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Background Abnormal cellular lipid metabolism appears to underlie SARS-CoV-2 cytotoxicity and may involve inhibition of peroxisome proliferator activated receptor alpha (PPARα). Fenofibrate, a PPAR-α activator, modulates cellular lipid metabolism. Fenofibric acid has also been shown to affect the dimerization of angiotensin-converting enzyme 2, the cellular receptor for SARS-CoV-2. Fenofibrate and fenofibric acid have been shown to inhibit SARS-CoV-2 replication in cell culture systems in vitro. Methods We randomly assigned 701 participants with COVID-19 within 14 days of symptom onset to 145 mg of fenofibrate (nanocrystal formulation with dose adjustment for renal function or dose-equivalent preparations of micronized fenofibrate or fenofibric acid) vs. placebo for 10 days, in a double-blinded fashion. The primary endpoint was a ranked severity score in which participants were ranked across hierarchical tiers incorporating time to death, duration of mechanical ventilation, oxygenation parameters, subsequent hospitalizations and symptom severity and duration. ClinicalTrials.gov registration: NCT04517396. Findings: Mean age of participants was 49 ± 16 years, 330 (47%) were female, mean BMI was 28 ± 6 kg/m2, and 102 (15%) had diabetes mellitus. A total of 41 deaths occurred. Compared with placebo, fenofibrate administration had no effect on the primary endpoint. The median (interquartile range [IQR]) rank in the placebo arm was 347 (172, 453) vs. 345 (175, 453) in the fenofibrate arm (P = 0.819). There was no difference in various secondary and exploratory endpoints, including all-cause death, across randomization arms. These results were highly consistent across pre-specified sensitivity and subgroup analyses. Conclusion Among patients with COVID-19, fenofibrate has no significant effect on various clinically relevant outcomes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cytotoxicity may involve inhibition of peroxisome proliferator-activated receptor alpha. Fenofibrate activates peroxisome proliferator-activated receptor alpha and inhibits SARS-CoV-2 replication in vitro. Whether fenofibrate can be used to treat coronavirus disease 2019 (COVID-19) infection in humans remains unknown. Here, we randomly assigned inpatients and outpatients with COVID-19 within 14 d of symptom onset to 145 mg of oral fenofibrate nanocrystal formulation versus placebo for 10 d, in a double-blinded fashion. The primary endpoint was a severity score whereby participants were ranked across hierarchical tiers incorporating time to death, mechanical ventilation duration, oxygenation, hospitalization and symptom severity and duration. In total, 701 participants were randomized to fenofibrate (n = 351) or placebo (n = 350). The mean age of participants was 49 ± 16 years, 330 (47%) were female, mean body mass index was 28 ± 6 kg/m

Introduction: Hyperlipidemia, traditionally defined with fasting lipid values, is a common cardiovascular risk factor, particularly in patients with insulin resistance, prediabetes and type 2 diabetes mellitus (DM). Nonfasting triglyceride levels (TG), however, have shown a stronger association with heart disease and stroke than fasting levels, independent of traditional CV risk factors. The objective of this study was to determine the relationship between TG and glucose levels after administration of a sucrose load (equal parts glucose and fructose) in individuals without a previous diagnosis of DM. Hypothesis: Sugar as a sole energy source will elicit both a lipemic and a glycemic response. Methods: We use a unique dataset from a single health clinic in Barranquilla, Colombia in which 1,446 adults aged 18 to 80 years (mean age, 49 years, 3 months, 77 percent female) were enrolled from 2002 - 2005. Serum TG and glucose levels were measured after an overnight fast and at two hours after administration of 75 gm of mixed carbohydrate in the form of Panela, a mixed carbohydrate made from an unrefined whole cane sugar used in beverages and in cooking in this area of Colombia. A solid form of sucrose, it contains equal parts of glucose and fructose. Regression analysis was performed to evaluate factors associated with the glycemic and lipemic responses. Results: We found that the absolute 2-hour glucose (range: 32-526 mg/dL) is significantly associated (p Conclusion: These data suggest that a diet rich in refined carbohydrate may pose a significant risk for hyperlipidemia, particularly in younger patients. The independent role of fructose as a trigger for de novo lipogenesis may be relevant in the observed response