Research Article Details
| Article ID: | A50788 |
| PMID: | 35266164 |
| Source: | Aliment Pharmacol Ther |
| Title: | Review article: role of glucagon-like peptide-1 receptor agonists in non-alcoholic steatohepatitis, obesity and diabetes-what hepatologists need to know. |
| Abstract: | BACKGROUND: Non-alcoholic steatohepatitis (NASH) is characterised by hepatic lipid accumulation, cell injury, inflammation and fibrosis. Insulin resistance, a hallmark of type 2 diabetes (T2D) and obesity, is a key pathogenic driver of NASH. Other than difficult-to-maintain lifestyle changes, there are no approved treatments for NASH. Due to their effects on multiple pathophysiological processes, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been tested in disorders related to insulin resistance and metabolic defects. AIMS: To summarise studies of GLP-1RAs relevant to the treatment of NASH. METHODS: PubMed searches were performed and results were compiled. RESULTS: Large trials with GLP-1RAs in T2D demonstrate highly effective glucose lowering, with body weight loss, and in some cases, reduced cardiovascular events and improved liver transaminases. The GLP-1RAs, liraglutide and semaglutide, were associated with clinically relevant, sustained body weight reduction in individuals with overweight or obesity and without T2D. In a phase II trial in NASH, liraglutide reduced metabolic dysfunction, insulin resistance and lipotoxicity in key organs associated with NASH pathogenesis. Furthermore, liraglutide and semaglutide led to histological resolution of NASH in ~40% to 60% of patients, although a statistically significant effect on fibrosis has not been confirmed. Regarding safety, GLP-1RAs are associated with gastrointestinal and gallbladder-related adverse events, with the latter perhaps related to weight loss. Meta-analyses do not indicate increased risk of acute pancreatitis, pancreatic cancer or other malignancies with GLP-1RAs. CONCLUSIONS: These studies support the use of GLP-1RAs for the improvement of underlying metabolic dysfunction observed in NASH and suggest further long-term phase III trials are warranted. |
| DOI: | 10.1111/apt.16794 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D327 | Semaglutide | Chemical drug | DB13928 | GLP1R agonist | Antidiabetic drug | Under clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D207 | Liraglutide | Biological drug | DB06655 | GLP1R activator; GLP1R agonist; GCG receptor antagonist activity | Improve insulin resistance | Under clinical trials | Details |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D155 | Glucagon | Biological drug | DB00040 | GCGR agonist | Antidiabetic drug | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |