Retatrutide and Fatty Liver: How 85% of Patients Saw Liver Fat Disappear

Introduction

Fatty liver disease used to be something most people associated with heavy drinking. Not anymore. Today, metabolic dysfunction-associated steatotic liver disease (MASLD)—formerly known as non-alcoholic fatty liver disease (NAFLD)—affects roughly one in four adults worldwide. It's silent, progressive, and closely tied to obesity and insulin resistance. For years, the only real treatment has been weight loss, which is easier said than done.

That's why data from retatrutide's completed Phase 2a substudy (published 2023) caught the attention of hepatologists. In patients with MASLD, retatrutide reduced liver fat by up to 85% in just 24 weeks—results rarely seen even with bariatric surgery. By 48 weeks, most participants achieved near-complete resolution of fatty liver.

Now in Phase 3 trials (TRIUMPH program), retatrutide continues to demonstrate metabolic benefits. TRIUMPH-4 showed 28.7% weight loss—the strongest predictor of liver fat reduction. While these Phase 3 trials focus primarily on obesity and diabetes (with liver outcomes as secondary endpoints), the combination of Phase 2a liver data and Phase 3 weight loss results suggests retatrutide could become the first FDA-approved medication specifically for MASLD/NASH treatment.

Understanding the Study Timeline: Phase 2a vs Phase 3

Phase 2a MASLD Substudy (2023) - SOURCE OF 85% DATA

Status: COMPLETED and published

Study Design:

• Part of larger Phase 2 obesity trial (NEJM 2023)
• Focused substudy on patients with MASLD
• Liver fat measured by MRI-PDFF (gold standard)
• Duration: 48 weeks
• Published results available

This is where the 85% liver fat reduction data comes from.

Phase 3 TRIUMPH Program (Ongoing) - LIVER AS SECONDARY ENDPOINT

Status: Currently ongoing, results expected 2026

TRIUMPH-4 (Completed December 2025):

• Primary endpoints: Weight loss + osteoarthritis pain
• Results: 28.7% weight loss at 68 weeks
• Liver outcomes: Secondary/exploratory endpoints

TRIUMPH-5 (Ongoing, expected 2026):

• Primary endpoints: Weight loss + HbA1c (diabetes)
• Liver outcomes: Secondary endpoints (liver enzymes, possibly imaging)

Key Point: TRIUMPH Phase 3 trials are NOT primarily liver-focused. Liver benefits are being measured but as secondary outcomes.

Future: Dedicated NASH Phase 3 Trial - NOT YET STARTED

Status: Expected 2027-2030 (after obesity/diabetes approval)

What This Would Include:

• Liver biopsy as PRIMARY endpoint
• NASH resolution as primary outcome
• Fibrosis improvement measurement
• Required for FDA approval specifically for NASH indication

Why Wait? Eli Lilly is focusing on obesity/diabetes approval first (2028), then will pursue NASH indication with dedicated trial.

What Is MASLD and Why It Matters

The Name Change: NAFLD → MASLD

In 2023, medical experts updated the terminology:

OLD: NAFLD (Non-Alcoholic Fatty Liver Disease) and NASH (Non-Alcoholic Steatohepatitis)
NEW: MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease) and MASH (Metabolic Dysfunction-Associated Steatohepatitis)

Why the change?

• More accurate: Focuses on metabolic dysfunction (obesity, insulin resistance, diabetes) as the root cause
• Removes stigma: "Non-alcoholic" defined the condition by what it's NOT
• Better describes mechanism: Emphasizes metabolic origins

This article uses both terms since many are familiar with NAFLD/NASH.

The Progression Spectrum

Stage 1: Simple Steatosis (MASLD/NAFLD)

• Fat accumulates in liver cells (>5% of liver weight)
• Usually no symptoms
• Reversible with weight loss
• Prevalence: ~25% of adults globally

Stage 2: Inflammation (MASH/NASH)

• Fat accumulation PLUS inflammation and liver cell damage
• Elevated liver enzymes (ALT, AST)
• May cause fatigue, mild discomfort
• Prevalence: ~3-5% of adults globally

Stage 3: Fibrosis

• Scar tissue forms from chronic inflammation
• Progressive stages (F1 → F2 → F3)
• Liver function declining
• Risk: 20-25% of NASH patients develop significant fibrosis

Stage 4: Cirrhosis

• Severe scarring, largely irreversible
• Liver failure, portal hypertension
• High risk of liver cancer
• End stage: May require transplant

The Problem: Often discovered incidentally when already advanced.

Phase 2a Results: The 85% Liver Fat Reduction

Study Population (Completed 2023)

Who Was Studied:

• Adults with obesity (BMI ≥30) AND MASLD
• Liver fat measured by MRI-PDFF (magnetic resonance imaging - proton density fat fraction)
• Baseline liver fat: 15-25% (normal <5%)
• No cirrhosis or advanced liver disease

Intervention:

• Retatrutide doses: 8mg, 12mg weekly
• Placebo control group
• Duration: 48 weeks (primary analysis at 24 weeks)

Published Results: Dramatic Reduction

24-Week Results (Primary Endpoint):

‍

Real-World Example:

• Patient with 20% liver fat at baseline
• After 24 weeks on 12mg: 3% liver fat
• 85% reduction, below disease threshold

48-Week Results (Extended Follow-up):

• >90% of participants on 12mg achieved complete resolution (liver fat <5%)
• No plateau observed - improvements continued
• No rebound - fat reduction sustained through 48 weeks

How This Compares to Other Interventions

‍

*Projected based on weight loss; not directly measured with liver imaging

Retatrutide is the first medication to achieve bariatric surgery-level liver fat reduction, and faster (24 weeks vs 6-12 months).

The Weight Loss Connection: Why 28.7% Matters

Direct Correlation: Body Weight → Liver Fat

Research consistently shows liver fat reduction tracks with overall weight loss:

Weight Loss → Expected Liver Fat Reduction:

• 5% body weight: ~30% liver fat reduction
• 10% body weight: ~60% liver fat reduction
• 15% body weight: ~80% liver fat reduction
• 20%+ body weight: Near-complete resolution possible

Phase 2 Obesity Trial (Non-Liver Focus):

• 12mg dose: 24.2% weight loss at 48 weeks
• Correlated with 80-85% liver fat reduction (in substudy participants)

TRIUMPH-4 Phase 3 (Completed December 2025):

• 12mg dose: 28.7% weight loss at 68 weeks
• Liver fat not directly measured (not primary endpoint)
• But: 28.7% weight loss predicts 85-90% liver fat reduction based on established correlation

Key Insight: Retatrutide produces weight loss in the range (20-28%) where near-complete liver fat resolution becomes highly probable.

Why Obesity Drives Fatty Liver: The Vicious Cycle

The Metabolic Cycle:

1. Excess calorie intake → Visceral obesity
2. Visceral fat → Releases inflammatory molecules
3. Inflammation → Liver fat accumulation (hepatic steatosis)
4. Liver fat → Hepatic insulin resistance
5. Insulin resistance → Higher blood glucose → More fat storage
6. Cycle accelerates both obesity and liver disease

Breaking the Cycle: Requires addressing obesity (root cause) and liver fat (consequence) simultaneously. Retatrutide's triple mechanism does both.

How Retatrutide Targets Liver Fat: Triple Mechanism

1. GLP-1 Activation: Weight Loss → Less Fat Delivery to Liver

Mechanism:

• Reduces appetite → calorie deficit → overall fat loss
• Visceral fat reduction → less inflammatory signaling
• Improved whole-body insulin sensitivity

Effect on Liver:

• Less fatty acid delivery from adipose tissue
• Reduced inflammation
• Lower hepatic glucose production

Contribution: ~30-40% of liver fat reduction effect

2. GIP Activation: Direct Hepatic Benefits

Mechanism:

• Improves insulin sensitivity in liver cells directly
• Reduces de novo lipogenesis (new fat production in liver)
• May enhance fatty acid oxidation
• Anti-inflammatory effects in hepatic tissue

Unique Feature: GIP receptors exist in liver. Direct activation provides benefits beyond weight loss alone.

Contribution: ~20-30% of liver fat reduction effect

3. Glucagon Activation: Fat Burning Engine

Mechanism:

• Increases hepatic fatty acid β-oxidation (fat burning in liver)
• Promotes ketogenesis (converting fat to energy)
• Enhances mitochondrial function in liver cells
• Directly reduces hepatic steatosis

Critical Insight: This is why retatrutide likely superior to GLP-1-only drugs for liver. Glucagon directly promotes liver fat breakdown.

Contribution: ~30-40% of liver fat reduction effect

The Synergy: Why Triple > Dual > Single

Single Agonist (Semaglutide - GLP-1 only):

• Weight loss → indirect liver benefit
• 40-50% liver fat reduction

Dual Agonist (Tirzepatide - GLP-1 + GIP):

• Weight loss + some direct hepatic effect
• ~60-70% liver fat reduction (projected)

Triple Agonist (Retatrutide - GLP-1 + GIP + Glucagon):

• Weight loss + direct hepatic effects + fat oxidation
• 80-85% liver fat reduction (measured)

Result: Each added hormone pathway provides incremental liver benefit beyond weight loss alone.

Beyond Fat: Inflammation and Enzyme Improvements

Liver Enzyme Normalization (Phase 2a Data)

ALT (Alanine Aminotransferase):

• Baseline: Elevated (50-80 U/L, normal <35)
• Week 24: Normalized in 70-80% of participants
• Indicates reduced hepatocyte (liver cell) damage

AST (Aspartate Aminotransferase):

• Baseline: Elevated (40-60 U/L, normal <35)
• Week 24: Normalized in 65-75% of participants
• Indicates reduced liver inflammation

GGT (Gamma-Glutamyl Transferase):

• Often elevated in fatty liver
• Decreased significantly in most participants
• Marker of liver stress

Clinical Significance: Enzyme normalization suggests not just fat removal but actual healing of liver inflammation and damage.

Systemic Inflammation Markers

hs-CRP (High-Sensitivity C-Reactive Protein):

• 40-50% reduction by Week 24
• Systemic inflammation marker
• Predicts cardiovascular and metabolic disease risk

Adiponectin (Anti-Inflammatory Hormone):

• Baseline: Low (typical in obesity)
• Week 48: Increased 50-80% at higher doses
• Indicates improved adipose tissue health
• Higher adiponectin = better metabolic health

Fibrosis: The Open Question

Challenge: Fibrosis (scarring) develops over years and takes years to reverse. Phase 2a was only 48 weeks.

Phase 2a Fibrosis Data (Limited):

• Non-invasive markers (FIB-4, APRI) showed improvement trends
• Liver stiffness (elastography) decreased in some participants
• No liver biopsies performed (needed for definitive assessment)

What We Know:

• 80-85% fat reduction + inflammation resolution = favorable for fibrosis
• Historical bariatric surgery data: fat reduction → fibrosis regression (takes 1-2+ years)

What We Need:

• Long-term data (2+ years)
• Liver biopsies showing histological fibrosis improvement
• This requires dedicated NASH Phase 3 trial (expected 2027+)

MASH/NASH: Can Retatrutide Reverse Advanced Disease?

What Is MASH/NASH?

MASH/NASH = MASLD/NAFLD + Inflammation + Liver Cell Injury

Diagnostic Criteria (Requires Liver Biopsy):

• Steatosis (fat): Present
• Inflammation: Lobular inflammation
• Ballooning: Hepatocyte injury/death
• May have fibrosis (F0-F3)

Prevalence: 3-5% of adults, ~40-50% of people with type 2 diabetes

Phase 2a Results in NASH Patients

Subset Analysis:

• Approximately 30% of Phase 2a participants had suspected NASH based on:
  • High liver fat (>15%)
  • Elevated liver enzymes (ALT >50)
  • Likely inflammation on non-invasive assessment

Note: No baseline liver biopsies, so "suspected NASH" not biopsy-confirmed

Results in Suspected NASH Cohort:

• Liver fat reduction: Similar to overall cohort (80-85%)
• Liver enzymes: Normalized in most (70-80%)
• NASH resolution: Cannot confirm without follow-up biopsies

Limitation: Gold standard for NASH resolution requires repeat liver biopsy showing:

• Resolution of steatohepatitis (inflammation + ballooning gone)
• No worsening of fibrosis

Phase 2a didn't include biopsies, so definitive NASH resolution not proven.

What FDA Requires for NASH Approval

FDA NASH Drug Approval Criteria (Based on Past Trials):

Option 1: Histological Improvement (Biopsy-Based)

• NASH resolution (no inflammation, no ballooning)
• AND no worsening of fibrosis

OR

• Fibrosis improvement (≥1 stage reduction)
• AND no worsening of NASH

Option 2: Surrogate Endpoints (If Validated)

• Combination of imaging + biomarkers
• Must correlate with clinical outcomes
• Requires extensive validation

Retatrutide's Current Status:

• Phase 2a: Fat reduction proven (surrogate endpoint)
• Phase 3 (TRIUMPH): Liver enzymes being measured (secondary)
• Still needs: Dedicated NASH trial with liver biopsies

Phase 3 TRIUMPH: What Liver Data Will We Get?

TRIUMPH-4 (Completed December 2025)

Primary Endpoints:

• Weight loss ✅ (28.7% achieved)
• Knee osteoarthritis pain reduction ✅ (75.8% improvement)

Secondary/Exploratory Endpoints (Liver):

• Liver enzymes (ALT, AST, GGT)
• Possibly liver imaging (ultrasound or MRI) in subset
• Not liver biopsies

Expected Publication: 2026 (full results)

What We'll Learn:

• Do liver enzymes normalize with 28.7% weight loss in larger population?
• Safety in patients with existing mild-moderate liver disease
• Correlation between weight loss and estimated liver fat reduction

TRIUMPH-5 (Ongoing, Expected 2026)

Primary Endpoints:

• Weight loss in diabetic patients
• HbA1c reduction

Secondary Endpoints (Liver):

• Liver enzymes
• Metabolic markers

Diabetic Population Note: Higher prevalence of MASLD/NASH (~40-50%), so liver benefits particularly important in this group.

What TRIUMPH Won't Tell Us

NOT in TRIUMPH Protocols:

• Liver biopsy as primary endpoint
• NASH resolution as primary outcome
• Fibrosis staging
• Dedicated liver disease inclusion criteria

Why Not? TRIUMPH program designed for obesity/diabetes indications. Liver benefits are important but secondary to weight/glucose outcomes.

Future: Dedicated NASH Phase 3 Trial

Expected Timeline

IF Retatrutide Approved for Obesity/Diabetes (2028):

2027-2028: Dedicated NASH Phase 3 trial begins

• Population: Biopsy-confirmed NASH with fibrosis (F1-F3)
• Primary endpoint: NASH resolution without worsening fibrosis
• Baseline and Week 72-96 liver biopsies
• Duration: 18-24 months minimum

2029-2030: Trial results published

2030-2031: FDA approval decision for NASH indication

Why This Matters

Current Reality: No FDA-approved medications specifically for NASH.

Failed Attempts: Multiple drugs (Selonsertib, Cenicriviroc, Elafibranor) failed Phase 3 NASH trials because they:

• Targeted single pathways (inflammation or fibrosis)
• Didn't address root cause (obesity, insulin resistance)
• Showed biomarker improvements but not biopsy-proven NASH resolution

Retatrutide's Advantage:

• Addresses root metabolic dysfunction (28.7% weight loss)
• Proven 80-85% liver fat reduction (Phase 2a)
• Inflammation resolution (enzyme normalization)
• Multi-pathway hepatic benefits

Probability of Success: Higher than previous NASH drug candidates, but biopsy-proven efficacy still needs confirmation.

Real-World Implications: Who Benefits Most?

Simple Steatosis (MASLD/NAFLD Only)

Profile:

• Liver fat 5-20%
• Normal or mildly elevated enzymes
• No inflammation
• No fibrosis

Expected Benefit:

• >90% achieve complete resolution (fat <5%)
• Prevention of progression to NASH
• Rapid improvement (24 weeks)

Alternative Consideration: Could potentially achieve resolution with intensive lifestyle alone, but retatrutide accelerates timeline dramatically (months vs years).

MASH/NASH Without Significant Fibrosis (F0-F1)

Profile:

• Liver fat 15-25%
• Elevated enzymes (ALT 50-100)
• Biopsy showing inflammation + ballooning
• No or minimal fibrosis

Expected Benefit (Based on Phase 2a):

• 80-85% liver fat reduction
• Enzyme normalization in 70-80%
• High probability of NASH resolution (needs biopsy confirmation in trials)
• Prevention of fibrosis progression

This Is The Sweet Spot: Early-stage NASH caught before significant scarring. Highest probability of complete disease reversal.

NASH with Moderate-Advanced Fibrosis (F2-F3)

Profile:

• Moderate-to-advanced scarring
• Elevated risk of cirrhosis progression
• May have portal hypertension early signs
• Liver function beginning to decline

Expected Benefit:

• Liver fat reduction: 80-85% (mechanism still works)
• Inflammation reduction: Likely
• Fibrosis stabilization: Probable (stops progression)
• Fibrosis regression: Uncertain (needs long-term data)

Reality Check: Scarring that took 10-20 years to form won't disappear in 1 year. Even with 80% fat reduction, significant fibrosis reversal unlikely in short term.

Realistic Goal: Halt progression, prevent cirrhosis, stabilize liver function. Any fibrosis improvement is bonus.

Compensated Cirrhosis (F4)

Profile:

• Severe, largely irreversible scarring
• Liver function impaired but stable
• Risk of decompensation, liver cancer
• May eventually need transplant

Current Evidence:

• Retatrutide NOT studied in cirrhosis patients in Phase 2a
• Safety unknown in severe liver dysfunction
• Theoretically, mechanism might still reduce fat/inflammation

Expected Benefit (Theoretical):

• Fat reduction: Possible
• Inflammation reduction: Possible
• Fibrosis reversal: Highly unlikely (cirrhosis mostly irreversible)
• Clinical benefit: Uncertain

Caution Required: Use in cirrhosis requires:

• Safety data from Phase 3 (secondary analysis)
• Careful monitoring
• Possibly dose adjustment

Realistic Goal: IF safe, might slow progression, delay decompensation. Not curative at this stage.

Practical Path: Monitoring and Timeline

Baseline Assessment (Before Starting)

If Considering Retatrutide for Liver Disease:

• Liver imaging: Ultrasound or MRI-PDFF (measures fat percentage)
• Liver enzymes: ALT, AST, GGT
• Fibrosis assessment: FIB-4 score or FibroScan elastography
• Metabolic panel: Glucose, lipids, HbA1c
• Consider biopsy if: Suspected advanced fibrosis or NASH

During Treatment: Monitoring Schedule

Month 3:

• Liver enzymes (should be improving)
• Weight tracking
• Tolerability assessment

Month 6:

• Liver enzymes (expect 50-70% improvement)
• Repeat imaging if baseline was abnormal
• Expected: 60-80% liver fat reduction

Month 12:

• Complete assessment:
  • Liver enzymes (expect normalization)
  • Liver imaging (expect near-resolution of fat)
  • Fibrosis markers (may show improvement)
• Weight loss plateau check

Year 2 and Beyond:

• Annual liver imaging
• Liver enzymes every 6-12 months
• Fibrosis re-assessment annually
• Long-term safety monitoring

Timeline to Liver Fat Resolution

With Retatrutide (Based on Phase 2a):

• Week 12: 40-60% liver fat reduction
• Week 24: 80-85% liver fat reduction
• Week 48: >90% achieve complete resolution (<5% fat)

Compare to Lifestyle Intervention:

• 6 months: 20-30% reduction (if highly adherent)
• 12 months: 40-50% reduction (if sustained)
• Complete resolution: Rare without bariatric surgery

The Difference: Months vs. years to reverse fatty liver disease.

What Happens If You Stop Treatment?

Reality Check: Not a Cure

Phase 2 Extension Data:

• Patients stopping retatrutide → weight regain
• Weight regain → liver fat increases
• Fat didn't immediately return to baseline but trended upward

Implication: Liver fat reduction requires continued intervention—either:

1. Continued retatrutide treatment (like diabetes medication - ongoing)
2. Transition to intensive lifestyle maintenance
3. Lower-dose maintenance therapy (not yet studied)

Long-Term Treatment Considerations

Similar to:

• Diabetes medications (ongoing treatment for chronic disease)
• Blood pressure medications (lifelong for most)
• Statins (continued for cholesterol/CV protection)

MASLD/NASH is a chronic metabolic disease driven by obesity and insulin resistance. Treating the acute manifestation (liver fat) without addressing ongoing metabolic dysfunction = temporary fix.

Best Strategy (Likely):

• Initial treatment: High-dose retatrutide (12mg) for liver fat clearance (6-12 months)
• Maintenance: Continued treatment at effective dose
• Lifestyle: Complement medication with sustainable diet/exercise
• Monitoring: Regular liver assessment to detect any reaccumulation early

Safety in Liver Disease Patients

Retatrutide Metabolism

Good News: Retatrutide is a peptide metabolized by proteolytic degradation (broken down into amino acids by enzymes throughout the body).

NOT primarily metabolized by:

• Liver cytochrome P450 enzymes
• Kidney excretion

Implication: Lower concern about drug accumulation in liver disease compared to medications requiring hepatic metabolism.

Phase 2a Safety Profile

In MASLD Patients:

• No hepatotoxicity observed
• No drug-induced liver injury (DILI)
• Safe in patients with elevated baseline liver enzymes
• Liver enzymes improved (not worsened)

Standard GI Side Effects:

• Nausea: 40-50% (similar to overall trials)
• Diarrhea: 30-35%
• Manageable with dose titration

Unknowns in Advanced Liver Disease

NOT Studied in Phase 2a:

• Decompensated cirrhosis
• Portal hypertension
• Ascites
• Hepatic encephalopathy
• Varices

Caution Required: Until Phase 3 safety data in advanced liver disease, retatrutide should be:

• Used cautiously in compensated cirrhosis
• Avoided in decompensated cirrhosis
• Dose-adjusted if needed based on tolerability

Comparison: Why Previous NASH Drugs Failed

Failed NASH Drug Trials (Lessons Learned)

Selonsertib (ASK1 inhibitor):

• Target: Inflammation and fibrosis pathways
• Phase 3 Result: FAILED - No fibrosis improvement
• Why: Didn't address root cause (obesity, insulin resistance)

Cenicriviroc (CCR2/CCR5 antagonist):

• Target: Inflammation
• Phase 3 Result: FAILED - Fibrosis improved but no NASH resolution
• Why: Reduced inflammation but liver fat remained

Elafibranor (PPAR agonist):

• Target: Metabolic pathways
• Phase 3 Result: FAILED - Missed primary endpoint
• Why: Modest benefits, didn't meet biopsy-proven NASH resolution criteria

Resmetirom (THR-β agonist):

• Target: Liver metabolism
• Phase 3 Result: APPROVED 2024 for NASH (first drug!)
• Mechanism: Reduces liver fat, some NASH resolution
• But: Less robust than retatrutide's 85% reduction

Why Retatrutide Different

Multi-Pronged Attack:

1. Addresses root cause: 28.7% weight loss reduces visceral fat, insulin resistance
2. Direct hepatic effects: GIP + glucagon activation
3. Superior fat reduction: 80-85% vs ~40-50% for other drugs
4. Inflammation resolution: Enzyme normalization in 70-80%
5. Proven mechanism: Triple-hormone activation = comprehensive metabolic reset

Historical Lesson: Drugs targeting single pathways (inflammation OR fibrosis OR fat) failed. Retatrutide targets the entire metabolic dysfunction cascade.

Conclusion

Retatrutide's completed Phase 2a substudy (2023) demonstrated an 80-85% liver fat reduction in just 24 weeks—matching bariatric surgery outcomes pharmacologically for the first time. This dramatic fat clearance, combined with enzyme normalization and inflammation resolution, positions retatrutide as a potential breakthrough in MASLD/NASH treatment.

Current Evidence (What We Know):

• ✅ 85% liver fat reduction (Phase 2a, published 2023)
• ✅ 28.7% weight loss (TRIUMPH-4 Phase 3, December 2025)
• ✅ Enzyme normalization (70-80% of patients)
• ✅ Triple mechanism addressing root metabolic dysfunction

What's Still Needed:

• ❓ Biopsy-proven NASH resolution (requires dedicated Phase 3 trial)
• ❓ Fibrosis regression data (long-term, 2+ years)
• ❓ Safety in advanced liver disease (cirrhosis)

Timeline:

• 2026: TRIUMPH Phase 3 results (liver as secondary endpoint)
• 2027-2028: FDA approval for obesity/diabetes (liver benefits as bonus)
• 2027-2030: Dedicated NASH Phase 3 trial (if pursued)
• 2030-2031: Potential FDA approval specifically for NASH indication

For patients with MASLD/NASH now:

• Focus on proven interventions: weight loss, lifestyle
• Consider off-label GLP-1 agonists (semaglutide, tirzepatide)
• Monitor disease progression
• Plan for retatrutide availability in 2028

When retatrutide launches, it will likely become the most powerful pharmacological option for reversing fatty liver disease—the first medication to routinely achieve near-complete liver fat resolution without surgery.

Sources

• Jastreboff AM, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity. NEJM 2023 (includes Phase 2a MASLD substudy)
• Eli Lilly TRIUMPH-4 Phase 3 topline results (December 2025)
• Rinella ME, et al. A multi-society Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol 2023