Department of Pharmaceutical Chemistry, Kanak Manjari Institute of Pharmaceutical Sciences, Chhend, Rourkela, 769015, Odisha, India.
YaAn Pharmaceutical and Medical Communications, 1798, Balaji Nagar, Sithurajapuram, Sivakasi, 626189, Tamilnadu, India.
Pharm Res. 2022 Jun;39(6):1233-1248. doi: 10.1007/s11095-022-03302-1. Epub 2022 Jun 1.
Semaglutide, a peptidic GLP-1 receptor agonist, has been clinically approved for treatment of type 2 diabetes mellitus and is available in subcutaneous and oral dosage form. Diabetes, insulin resistance, and obesity are responsible for the pathological manifestations of non-alcoholic steatohepatitis (NASH). Similarly, insulin resistance in brain is also responsible for neurodegeneration and impaired cognitive functions.
Observations from phase-3 clinical trials like SUSTAIN and PIONEER indicated anti-obesity potential of semaglutide, which was established in STEP trials. Various pre-clinical and phase-2 studies have indicated the therapeutic potential of semaglutide in non-alcoholic steatohepatitis and neurodegenerative disorders like Parkinson's and Alzheimer's disease.
Significant weight reduction ability of semaglutide has been demonstrated in various phase-3 clinical trials, for which recently semaglutide became the first long-acting GLP-1 receptor agonist to be approved by the United States Food and Drug Administration for management of obesity. Various pre-clinical and clinical studies have revealed the hepatoprotective effect of semaglutide in NASH and neuroprotective effect in Parkinson's and Alzheimer's disease.
Many GLP-1 receptor agonists have shown hepatoprotective and neuroprotective activity in animal and human trials. As semaglutide is an already clinically approved drug, successful human trials would hasten its inclusion into therapeutic treatment of NASH and neurodegenerative diseases. Semaglutide improves insulin resistance, insulin signalling pathway, and reduce body weight which are responsible for prevention or progression of NASH and neurodegenerative diseases.
司美格鲁肽是一种肽类 GLP-1 受体激动剂，已被临床批准用于治疗 2 型糖尿病，并有皮下和口服剂型。糖尿病、胰岛素抵抗和肥胖是导致非酒精性脂肪性肝炎（NASH）病理表现的原因。同样，大脑中的胰岛素抵抗也是导致神经退行性变和认知功能障碍的原因。
像 SUSTAIN 和 PIONEER 这样的 3 期临床试验的观察结果表明司美格鲁肽具有减肥潜力，这在 STEP 试验中得到了证实。各种临床前和 2 期研究表明，司美格鲁肽在非酒精性脂肪性肝炎和神经退行性疾病（如帕金森病和阿尔茨海默病）方面具有治疗潜力。
在各种 3 期临床试验中已经证明了司美格鲁肽显著的减重能力，最近，司美格鲁肽成为第一个被美国食品和药物管理局批准用于肥胖管理的长效 GLP-1 受体激动剂。各种临床前和临床研究表明，司美格鲁肽在 NASH 中具有肝保护作用，在帕金森病和阿尔茨海默病中具有神经保护作用。
许多 GLP-1 受体激动剂在动物和人类试验中显示出肝保护和神经保护活性。由于司美格鲁肽已被临床批准，成功的人体试验将加速其纳入 NASH 和神经退行性疾病的治疗。司美格鲁肽可改善胰岛素抵抗、胰岛素信号通路，并减轻体重，从而预防或延缓 NASH 和神经退行性疾病的发生和发展。
