Trial reportNature medicine2021
ACC inhibitor alone or co-administered with a DGAT2 inhibitor in patients with non-alcoholic fatty liver disease: two parallel, placebo-controlled, randomized phase 2a trials.
Trial report in Nature medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 118 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A phase 2a, randomized, double-blind, placebo-controlled, dose-ranging, parallel group study to evaluate safety, tolerability, and pharmacodynamics of pf-05221304 administered daily for 16-weeks to adult subjects with nonalcoholic fatty liver disease
A phase 2a, randomized, double blind (sponsor-open), placebo controlled, parallel group study to assess the pharmacodynamics, safety and tolerability of pf-05221304 and pf-06865571 co-administered for 6 weeks in adults with non-alcoholic fatty liver disease (nafld)
Who cites it
118 citing papers in PubMed, 1 synthesis or guideline pooled it, 210 citations in OpenAlex.
- The role of lipid metabolic reprogramming in tumor microenvironment.Theranostics · 2023Pooled it
- Pharmacokinetics and Safety of Fenofibrate in Participants with Mild Hepatic Impairment or with Advanced Fibrosis due to Metabolic-Associated Fatty Liver Disease.Journal of clinical pharmacology · 2025Trial
- Exposure-response modeling of liver fat imaging endpoints in non-alcoholic fatty liver disease populations administered ervogastat alone and co-administered with clesacostat.CPT: pharmacometrics & systems pharmacology · 2025Trial
- SomaLogic proteomics reveals new biomarkers and provides mechanistic, clinical insights into Acetyl coA Carboxylase (ACC) inhibition in Non-alcoholic Steatohepatitis (NASH).Scientific reports · 2024Trial
- A membrane homeostatic response to lipid overload coordinates fatty acid metabolism.bioRxiv : the preprint server for biology · 2026Article
- Hepatic Lipoprotein Production, Cardiometabolic Phenotypes, and Subtypes of Steatotic Liver Disease.Circulation research · 2026Review
- The Pathophysiological Interrelationship Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Cardiovascular Disease.Antioxidants (Basel, Switzerland) · 2026Review
- Pharmacologic management of metabolic and alcohol-associated liver disease.Metabolism and target organ damage · 2026Article
- Tumor cell-specific loss of GPX4 reprograms triacylglycerol metabolism to escape ferroptosis and impair antitumor immunity in non-small cell lung cancer.Protein & cell · 2026Article
- Selenoprotein H Functions as a PPARα Coactivator to Link Selenium Homeostasis to Hepatic Lipid Metabolism and Protect against Steatohepatitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lipid metabolism in pancreatic cancer treatment.World journal of clinical oncology · 2026Review
- Review
- From lipid function to dysfunction: Very long-chain fatty acids as emerging regulators of neuroinflammatory pathways.iScience · 2026Review
- A Global Perspective on Metabolic Dysfunction-Associated Steatotic Liver Disease: From Molecular Mechanisms to Therapeutic Strategy Innovation.Nutrients · 2026Review
- MASH in Type 2 Diabetes: Pathophysiology, Diagnosis, and Therapeutic Management-A Narrative Review.Medicina (Kaunas, Lithuania) · 2026Review
- Metabolic dysfunction-associated steatotic liver disease and heart failure with preserved ejection fraction: mechanisms and clinical implications from a heart-liver metabolic axis perspective.Frontiers in pharmacology · 2026Review
- Mitochondrial Dysfunction in MASLD: Evidence in Dietary Models and Potential Therapeutic Interventions.Biochemistry research international · 2026Review
- Triglyceride-lowering therapies for hepatic steatosis: mechanisms, efficacy, and clinical perspectives.Frontiers in pharmacology · 2026Review
- Beyond Discrete Diagnoses: Conceptualizing Obesity-associated Metabolic Disorders as a Unified, Dynamic Continuum.Current obesity reports · 2025Review
- Lipid metabolism in cancer cells: Its role in hepatocellular carcinoma progression and therapeutic resistance.Hepatology communications · 2025Review
58 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alterations in lipid metabolism might contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, no pharmacological agents are currently approved in the United States or the European Union for the treatment of NAFLD. Two parallel phase 2a studies investigated the effects of liver-directed ACC1/2 inhibition in adults with NAFLD. The first study ( NCT03248882 ) examined the effects of monotherapy with a novel ACC1/2 inhibitor, PF-05221304 (2, 10, 25 and 50 mg once daily (QD)), versus placebo at 16 weeks of treatment; the second study ( NCT03776175 ) investigated the effects of PF-05221304 (15 mg twice daily (BID)) co-administered with a DGAT2 inhibitor, PF-06865571 (300 mg BID), versus placebo after 6 weeks of treatment. The primary endpoint in both studies was percent change from baseline in liver fat assessed by magnetic resonance imaging-proton density fat fraction. Dose-dependent reductions in liver fat reached 50-65% with PF-05221304 monotherapy doses ≥10 mg QD; least squares mean (LSM) 80% confidence interval (CI) was -7.2 (-13.9, 0.0), -17.1 (-22.7, -11.1), -49.9 (-53.3, -46.2), -55.9 (-59.0, -52.4) and -64.8 (-67.5, -62.0) with 16 weeks placebo and PF-05221304 2, 10, 25 and 50 mg QD, respectively. The overall incidence of adverse events (AEs) did not increase with increasing PF-05221304 dose, except for a dose-dependent elevation in serum triglycerides (a known consequence of hepatic acetyl-coenzyme A carboxylase (ACC) inhibition) in 23/305 (8%) patients, leading to withdrawal in 13/305 (4%), and a dose-dependent elevation in other serum lipids. Co-administration of PF-05221304 and PF-06865571 lowered liver fat compared to placebo (placebo-adjusted LSM (90% CI) -44.6% (-54.8, -32.2)). Placebo-adjusted LSM (90% CI) reduction in liver fat was -44.5% (-55.0, -31.7) and -35.4% (-47.4, -20.7) after 6 weeks with PF-05221304 or PF-06865571 alone. AEs were reported for 10/28 (36%) patients after co-administered PF-05221304 and PF-06865571, with no discontinuations due to AEs, and the ACC inhibitor-mediated effect on serum triglycerides was mitigated, suggesting that PF-05221304 and PF-06865571 co-administration has the potential to address some of the limitations of ACC inhibition alone.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.