Executive Summary
Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the world's most common liver disorder, affecting approximately one billion individuals globally, with its inflammatory subtype — metabolic dysfunction-associated steatohepatitis (MASH) — representing a leading driver of cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation. The convergence of obesity, type 2 diabetes mellitus (T2DM), dyslipidemia, and hypertension creates a complex, multisystem pathophysiology requiring agents capable of simultaneously addressing metabolic dysfunction and hepatic injury.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as transformative pharmacotherapies in this landscape. Originally developed for glycemic control, their pleiotropic effects — encompassing weight reduction, improved insulin sensitivity, suppression of hepatic de novo lipogenesis (DNL), anti-inflammatory activity, and direct hepatoprotective actions — position them uniquely in the MASLD/MASH treatment algorithm.
The Phase 3 ESSENCE trial (NEJM, June 2025) demonstrated that semaglutide 2.4 mg achieved MASH resolution in 62.9% of patients versus 34.3% with placebo, and improved liver fibrosis by at least one stage in 36.8% versus 22.4% — both primary endpoints met with P<0.001. This positions semaglutide as only the second drug ever approved specifically for MASH, and the first with simultaneous weight, cardiovascular, and renal risk-reduction indications.
| Agent | Trial / Year | N / Design | MASH Resolution | Fibrosis ≥1 Stage | Phase |
|---|---|---|---|---|---|
| Semaglutide 2.4 mg | ESSENCE 2025 | 800, F2-F3, 72 wk | 62.9% vs 34.3% | 36.8% vs 22.4% | Phase 3 |
| Tirzepatide 15 mg | SYNERGY-NASH 2024 | 190, F2-F3, 52 wk | 62% vs 10% | 51% vs 30% | Phase 2 |
| Survodutide 4.8 mg | Sanyal et al. 2024 | 293, F1-F3, 48 wk | 62% improvement vs 14% | 36% vs 22% | Phase 2 |
| Semaglutide 0.4 mg | Newsome et al. 2021 | 320, F1-F3, 72 wk | 59% vs 17% | No sig. difference* | Phase 2b |
| Liraglutide 1.8 mg | LEAN 2016 | 52, 48 wk | 39% vs 9% | Trend, non-sig. | Phase 2a |
*PathAI machine-learning re-analysis of Phase 2b biopsies detected significant antifibrotic effects not identified by conventional pathologist scoring.
Epidemiology & Disease Burden
1.1 Global Prevalence
MASLD (renamed by multisociety Delphi consensus in 2023, replacing "NAFLD") affects an estimated 30–32% of the global adult population — approximately one billion individuals. The inflammatory subtype MASH is present in approximately 5–6% of adults, representing 250–320 million people worldwide. As obesity and T2DM prevalence continue to rise, the number progressing to advanced MASH stages is projected to double by 2030.
In the United States, approximately 1 in 20 adults has MASH. MASH is now the second most common indication for liver transplantation in the US, and MASH-related cirrhosis is among the fastest-growing causes of HCC. MASLD accounted for a significant and growing share of liver-related disability-adjusted life years between 2010 and 2021.
1.2 Cardiometabolic Co-morbidity Profile
- Type 2 Diabetes: 55–70% of patients with MASH have coexisting T2DM; T2DM confers a fourfold elevated risk of HCC in patients with cirrhosis from MASLD.
- Obesity: MASLD affects approximately 75% of individuals with obesity; roughly one-third develop MASH.
- Cardiovascular Disease: MASLD is independently associated with major adverse cardiovascular events (MACE); fibrosis stage is the strongest predictor of liver-related and overall mortality.
- Chronic Kidney Disease: A bidirectional pathophysiological relationship is increasingly recognized between MASLD and CKD.
- Weight-loss threshold: ≥5% reduces hepatic steatosis; ≥7% may reverse MASH; ≥10% can stabilize or reverse fibrosis — the central mechanistic rationale for GLP-1 RA therapy.
1.3 Unmet Medical Need
Until March 2024, no drug had received regulatory approval for MASLD or MASH. Resmetirom (Rezdiffra), a liver-directed thyroid hormone receptor-β agonist, became the first approved therapy for non-cirrhotic MASH with moderate-to-advanced fibrosis. However, resmetirom is weight-neutral and lacks impact on insulin resistance or cardiovascular risk — creating a compelling rationale for GLP-1 RAs, which simultaneously target the metabolic underpinnings of MASLD, liver histology, and cardiometabolic outcomes.
Pharmacology & Mechanisms of Hepatic Benefit
2.1 GLP-1 RA Drug Classes
2.2 Mechanisms of Hepatic Benefit
Indirect (Weight-Mediated) Mechanisms
- Central appetite suppression via hypothalamic and brainstem GLP-1 receptor activation, reducing caloric intake by 15–25%.
- Delayed gastric emptying prolongs satiety signals and reduces postprandial glucose excursions.
- Dose-dependent weight loss: semaglutide 2.4 mg achieves ≥10% body weight loss in ~75% of patients — the threshold associated with meaningful fibrosis regression.
- Reduced visceral adiposity decreases hepatic free fatty acid (FFA) flux from lipolysis, diminishing lipotoxic substrate delivery.
Direct Hepatic Mechanisms (Weight-Independent)
A landmark study (Shantaram et al., Diabetes, August 2025) using pair-fed LDLR⁻/⁻ mice demonstrated that dulaglutide attenuates hepatic steatosis through weight-independent mechanisms — specifically via decreased de novo lipogenesis and reduced adipose tissue lipolysis. This confirms a dual-action model where GLP-1 RAs exert both weight-dependent and weight-independent hepatoprotective effects that synergize.
Suppression of SREBP-1c and ChREBP transcription factors, reducing hepatocyte lipid synthesis. AMPK phosphorylation stimulates β-oxidation via CPT1/PPARα upregulation.
Enhanced AKT/PDK-1/PKC-ζ phosphorylation downstream of IRS-2, correcting post-receptor insulin resistance that drives hepatocyte triglyceride accumulation.
Reduction of circulating TNF-α, IL-6, IL-1β, CRP. Suppression of M1 macrophage/Kupffer cell activation, attenuating hepatic lobular inflammation.
Decreased ROS generation, upregulated antioxidant pathways in hepatocytes, reduced lipid peroxidation contributing to hepatocyte ballooning.
Suppression of HSC activation via reduced TGF-β signaling. CTGF and MMP inhibitor downregulation. ML-assisted re-analysis of biopsies reveals earlier antifibrotic signals than conventional staging detects.
Significant increase in adiponectin (anti-inflammatory, anti-fibrotic) and reduction in leptin, favorably altering the adipose-liver axis communication.
Phase 2 Clinical Evidence
First randomized, double-blind, placebo-controlled trial demonstrating histological improvement with a GLP-1 RA in MASH. Established proof-of-concept for the class.
Three semaglutide doses versus placebo. MASH resolution across dose arms: 40%, 36%, and 59% (highest dose) vs 17% placebo. 13% mean body weight reduction at top dose. Fibrosis improvement was not statistically superior to placebo by conventional scoring — but PathAI ML re-analysis detected significant antifibrotic signals, informing the design of the Phase 3 ESSENCE trial at the 2.4 mg dose.
Highest MASH resolution rates ever reported in an RCT at the time of publication. The 2025 post-hoc analysis confirmed that metabolic improvements — particularly adipose tissue insulin sensitivity — were proportional to body weight loss and strongly correlated with histological response.
Dual GLP-1/glucagon agonism targets hepatic β-oxidation directly. Liver fat reduction ≥30% achieved in 63–67% with survodutide vs 14% with placebo. Phase 3 trials for MASH and cirrhosis are now enrolling (NCT06632457, NCT06632444). Early Phase 2 cirrhosis data showed trends toward decreasing liver stiffness and Pro-C3 fibrogenesis markers.
ESSENCE Phase 3 Trial — Definitive Evidence
N=1,197 patients across 253 sites in 37 countries. Biopsy-proven MASH with fibrosis stages F2 or F3. Randomized 2:1 to semaglutide 2.4 mg SC weekly vs placebo for 240 weeks. Part 1 (72-week histological endpoint, n=800) reported at AASLD 2024 and published in NEJM June 2025.
(no worsening of fibrosis)
(no worsening of MASH)
NNT and Clinical Significance
| Endpoint | Semaglutide | Placebo | Absolute Difference | NNT |
|---|---|---|---|---|
| MASH Resolution | 62.9% | 34.3% | +28.6 pp | ~3.5 |
| Fibrosis Improvement ≥1 | 36.8% | 22.4% | +14.4 pp | ~7 |
| Dual endpoint | 32.7% | 16.1% | +16.5 pp | ~6 |
Regulatory Trajectory
Meta-Analyses & Evidence Synthesis
Most comprehensive MASH meta-analysis to date: 13 Phase 2–3 RCTs, n=1,811 patients. Pooled OR for MASH resolution vs placebo: 3.48 (95% CI 2.69–4.51; I²=0% — exceptional consistency across agents and trials). Pooled OR for fibrosis improvement ≥1 stage: 1.79 (95% CI 1.37–2.35; I²=0%).
| Outcome | Pooled Effect | 95% CI | I² | Trials |
|---|---|---|---|---|
| MASH Resolution | OR 3.48 | 2.69–4.51 | 0% | 13 RCTs |
| Fibrosis Improvement ≥1 Stage | OR 1.79 | 1.37–2.35 | 0% | 13 RCTs |
| Liver Fat (MRI-PDFF) | WMD −4.50% | −6.60 to −2.40 | 95.9%* | Multiple |
| ALT | WMD −10.31 U/L | −14.73 to −5.88 | Moderate | 32 RCTs |
| AST | WMD −6.27 U/L | −10.11 to −2.43 | Moderate | 32 RCTs |
| GGT | WMD −9.64 U/L | −15.17 to −4.10 | Moderate | 32 RCTs |
*High I² for liver fat reflects heterogeneity in agents, doses, and imaging protocols — not inconsistency of treatment effect direction.
Comparative Efficacy & Special Populations
6.1 GLP-1 RAs vs Resmetirom
GLP-1 RAs (Semaglutide 2.4 mg)
Resmetirom (Rezdiffra)
Semaglutide + resmetirom represents a compelling emerging approach, leveraging complementary mechanisms: systemic metabolic correction (GLP-1 RA) plus liver-directed THR-β agonism (resmetirom). Combination trials are in active development.
6.2 Compensated Cirrhosis (F4)
The semaglutide 0.4 mg cirrhosis RCT demonstrated safety and metabolic benefits (weight reduction, lipid and glycemic improvements) but did not achieve MASH resolution or fibrosis improvement vs placebo — suggesting that established cirrhosis may represent a histological limit of GLP-1 RA efficacy, possibly due to irreversible architectural changes. However, population-based cohort data (Kanwal et al., JAMA Internal Medicine 2024) showed GLP-1 RA use associated with reduced cirrhosis, hepatic decompensation, and HCC risk — findings requiring prospective RCT confirmation. ESSENCE Part 2 outcomes (2029) will provide definitive data.
6.3 Non-Diabetic Obesity
ESSENCE included ~45% non-diabetic participants and demonstrated consistent primary endpoint achievement across both diabetic and non-diabetic subgroups. This supports GLP-1 RA use for obesity-associated MASH regardless of T2DM status, once regulatory approval is obtained. A 2025 JHEP Reports randomized trial found that matched weight loss from GLP-1 RA therapy vs structured lifestyle intervention produced similar liver fat reductions, but GLP-1 RAs additionally improved glucose homeostasis and exhibited distinct plasma proteomic and adipose transcriptomic signatures — suggesting mechanistically complementary effects beyond weight loss alone.
Next-Generation Incretin-Based Therapies
Multi-receptor engagement targets MASLD at several pathophysiological nodes simultaneously: GLP-1R agonism addresses insulin resistance, appetite, and hepatic DNL; GIPR agonism potentiates adipose insulin sensitivity; glucagon receptor agonism promotes hepatic β-oxidation, increases energy expenditure, and reduces hepatic lipid through mechanisms independent of GLP-1/GIP. The result is additive or synergistic histological benefit exceeding GLP-1 monotherapy.
| Agent | Receptor Targets | MASH Resolution | Fibrosis ≥1 Stage | Weight Loss | Phase |
|---|---|---|---|---|---|
| Semaglutide 2.4 mg | GLP-1 | 62.9% vs 34.3% | 36.8% vs 22.4% | −10.5% | Phase 3 ✓ |
| Tirzepatide 15 mg | GIP + GLP-1 | 62% vs 10% | 51% vs 30% | −15.6% | Ph2 → Ph3 |
| Survodutide 4.8 mg | GLP-1 + Glucagon | 62% vs 14% | 36% vs 22% | ~−13% | Ph2 → Ph3 |
| Retatrutide | GIP + GLP-1 + Glucagon | Ongoing | Ongoing | ~−17–24% | Phase 2a |
| Efocipegtrutide | GIP + GLP-1 + Glucagon | Ongoing | Ongoing | TBD | Phase 2 |
A 2025 case report (Oe et al., Frontiers in Endocrinology) documented a patient with severe MASH in whom liraglutide over 3 years failed to prevent progression to cirrhosis; switching to tirzepatide resulted in marked histological improvement on repeat biopsy. While a single case, this raises clinically relevant hypotheses about superior GIP/GLP-1 dual agonism in patients with inadequate response to conventional GLP-1 RA therapy.
Safety Profile in MASLD/MASH
| Adverse Event Domain | Incidence | Severity | Clinical Management |
|---|---|---|---|
| Nausea | 30–50% (dose-dependent) | Mostly mild-moderate; transient | Gradual dose escalation 4–16 weeks |
| Vomiting | 10–25% | Mostly mild-moderate | Dose reduction, hydration, anti-emetics |
| Diarrhea | 15–35% (higher with dual agonists) | Mostly mild-moderate | Dietary adjustments, loperamide PRN |
| Hepatotoxicity | None documented | Not a concern | No hepatic dose adjustment needed |
| Cardiovascular | MACE reduction (SELECT trial) | Favorable | Established benefit in high-risk patients |
| Cholelithiasis | Slightly increased (rapid weight loss) | Low absolute risk | Monitor; gradual weight loss pace |
| Lean Mass Loss | 15–30% of weight loss | Moderate clinical concern | Resistance training; protein intake |
The SELECT trial (semaglutide 2.4 mg) demonstrated a 20% relative risk reduction in MACE in non-diabetic patients with obesity and established CVD. Given the high cardiovascular burden in MASLD, this represents a major competitive advantage over resmetirom and all other liver-targeted MASH therapies. Heart failure hospitalization reduction and renal protection add to the holistic cardio-kidney-metabolic profile.
Real-World Evidence & Long-Term Outcomes
9.1 Cirrhosis and Hepatic Decompensation Risk
Kanwal et al. (JAMA Internal Medicine, 2024) conducted a large population-based cohort study finding that GLP-1 RA use was significantly associated with reduced risk of cirrhosis, liver-related complications, hospitalization, and all-cause mortality. Comparable findings from Taiwanese population databases showed GLP-1 RA use in T2DM patients with liver cirrhosis lowered risk for death, CVD events, and hepatic decompensation events.
9.2 HCC Risk Reduction
Retrospective studies signal a potential reduction in HCC risk with GLP-1 RA use in MASLD with T2DM. Biological plausibility is high: T2DM confers a 4-fold elevated HCC risk in MASLD-related cirrhosis, and GLP-1 RAs meaningfully reduce insulin resistance, hepatic inflammation, and visceral adiposity — all established HCC risk factors. Prospective confirmation awaited through long-term ESSENCE Part 2 data (2029).
9.3 Non-Invasive Biomarker Improvement
- FIB-4 Index: Consistently improved with injectable and oral semaglutide in clinical practice settings after 6 and 12 months.
- FibroScan (LSM and CAP): Significant reduction in liver stiffness and controlled attenuation parameter.
- ELF Test: Significant reduction reported in ESSENCE interim data — now a validated FDA-accepted surrogate endpoint for MASH trials.
- Oral semaglutide: A 2025 real-world study confirmed FIB-4 and ELF improvements with the oral formulation, expanding access for needle-averse patients.
Clinical Guidelines & Practical Recommendations
10.1 Current Guideline Positioning
The 2024 EASL-EASD-EASO Clinical Practice Guidelines on MASLD acknowledge GLP-1 RAs as safe for their approved indications (T2DM, obesity) in MASLD patients, and recommend them for cardiometabolic benefits. They stop short of a formal MASH-specific recommendation, as ESSENCE data were not available at publication. An updated guideline revision incorporating Phase 3 data is anticipated following regulatory approval of semaglutide for MASH.
10.2 Patient Selection Framework
- MASH with overweight/obesity ± T2DM: Primary target population — simultaneous metabolic and hepatic benefit.
- MASH with high cardiovascular risk: GLP-1 RAs reduce MACE, HF hospitalization, and renal events.
- MASH with F2–F3 fibrosis: Highest-quality evidence; both ESSENCE and SYNERGY-NASH conducted in this population.
- Patients failing lifestyle interventions: ~90% of patients do not achieve ≥10% weight loss with lifestyle alone; GLP-1 RAs achieve this threshold in ~75%.
- Non-diabetic obesity: ESSENCE demonstrated consistent benefit in non-diabetic subgroup.
10.3 Clinical Monitoring Protocol
- Baseline: Liver biopsy or validated non-invasive assessment (FibroScan, FIB-4, ELF, MRI-PDFF) to establish disease severity.
- Biochemical: LFTs, HbA1c, lipid panel, renal function at baseline and 3–6 monthly intervals.
- Non-invasive imaging: MRI-PDFF or FibroScan at 12–24 months to assess treatment response.
- Body weight: Monthly during dose escalation; quarterly thereafter.
- Combination therapy: GLP-1 RAs can be safely combined with SGLT2 inhibitors (independent liver benefits) and resmetirom (complementary mechanisms).
| Combination | Rationale | Status |
|---|---|---|
| GLP-1 RA + Resmetirom | Systemic metabolic correction + liver-directed THR-β agonism; complementary, non-overlapping mechanisms | Trials in development |
| GLP-1 RA + SGLT2i | Synergistic weight, glycemic, renal, and hepatic benefits; increasingly used in practice | Observational evidence; formal trials planned |
| GLP-1 RA + FGF21 analogue | Complementary lipid and fibrosis pathways; efruxifermin (FGF21) in Phase 3 MASH | Combination trials anticipated |
| GLP-1 RA foundation + antifibrotic | Address residual fibrosis burden after metabolic control; sequential treatment model | Conceptual; trial design phase |
Future Directions
11.1 Ongoing Phase 3 Trials
| Trial / Agent | Design | Primary Endpoint | Expected Readout |
|---|---|---|---|
| ESSENCE Part 2 Semaglutide 2.4 mg | Phase 3, 240 wk, n=1,197, F2–F3 | Clinical outcomes: cirrhosis-free survival, liver events | 2029 |
| Tirzepatide Phase 3 NCT05751720 / NCT06374875 | Phase 3 MASH confirmatory | MASH resolution + fibrosis improvement | 2026–2028 |
| Survodutide Phase 3 NCT06632457 / NCT06632444 | MASH + cirrhosis arms | Histological + clinical outcomes | 2027–2028 |
| Efocipegtrutide HM-TRIA-201 Phase 2 | n=240, MASH F1–F3 | MASH resolution without fibrosis worsening | Nov 2025 |
| Retatrutide Phase 3 MASH | Phase 3 in planning | MASH resolution + fibrosis improvement | TBD |
11.2 AI & Digital Pathology
Machine learning-assisted digital pathology (PathAI) applied to MASH biopsy assessment represents a transformative methodological advance. PathAI models applied to semaglutide Phase 2b biopsy slides detected significant fibrosis reduction not identified by conventional pathologist scoring — raising the possibility that earlier pivotal trials underestimated antifibrotic GLP-1 RA effects. Integration of AI pathology into Phase 3 trials will improve sensitivity, reduce observer variability, and potentially revise regulatory endpoint thresholds.
11.3 Precision Medicine & Biomarkers
- MRI-PDFF and MRE: Quantitative liver fat and stiffness with excellent reproducibility — increasingly accepted as FDA surrogate endpoints.
- ELF test: Validated composite serum biomarker with FDA-accepted surrogate use in MASH trials.
- Pro-C3: N-terminal propeptide of type III collagen as dynamic fibrogenesis marker.
- Multi-omics integration: Proteomics, metabolomics, and gut microbiome profiling for treatment response prediction and patient stratification.
- Gut microbiome: GLP-1 RAs influence gut motility and potentially microbiome composition; whether direct microbiome effects contribute to hepatic benefits is an active research area.
Following anticipated semaglutide FDA approval for MASH, key challenges will include: insurance coverage parity for a MASH-specific indication; long-term adherence strategies (weight regain occurs on discontinuation); integration with bariatric surgery pathways; and scaling non-invasive liver disease monitoring infrastructure (FibroScan, MRI-PDFF) in primary care and diabetes clinic settings to identify and track MASH patients on pharmacotherapy.
- Level I (Phase 3): ESSENCE — semaglutide 2.4 mg meets both FDA-required histological endpoints in MASH F2–F3. MASH resolution 62.9% vs 34.3%; Fibrosis improvement 36.8% vs 22.4%.
- Level I (Phase 2 RCT): SYNERGY-NASH — tirzepatide MASH resolution 62% vs 10%; Fibrosis 51% vs 30%. Phase 3 confirmatory trials underway.
- Level I (Phase 2 RCT): Survodutide MASH improvement 62% vs 14%; Phase 3 initiated.
- Level I-A (Meta-analysis): 13 RCTs, n=1,811; pooled OR for MASH resolution 3.48 (I²=0%); Fibrosis OR 1.79 (I²=0%) — consistent benefit across agents.
- Level II (Real-world): GLP-1 RAs associated with reduced cirrhosis, hepatic decompensation, and HCC risk in observational cohort databases.
- Level II (Mechanistic): Both weight-dependent and weight-independent hepatoprotective mechanisms confirmed in 2025 preclinical studies.
Key References
- Sanyal AJ, Newsome PN, Kliers I, et al. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. N Engl J Med. 2025;392(21):2089–2099.
- Loomba R, Hartman ML, Lawitz EJ, et al. Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis. N Engl J Med. 2024;391(4):299–310.
- Sanyal AJ, Bedossa P, Fraessdorf M, et al. A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis. N Engl J Med. 2024;391(4):311–319.
- Mantovani A, Morandin R, Fiorio V, et al. GLP-1RAs Improve MASH and Liver Fibrosis: A Meta-Analysis of Randomised Controlled Trials. Liver International. 2025;45(9):e70256.
- Liu L, Xia Y, Wang B, Zhang Y. Efficacy of incretin-based therapies in patients with MASLD: an updated systematic review and meta-analysis of RCTs. J Gastroenterol Hepatol. 2025.
- Kanwal F, Kramer JR, Li L, et al. GLP-1 Receptor Agonists and Risk for Cirrhosis and Related Complications in Patients With MASLD. JAMA Intern Med. 2024;184(11):1314–1323.
- Shantaram D, Rima XY, Bradley D, et al. The GLP-1 Receptor Agonist Dulaglutide Attenuates Hepatic Steatosis in Obesity via a Weight-Independent Mechanism. Diabetes. 2025;74(9):1512–1524.
- Zafer M, Tavaglione F, Romero-Gómez M, Loomba R. GLP-1 Receptor Agonists and Glucagon/GIP/GLP-1 Receptor Dual or Triple Agonists in MASLD. Aliment Pharmacol Ther. 2025;61(12):1872–1888.
- Newsome PN, Buchholtz K, Cusi K, et al. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med. 2021;384(12):1113–1124.
- Armstrong MJ, Gaunt P, Aithal GP, et al. Liraglutide Safety and Efficacy in Patients with Non-Alcoholic Steatohepatitis (LEAN): A Multicentre, Double-Blind, Randomised, Placebo-Controlled Phase 2 Study. Lancet. 2016;387:679–690.
- Rinella ME, Lazarus JV, Ratziu V, et al. A Multisociety Delphi Consensus Statement on New Fatty Liver Disease Nomenclature. J Hepatol. 2023;79:1542–1556.
- EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease. J Hepatol. 2024;81:492–542.
- Caussy C, Cusi K, Rosenstock J, et al. Relationship Between Metabolic and Histological Responses in MASH: Participant-Level Exploratory Analysis of SYNERGY-NASH. Diabetes Care. 2025;48(12):2074–2083.