From the Guidelines
Pioglitazone (15-45 mg daily) is the most effective medication for treating non-alcoholic steatohepatitis (NASH) in patients with type 2 diabetes, as it has been shown to improve glucose and lipid metabolism, reverse steatohepatitis, and slow fibrosis progression 1.
Treatment Overview
The primary focus of treatment for non-alcoholic fatty liver disease (NAFLD) is lifestyle modification, including weight loss through diet and exercise. For patients with more advanced NASH, medications such as pioglitazone and GLP-1 receptor agonists like semaglutide may be considered.
Medication Options
- Pioglitazone: improves glucose and lipid metabolism, reverses steatohepatitis, and slows fibrosis progression in patients with type 2 diabetes and NASH 1.
- GLP-1 receptor agonists: emerging treatments that have shown promise in clinical trials for NASH resolution, though not yet approved for this indication 1.
- Vitamin E: may be considered for non-diabetic patients with biopsy-proven NASH to reduce liver inflammation, at a dose of 800 IU daily 1.
Lifestyle Modifications
- Weight loss: a 7-10% weight reduction through calorie restriction and regular exercise (150+ minutes weekly of moderate activity) can significantly improve liver histology and reduce fat accumulation in the liver 1.
- Diet: a Mediterranean diet has the best evidence for improving liver and cardiometabolic health, and should include a reduction of macronutrient content, limiting saturated fat, starch, and added sugar, with adoption of healthier eating patterns 1.
- Exercise: both aerobic and resistance training improve NAFLD in proportion to treatment engagement and intensity of the program 1.
From the FDA Drug Label
Clinical studies demonstrate that ACTOS improves insulin sensitivity in insulin-resistant patients. ACTOS enhances cellular responsiveness to insulin, increases insulin-dependent glucose disposal, improves hepatic sensitivity to insulin, and improves dysfunctional glucose homeostasis
The medication pioglitazone (PO), also known as ACTOS, is used in the management of type 2 diabetes mellitus and has been shown to improve insulin sensitivity.
- Key benefits of pioglitazone include:
- Improving insulin sensitivity in insulin-resistant patients
- Enhancing cellular responsiveness to insulin
- Increasing insulin-dependent glucose disposal
- Improving hepatic sensitivity to insulin
- Improving dysfunctional glucose homeostasis
- Clinical effects of pioglitazone include:
- Lower plasma glucose concentrations
- Lower plasma insulin levels
- Lower HbA1c values
- Mean decreases in triglycerides
- Mean increases in HDL cholesterol 2
From the Research
Medications for NAFLD
- There are currently no approved pharmacotherapies for nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) 3, 4, 5.
- Vitamin E and pioglitazone have shown therapeutic efficacy in NASH, but their use remains off-label and has limitations 3, 4, 5.
- Several medications are currently in phase 3 clinical trials for the treatment of NASH, including:
- Obeticholic acid (a farnesoid X receptor agonist) 4, 5
- Elafibranor (a peroxisome proliferator activated receptor [PPAR]-α/δ dual agonist) 4, 5
- Cenicriviroc (a CC chemokine receptor antagonist) 4, 5
- MSDC-0602K (a PPAR sparing modulator) 4
- Selonsertib (an apoptosis signal-regulating kinase-1 inhibitor) 4
- Resmetirom (a thyroid hormone receptor agonist) 4
- Other potential therapeutic options for NASH include:
- GLP-1RA and SGLT2 inhibitors, which are currently approved for use in diabetes 5
- Pemafibrate, a medication that targets peroxisome proliferator-activator receptors 5
- Aramchol, an inhibitor of de novo lipogenesis 5
- Fibroblast growth factor-21 analogues 5
- Apoptosis signaling kinase 1 (ASK1) inhibitor and emricasan (an irreversible caspase inhibitor) 5
- Intestinal microbiomes and metabolic endotoxemia-targeting agents, such as IMMe124, TLR4 antagonist, and solithromycin (macrolide antibiotics) 5
- Antifibrotic agents, such as cenicriviroc (CVC) and galectin 3 antagonist 5
Treatment Approach
- Lifestyle modification, including weight loss through diet and exercise, is the primary treatment for NAFLD 3, 6, 7.
- Bariatric surgery may be considered for obese patients with NAFLD 3, 7.
- Vitamin E supplements and pharmacologic therapy with thiazolidinediones or glucagon-like peptide-1 analogues may be considered for patients with NASH, but data are limited and these therapies are not considered routine treatments 7.