Research Article Details
| Article ID: | A13245 |
| PMID: | 30066148 |
| Source: | Diabetologia |
| Title: | Empagliflozin is associated with improvements in liver enzymes potentially consistent with reductions in liver fat: results from randomised trials including the EMPA-REG OUTCOME® trial. |
| Abstract: | AIMS/HYPOTHESIS: In addition to beneficial effects on glycaemia and cardiovascular death, empagliflozin improves adiposity indices. We investigated the effect of empagliflozin on aminotransferases (correlates of liver fat) in individuals with type 2 diabetes. METHODS: Changes from baseline alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assessed in the EMPA-REG OUTCOME® trial (n = 7020), pooled data from four 24-week placebo-controlled trials (n = 2477) and a trial of empagliflozin vs glimepiride over 104 weeks (n = 1545). Analyses were performed using data from all participants and by tertiles of baseline aminotransferases. RESULTS: In the EMPA-REG OUTCOME® trial, mean ± SE changes from baseline ALT at week 28 were -2.96 ± 0.18 and -0.73 ± 0.25 U/l with empagliflozin and placebo, respectively (adjusted mean difference: -2.22 [95% CI -2.83, -1.62]; p < 0.0001). Reductions in ALT were greatest in the highest ALT tertile (placebo-adjusted mean difference at week 28: -4.36 U/l [95% CI -5.51, -3.21]; p < 0.0001). The adjusted mean difference in change in ALT was -3.15 U/l (95% CI -4.11, -2.18) with empagliflozin vs placebo at week 24 in pooled 24-week data, and -4.88 U/l (95% CI -6.68, -3.09) with empagliflozin vs glimepiride at week 28. ALT reductions were largely independent of changes in weight or HbA1c. AST changes showed similar patterns to ALT, but the reductions were considerably lower. CONCLUSIONS/INTERPRETATION: These highly consistent results suggest that empagliflozin reduces aminotransferases in individuals with type 2 diabetes, in a pattern (reductions in ALT>AST) that is potentially consistent with a reduction in liver fat, especially when ALT levels are high. |
| DOI: | 10.1007/s00125-018-4702-3 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs |
|---|
| 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 | |
|---|---|---|---|---|---|---|---|
| D353 | Sulfonylurea | Chemical drug | -- | -- | -- | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D154 | Glimepiride | Chemical drug | DB00222 | ABCC8 binder; KCNJ1 inhibitor; KCNJ11 inhibitor; KCNJ11 potassium channel inhibitor | Antidiabetic drug | Under clinical trials | Details |
| D122 | Empagliflozin | Chemical drug | DB09038 | SLC5A2 inhibitor; SGLT-2 inhibitor | Improve insulin resistance | 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 |