Research Article Details

Article ID: A18554
PMID: 28702244
Source: Clin Diabetes Endocrinol
Title: Treatment of Nonalcoholic Fatty Liver Disease (NAFLD) in patients with Type 2 Diabetes Mellitus.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is believed to be the most common chronic liver disease, affecting at least one-third of the population worldwide. The more aggressive form is known as nonalcoholic steatohepatitis (NASH) and characterized by hepatocyte necrosis and inflammation. The presence of fibrosis is not uncommon. Fibrosis indicates a more aggressive course and patients with NASH that are at high-risk of cirrhosis and premature mortality, as well as at increased risk of hepatocellular carcinoma (HCC). Patients with type 2 diabetes mellitus (T2DM) are at the highest risk for the development of NASH, even in the setting of normal plasma aminotransferase levels. The presence of dysfunctional adipose tissue in most overweight and obese subjects, combined with insulin resistance, hyperglycemia, and atherogenic dyslipidemia, contribute to their increased cardiovascular risk. Many therapeutic agents have been tested for the treatment of NASH but few studies have focused in patients with T2DM. At the present moment, the only FDA-approved agents that in controlled studies have shown to significantly improve liver histology in patients with diabetes are pioglitazone and liraglutide. Current research efforts are centering on the mechanisms for intrahepatic triglyceride accumulation and for the development of steatohepatitis, the role of mitochondrial dysfunction in NASH, and the impact of improving glycemic control per se on the natural history of the disease. This brief review summarizes our current knowledge on the pharmacological agents available for the treatment of NASH to assist healthcare providers in the management of these challenging patients.
DOI: 10.1186/s40842-016-0027-7

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

Target ID Target Name GENE Action Class UniProtKB ID Entry Name
T02 Sodium/glucose cotransporter 2 SLC5A2 inhibitor Transporter P31639 SC5A2_HUMAN Details
T18 Acetyl-CoA carboxylase 1 ACACA inhibitor Enzyme Q13085 ACACA_HUMAN Details
T06 Glucagon-like peptide 1 receptor GLP1R agonist GPCR P43220 GLP1R_HUMAN Details

Diseases ID DO ID Disease Name Definition Class
I13 3146 Lipid metabolism disorder An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism disease of metabolism/ inherited metabolic disorder Details
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
D225 Metformin Chemical drug DB00331 PRKAB1 inducer activator; ETEDH inhibitor; GPD1 inhibitor 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
D275 Pioglitazone Chemical drug DB01132 PPARG agonist Improve insulin resistance Advanced in 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
D157 Glucophage Chemical drug DB00331 -- -- Under clinical trials Details