Six-month efficacy of benfluorex vs. placebo or metformin in diet-failed type 2 diabetic patients

Abstract.

Six-month efficacy of benfluorex (Mediator) (150–450 mg/day) was assessed in a double-blind multicenter study vs. placebo or metformin hydrochloride (850–2550 mg/day). After a 2-month run-in period of strict dieting, 722 type 2 diabetic patients were randomized (1:2:2) to receive placebo (n=144), benfluorex (n=294) or metformin (n=284). After a 5-week dose-finding phase, the efficacy of benfluorex was compared with that of placebo (test for difference, main analysis) and metformin (non-inferiority test, secondary analysis) during a 6-month fixed-dose treatment. At entry after strict dieting, there was no difference between groups for HbA_1C (placebo, 7.4%±1.5%; benfluorex, 7.7%±1.6%; metformin, 7.8%±1.6%) and fasting plasma glucose (FPG; placebo, 9.7±2.3 mmol/l; benfluorex, 10.0±2.0 mmol/l; metformin, 10.2±2.5 mmol/l). At the end of the dose-finding phase, mean doses were 2.71 tablets/day for placebo group, 2.65 tablets/day for benfluorex (397.5 mg/day) and 2.50 tablets/day for metformin (2125 mg/day). At the end of treatment, HbA_1C level decreased by 0.60% (p<0.001) in benfluorex patients while it increased by 0.50% (p<0.001) with placebo (intent-to-treat analysis). The mean endpoint difference was −0.86% (SE, 0.17%; p<0.001). Mean endpoint difference in HbA_1C between benfluorex and metformin was 0.28% (SE, 0.12%) [90% CI, 0.07 to 0.48] (non-inferiority test, p=0.037). Treatment with benfluorex was well tolerated; 39% of these patients reported one or more emergent adverse events (compared to 38% on placebo and 43% on metformin) and only two patients suffered a treatment-related, serious adverse event. This study demonstrates that benfluorex: (1) significantly reduces HbA1C and fasting plasma glucose when compared to placebo; (2) has a good safety profile; and (3) has relatively lower potency compared to metformin, although the non-inferiority test (equivalence limit for HbA_1C of 0.5%) was significant.