Normalization of metabolic syndrome using fenofibrate, metformin or their combination.

AIM: The aim of this study was to evaluate whether and to what extent fenofibrate (F), metformin (M) or a combination of these drugs improve characteristics of the metabolic syndrome (MetS).

METHODS: MetS was defined as the presence of >/=3 National Cholesterol Education Programme criteria, including >/=2 biochemical abnormalities. Patients with MetS were randomized to receive one of seven treatments twice daily for three months: F 80 mg + M 850 mg, F 80 mg + M 500 mg, F 40 mg + M 850 mg, F 40 mg + M 500 mg, F 80 mg + placebo, M 850 mg + placebo or placebo. 'Normalized' was defined as not having MetS biochemical abnormalities at the 3-month treatment period. A total of 681 patients were analysed (mean age 56 years, 59% men, mean body mass index 31.6 and 33.3 in male and female patients respectively).

RESULTS: High dose combination therapy led to normalization of biochemical parameters in 17.4% of patients, whereas only 5.8% of patients during F (p = 0.009) and 5.0% during M monotherapy (p = 0.005) exhibited normal biochemical values. Accordingly, F 80 mg + M 850 mg twice daily was most effective for normalizing triglycerides (55.0%), high-density lipoprotein cholesterol (35.0%) and fasting glucose (39.4%). All the treatments were well tolerated, with comparable adverse-event rates between groups.

CONCLUSIONS: Treatment with fenofibrate and metformin in combination led to normalization of biochemical abnormalities associated with the MetS more effectively compared with either therapy alone, without additional adverse effects. These data imply that high-dose combination therapy may offer additional therapeutic benefit particularly in patients with MetS.