Diabet. Med. 27, 1312–1317 (2010)

Aims  Lipotoxicity has recently been shown to be an important risk factor underlying the pathogenesis of pre‐diabetes. However, clinical evidence supporting the treatment of pre‐diabetes by improving lipotoxicity is lacking. Here, we conducted an open‐label, randomized, controlled trial to investigate whether fenofibrate, the widely used hypolipidaemic agent, might benefit pre‐diabetes, with metfomin and diet control, the recommended intervention methods, as positive controls.

Methods  Newly diagnosed pre‐diabetes patients (n = 120) with hypertriglyceridaemia (plasma triglyceride levels between 1.8 and 4.5 mmol/l) were randomly assigned by computer‐generated randomization sequence to either control group (no intervention), fenofibrate group (200 mg once a day), metformin group (500 mg three times a day) or diet‐controlled group (diet recommendation). Plasma biochemistry examination was performed every 2 months. The primary endpoint was the outcome of the natural course of pre‐diabetes, evaluated by oral glucose tolerance test after 6‐month follow‐up.

Results  Twenty subjects in the fenofibrate group, 24 subjects in the metformin group and 25 subjects in both the diet‐controlled group and the control group finished the trial. Fenofibrate, metformin and diet control had protective effects on hypertriglyceridaemic pre‐diabetes, evidenced by 53.3, 70 and 30% participants regressed to normoglycaemia, respectively. The effects of fenofibrate and metformin were comparable (P > 0.05), while diet control was less effective (P < 0.05). Liver damage occurred in six subjects in the fenofibrate group and gastrointestinal symptoms occurred in four subjects in the metformin group. No serious adverse events occurred.

Conclusion  Controlling lipotoxicity by fenofibrate could effectively ameliorate the natural course of hypertriglyceridaemic pre‐diabetes.