Introduction
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.
Background
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.
Discussion
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.
Conclusion
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.
Semaglutide, a glucagon like peptide-1 (GLP-1) receptor agonist, is available as monotherapy in both subcutaneous as well as oral dosage form (first approved oral GLP-1 receptor agonist). It has been approved as a second line treatment option for better glycaemic control in type 2 diabetes and currently under scrutiny for anti-obesity purpose. Semaglutide has been proved to be safe in adults and elderly patients with renal or hepatic disorders demanding no dose modification. Cardiovascular (CV) outcome trials established that it can reduce various CV risk factors in patients with established CV disorders. Semaglutide is well tolerated with no risk of hypoglycaemia in monotherapy but suffers from gastrointestinal adverse effects. A large population affected with COVID-19 infection were diabetic; therefore use of semaglutide in diabetes as well as CV patients would be very much supportive in maintaining health care system during this pandemic situation. Hence, this peptidic drug can be truly considered as a quintessential of GLP-1 agonists for management of type 2 diabetes.
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