Research Article Details
| Article ID: | A20174 |
| PMID: | 26111358 |
| Source: | J Gastroenterol Hepatol |
| Title: | Incretin-based therapies for the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis. |
| Abstract: | BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease in Western societies. Despite its significance, there are no well-proven pharmacological treatments. Two novel classes of potential pharmacotherapies are the glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase-4 inhibitors (DPP-4I), collectively known as incretin-based therapies. These have several metabolic and anti-inflammatory actions that may be of benefit in NAFLD. The aim of this meta-analysis was to evaluate their efficacy via a structured retrieval and pooled analysis of relevant studies. METHODS: Studies were sourced from electronic databases and meeting abstracts. Main inclusion criteria were original studies investigating treatment of adults with NAFLD using GLP-1 RA/DPP-4I. Key outcomes were a change in serum alanine transaminase (ALT), as a marker of liver inflammation, and improvement in disease status measured by imaging or histology. RESULTS: Initial searching retrieved 1357 peer-reviewed articles and abstracts. Four studies met all inclusion and exclusion criteria. There were a total of 136 participants with NAFLD and concomitant type 2 diabetes mellitus (T2DM). Meta-analysis (random-effects model) revealed a significant decrease in serum ALT following treatment (mean reduction 14.1 IU/L, 95% confidence intervals [CI] 8.3-19.8, P < 0.0001). In two studies with imaging and tissue data, treatment was found to significantly reduce steatosis, inflammation, and fibrosis. CONCLUSION: The significant decrease in a key biochemical marker of hepatic inflammation following treatment with incretin-based therapies, as well as improvements in imaging and histology, suggests these agents may be effective options for managing NAFLD with comorbid T2DM. |
| DOI: | 10.1111/jgh.13026 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| 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 |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | 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 |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |