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 metformin 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.