AI Summary In the PIVENS trial, vitamin E (800 IU daily) led to a significantly higher rate of NASH resolution than placebo in adults without diabetes.
Medically reviewed.
Additional metabolic therapies are medications and supplements used alongside primary MASLD and MASH treatment — such as GLP-1/incretin-based therapy and THR-β agonist therapy — to help manage the metabolic risk factors that drive liver fat, inflammation, and fibrosis. This group includes pioglitazone (Actos), vitamin E (alpha-tocopherol), and SGLT2 inhibitors such as empagliflozin (Jardiance), dapagliflozin (Farxiga/Forxiga), canagliflozin (Invokana), and ertugliflozin (Steglatro).
This page explains what these therapies are, who may benefit, and how the evidence for liver health compares with their approved uses in diabetes and cardiovascular care. You can also connect with a liver specialist to discuss whether one of these therapies fits your care plan.
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ADDITIONAL METABOLIC THERAPIES OVERVIEW
Additional metabolic therapies are medications used alongside primary MASLD and MASH treatments — such as GLP-1/incretin-based therapy and THR-β agonist therapy — to manage the metabolic risk factors that drive liver fat, inflammation, and fibrosis. This group includes pioglitazone (a diabetes medication sometimes used for MASH), vitamin E (an antioxidant supplement), and SGLT2 inhibitors (a class of diabetes medications). Care built around these therapies typically combines the medication with lifestyle changes and regular monitoring, and treatment plans are personalized based on a person's diagnosis, overall health, and individual needs.
You can explore the individual additional metabolic therapies below and learn how they may support blood sugar control, insulin sensitivity, and — in some cases — liver fat and inflammation improvement. Because eligibility depends on your specific diagnosis and health history, connecting with a liver specialist can help you understand which option fits your care plan.
Pioglitazone is a thiazolidinedione (TZD) medication approved to improve insulin sensitivity in adults with type 2 diabetes. Because insulin resistance is a central driver of MASLD and MASH, some healthcare providers prescribe it for selected patients with these conditions to help reduce liver fat and improve certain features of MASH.
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Vitamin E is a dietary antioxidant supplement studied in adults with MASH. It helps reduce oxidative stress, which contributes to liver inflammation and cell injury. It is not FDA-approved specifically for MASH but may be considered as adjunct therapy for selected patients without advanced cirrhosis.
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SGLT2 inhibitors — empagliflozin (Jardiance), dapagliflozin (Farxiga/Forxiga), canagliflozin (Invokana), and ertugliflozin (Steglatro) — are diabetes medications that lower blood sugar by increasing glucose excretion through the kidneys. Because obesity, insulin resistance, and type 2 diabetes are closely linked to MASLD and MASH, providers may consider these medications to help manage underlying metabolic risk factors.
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Healthcare providers may consider these additional metabolic therapies for adults with type 2 diabetes, insulin resistance, or cardiovascular risk factors who also have MASLD or MASH, especially when diet and exercise alone have not achieved treatment goals. They are typically used alongside — not instead of — primary MASLD/MASH-directed treatment.
DIET & LIFESTYLE SUPPORT
Additional metabolic therapies work best when combined with lifestyle changes. Nutrition, physical activity, weight management, and control of related metabolic conditions all support the benefits these medications and supplements can offer for blood sugar, insulin sensitivity, and liver health.
A calorie-appropriate, liver-friendly diet supports the blood sugar and insulin sensitivity changes these therapies target, and may add to their effect on liver fat.
Managing related conditions such as diabetes, high cholesterol, and high blood pressure remains an essential part of MASLD and MASH care alongside medication.
Regular physical activity supports metabolic health and works alongside medication to help manage blood sugar and weight.
A nutrition bar designed for liver health can be a simple way to support your eating habits alongside medication.
Explore Liver Health Nutrition Bars
EVIDENCE AND METABOLIC LIVER DISEASE
Pioglitazone, vitamin E, and SGLT2 inhibitors were first developed for type 2 diabetes management (pioglitazone and SGLT2 inhibitors) or as a general antioxidant supplement (vitamin E), and none currently carries an FDA approval specifically for MASLD or MASH. Their liver-related use is supported by clinical trial evidence showing improvements in liver fat, inflammation, or fibrosis markers in selected patients, alongside their approved effects on blood sugar and cardiovascular risk.
Because insulin resistance, obesity, and oxidative stress all contribute to MASLD and MASH, these therapies are often considered part of a broader metabolic liver disease care plan rather than a first-line, liver-directed treatment. The evidence below reflects clinical trial results rather than an approved liver-disease indication.
In the PIVENS trial, pioglitazone improved several histologic features of nonalcoholic steatohepatitis (NASH, now called MASH) compared with placebo, including reductions in liver fat and inflammation, though it did not significantly improve fibrosis.
In the same PIVENS trial, vitamin E (800 IU daily) led to a significantly higher rate of NASH resolution than placebo in adults without diabetes, with improvements in liver inflammation and fat.
SGLT2 inhibitors such as empagliflozin, dapagliflozin, canagliflozin, and ertugliflozin are approved for type 2 diabetes, and some have shown cardiovascular or kidney benefits in dedicated outcomes trials. Their effect on liver fat is an area of ongoing study rather than an approved liver indication.
None of these therapies currently carries an FDA approval specifically for MASLD or MASH; approvals are for type 2 diabetes, cardiovascular risk reduction, or general antioxidant supplementation. Your healthcare provider weighs the liver-related evidence alongside your diagnosis when deciding if one of these therapies fits your plan.
TREATMENT MONITORING
Regular monitoring helps your healthcare provider evaluate how your body is responding to additional metabolic therapies and track any liver-related changes over time. Follow-up care may include blood tests, imaging, and fibrosis assessments alongside routine diabetes or metabolic monitoring.
Liver function tests track enzymes and other markers that show how your liver is responding to treatment and help flag any changes early.
Providers use metabolic markers alongside liver tests to track blood sugar, liver fat, and related risk factors over time.
Imaging and, in selected cases, biopsy can assess liver fat and fibrosis directly and help guide treatment decisions during long-term therapy.
Only a qualified healthcare provider can adjust your treatment plan based on your test results and health history.
COMMON QUESTIONS
Additional metabolic therapies are medications and supplements used alongside primary MASLD/MASH treatments to help manage the metabolic risk factors that contribute to liver fat, inflammation, and fibrosis. This group includes pioglitazone (Actos), vitamin E (alpha-tocopherol), and SGLT2 inhibitors such as empagliflozin (Jardiance), dapagliflozin (Farxiga/Forxiga), canagliflozin (Invokana), and ertugliflozin (Steglatro). Talk with your healthcare provider about whether one of these therapies fits your treatment plan.
Pioglitazone improves insulin sensitivity in the liver, muscle, and fat tissue, which can help reduce liver fat and improve certain features of MASH in selected patients. Vitamin E acts as an antioxidant that helps reduce oxidative stress, a process believed to contribute to liver inflammation and cell injury. SGLT2 inhibitors lower blood sugar by increasing glucose excretion through the kidneys, which helps manage the insulin resistance and metabolic risk factors linked to MASLD and MASH.
Healthcare providers typically consider these therapies for adults with type 2 diabetes, insulin resistance, or cardiovascular risk factors who also have MASLD or MASH, especially when diet and exercise alone have not achieved treatment goals. Pioglitazone and vitamin E are generally considered for patients with confirmed MASH without advanced cirrhosis, while SGLT2 inhibitors are considered for patients with type 2 diabetes and related metabolic risk. Eligibility depends on your specific diagnosis and health history.
In the PIVENS trial, pioglitazone improved liver fat and inflammation in adults with NASH (now called MASH) compared with placebo, though it did not significantly improve fibrosis. Vitamin E, at 800 IU daily, led to a significantly higher rate of NASH resolution than placebo in adults without diabetes. SGLT2 inhibitors have shown benefits for blood sugar, cardiovascular risk, and in some trials kidney function, with liver fat effects still under study. Results vary by individual, so discuss your specific expectations with your healthcare provider.
Common side effects of pioglitazone include weight gain, fluid retention, and swelling of the legs or ankles. Vitamin E's most common side effects include nausea, headache, fatigue, and increased bleeding risk at high doses. SGLT2 inhibitors commonly cause urinary tract infections, genital yeast infections, increased urination, dehydration, and dizziness. Your healthcare provider will monitor you regularly and can help manage any side effects that arise.
No, additional metabolic therapies work alongside lifestyle changes rather than replacing them. A liver-friendly diet, regular physical activity, weight management, and control of related conditions like diabetes and high cholesterol remain essential parts of MASLD and MASH care. These medications can support blood sugar control, insulin sensitivity, and liver health, but they work best when combined with these ongoing habits. Ask your healthcare provider how to build a plan that pairs medication with lifestyle support.
No, not currently. Pioglitazone and the SGLT2 inhibitors are FDA-approved for type 2 diabetes, and some SGLT2 inhibitors also carry cardiovascular or kidney approvals; vitamin E is an over-the-counter antioxidant supplement. None carries an FDA approval specifically for MASLD or MASH. Clinical trial evidence shows liver-related benefits for some of these therapies, but a liver-specific approval has not been granted. Your healthcare provider can explain how the evidence applies to your diagnosis.
Medical disclaimer: LiverDirectory provides educational information and a directory of providers. It does not provide medical advice, diagnosis, or treatment. Always consult a licensed physician regarding any medical condition.
