Research Article Details
| Article ID: | A12164 |
| PMID: | 30577089 |
| Source: | Hepatol Res |
| Title: | Impact of sodium glucose cotransporter 2 inhibitor on histological features and glucose metabolism of non-alcoholic fatty liver disease complicated by diabetes mellitus. |
| Abstract: | AIM: The aim of this study was to investigate the therapeutic potential of sodium glucose cotransporter 2 inhibitor (SGLT2I) as an effective therapeutic option for non-alcoholic fatty liver disease (NAFLD). METHODS: In this prospective study, nine patients with NAFLD complicated by type 2 diabetes mellitus (DM), were introduced to the regimen of canagliflozin 100 mg once daily for 24 weeks and were evaluated by liver histology at pretreatment and at 24 weeks after the start of treatment. The primary outcome was histological improvement, defined as a decrease in NAFLD activity score of one point or more without worsening in fibrosis stage. Glucose metabolism was evaluated based on the meal tolerance test. The usefulness of extracellular and exosome microRNA-122 (miR-122) as early predictors of histological improvement was investigated. RESULTS: All of the nine patients achieved histological improvement. Scores of steatosis, lobular inflammation, ballooning, and fibrosis stage decreased by 78%, 33%, 22%, and 33% at 24 weeks compared to the pretreatment, respectively. Six patients showed improvement in insulin resistance, and the other three patients showed partial improvement of insulin secretion function. Six patients, who showed a decrease in both extracellular and exosome miR-122 ratios (the ratio of miR-122 levels at 1 day after treatment to that at baseline), showed histological improvement. Furthermore, one patient, who showed a decrease in exosome miR-122 ratios regardless of the increase in extracellular miR-122 ratios, also showed decreases in NAFLD activity score and fibrosis stage. CONCLUSION: A prospective study showed that SGLT2I for NAFLD complicated by DM improved histological features in connection with glucose metabolism. This trial was registered as clinical trial UMIN000018166. |
| DOI: | 10.1111/hepr.13304 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D058 | Canagliflozin | Chemical drug | DB08907 | SGLT2 inhibitor | Improve insulin resistance | 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 |