Peptides for Fatty Liver (MASLD): What the Research Shows

Weight Loss & Metabolism Research

Peptides for fatty liver have moved from theory to hard trial data: the multi-receptor peptides that lead the weight-loss research now have liver-fat scans and liver biopsies behind them. In one trial, 86% of participants on the highest dose of reta (GLP-3) reached normal liver fat within 24 weeks; in another, steatohepatitis resolved on biopsy in up to 62% of participants on tirzepatide, against 10% on placebo. This guide explains what fatty liver (now called MASLD) is, how much weight loss the liver research ties to improvement, and what each peptide trial found.

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Findings

• Fatty liver affects an estimated 25 to 30% of adults, and 30 to 75% of people with type 2 diabetes (AASLD guidance, 2023). In 2023 it was renamed MASLD.
• Liver guidance ties 3 to 5% weight loss to less liver fat, and more than 10% to improvement in inflammation and scarring. In a 293-person study, steatohepatitis resolved in 90% of those who lost 10% or more.
• Reta (GLP-3) cut liver fat by up to 86% at 48 weeks in a 98-person trial (Nature Medicine, 2024); at the two highest doses, 79% and 86% reached normal liver fat by 24 weeks, against 0% on placebo.
• On tirzepatide, steatohepatitis resolved in 44 to 62% of participants, against 10% on placebo, in a 190-person biopsy trial (NEJM, 2024).
• Tesamorelin lowered liver fat by 37% relative to placebo over 12 months in people with HIV (Lancet HIV, 2019).

What fatty liver is, and why it is now called MASLD

Fatty liver means fat building up inside liver cells. For decades it was called non-alcoholic fatty liver disease (NAFLD). In 2023 a consensus process led by three large international liver associations, with 236 panellists from 56 countries, renamed it metabolic dysfunction-associated steatotic liver disease (MASLD). The new definition pairs liver fat with at least one of five cardiometabolic risk factors, such as excess weight, raised blood sugar or high blood pressure, and the inflamed form, once NASH, is now MASH.

It is common. The American Association for the Study of Liver Diseases (AASLD) estimates it in 25 to 30% of adults and 30 to 75% of people with type 2 diabetes. Trials measure it two ways: MRI scans that report liver fat as a percentage, with under 5% counted as normal, and liver biopsies that grade inflammation and scarring (fibrosis).

How do people get rid of fatty liver? What the evidence shows

Weight loss is the lever with the strongest evidence. The 2023 AASLD guidance states that losing 3 to 5% of body weight improves liver fat, and that more than 10% is generally needed to improve steatohepatitis and fibrosis.

The clearest dose-response data come from a 2015 Gastroenterology study that followed 293 people with biopsy-proven steatohepatitis through 52 weeks of lifestyle change, with a second biopsy at the end. The more weight people lost, the more their livers improved:

• 5% or more lost: steatohepatitis resolved in 58%.
• 10% or more lost: steatohepatitis resolved in 90%, fibrosis regressed in 45%, and every participant’s disease-activity score improved.

Reaching those numbers is the hard part. Only 30% of people in that study lost 5% or more, and the AASLD notes that 10% or fewer patients reach effective weight loss in structured programmes at one year, with fewer than half of those keeping it off at five years. Bariatric surgery, which the guidance credits with sustained weight loss of up to 30%, resolved steatohepatitis without worsening fibrosis in 80% of patients a year after the operation. That gap, between the weight loss the liver responds to and what diet alone usually delivers, is where the peptide research comes in.

Peptide trials for fatty liver at a glance

Peptide	Study	Liver result
Reta (GLP-3)	98 adults, 48 weeks (Nat Med 2024)	Liver fat down up to 86%
Tirzepatide	190 adults with MASH, 52 weeks (NEJM 2024)	MASH resolved in 44 to 62% vs 10%
Tirzepatide	296 adults with type 2 diabetes, 52 weeks	Liver fat down 8.09 points vs 3.38
Semaglutide	800 adults with MASH, 72 weeks (NEJM 2025)	MASH resolved in 62.9% vs 34.3%
Tesamorelin	61 adults with HIV, 12 months (Lancet HIV 2019)	Liver fat down 37% vs placebo

Reta (GLP-3) and liver fat

The 2024 Nature Medicine trial enrolled 98 adults with MASLD and at least 10% liver fat on MRI, drawn from a 48-week phase 2 obesity trial in people without type 2 diabetes. Participants were randomised to one of four once-weekly reta doses or placebo.

• At 24 weeks: liver fat fell by 42.9% at the lowest dose and by 81.4% and 82.4% at the two highest, while it rose 0.3% on placebo.
• Normal liver fat (under 5%) by 24 weeks: 27%, 52%, 79% and 86% across the four doses, against 0% on placebo.
• At 48 weeks: reductions of 51.3% to 86.0%, against 4.6% on placebo; at the two highest doses, 89% and 93% had normal liver fat.

Liver fat fell in step with body weight, abdominal fat and markers of better insulin sensitivity, and the near-maximal liver response came alongside roughly 20% weight loss. The authors suggest reta’s glucagon-receptor activity may also act on the liver directly. Gastrointestinal events were the most common side effects, and no liver-toxicity signals were seen through 48 weeks. Our full write-up of the reta liver trial has the detail, and Vistara Labs supplies reta (GLP-3).

Tirzepatide: liver fat and biopsy results

Tirzepatide has both kinds of liver data. In a 2022 MRI substudy (Lancet Diabetes and Endocrinology) of 296 adults with type 2 diabetes, liver fat started at an average of 15.71% and fell by 8.09 percentage points over 52 weeks on the two higher doses, against 3.38 points on insulin degludec. The drop tracked reductions in body weight and abdominal fat.

The 2024 NEJM phase 2 trial went further, with liver biopsies in 190 adults with MASH and moderate or severe fibrosis over 52 weeks:

• MASH resolved without worsening fibrosis: 44%, 56% and 62% across the three doses, against 10% on placebo.
• Fibrosis improved by at least one stage without worsening MASH: 51 to 55%, against 30%.

Gastrointestinal events were the most common side effects, mostly mild or moderate. Vistara Labs supplies tirzepatide, and our GLP-1 for diabetes article covers its blood-sugar trials.

Semaglutide: the phase 3 biopsy trial

Semaglutide, the molecule sold as Ozempic, acts on the GLP-1 receptor alone. Its 2025 NEJM phase 3 trial enrolled 1,197 adults with biopsy-confirmed MASH and moderate or severe fibrosis, and an interim analysis at 72 weeks covered the first 800. MASH resolved without worsening fibrosis in 62.9% on semaglutide against 34.3% on placebo, fibrosis improved in 36.8% against 22.4%, and weight fell 10.5% against 2.0%.

No trial has yet compared these peptides on the liver directly. In the two trials that compared tirzepatide with semaglutide head to head, tirzepatide produced the greater weight loss both times, including 20.2% against 13.7% at 72 weeks in adults with obesity (NEJM, 2025), and the liver studies above tie liver improvement closely to weight loss.

Tesamorelin and liver fat in people with HIV

Tesamorelin is a growth hormone-releasing hormone (GHRH) analogue, and its liver research comes from people with HIV, in whom abdominal fat gain is common. A 2014 JAMA trial of 50 adults with HIV found visceral fat fell 34 cm² in six months (placebo: up 8 cm²) and liver fat fell 2.9 percentage points net of placebo.

The 2019 Lancet HIV trial targeted fatty liver directly: 61 adults with HIV and at least 5% liver fat, 12 months, double-blind. Liver fat fell 4.1 percentage points more than on placebo, a 37% relative reduction, and 35% ended the year under 5% against 4% on placebo. On biopsy, fibrosis progressed in 10.5% on tesamorelin against 37.5% on placebo, and fasting glucose and HbA1c did not differ between groups. More in our tesamorelin and liver fat article and the visceral fat trial record; Vistara Labs supplies tesamorelin.

MOTS-c and 5-Amino-1MQ: early-stage research

Two more compounds come up in fatty liver discussions, with evidence still in cell and animal models. In a 2024 Cell Reports study, MOTS-c, a peptide encoded in mitochondrial DNA, reduced liver fat, inflammation and fibrosis in a diet-induced steatohepatitis model, and a separate 2023 study of 234 people found lower blood MOTS-c levels in those with fatty liver than in healthy controls. 5-Amino-1MQ, an NNMT inhibitor and strictly a small molecule rather than a peptide, rapidly normalised body fat and weight in diet-induced obese mice when combined with a low-fat diet (Scientific Reports, 2022). Neither has a liver trial in people yet; What Is MOTS-c? and the NNMT research cover each in more depth.

Frequently asked questions

Which peptides have been studied for fatty liver?

The strongest data are for reta (GLP-3), tirzepatide and semaglutide, each tested with MRI liver-fat scans or liver biopsies in randomised trials, and for tesamorelin in people with HIV. MOTS-c and 5-Amino-1MQ have early-stage laboratory data only.

How do I get rid of fatty liver?

Weight loss has the strongest evidence. The 2023 AASLD guidance ties 3 to 5% weight loss to less liver fat and more than 10% to improvement in inflammation and fibrosis, and in a 293-person study steatohepatitis resolved in 90% of those who lost 10% or more. The peptide trials on this page measured how far reta (GLP-3), tirzepatide and semaglutide moved those same liver markers.

How much did reta (GLP-3) reduce liver fat?

In a 98-person trial published in Nature Medicine in 2024, liver fat fell by up to 82.4% at 24 weeks and 86.0% at 48 weeks, against almost no change on placebo. At the two highest doses, 79% and 86% of participants reached normal liver fat (under 5%) by 24 weeks.

What did tirzepatide show in fatty liver trials?

In a 190-person NEJM trial (2024) of adults with MASH and moderate or severe fibrosis, MASH resolved without worsening fibrosis in 44 to 62% on tirzepatide against 10% on placebo, and fibrosis improved in 51 to 55% against 30%.

What did semaglutide (Ozempic) show in fatty liver trials?

In a phase 3 NEJM trial (2025), MASH resolved without worsening fibrosis in 62.9% of 534 people on semaglutide against 34.3% on placebo at 72 weeks. In the head-to-head weight-loss trials, tirzepatide outperformed semaglutide.

Where can I buy reta and tirzepatide in Canada?

Vistara Labs supplies reta (GLP-3) and tirzepatide, along with tesamorelin, MOTS-c and 5-Amino-1MQ, shipped from within Canada to every province.

Sources: Rinella ME et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023. PMID 37363821. Rinella ME et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023. PMID 36727674. Vilar-Gomez E et al. Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis. Gastroenterology. 2015. PMID 25865049. Sanyal AJ et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024. PMID 38858523. Gastaldelli A et al. Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes: a substudy of a randomised, open-label, parallel-group, phase 3 trial. Lancet Diabetes Endocrinol. 2022. PMID 35468325. Loomba R et al. Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis. N Engl J Med. 2024. PMID 38856224. Sanyal AJ et al. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. N Engl J Med. 2025. PMID 40305708. Frías JP et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021. PMID 34170647. Aronne LJ et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med. 2025. PMID 40353578. Stanley TL et al. Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. JAMA. 2014. PMID 25038357. Stanley TL et al. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. Lancet HIV. 2019. PMID 31611038. Lu H et al. The mitochondrial genome-encoded peptide MOTS-c interacts with Bcl-2 to alleviate nonalcoholic steatohepatitis progression. Cell Rep. 2024. PMID 38206815. Kirik A et al. The relationship of circulating MOTS-c level with liver fibrosis and metabolic components in patients with metabolic dysfunction-associated fatty liver disease. Eur Rev Med Pharmacol Sci. 2023. PMID 37750635. Dimet-Wiley A et al. Reduced calorie diet combined with NNMT inhibition establishes a distinct microbiome in DIO mice. Sci Rep. 2022. PMID 35013352.

References

Retatrutide has been evaluated in randomised, placebo-controlled human trials through phase 3.

1. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 TrialJastreboff AM et al. · N Engl J Med 2023 · PMID 37366315Randomised, double-blind, placebo-controlled phase 2 obesity trial, 48 weeks.
2. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USARosenstock J et al. · Lancet 2023 · PMID 37385280Randomised, double-blind, placebo- and active-controlled phase 2 trial; 281 participants with type 2 diabetes.
3. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trialSanyal AJ et al. · Nat Med 2024 · PMID 38858523Randomised phase 2a substudy; 98 participants with metabolic dysfunction-associated steatotic liver disease.
4. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise: a double-blind, randomised, phase 3 trialBajaj HS et al. · Lancet 2026 · PMID 42250575Double-blind randomised phase 3 trial in type 2 diabetes.

Links open the study record on PubMed so the source can be checked directly. Listing a study is not a claim that its findings apply to any other use, product or route of administration. Research use only.