为什么SGLT2抑制剂未能在COVID-19中取得预期的成功?
Medine Cumhur Cure1, Erkan Cure2
1Medilab Laboratory and Imaging Center, Department of Biochemistry, Sisli, Istanbul, Turkey.
Current pharmaceutical design
|April 3, 2024
概括
-葡萄糖运输蛋白2 (SGLT2) 抑制剂在糖尿病患者治疗COVID-19方面表现有前途,但没有有效. 本综述探讨了它们失败的潜在原因,包括药物相互作用和生理影响.
科学领域:
- 传染性疾病 传染性疾病
- 内分泌学 在内分泌学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 导致全球大流行,导致COVID-19,这是一种具有复杂病理生理学的疾病,包括细胞毒性,炎症和氨酸-血管新生素系统 (RAS) 激活.
- -葡萄糖运输蛋白2 (SGLT2) 抑制剂 (SGLT2i) 提供诸如减肥,改善血糖控制和增强血管功能等好处,为在COVID-19的糖尿病患者中使用它们带来了希望.
- 现有的文献提出了相互矛盾的数据和关于SGLT2i在治疗COVID-19糖尿病患者的疗效的混.
研究的目的:
- 调查和澄清SGLT2抑制剂在治疗COVID-19糖尿病患者中无效的原因.
- 在SARS-CoV-2感染的背景下分析SGLT2抑制剂的潜在有害影响和相互作用.
- 为了协调有关SGLT2抑制剂和COVID-19的文献中的相互矛盾的发现.
主要方法:
- 审查有关SARS-CoV-2,COVID-19,SGLT2抑制剂及其相互作用的现有科学文献.
- 分析SGLT2抑制剂的生理效应,包括对葡萄糖运输,红色素形成和氨酸-血管新生系统的影响.
- 探索潜在的混杂因素,如药物联合使用,酸性风险和电解质失衡.
主要成果:
- 目前的数据表明,SGLT2抑制剂在治疗COVID-19中并不高效,即使在糖尿病患者中也是如此.
- 几个因素可能导致缺乏疗效,包括增加SGLT1活性,缺乏血管激素受体阻断剂的同时使用,以及可能发生酸性脂肪酸症和损伤等不良事件.
- 使用SGLT2抑制剂的持续时间及其对红色形成,血液粘度和脂质样本的影响也可能影响了结果.
结论:
- 由于药理和生理因素的结合,SGLT2抑制剂未能在COVID-19糖尿病患者中显示出显著的治疗益处.
- 需要进一步的研究,以充分理解SGLT2抑制和SARS-CoV-2感染之间的复杂相互作用,以指导未来的治疗策略.
- 这些发现强调了在流行病期间评估治疗疗效时考虑药物特异性机制和患者特异性条件的重要性.
相关概念视频
Glucose Transporters
22.7K
Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
22.7K
Dipeptidyl Peptidase 4 Inhibitors
184
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
184
Secondary Active Transport
119.7K
One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme “pump” embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
119.7K
Oral Hypoglycemic Agents: α-Glucosidase Inhibitors
174
α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are...
Acarbose and miglitol are...
174
Heart Failure Drugs: Inotropic Agents
578
Positive inotropic agents are commonly used as the first line of treatment for heart failure. One such agent is digoxin, derived from the genus Digitalis, which has been known for centuries but effectively utilized since 1785. However, these cardiac glycosides can have potentially toxic effects due to their mechanism of action, which involves inhibiting Na+/K+-ATPase and increasing contractility. Digoxin is absorbed orally and distributed in various tissues, including the CNS. It has a long...
578
Drugs Affecting GI Tract Motility: Antimicrobials as Antidiarrheal Agents
119
Acute diarrhea, a common gastrointestinal disturbance, is characterized by the rapid evacuation of fluid stools, leading to an excessive weight in fluid. This condition typically arises from disorders affecting intestinal water and electrolyte transport. It can be triggered by an increased osmotic load within the intestine, excessive secretion of electrolytes and water, mucosal exudation of protein and fluid, or altered intestinal motility. The primary risks of acute diarrhea are dehydration...
119


