Fatty liver, especially MASLD (Metabolic Abnormalities Related Fatty Liver Disease), which has received much attention in recent years, is a disease associated with metabolic abnormalities such as diabetes, hypertension, and lipid abnormalities in addition to fat accumulation in the liver. If left untreated, MASLD can progress to cirrhosis and liver cancer, so aggressive intervention is recommended.
❖ In Japan, drug therapy is "free" in principle
At present (as of 2025), there is no drug that is covered by insurance for MASLD in Japan. Therefore, it is necessary to introduce the drug carefully with sufficient explanation and consent on the assumption that it will be used in an unrestricted manner.
Major drug therapies that have been shown to be effective for fatty liver and MASH
The following are drugs that can be introduced in Japan and have been reported to be effective based on evidence. Although it is up to the physician's discretion and individual judgment based on the patient's condition, the following is a list of options that may be considered in actual clinical practice.
Semaglutide (GLP-1 receptor agonist)
- Product name: Ozempic (subcutaneous injection), Liberusas (oral)
- Mode of action: Acts on GLP-1 receptors, resulting in weight loss and improvement of glucose metabolism by suppressing appetite, promoting insulin secretion, and delaying gastric emptying.
- Evidence: biopsy-confirmed improvement in MASH (formerly NASH) (limited improvement in Fibrosis)
‣ Newsome PN et al., Lancet. 2021;397(10290):2180-2193. - Notes:
- Gastrointestinal symptoms such as nausea and vomiting
- High cost (tens of thousands of yen per month)
- Indicated for type 2 diabetes in Japan
- Gastrointestinal symptoms such as nausea and vomiting
(ii) Tilzepatide (GIP/GLP-1 dual agonist)
- Product name: Manjaro
- Mechanism of action: Dual stimulation of GIP and GLP-1 for more potent weight loss and improved insulin sensitivity
- Evidence: Recent studies have demonstrated a significant reduction in liver fat mass, suggesting a MASH-improving effect
‣ Hartman ML et al., Obesity (Silver Spring). 2023;31(4):924-933. - Notes:
- Side effects and price similar to or higher than semaglutide
- Currently uninsured use (use in accordance with diabetes)
- Side effects and price similar to or higher than semaglutide
Pioglitazone (PPARγ agonist)
- Product name: Actos
- Mechanism of action: improves insulin sensitivity, redistribution of fatty acids, suppresses inflammation
- Evidence: Effective in improving MASH (especially in cases of diabetes complications)
‣ Cusi K et al., Ann Intern Med. 2016;165(5):305-315. - Notes:
- Risk of weight gain, edema, worsening heart failure
- Bladder cancer risk concerns
- Risk of weight gain, edema, worsening heart failure
4) SGLT2 inhibitors (e.g., empagliflozin, dapagliflozin)
- Mode of action: Excretes sugar in urine and contributes to liver fat reduction through weight loss and improvement of blood sugar and lipids
- Evidence: Multiple RCTs and meta-analyses have shown liver fat reduction and liver enzyme reduction
‣ Mantovani A et al., Diabetes Metab. 2020;46(6):427-434. - Notes:
- Urinary tract infection, dehydration, ketoacidosis
- Cautious indication (off-label use) in the absence of diabetes mellitus
- Urinary tract infection, dehydration, ketoacidosis
5) Sargligliptin (novel PPARα/δ agonist, under development)
- Although not approved in Japan, this candidate drug is expected to be effective for both steatohepatitis and fibrosis.
- Overseas clinical trial stage (Lanifibranor, Aramchol, Resmetirom, etc.)
Basis and positioning of treatment strategies
| stage | Main Treatment Policies | Recommended drugs (including free drugs) |
| Early stage (fatty liver only, no abnormal blood draws) | Lifestyle modification + GLP-1 system if desired | Semaglutide, Tilzepatide |
| Mid-term (elevated ALT and AST, metabolic abnormalities) | Above + SGLT2 or Pioglitazone consideration | same as on the left |
| Late stage (MASH, fibrosis on biopsy) | Strong intervention, anti-fibrotic drugs in the future. | Tilzepatide, Pioglitazone, Advanced Facility Referral |
Conclusion
MASLD is a serious disease that can be improved by lifestyle, but if it progresses, it can develop into liver cirrhosis and cancer. The key to treatment is a combination of appropriate drug therapy based on diet and exercise.
In Japan, there are no drugs covered by insurance at this time, so it is important to understand the clear objectives and risks as an unrestricted treatment.
The introduction of pharmacotherapy should be done carefully based on clinical symptoms, laboratory values, and imaging evaluation.
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