What does the research show about ezetimibe and fenofibrate?

Ezetimibe and fenofibrate

Ezetimibe lowered LDL cholesterol about 18% alone and, added to a statin, cut heart attacks and strokes about 6% without lowering deaths. Fenofibrate lowered triglycerides 29% to 55% and slowed diabetic eye disease, but did not lower coronary events in its main trial or when added to a statin. Fenofibrate raised liver enzymes, creatinine and blood clots.

Add to Bio HackChecked 2026-11-13

Status: Prescription drugs in the US. Ezetimibe is FDA-approved to lower LDL cholesterol, with a statin or alone when more LDL lowering is needed and a statin is not possible, and with fenofibrate in mixed hyperlipidemia. Fenofibrate is approved to lower LDL cholesterol, total cholesterol, triglycerides and ApoB, to raise HDL cholesterol, and for severe high triglycerides. Its label states it was not shown to reduce coronary heart disease illness or death in type 2 diabetes.
Also called: ezetimibe, Zetia, Vytorin (ezetimibe with simvastatin), Roszet (ezetimibe with rosuvastatin), Nexlizet (ezetimibe with bempedoic acid), fenofibrate, Tricor, Trilipix, Fenoglide, Lipofen, Antara, Triglide, fenofibric acid, fibrates, cholesterol absorption inhibitor
Taken for: high cholesterol, LDL, high triglycerides, low HDL, heart attack prevention, stroke prevention, statin intolerance, diabetic eye disease, gout, uric acid

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help8

StrongShown to lower LDL cholesterol about 18% more than placebo when taken alone, with ApoB about 16% lower, and to lower LDL further when added to a statin.
ModerateShown to lower heart attacks, strokes and related events about 6% when added to a statin, 267 against 284 per 1,000, mostly in people with recent heart disease.
ModerateShown to lower triglycerides about 29% and LDL cholesterol 21% and to raise HDL 11% against placebo, with triglycerides 46% to 55% lower in severe high triglycerides.
ModerateShown to slow diabetic retinopathy in people with early eye changes, 22.7% against 29.2% over 4 years in the largest eye trial, without changing vision.
ModerateShown to slow the progression of albumin in the urine, by 14% across fibrate trials, with less progression on fenofibrate in its main diabetes trial.
LimitedOne open-label trial found ezetimibe lowered heart events about a third against usual care in Japanese adults 75 or older without heart disease, with no change in deaths or strokes.
LimitedOne trial found a moderate statin with ezetimibe matched a high-intensity statin on heart events over 3 years, 9.1% against 9.9%, with fewer people stopping for intolerance.
LimitedOne trial's later analysis found fenofibrate lowered uric acid about 20% and nearly halved first gout attacks over 5 years in type 2 diabetes, 2% against 3%.

Reported risks14

ModerateMixed results: the label reports more liver enzyme rises with ezetimibe plus a statin, 1.3% against 0.4%, while a Cochrane review found little or no difference in liver problems.Common
ModerateShown to slightly raise colds, diarrhea, joint pain and tiredness in label trials, with upper respiratory infection in 4.3% against 2.5% on placebo.Common
ModerateShown to raise ALT above 3 times normal in 5.3% against 1.1% on placebo. The label warns of serious liver injury after approval, including transplant and death.Common
LimitedOne trial found more pulmonary embolism on fenofibrate than placebo, 1.1% against 0.7%, and more deep vein clots. The label warns of it.Common
LimitedThe label warns fibrates raise muscle injury risk with statins, most with gemfibrozil, and in trials creatine kinase rose in 3.0% on fenofibrate against 1.4% on placebo.Common
LimitedOne trial found slightly more pancreatitis on fenofibrate than placebo, 0.8% against 0.5%, over 5 years. The label reports pancreatitis with fibrates.Uncommon
ModerateShown to raise serum creatinine about twice as often as placebo across fibrate trials. The label says the rise tends to reverse after stopping.How often is not known
ModerateMixed results: a Cochrane review found more serious adverse events on fenofibrate than placebo, while a pooled analysis of fibrate trials found no significant rise in drug-related serious events.How often is not known
LimitedMixed results: the label warns ezetimibe may cause muscle damage, mostly in people also taking a statin, while pooled trials were too uncertain to tell.How often is not known
LimitedThe label reports cyclosporine raises ezetimibe and cyclosporine levels, cholestyramine lowers ezetimibe exposure, and combining it with fibrates other than fenofibrate is not advised.How often is not known
LimitedThe label warns fenofibrate, like other fibrates, may raise cholesterol in bile and lead to gallstones.How often is not known
LimitedCase reports: the label reports rare severe drops in HDL cholesterol, as low as 2 mg/dL, after starting fibrates, which reversed after stopping.How often is not known
LimitedThe label reports mild to moderate drops in hemoglobin, hematocrit and white cells after starting fenofibrate that then stabilized, with rare low platelets or white cells.How often is not known
LimitedThe label warns fenofibrate strengthens the effect of coumarin anticoagulants such as warfarin on clotting time, with bleeding possible.How often is not known

What people take it for, and what was found

Shown to help8

Strong

Ezetimibe: LDL cholesterol and ApoB

Shown to lower LDL cholesterol about 18% more than placebo when taken alone, with ApoB about 16% lower, and to lower LDL further when added to a statin.

Compared with placebo [1][2]; a statin or fenofibrate alone [3][4]

The numbers and sources

Effect: Across 8 placebo-controlled 12-week trials, ezetimibe 10 mg lowered LDL cholesterol 18.58% more than placebo (95% CI 17.48 to 19.67), total cholesterol 13.46% more and triglycerides 8.06% more, and raised HDL cholesterol 3.00% [1]. In two label trials, LDL cholesterol fell 18% and ApoB 16% on ezetimibe against a 1% rise and 2% fall on placebo [2]. Added to a statin or fenofibrate, ezetimibe lowered LDL cholesterol, total cholesterol and triglycerides further and likely raised HDL [3]. After an acute coronary syndrome, time-averaged LDL was 53.7 mg/dL on simvastatin with ezetimibe against 69.5 mg/dL on simvastatin alone [4].
Population: 2,722 people with primary hypercholesterolemia in 8 trials [1]; 1,719 adults in two trials [2]; 23,499 people in 26 trials [3]; 18,144 patients [4].
Sources: [1], [2], [3], [4]
Caveats: Lipid trials alone lasted 12 weeks [1]. Heterogeneity was substantial in the combination analyses [3].

Moderate

Ezetimibe added to a statin: heart attacks and strokes

Shown to lower heart attacks, strokes and related events about 6% when added to a statin, 267 against 284 per 1,000, mostly in people with recent heart disease.

Compared with a statin alone or with placebo [3][4]

The numbers and sources

Effect: Adding ezetimibe to a statin lowered major cardiovascular events (RR 0.94, 95% CI 0.90 to 0.98), from 284 to 267 per 1,000, nonfatal heart attack (RR 0.88, 105 to 92 per 1,000) and nonfatal stroke (RR 0.83, 32 to 27 per 1,000) [3]. In the largest trial, the 7-year event rate was 32.7% on simvastatin with ezetimibe and 34.7% on simvastatin alone (HR 0.936, 95% CI 0.89 to 0.99), an absolute difference of 2.0 points [4].
Population: 21,727 people in 10 trials, mostly with established heart disease [3]; 18,144 patients within 10 days of an acute coronary syndrome, median follow-up 6 years [4].
Sources: [3], [4]
Caveats: The pooled result is driven by one trial, which carried 41.5% to 98.4% of the weight [3]. That trial was funded by the maker [4]. Evidence for people without heart disease and for ezetimibe alone is limited [3].

Limited

Ezetimibe alone in adults 75 and older

One open-label trial found ezetimibe lowered heart events about a third against usual care in Japanese adults 75 or older without heart disease, with no change in deaths or strokes.

Compared with usual care with dietary counseling [5]

The numbers and sources

Effect: The composite of sudden cardiac death, heart attack, coronary revascularization or stroke was lower on ezetimibe 10 mg (HR 0.66, 95% CI 0.50 to 0.86), with fewer cardiac events (HR 0.60) and revascularizations (HR 0.38). Stroke, all-cause mortality and adverse events did not differ [5].
Population: 3,796 adults aged 75 or older in Japan with raised LDL and no coronary disease, 3,411 analyzed, median follow-up 4.1 years [5].
Sources: [5]
Caveats: Open-label, stopped early, with follow-up problems and 10% excluded after randomization, which the authors say call for caution [5].
Why limited: This rests on one trial, of 3,796 people. Strength counts independent studies that agree, so one trial is limited at any size.

Limited

Ezetimibe with a moderate statin against a high-dose statin

One trial found a moderate statin with ezetimibe matched a high-intensity statin on heart events over 3 years, 9.1% against 9.9%, with fewer people stopping for intolerance.

Compared with high-intensity statin alone, rosuvastatin 20 mg [6]

The numbers and sources

Effect: The 3-year composite of cardiovascular death, major cardiovascular events or nonfatal stroke was 9.1% on rosuvastatin 10 mg with ezetimibe and 9.9% on rosuvastatin 20 mg, meeting the trial's noninferiority margin. LDL below 70 mg/dL was reached by 72% to 75% against 55% to 60%, and drug stopping or dose cuts for intolerance were 4.8% against 8.2% [6].
Population: 3,780 patients with atherosclerotic heart disease at 26 centers in South Korea [6].
Sources: [6]
Caveats: Open-label, a noninferiority design, and funded by a manufacturer [6].
Why limited: This rests on one trial, of 3,780 people. Strength counts independent studies that agree, so one trial is limited at any size.

Moderate

Fenofibrate: triglycerides, HDL and LDL cholesterol

Shown to lower triglycerides about 29% and LDL cholesterol 21% and to raise HDL 11% against placebo, with triglycerides 46% to 55% lower in severe high triglycerides.

Compared with placebo [7]

The numbers and sources

Effect: In four placebo-controlled trials of 3 to 6 months, fenofibrate at the 145 mg dose changed triglycerides by -28.9% against +7.7% on placebo, LDL cholesterol by -20.6% against -2.2%, total cholesterol by -18.7% against -0.4%, and HDL by +11.0% against +0.7%. ApoB fell 25.1% against a 2.4% rise. In severe high triglycerides, triglycerides fell 46.2% (baseline 432 mg/dL) and 54.5% (baseline 726 mg/dL) against -0.5% and +7.2% on placebo, while LDL cholesterol rose in both groups [7].
Population: 646 adults with high cholesterol or mixed dyslipidemia in 4 trials, and 147 adults with high triglycerides in 2 trials of 8 weeks [7].
Sources: [7]
Caveats: Label trials, short-term. The label reports rare severe paradoxical drops in HDL, listed under Risks [7].

Moderate

Fenofibrate: diabetic eye disease

Shown to slow diabetic retinopathy in people with early eye changes, 22.7% against 29.2% over 4 years in the largest eye trial, without changing vision.

Compared with placebo [12][13]; placebo or observation [14]

The numbers and sources

Effect: Referable retinopathy or maculopathy, or treatment for it, occurred in 22.7% on fenofibrate 145 mg and 29.2% on placebo (HR 0.73, 95% CI 0.58 to 0.91), with no effect on visual function, quality of life or acuity [12]. Pooling three trials, retinopathy progression fell (RR 0.77, 95% CI 0.68 to 0.88), 45 fewer per 1,000, and no trial found a benefit for vision [13]. An earlier Cochrane review found little to no difference in a mixed group (RR 0.86, 95% CI 0.60 to 1.25) but slower progression in people with retinopathy at the start (RR 0.21, 95% CI 0.06 to 0.71) [14]. In the main heart trial, laser treatment was needed by 3.6% on fenofibrate and 5.2% on placebo [8].
Population: 1,151 adults with diabetes and early retinal changes in Scotland, median 4 years [12]; 3,756 people in 3 trials [13]; 15,313 people with type 2 diabetes in 2 trials [14]; 9,795 adults [8].
Sources: [12], [13], [14], [8]
Caveats: Mostly type 2 diabetes. The earlier Cochrane review predates the largest eye trial [14].

Limited

Fenofibrate: uric acid and gout

One trial's later analysis found fenofibrate lowered uric acid about 20% and nearly halved first gout attacks over 5 years in type 2 diabetes, 2% against 3%.

Compared with placebo [15]

The numbers and sources

Effect: Uric acid fell 20.2% during the fenofibrate run-in and stayed 20.1% lower than placebo at 1 year. First gout events were 81 (2%) on fenofibrate and 151 (3%) on placebo over 5 years (HR 0.54, 95% CI 0.41 to 0.70), and all gout events halved (HR 0.48) [15].
Population: 9,795 adults aged 50 to 75 with type 2 diabetes [15].
Sources: [15]
Caveats: A post hoc analysis of a heart trial, not a gout trial.
Why limited: This rests on one trial, of 9,795 people. Strength counts independent studies that agree, so one trial is limited at any size.

Moderate

Fenofibrate and fibrates: protein in the urine

Shown to slow the progression of albumin in the urine, by 14% across fibrate trials, with less progression on fenofibrate in its main diabetes trial.

Compared with placebo [9][8]

The numbers and sources

Effect: Fibrates lowered the risk of albuminuria progression by 14% (95% CI 2 to 25) [9]. Fenofibrate was associated with less albuminuria progression in people with type 2 diabetes (p=0.002) [8].
Population: Fibrate trials [9]; 9,795 adults with type 2 diabetes [8].
Sources: [9], [8]
Caveats: Albuminuria is a marker of kidney damage, not kidney failure. Fenofibrate raises creatinine, listed under Risks.

Mixed results1

Moderate

Fenofibrate and fibrates: heart attacks and strokes

Mixed results: pooled fibrate trials showed about 10% fewer major heart events and 13% fewer coronary events, but fenofibrate's main trial missed its coronary goal and deaths did not fall.

Compared with placebo [8][9]; placebo or usual care [10]

The numbers and sources

Effect: In people with type 2 diabetes, coronary events were 5.2% on fenofibrate and 5.9% on placebo (HR 0.89, 95% CI 0.75 to 1.05), not significant. Total cardiovascular events fell from 13.9% to 12.5% (HR 0.89, 95% CI 0.80 to 0.99), with 24% fewer nonfatal heart attacks and a nonsignificant rise in coronary deaths (HR 1.19) [8]. Across 18 fibrate trials, major cardiovascular events fell 10% (95% CI 0 to 18), coronary events 13%, and stroke, cardiovascular death and all-cause death did not change [9]. In primary prevention, fibrates lowered cardiovascular death, heart attack or stroke (RR 0.84, 95% CI 0.74 to 0.96), with absolute reductions under 1% [10]. The fenofibrate label states it was not shown to reduce coronary heart disease illness and death in type 2 diabetes [7].
Population: 9,795 adults aged 50 to 75 with type 2 diabetes, 5 years [8]; 45,058 people in 18 trials [9]; 16,135 people in 6 primary prevention trials [10].
Sources: [8], [9], [10], [7]
Caveats: [9] and [10] pool fibrates as a class, including gemfibrozil and bezafibrate, not fenofibrate alone. More placebo patients started statins in [8], which the authors say may have masked a benefit.

Not shown to help2

Moderate

Ezetimibe: death from any cause

Not shown to lower deaths from any cause or from heart disease when ezetimibe was added to a statin or fenofibrate.

Compared with a statin or fenofibrate alone [3]

The numbers and sources

Effect: All-cause mortality did not differ (RR 0.98, 95% CI 0.91 to 1.05), nor did cardiovascular mortality (RR 1.00, 95% CI 0.89 to 1.12) [3].
Population: 21,222 people in 8 trials for all-cause and 19,457 in 6 trials for cardiovascular mortality [3].
Sources: [3]
Caveats: Trials ran a median of up to 6 years.

Moderate

Fenofibrate added to a statin

Not shown to lower heart attacks, strokes or heart deaths when fenofibrate was added to simvastatin in type 2 diabetes, 2.2% against 2.4% a year.

Compared with simvastatin with placebo [11]; statins alone [10]

The numbers and sources

Effect: The annual rate of nonfatal heart attack, nonfatal stroke or cardiovascular death was 2.2% on fenofibrate with simvastatin and 2.4% on simvastatin with placebo (HR 0.92, 95% CI 0.79 to 1.08), and no secondary outcome differed. Annual deaths were 1.5% and 1.6%. A subgroup with high triglycerides and low HDL suggested possible benefit, and results differed by sex [11]. In the Cochrane review, the two trials of fibrates on top of statins showed no benefit [10].
Population: 5,518 patients with type 2 diabetes, mean follow-up 4.7 years [11]; 2 trials [10].
Sources: [11], [10]
Caveats: Subgroup findings were prespecified but not confirmed [11].

Doses studied

Ezetimibe was given at 10 mg once daily alone [1][2], with simvastatin 40 mg [4] or with rosuvastatin 10 mg [6]. Fenofibrate label trials used a dose equivalent to 145 mg of the Tricor tablet a day [7]. The main diabetes trial used micronised fenofibrate 200 mg daily [8], and the retinopathy trial 145 mg daily, or on alternate days with impaired kidney function [12].

Risks

Reported risks11

ModerateCommon

Ezetimibe: common side effects

Shown to slightly raise colds, diarrhea, joint pain and tiredness in label trials, with upper respiratory infection in 4.3% against 2.5% on placebo.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: Upper respiratory tract infection was 4.3% on ezetimibe and 2.5% on placebo, diarrhea 4.1% and 3.7%, joint pain 3.0% and 2.2%, sinusitis 2.8% and 2.2%, and fatigue 2.4% and 1.5% [2].
Population: 2,396 people on ezetimibe and 1,159 on placebo in placebo-controlled trials [2].
Sources: [2]
Caveats: Small differences from placebo.

ModerateCommon

Fenofibrate: liver enzymes and liver injury

Shown to raise ALT above 3 times normal in 5.3% against 1.1% on placebo. The label warns of serious liver injury after approval, including transplant and death.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: In 10 placebo-controlled trials, ALT rose above 3 times the upper limit in 5.3% on fenofibrate and 1.1% on placebo. In label trials, increased AST was 3.4% against 0.5% and abnormal liver tests 7.5% against 1.4%, and raised liver tests caused 1.6% to stop. In an 8-week study, ALT or AST rises of 3 times or more reached 13% at the higher doses. The label reports serious drug-induced liver injury after approval [7].
Population: 439 people on fenofibrate and 365 on placebo, and a pooled 10-trial analysis [7].
Sources: [7]
Caveats: Postmarketing liver injury reports have no denominator.

LimitedCommon

Fenofibrate: blood clots in the lungs and legs

One trial found more pulmonary embolism on fenofibrate than placebo, 1.1% against 0.7%, and more deep vein clots. The label warns of it.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: Pulmonary embolism occurred in 53 of 4,895 on fenofibrate and 32 of 4,900 on placebo (p=0.022), and deep vein thrombosis in 67 against 48 (p=0.074) [7]. A meta-analysis of fenofibrate trials found more venous clots (RR 1.52, 95% CI 1.12 to 2.06), an estimate drawn entirely from this trial [13].
Population: 9,795 adults with type 2 diabetes [7][13].
Sources: [7], [13]
Caveats: One trial.
Why limited: This rests on one trial, of 9,795 people. Strength counts independent studies that agree, so one trial is limited at any size.

LimitedCommon

Fenofibrate: muscle injury with statins

The label warns fibrates raise muscle injury risk with statins, most with gemfibrozil, and in trials creatine kinase rose in 3.0% on fenofibrate against 1.4% on placebo.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: Increased creatine kinase was reported in 3.0% on fenofibrate and 1.4% on placebo. Observational studies indicate rhabdomyolysis risk rises when fibrates, in particular gemfibrozil, are given with a statin [7].
Population: 439 people on fenofibrate and 365 on placebo, and observational data cited in the label [7].
Sources: [7]
Caveats: The label gives no rate for the combination.

LimitedUncommon

Fenofibrate: pancreatitis

One trial found slightly more pancreatitis on fenofibrate than placebo, 0.8% against 0.5%, over 5 years. The label reports pancreatitis with fibrates.

The numbers and sources

How common: Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect: Pancreatitis occurred in 0.8% on fenofibrate and 0.5% on placebo (p=0.031) [8]. The label reports pancreatitis with fenofibrate, gemfibrozil and clofibrate [7].
Population: 9,795 adults with type 2 diabetes [8].
Sources: [8], [7]
Caveats: One trial.
Why limited: This rests on one trial, of 9,795 people. Strength counts independent studies that agree, so one trial is limited at any size.

LimitedHow often is not known

Ezetimibe: drug interactions

The label reports cyclosporine raises ezetimibe and cyclosporine levels, cholestyramine lowers ezetimibe exposure, and combining it with fibrates other than fenofibrate is not advised.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Taking ezetimibe with cyclosporine raised levels of both drugs. Cholestyramine reduced total ezetimibe exposure, so the label separates their doses. Fenofibrate and ezetimibe may both raise cholesterol in bile and gallstone risk, and use with other fibrates is not advised [2].
Population: Pharmacokinetic studies in the label [2].
Sources: [2]
Caveats: Drug level studies, not outcome trials.

ModerateHow often is not known

Fenofibrate: raised creatinine

Shown to raise serum creatinine about twice as often as placebo across fibrate trials. The label says the rise tends to reverse after stopping.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Increases in serum creatinine were common on fibrates (RR 1.99, 95% CI 1.46 to 2.70) [9]. The fenofibrate label reports creatinine rises that tend to return to baseline after stopping, with unknown clinical significance [7].
Population: Fibrate trials [9]; label statement [7].
Sources: [9], [7]
Caveats: A creatinine rise on fenofibrate may not reflect a fall in kidney filtration, and protein in the urine fell in trials.

LimitedHow often is not known

Fenofibrate: gallstones

The label warns fenofibrate, like other fibrates, may raise cholesterol in bile and lead to gallstones.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Fenofibrate, like clofibrate and gemfibrozil, may increase cholesterol excretion into bile, leading to gallstones. A clofibrate trial found more gallstones and gallbladder inflammation than placebo [7]. The ezetimibe label adds that both drugs may raise this risk together [2].
Population: Label statements [7][2].
Sources: [7], [2]
Caveats: The label cites older fibrate trials, not a fenofibrate rate.

LimitedHow often is not known

Fenofibrate: paradoxical drop in HDL

Case reports: the label reports rare severe drops in HDL cholesterol, as low as 2 mg/dL, after starting fibrates, which reversed after stopping.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Postmarketing and trial reports describe HDL falling as low as 2 mg/dL, mirrored by a fall in apolipoprotein A1, from 2 weeks to years after starting a fibrate, with rapid recovery after stopping [7].
Population: Diabetic and nondiabetic patients in reports [7].
Sources: [7]
Caveats: Reports without a denominator. On average HDL rose in trials.

LimitedHow often is not known

Fenofibrate: blood counts

The label reports mild to moderate drops in hemoglobin, hematocrit and white cells after starting fenofibrate that then stabilized, with rare low platelets or white cells.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Mild to moderate decreases in hemoglobin, hematocrit and white blood cells were observed after starting fenofibrate and stabilized with long-term use. Thrombocytopenia and agranulocytosis have been reported [7].
Population: People starting fenofibrate [7].
Sources: [7]
Caveats: The label gives no sizes or rates.

LimitedHow often is not known

Fenofibrate: interaction with warfarin-type blood thinners

The label warns fenofibrate strengthens the effect of coumarin anticoagulants such as warfarin on clotting time, with bleeding possible.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Fenofibrate potentiates coumarin anticoagulants in prolonging the prothrombin time and INR, and the label advises adjusting the anticoagulant dose to prevent bleeding [7].
Population: Label statement [7].
Sources: [7]
Caveats: No rate given.

Mixed results3

ModerateCommon

Ezetimibe: liver enzymes

Mixed results: the label reports more liver enzyme rises with ezetimibe plus a statin, 1.3% against 0.4%, while a Cochrane review found little or no difference in liver problems.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: Consecutive transaminase rises of 3 times the upper limit or more occurred in 1.3% on ezetimibe with a statin and 0.4% on a statin alone [2]. Adding ezetimibe to a statin may make little or no difference to hepatopathy (RR 1.14, 95% CI 0.96 to 1.35) [3].
Population: 11,308 patients in 28 label trials, median 8 weeks [2]; 20,687 people in 4 trials [3].
Sources: [2], [3]
Caveats: Low-quality evidence in [3].

LimitedHow often is not known

Ezetimibe: muscle problems

Mixed results: the label warns ezetimibe may cause muscle damage, mostly in people also taking a statin, while pooled trials were too uncertain to tell.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: It was uncertain whether adding ezetimibe to a statin changed myopathy (RR 1.31, 95% CI 0.72 to 2.38) or rhabdomyolysis, given few events [3]. The label reports myopathy and rhabdomyolysis after approval, mostly in people taking a statin or other drugs linked to it [2].
Population: 20,581 people in 3 trials [3]; postmarketing reports [2].
Sources: [3], [2]
Caveats: Very low quality evidence [3].

ModerateHow often is not known

Fenofibrate: serious adverse events

Mixed results: a Cochrane review found more serious adverse events on fenofibrate than placebo, while a pooled analysis of fibrate trials found no significant rise in drug-related serious events.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Fenofibrate increased severe adverse effects (RR 1.55, 95% CI 1.05 to 2.27, high certainty), which were rare [14]. Across fibrate trials, serious drug-related adverse events were not significantly raised (RR 1.21, 95% CI 0.91 to 1.61) [9].
Population: 15,313 people with type 2 diabetes in 2 trials [14]; 17,413 people in fibrate trials [9].
Sources: [14], [9]
Caveats: [9] counts only events judged drug related and pools several fibrates.

Possible, not studied in people1

Untested

Use in pregnancy

Not studied in people. Animal studies found no birth defects from ezetimibe or from fenofibrate at usual doses, with harm from fenofibrate only at doses toxic to the mother.

No study in people. This rests on animal studies.

The numbers and sources

Effect: The ezetimibe label states human data are insufficient, and rats and rabbits showed no developmental effects at 10 and 150 times human exposure [2]. The fenofibrate label states human data are insufficient, with no embryo or fetal toxicity in rats and rabbits at doses up to the 145 mg human dose and adverse outcomes at higher doses with maternal toxicity [7].
Population: Rats and rabbits [2][7].
Sources: [2], [7]
Caveats: Animal data only. With a statin, the statin label also applies [2].

Claims tested and not found

That ezetimibe lowers deaths. All-cause mortality did not differ when ezetimibe was added to a statin or fenofibrate (RR 0.98) [3].
That ezetimibe raises cancer risk. Pooled trials found little or no difference in cancer [3], and cancer rates were similar in the 18,144-patient trial [4].
That fenofibrate added to a statin lowers heart events. Events were 2.2% against 2.4% a year (HR 0.92) [11].
That fibrates lower deaths. All-cause mortality did not change across 18 fibrate trials [9], and deaths were 7.3% on fenofibrate against 6.6% on placebo in its main diabetes trial [8].
That fenofibrate improves vision in diabetic eye disease. Visual function and acuity did not change despite slower retinopathy progression [12][13].

Statins

Sources

Pandor A, Ara RM, Tumur I, et al. Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta-analysis of randomized controlled trials. Journal of Internal Medicine. 2009. https://doi.org/10.1111/j.1365-2796.2008.02062.x
U.S. Food and Drug Administration. ZETIA (ezetimibe) tablets, prescribing information. 2025. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=174e45e0-45bb-48b7-9e60-8f6cfc1d22bb
Zhan S, Tang M, Liu F, et al. Ezetimibe for the prevention of cardiovascular disease and all-cause mortality events. Cochrane Database of Systematic Reviews. 2018. https://doi.org/10.1002/14651858.CD012502.pub2
Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. New England Journal of Medicine. 2015. https://doi.org/10.1056/NEJMoa1410489
Ouchi Y, Sasaki J, Arai H, et al. Ezetimibe Lipid-Lowering Trial on Prevention of Atherosclerotic Cardiovascular Disease in 75 or Older (EWTOPIA 75): A Randomized, Controlled Trial. Circulation. 2019. https://doi.org/10.1161/CIRCULATIONAHA.118.039415
Kim BK, Hong SJ, Lee YJ, et al. Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial. The Lancet. 2022. https://doi.org/10.1016/S0140-6736(22)00916-3
U.S. Food and Drug Administration. TRICOR (fenofibrate) tablets, prescribing information. 2024. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=84b2af1b-365e-4723-ac5f-bc826ec47772
FIELD study investigators. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. The Lancet. 2005. https://doi.org/10.1016/S0140-6736(05)67667-2
Jun M, Foote C, Lv J, et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. The Lancet. 2010. https://doi.org/10.1016/S0140-6736(10)60656-3
Jakob T, Nordmann AJ, Schandelmaier S, et al. Fibrates for primary prevention of cardiovascular disease events. Cochrane Database of Systematic Reviews. 2016. https://doi.org/10.1002/14651858.CD009753.pub2
ACCORD Study Group. Effects of combination lipid therapy in type 2 diabetes mellitus. New England Journal of Medicine. 2010. https://doi.org/10.1056/NEJMoa1001282
Preiss D, Logue J, Sammons E, et al. Fenofibrate and progression of retinopathy in adults with diabetes: the randomised placebo-controlled LENS trial. Health Technology Assessment. 2026. https://doi.org/10.3310/aaph5610
Bhandari M, Devkota S, Dhital R, et al. Effect of fenofibrate on diabetic retinopathy progression: an RCT-Only systematic review and meta-analysis incorporating the LENS trial. Diabetes Research and Clinical Practice. 2026. https://doi.org/10.1016/j.diabres.2026.113543
Kataoka SY, Lois N, Kawano S, et al. Fenofibrate for diabetic retinopathy. Cochrane Database of Systematic Reviews. 2023. https://doi.org/10.1002/14651858.CD013318.pub2
Waldman B, Ansquer JC, Sullivan DR, et al. Effect of fenofibrate on uric acid and gout in type 2 diabetes: a post-hoc analysis of the randomised, controlled FIELD study. The Lancet Diabetes and Endocrinology. 2018. https://doi.org/10.1016/S2213-8587(18)30029-9

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Shown to help8

Reported risks14

What people take it for, and what was found

Shown to help8

Mixed results1

Not shown to help2

Doses studied

Risks

Reported risks11

Mixed results3

Possible, not studied in people1

Claims tested and not found

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