The Fibrates Story — A Tepid End to a PROMINENT Drug
Abstract
Pemafibrate is a selective peroxisome proliferator–activated receptor α modulator that has putative greater triglyceride-lowering and high-density lipoprotein (HDL) cholesterol–raising properties than other fibrates.1 Now in the Journal, Das Pradhan et al.2 describe the results of the Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT) trial. In this trial, 10,497 patients with type 2 diabetes, a triglyceride level between 200 and 499 mg per deciliter, and an HDL cholesterol level of 40 mg per deciliter or less were randomly assigned to receive 0.2-mg tablets of pemafibrate twice daily or placebo. In the PROMINENT trial, two cohorts . . .
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The lack of MACE reduction with pemafibrate is likely due to a lack of effect on apoB-containing particle number and modest increases in LDL-C.
“Although pemafibrate significantly reduced TGs (–26.2%), VLDL-C, and remnant cholesterol, it did not reduce MACE compared to placebo, likely due to a lack of effect on apoB-containing particle number and modest increases in LDL-C [64, 65].”
From Targeting Triglycerides in Cardiovascular Disease Prevention: Evidence, Mechanisms, and Emerging Therapies (2026) · cites this paper as [65]
In PROMINENT, pemafibrate did not reduce MACE compared to placebo.
“Although pemafibrate significantly reduced TGs (–26.2%), VLDL-C, and remnant cholesterol, it did not reduce MACE compared to placebo, likely due to a lack of effect on apoB-containing particle number and modest increases in LDL-C [64, 65].”
From Targeting Triglycerides in Cardiovascular Disease Prevention: Evidence, Mechanisms, and Emerging Therapies (2026) · cites this paper as [65]
In PROMINENT, pemafibrate significantly reduced TGs (-26.2%), VLDL-C, and remnant cholesterol.
“Although pemafibrate significantly reduced TGs (–26.2%), VLDL-C, and remnant cholesterol, it did not reduce MACE compared to placebo, likely due to a lack of effect on apoB-containing particle number and modest increases in LDL-C [64, 65].”
From Targeting Triglycerides in Cardiovascular Disease Prevention: Evidence, Mechanisms, and Emerging Therapies (2026) · cites this paper as [65]
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- Authors
- Virani, S. S.
- Affiliations
- Michael E. DeBakey VA Medical Center (US)
- Corresponding author
- Virani, Salim S.
- ORCID
- Virani, Salim S.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2022-11-24
- Volume
- 387
- Issue
- 21
- Pages
- 1991-1992
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W4308258594
- Cited by
- 40
- References
- 8
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 7 · 2023: 19 · 2022: 2
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- eCommons - AKU (Aga Khan University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- pemafibrate, fibrates, PPARα modulator, type 2 diabetes, hypertriglyceridemia, triglyceride-lowering therapy, HDL cholesterol, cardiovascular outcomes, drug discontinuation
- MeSH terms
- Cardiopulmonary Bypass, Fever, Humans, Fibric Acids
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