MASH Drug Development 2025: Clinical vs Preclinical Data
MASH therapeutics after Resmetirom + Wegovy MASH approval: Phase 2/3 data vs. GAN DIO-MASH for Semaglutide, Lanifibranor, Efruxifermin, Lean MASH.
1. Introduction: The Paradigm Shift in MASH Drug Development
Evolution of the Disease Concept and Unmet Medical Needs
The disease formerly known as Non-Alcoholic Steatohepatitis (NASH) has recently been renamed to Metabolic dysfunction-associated Steatohepatitis (MASH) to more accurately reflect its pathophysiological essence. This change is more than a mere terminology update; it emphasizes that the accumulation of metabolic factors such as obesity, type 2 diabetes, and dyslipidemia is deeply involved in the progression of liver pathology. This shift has broadened the target of drug development to systemic metabolic improvement.
MASH is a chronic, progressive disease that advances from simple steatosis to hepatocellular ballooning, inflammation, and ultimately fibrosis. It is well established that patients, especially those with moderate (F2) and severe (F3) fibrosis stages, face a dramatically increased risk of liver-related mortality.
In this field, often referred to as a "valley of death" where no pharmacological therapies existed for decades, 2024 marked a historic turning point. The approval of Resmetirom by the US FDA became the first success story in MASH treatment, accelerating subsequent drug development.
[!NOTE] Purpose of this Article This article provides a comprehensive comparison and analysis of clinical trial results and preclinical data for the approved drug Resmetirom and promising compounds currently in late-stage clinical development (Semaglutide, Lanifibranor, Efruxifermin, Denifanstat, etc.). We will explore how mechanisms in preclinical models can predict clinical outcomes and outline the formation of future Standards of Care (SoC), including strategies for "Lean MASH," a phenotype common in Asian populations.
2. In-Depth Analysis of the Approved Drug Resmetirom (THR-β Agonist)
Resmetirom (Brand name: Rezdiffra) received US FDA accelerated approval on March 14, 2024 as the world's first drug for "adult patients with noncirrhotic MASH with moderate to advanced liver fibrosis (F2-F3)." In the EU, it received a conditional marketing authorisation from the EMA on August 18, 2025[ref-Rezdiffra-EMA] (US accelerated approval and EU conditional marketing authorisation are distinct regulatory frameworks). Conversion of the US accelerated approval to traditional (full) approval remains pending the 54-month MAESTRO-NASH outcomes data as of May 2026.
Mechanism of Action (MOA): Establishing Safety via Liver Selectivity
Resmetirom is an oral, selective agonist for the Thyroid Hormone Receptor beta (THR-β).
- THR-β: Highly expressed in the liver, regulating lipid metabolism and mitochondrial function.
- THR-α: Distributed in the heart and bones; overstimulation poses risks of tachycardia and osteoporosis.
Resmetirom has approximately 28-fold preferentiality for THR-β over THR-α, designed to mitigate cardiac and skeletal side effects associated with THR-α stimulation. It exerts T3-like effects (promoting mitochondrial β-oxidation, suppressing de novo lipogenesis) primarily via THR-β expressed in the liver — but as an oral drug systemic exposure exists; the activity is liver-preferential, not exclusively liver-restricted.
Phase 3 MAESTRO-NASH Trial: Details of the Historic Data
The Phase 3 trial (biopsy data at 52 weeks), which served as the basis for FDA approval, achieved statistically significant differences in both surrogate endpoints proposed by the FDA—making it the first trial in history to do so.
Trial Information: MAESTRO-NASH (NCT03900429)
| Endpoint | Placebo (n=321) | Resmetirom 80mg (n=322) | Resmetirom 100mg (n=323) | P-Value |
|---|---|---|---|---|
| MASH Resolution (no worsening of fibrosis) | 9.7% | 25.9% | 29.9% | < 0.0001 |
| Fibrosis Improvement (≥1 stage & no NAS worsening) | 14.2% | 24.2% | 25.9% | < 0.0001 |
| LDL-C Change (24 weeks) | +0.1% | -13.6% | -16.3% | < 0.0001 |
- MASH Resolution: Response rate approximately 3 times that of placebo. Inflammation and ballooning were resolved.
- Fibrosis Improvement: Improvement was confirmed even in advanced cases such as F3 (severe fibrosis).
- Safety: Primary side effects were diarrhea and nausea (mild to moderate). No severe hepatotoxicity signals.
Retrospective Concordance with Preclinical Data
Resmetirom's preclinical data are retrospectively concordant with later clinical results, but a prospective predictive accuracy of preclinical models for clinical outcomes is not formally established. GAN DIO-MASH mouse model data showed directional consistency with subsequent clinical findings.
- Liver Steatosis and Inflammation: Reductions in hepatic triglycerides and suppression of inflammatory cytokines (TNF-α, MCP-1) in mice directionally align with MRI-PDFF reductions (-30% to -50%) seen in clinical trials.
- Fibrosis Repair: Preclinical data suggest that the effect on fibrosis is a secondary "hepatocyte recovery" downstream of lipotoxicity and inflammation relief, rather than a direct anti-fibrotic effect — a framing that aligns directionally with the clinical observation that MASH resolution and fibrosis improvement occurred in parallel.
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3. The Next-Generation Frontrunners: Incretin-Based Therapies
Incretin-based therapies, primarily GLP-1 receptor agonists, represent the "metabolic improvement approach" that ameliorates MASH through potent weight loss effects.
Semaglutide (GLP-1): High MASH Resolution Rates
Novo Nordisk's Semaglutide demonstrated histological improvements in the Phase 3 ESSENCE trial that numerically exceeded the MASH resolution rates seen with Resmetirom (head-to-head comparisons are not available; trial designs and populations differ). In 2026, the US FDA granted accelerated approval to Wegovy for the MASH indication (DailyMed Wegovy label, revision March 19, 2026)[ref-Wegovy].
Trial Information: ESSENCE (NCT04822181), PMID 40305708 (Sanyal AJ, Newsome PN, N Engl J Med 2025;392(21):2089-2099).
ESSENCE Part 1 (F2-F3 MASH, 72 weeks; first 800 randomised participants) Results Summary
- MASH Resolution: Semaglutide 2.4 mg 62.9% vs Placebo 34.1%
- Fibrosis Improvement: Semaglutide 2.4 mg 37.0% vs Placebo 22.5%
- Weight Loss: Semaglutide -10.5% vs Placebo -2.0%
The 62.9% MASH resolution rate strongly suggests that profound weight loss contributes substantially to improvements in liver pathology (the contributions of weight-loss-dependent vs weight-loss-independent effects have not been formally separated). Preclinically, in addition to indirect effects via caloric restriction, direct effects such as De Novo Lipogenesis (DNL) reduction via PI3K/AKT/mTORC1 pathway suppression have also been suggested.
Tirzepatide & Survodutide: The Power of Dual Agonists
Dual agonists, which possess even stronger metabolic improvement effects, have also produced astonishing data.
| Drug Name | Mechanism | Trial (NCT) | MASH Resolution | Fibrosis Improvement | Features |
|---|---|---|---|---|---|
| Tirzepatide | GLP-1/GIP | SYNERGY-NASH (Ph2b, 52w) | 73.3% (15mg) | 54.2% | Maximum class weight loss and MASH resolution. Ph3 in preparation. |
| Survodutide | GLP-1/Glucagon | Ph2 MASH (48 w, Sanyal AJ, NEJM 2024, PMID 38847460) | 47-62% | 34-36% (ITT) 64.5% (F2-F3 subgroup post-hoc) | Increased energy expenditure via glucagon. Fibrosis ≥1-stage improvement at 4.8 mg (34-36%) is similar to Semaglutide monotherapy (36.8%); the clearer superiority is in liver fat reduction (≥30% reduction 67%). LIVERAGE Ph3 + Cirrhosis Ph3 ongoing. See Survodutide deep-dive. |
4. Direct Approaches to Fibrosis: FGF21 & PPAR & FASN
Unlike incretins, drug classes that act more directly on liver fibrosis and inflammation are critical for patients with advanced fibrosis (F3-F4) or those who do not necessarily require massive weight loss.
Efruxifermin (FGF21): Fibrosis-Improvement Endpoint Data in F4 Cirrhosis
Efruxifermin, an FGF21 analog, has shown high fibrosis-improvement endpoint achievement rates with long-term administration. In December 2025, Novo Nordisk announced completion of the Akero Therapeutics acquisition (refer to Novo Nordisk / Akero official IR releases for primary documentation). See the Efruxifermin deep-dive for details.
- HARMONY Trial (Ph2b, 96 weeks) [NCT04767529, Noureddin M et al, Lancet 2025;406(10504):719-730, PMID 40818852[ref-HARMONY-96]]: 50 mg group achieved ≥1-stage fibrosis improvement in 49% (21/43) vs placebo 19% (8/43), p=0.0030, in F2-F3 patients.
- SYMMETRY Trial (F4 compensated cirrhosis, Ph2b) [NCT05039450, Noureddin M, Rinella ME, et al, N Engl J Med 2025;392(24):2413-2424, PMID 40341827[ref-SYMMETRY]]: The 36-week primary endpoint did not show a significant between-group difference between efruxifermin and placebo; an extended 96-week analysis reported a higher proportion achieving the fibrosis-improvement endpoint in the 50-mg arm (29% [18/63] vs placebo 11% [7/61]). Calling this "cirrhosis reversal" overstates the evidence; clinical outcomes (decompensation, mortality) require separate confirmation.
- Current Status: Ph3 SYNCHRONY programme — three trials (Histology NCT06215716 / Real-World NCT06161571 / Outcomes NCT06528314) — is ongoing (2026-2027 readouts).
Lanifibranor (Pan-PPAR): Omnidirectional Liver Protection
A Pan-PPAR agonist that simultaneously activates PPARα/δ/γ.
- NATIVE Trial (Ph2b) [NCT03008070, Francque SM et al, N Engl J Med 2021;385(17):1547-1558, PMID 34670042[ref-NATIVE]]: Reported as an oral agent achieving the composite endpoint combining MASH resolution and ≥1-stage fibrosis improvement (head-to-head comparisons against other agents are not available; "only" claims should be framed within the comparison scope of available trials).
- NATiV3 Trial (Ph3) [NCT04849728]: Targets F2-F3 patients; enrollment of 1,009 patients complete. Topline results expected late 2026.
- Features: In mouse models (GAN DIO-NASH), fibrosis-stage regression findings have been reported, supporting an anti-fibrotic profile in preclinical evidence. Development in Japan is also underway (Ph1 initiated by Hepalys Pharma).
Denifanstat (FASN Inhibitor): Direct Blockade of Lipogenesis
Blocks De Novo Lipogenesis (DNL) at the rate-limiting enzyme level.
- FASCINATE-2 Trial (Ph2b) [NCT04906421, Loomba R et al, Lancet Gastroenterol Hepatol 2024, PMID 39396529]: 52 weeks, F2-F3 patients. Fibrosis improvement rate 30% (ITT) / 41% (mITT) vs Placebo 14% / 18%. Reported as effective in F3 patients.
- Ph3 Transition: FDA Breakthrough Therapy designation has been reported (company disclosure; direct verification against FDA-published documentation is preferred).
- Features: Oral drug. Its mechanism is distinct from Resmetirom, and a combination strategy is being discussed as a possibility for future trials.
5. Integrated Comparison of Clinical Data and Preclinical Models
Below is a comparative summary of major clinical trial data and the underlying preclinical mechanisms supporting them.
Clinical Data Comparison Summary of Major Drugs (Phase 2b/3)
The following table summarizes the achievement rates of primary endpoints in placebo-controlled trials for each drug. Note that this is not a head-to-head comparison, as trial designs and patient populations differ.
| Drug (Class) | Trial (NCT) | MASH Resolution Rate (Active vs PBO) | Fibrosis Improvement Rate (Active vs PBO) | Key Preclinical Findings |
|---|---|---|---|---|
| Resmetirom (THR-β) | MAESTRO-NASH | ~30% vs 10% | ~26% vs 14% | Massive improvement in liver fat/inflammation precedes fibrosis improvement in GAN DIO-MASH. |
| Semaglutide (GLP-1) | ESSENCE | ~63% vs 34% | ~37% vs 23% | Dramatic liver fat clearance dependent on weight loss. Fibrosis regression in models is moderate. |
| Tirzepatide (GLP-1/GIP) | SYNERGY-NASH | ~73% vs 13% | ~54% vs 33% | Maximum metabolic improvement. Exceptional fat reduction in models. |
| Survodutide (GLP-1/Glucagon) | Ph2 MASH (NEJM 2024) | 47-62% vs 14% | 34-36% (ITT) / 64.5% (F2-F3 post-hoc) vs 25.9% | Potent anti-fibrotic signaling driven by glucagon agonism. |
| Efruxifermin (FGF21) | HARMONY | ~62% vs 24% | 49% vs 19% (96w extension) | Confirmed strong direct anti-fibrotic action beyond weight loss effects. |
| Lanifibranor (Pan-PPAR) | NATIVE | ~49% vs 22% | ~48% vs 29% | Clear fibrosis stage regression in models, aligning with high clinical fibrosis improvement rates. |
| Denifanstat (FASN) | FASCINATE-2 | ~36% vs 13% | ~41% vs 18% | Direct lipotoxicity relief via DNL inhibition. Effective against F3 fibrosis. |
Insights from Preclinical Models
- Utility of the GAN DIO-MASH Model: The GAN DIO-MASH mouse is a widely used model that replicates biopsy-confirmed NASH, progressive fibrosis, and progression to HCC. Observations for Resmetirom and Lanifibranor have been retrospectively concordant with subsequent clinical outcomes (rather than constituting validated prospective predictive accuracy).
- Mechanistic Differences: GLP-1 therapies exhibit a "fat disappearance-first" behavior, whereas Lanifibranor and Efruxifermin display a "fibrosis-parallel" behavior. Clinically, GLP-1s show higher numbers for MASH resolution (fat/inflammation), while FGF21 and PPAR agonists show comparable or higher numerical fibrosis-improvement rates — but these comparisons are across separate trials with different designs and populations, not head-to-head.
6. The "Lean MASH" Prospect and Development in Asia
While many MASH patients in the US and Europe are severely obese with a BMI over 30, a sizable fraction of MASH/NAFLD in Asia — including Japan — occurs in lean individuals (BMI <25), referred to as "Lean MASH." Global meta-analyses report that approximately 19.2% of NAFLD patients fall into the lean phenotype (Ye Q, et al, Lancet Gastroenterol Hepatol 2020, PMID 32413340); lean NAFLD prevalence is reported as higher in Asian populations than elsewhere (Lu FB, et al, J Gastroenterol Hepatol 2020, PMID 32573017; Eslam M, Clin Liver Dis (Hoboken) 2021, PMID 33489095). Japanese cohort estimates of lean-MASH fraction have been reported on the order of 20-30%, although point estimates vary by region, era, and diagnostic criteria.
- The Challenge: Potent weight-loss drugs like Semaglutide and Tirzepatide may pose risks of muscle mass reduction (sarcopenia) in lean patients and might be unsuitable for this demographic.
- Possible Direction: Drugs that do not rely on systemic weight loss — such as Resmetirom (THR-β), Lanifibranor (PPAR), and Denifanstat (FASN) — may have higher relative importance in Asia. Resmetirom in particular has been reported to have a neutral effect on body weight, which could be advantageous in lean patients; however, Resmetirom is currently unapproved in Japan as of this article's publication (May 2026), so its role in the Japanese clinical setting depends on future regulatory decisions.
7. Conclusion and Future Perspectives: The Era of Combination Therapies and NITs
MASH treatment has taken its first steps toward becoming a "manageable disease" with the advent of Resmetirom. Looking ahead, three key areas will define the landscape:
- Treatment Stratification (Precision Medicine):
- Obesity/Diabetes Comorbidity → Incretins (Semaglutide, Tirzepatide)
- Advanced Fibrosis (F3-F4) / Non-Obese → Liver Targets (Resmetirom, Efruxifermin, Lanifibranor)
- Investigational Combination Strategies: Combining "systemic metabolic improvement" (GLP-1) with "direct liver action" (THR-β/FASN), such as Semaglutide + Resmetirom, is an investigational combination strategy aimed at deeper remission and fibrosis improvement. As of this publication, head-to-head or combination randomized trials supporting this approach are not available; it is a plausible future direction rather than current standard of care.
- Establishment of Non-Invasive Tests (NITs): The widespread adoption of MRI-PDFF and blood biomarkers (FIB-4, ELF, Mac-2bpGi) as alternatives to liver biopsy will exponentially improve treatment access in real-world clinical practice.
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Appendix: Comprehensive MASH Therapeutics Data Analysis
Table 1: Approved and Phase 3 MASH Therapeutics
| Drug Name | Brand Name | Mechanism of Action | Approval Status (JP/US/EU) | Clinical Trials & Features |
|---|---|---|---|---|
| Resmetirom | Rezdiffra | THR-β preferential agonist | Unapproved / US accelerated approval (2024.3) / EU conditional marketing authorisation (2025.8.18)[ref-Rezdiffra-EMA] | MAESTRO-NASH [NCT03900429, PMID 38324483] World's first MASH-approved drug. Targets F2-F3. |
| Semaglutide | Wegovy/Ozempic | GLP-1 Receptor Agonist | Approved (Obesity) / MASH indication FDA accelerated approval (DailyMed Wegovy label 2026-03-19)[ref-Wegovy] / Approved (Obesity) | ESSENCE [NCT04822181, PMID 40305708] MASH resolution 62.9%. Japan MASH indication under future consideration. |
Table 2: Pipeline of Promising Phase 2/3 Clinical Trials
| Phase | Drug Name (Code) | Mechanism/Target | Clinical Trial Links | Clinical Summary & Key Results |
|---|---|---|---|---|
| Ph3 | Semaglutide | GLP-1 Receptor Agonist | NCT04822181 (ESSENCE) | ESSENCE Ph3: MASH resolution 62.9% vs 34.1%. Fibrosis improvement 36.8% vs 22.4%. Weight -10.5%. |
| Ph3 Prep | Tirzepatide | GLP-1/GIP Dual Agonist | NCT04166773 (SYNERGY-NASH) | SYNERGY-NASH Ph2b: MASH resolution 73.3% in 15mg group. Highest response rate to date. |
| Ph3 | Survodutide | GLP-1/Glucagon Dual | NCT04771273 (Ph2 MASH) NCT06632444 (LIVERAGE) NCT06632457 (LIVERAGE-Cirrhosis) | Ph2 (NEJM 2024): Fibrosis improvement 64.5% vs 25.9% (F2-F3 post-hoc). FDA Breakthrough 2024/10. See Survodutide deep-dive. |
| Ph3 | Efruxifermin (EFX) | FGF21 Analog | NCT04767529 (HARMONY) NCT05039450 (SYMMETRY) NCT06215716 (SYNCHRONY Histology) NCT06528314 (SYNCHRONY Outcomes) | HARMONY Ph2b 96 w: 50 mg fibrosis improvement 49% (21/43) vs placebo 19% (8/43), p=0.0030 (Lancet 2025, PMID 40818852). SYMMETRY (F4): 36-week primary endpoint not significant; extended 96-week 50 mg 29% (18/63) vs placebo 11% (7/61) (NEJM 2025, PMID 40341827). Novo Nordisk acquisition completed Dec 2025 (per company announcements). See Efruxifermin deep-dive. |
| Ph3 | Lanifibranor | Pan-PPAR (α/δ/γ) | NCT03008070 (NATIVE) NCT04849728 (NATiV3) | NATIVE Ph2b: Achieved composite of MASH resolution + fibrosis improvement. NATiV3 Ph3: 1,009 patients enrolled, results late 2026. Ph1 ongoing in Japan. |
| Ph3 Prep | Denifanstat | FASN Inhibitor | NCT04906421 (FASCINATE-2) | FASCINATE-2 Ph2b: Fibrosis improvement 41% (mITT) vs 18%. NNT=4-6. Highly effective for F3. |
| Ph3 Prep | Pegozafermin (PEG-FGF21) | FGF21 Analog (PEGylated) | NCT04929483 (ENLIVEN, PMID 37356033) NCT05931887 (ENLIGHTEN-Fibrosis) | ENLIVEN Ph2b (Loomba R, NEJM 2023;389(11):998-1008): Fibrosis improvement 26% (30 mg weekly) vs 7%. ENLIGHTEN Ph3: Results expected early 2027. |
Table 3: Preclinical Data (Models and Key Findings)
| Drug Name | Preclinical Model | Key Findings & Endpoints | Translational Accuracy |
|---|---|---|---|
| Resmetirom | GAN DIO-MASH Mouse | Improved NAS score ≥2, reduced liver TG/TC, decreased α-SMA expression (across all models), reduced Sirius Red area. | High: Highly concordant with clinical MASH resolution and fibrosis improvement rates. |
| Semaglutide | GAN DIO-MASH Mouse | Improved NAS score ≥2, weight loss 22%, significant improvement in steatosis/inflammation, decreased α-SMA. Fibrosis stage regression unclear. | Moderate: Predicted high MASH resolution. Clinical fibrosis improvement exceeded model expectations. |
| Lanifibranor | GAN DIO-MASH Mouse | Improved NAS score ≥2-3 (14/15 mice), weight loss 28.9%, fibrosis-stage regression findings reported (within the comparison scope of the trial, not head-to-head). | Concordant: Anti-fibrotic findings reported preclinically, directionally consistent with subsequent Phase 2b clinical observations. |
| Efruxifermin | db/db Mouse, STAM Model | Increased adiponectin, decreased PRO-C3, blood glucose reduction 30-60%. Improved fibrosis markers. | High: Accurately suggested long-term fibrosis improvement effects. |
References
Clinical Trial Registries (ClinicalTrials.gov)
- MAESTRO-NASH (Resmetirom): NCT03900429
- ESSENCE (Semaglutide): NCT04822181
- SYNERGY-NASH (Tirzepatide): NCT04166773
- Survodutide Ph2 MASH: NCT04771273
- LIVERAGE (Survodutide Ph3 F2-F3): NCT06632444
- LIVERAGE-Cirrhosis (Survodutide Ph3 F4): NCT06632457
- HARMONY (Efruxifermin F2-F3): NCT04767529
- SYMMETRY (Efruxifermin F4): NCT05039450
- SYNCHRONY Histology (Efruxifermin Ph3): NCT06215716
- SYNCHRONY Real-World (Efruxifermin Ph3): NCT06161571
- SYNCHRONY Outcomes (Efruxifermin Ph3 F4): NCT06528314
- NATIVE (Lanifibranor Ph2b): NCT03008070
- NATiV3 (Lanifibranor Ph3): NCT04849728
- FASCINATE-2 (Denifanstat): NCT04906421
- ENLIVEN (Pegozafermin Ph2b): NCT04929483
- ENLIGHTEN-Fibrosis (Pegozafermin Ph3): NCT05931887
Key Publications / Official Labels (PubMed / DailyMed / EMA)
- Harrison SA, et al. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis (MAESTRO-NASH). N Engl J Med. 2024;390(6):497-509. PMID 38324483
- Sanyal AJ, Newsome PN, et al. Phase 3 Trial of Semaglutide in MASH (ESSENCE). N Engl J Med. 2025;392(21):2089-2099. PMID 40305708
- Loomba R, et al. Tirzepatide for MASH with Liver Fibrosis (SYNERGY-NASH). N Engl J Med. 2024;391(4):299-310. PMID 38856224
- Sanyal AJ, et al. A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis. N Engl J Med. 2024. PMID 38847460
- Noureddin M, Frias JP, Neff GW, et al. Safety and efficacy of once-weekly efruxifermin versus placebo in MASH (HARMONY): 96-week results. Lancet. 2025;406(10504):719-730. PMID 40818852
- Noureddin M, Rinella ME, Chalasani NP, et al. Efruxifermin in Compensated Liver Cirrhosis Caused by MASH (SYMMETRY). N Engl J Med. 2025;392(24):2413-2424. PMID 40341827 — 36-week primary endpoint not met; 96-week extended analysis.
- Francque SM, Bedossa P, Ratziu V, et al. A Randomized, Controlled Trial of the Pan-PPAR Agonist Lanifibranor in NASH (NATIVE). N Engl J Med. 2021;385(17):1547-1558. PMID 34670042
- Loomba R, Sanyal AJ, et al. Randomized, Controlled Trial of Pegozafermin in NASH (ENLIVEN). N Engl J Med. 2023;389(11):998-1008. PMID 37356033 / NCT04929483
- Harrison SA, et al. Efruxifermin in NASH (HARMONY 24-week): Phase 2b. Lancet Gastroenterol Hepatol. 2023;8(12):1080-1093. PMID 37802088
- Loomba R, et al. Denifanstat in NASH (FASCINATE-2): Phase 2b. Lancet Gastroenterol Hepatol. 2024. PMID 39396529
- EMA. Rezdiffra (resmetirom) EPAR — Conditional Marketing Authorisation, 2025-08-18. EMA official page
- FDA. Rezdiffra Prescribing Information (US accelerated approval, March 2024). DailyMed current label
- FDA. Wegovy (semaglutide) Prescribing Information; revised March 2026 — includes noncirrhotic MASH with moderate to advanced liver fibrosis indication (accelerated approval). DailyMed current label
Lean MASH / NAFLD Epidemiology
- Ye Q, Zou B, Yeo YH, et al. Global prevalence, incidence, and outcomes of non-obese or lean non-alcoholic fatty liver disease: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020;5(8):739-752. PMID 32413340
- Lu FB, Hu ED, Xu LM, et al. Global epidemiology of lean non-alcoholic fatty liver disease: A systematic review and meta-analysis. J Gastroenterol Hepatol. 2020;35(12):2041-2050. PMID 32573017
- Eslam M, Fan JG, Mendez-Sanchez N. NAFLD in Lean Asians. Clin Liver Dis (Hoboken). 2021;16(6):240-243. PMID 33489095