-based therapy sustains exposure of GLP-1 RA over 42 days, corresponding to a once-every-4-months therapy in humans. Hydrogel therapy maintains management of blood glucose and weight comparable to daily injections of a leading GLP-1 RA drug. This long-acting GLP-1 RA treatment is a promising therapy for more effective T2D management.
胰高血糖素样肽-1（GLP-1）是一种肠 L 细胞在响应营养物质时分泌的肠促胰岛素和神经递质，以葡萄糖依赖的方式刺激胰岛素分泌并抑制胰高血糖素分泌。长效 GLP-1 受体激动剂（GLP-1 RAs）已成为治疗 2 型糖尿病（T2D）的核心疗法；然而，这些疗法非常繁琐，因为它们必须每天或每周服用。能够实现更少频率给药的技术创新将降低患者负担并提高患者依从性。在此，我们利用可注射水凝胶库技术开发了一种能够实现数月 GLP-1 RA 递送的 GLP-1 RA 药物产品。我们使用 T2D 大鼠模型证实，一次水凝胶治疗可使 GLP-1 RA 暴露时间超过 42 天，相当于人类每四个月一次的治疗。水凝胶治疗可保持血糖和体重的管理与每日注射一种领先的 GLP-1 RA 药物相当。这种长效 GLP-1 RA 治疗是一种更有效的 T2D 管理的有前途的疗法。
