Therapeutic Potential of Semaglutide, a Newer GLP-1 Receptor Agonist, in Abating Obesity, Non-Alcoholic Steatohepatitis and Neurodegenerative diseases: A Narrative Review

Pharm Res. 2022 Jun;39(6):1233-1248. doi: 10.1007/s11095-022-03302-1. Epub 2022 Jun 1.

Abstract

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.

Keywords: GLP-1 receptor agonist; metabolic diseases; neurodegenerative diseases; obesity; semaglutide.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Animals
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Glucagon-Like Peptide-1 Receptor / therapeutic use
  • Glucagon-Like Peptides
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Insulin Resistance*
  • Neurodegenerative Diseases* / drug therapy
  • Non-alcoholic Fatty Liver Disease* / drug therapy
  • Obesity / drug therapy
  • Parkinson Disease* / drug therapy

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • semaglutide
  • Glucagon-Like Peptides