Use of fibrates in the metabolic syndrome: A review

Table 1 The thresholds defining the metabolic syndrome issued by individual organisations (reproduced from: Strange et al[23])

Group	WHO[24]	EGIR[25]	NCEP/ATP III[27]	AACE[26]	IDF consensus[28]	IDF consensus (10 to < 16 yr)[112]
Definition	IGT, IFG, T2DM or lowered insulin sensitivity plus 2 of the following	Plasma insulin > 75th percentile plus 2 of the following	3 of the following	IGT or IFG plus any of the following based on clinical judgement	See below
Europoid waist circumference (cm)	W:H > 0.90 M, W:H > 0.85 F or BMI > 30 kg/m2	≥ 94 M, ≥ 80 F	≥ 102 M, ≥ 88 F	BMI ≥ 25 kg/m2	≥ 94 M, ≥ 80 F or BMI > 30 kg/m2 plus 2 of the following	> 90th percentile plus 2 of the following
Triglyceride (mmol/L)	> 1.7	> 1.7	≥ 1.7	> 1.7	> 1.7	≥ 1.7
HDL (mmol/L)	< 0.91 M, < 1.01 F	< 0.91	< 1.03 M, < 1.29 F	< 1.03 M, < 1.29 F	< 1.03 M, < 1.29 F	< 1.03
BP (mmHg)	≥ 140/90	≥ 140/90 or on treatment	≥ 130/85	≥ 130/85	SBP ≥ 130 or DBP ≥ 85 or on treatment	SBP ≥ 130 and/or DBP ≥ 85
Glucose (mmol/L)	IGT, IFG or T2DM	IGT or IFG (but not diabetes)	≥ 5.6[113] or diabetes	IGT or IFG (but not diabetes)	≥ 5.6	≥ 5.6 or known T2DM
Others	Microalbuminuria ACR > 30 mg/g			Other features of IR1

¹Includes polycystic ovary syndrome, family history or ethnic group susceptible to type 2 diabetes, sedentary lifestyle and advancing age. ACR: Albumin creatinine ration; BMI: Body mass index; DBP: Diastolic blood pressure; F: Female; IFG: Impaired fasting glucose; IGT: Impaired glucose tolerance; IR: Insulin resistance; SBP: Systolic blood pressure; M: Male; T2DM: Type 2 diabetes mellitus; W:H: Waist to hip ratio; HDL: High density lipoprotein; WHO: World Health Organisation; NCEP: National cholesterol education program; EGIR: European group for the study of insulin resistance; IDF: International diabetes federation; AACE: American Association of Clinical Endocrinologists.

Table 2 Details of the large fibrate outcome trials in the total cohort are provided in this table

Trial	HHS	VA-HIT	BIP	FIELD	ACCORD
Drug	Gemfibrozil	Gemfibrozil	Bezafibrate	Fenofibrate	Fenofibrate
Dose	1200 mg/d	1200 mg/d	400 mg/d	200 mg/d	200 mg/d
Primary endpoint	MI (fatal and non-fatal), cardiac death	Combined incidence of nonfatal MI and death from CAD	MI (fatal and non-fatal), sudden death	CHD death, non-fatal MI	Non-fatal MI, non-fatal stroke, or CVD death
Mean follow-up (yr)	5	5	6	5	5
Patients (total)	Fibrate = 2051; placebo = 2030	Fibrate = 1264; placebo = 1267	Fibrate = 1548; placebo = 1542	Fibrate = 4895; placebo = 4900	Fibrate = 2765; placebo = 2753
Effect on Lipids (% change from baseline)	LDL-C: -10; TC: -11; TG: -43; HDL-C: +10	LDL-C: 0; TC: -4; TG: -31; HDL-C: +6	LDL-C: -6.5; TC: -4.5; TG: -21; HDL-C: +18	LDL-C: -12; TC: -11; TG: -29; HDL-C: +5	LDL-C: -19; TC: -14; TG: -22; HDL-C: +8.4
Outcomes	CHD: ↓ 34%; non-fatal MI: ↓ 37%; total mortality: No change	CHD and non-fatal MI: ↓ 22%; total mortality: ↓ 11% (NS)	Fatal and nonfatal MI and sudden death: ↓ 9% (NS); total mortality: No change	CHD and non-fatal MI: ↓ 11% (NS); total mortality: ↑ 19% (NS)	Nonfatal MI nonfatal stroke CVD death: ↓ 8% (NS); total mortality: ↓ 9 % (NS)

HHS: Helsinki Heart Study; VA-HIT: Veterans Affairs High-Density Cholesterol Intervention Trial; BIP: Bezafibrate Infarction Prevention; FIELD: Fenofibrate Intervention and Event Lowering in Diabetes; ACCORD: Action to Control Cardiovascular Risk in Diabetes; CVD: Cardiovascular disease; NS: Not significant; LDL-C: Low density lipoprotein cholesterol; TC: Total cholesterol; TG: Triglycerides; HDL-C: High density lipoprotein cholesterol; MI: Myocardial infarction; CAD: Coronary artery disease; CHD: Coronary heart disease.