| Benfluorex (2-[[l-methyl-2[3-(trifluoromethyl)-phenyl]ethyl]amino]ethanol benzoate ester), a trifluoro methyl phenylisopropylamine compound, which was initially on sale as a hypolipidemic drug in France in 1976. Several basic and clinical studies demonstrate that the drug possess antihyperglycemic properties, and now it is widely used for glycometabolism or lipometabolism disorders, diabetes mellitus and obesity[1-2]. It is the first clinical trial for benfluorex on Chinese type 2 diabetes, with metformine as positive control. Therefore, the aim of this clinical trial is to confirm the efficacy and safety of benfluorex treatment in type 2 diabetic patients as well as the change of insulin resistance.ObjectiveTo evaluate the efficacy and safety of benfluorex treatment in type 2 diabetic patients as well as the change of insulin resistance as compared with metformin hydrochloride tablets.MethodsA multicenter, randomized, double-blinded, single-stimulation and parallel positive drug controlled clinical trial was performed. During this 17-week trial, five clinical research centers were involved in this study. The trial comprised one-week selection period and 16-week treatment period. 262 type 2 diabetes patients screened, 240 patients enrolled (first-treatment 160, secondary-treatment 80). 240 patients were randomized into benfluorex(120) or metformin(120) for 16 weeks respectively. Compairson of HbA1c,FPG,PPG,insulin and adverse events before and after treatment between two group. The change of insulin resistance was investigated by serum radio-immunity method.Results1. Comparision of HbA1c level between group metformin and benfluorex group: Among FAS population, after 16-week treatment, HbA1c level decreased by 1.46% (from7.95% to 6.49%) in metformine group while it decreased by 1.30% (from7.89% to 6.59%) in benfluorex group. The difference of HbA1c level between pretreatment and posttreatment in each group were proved statistically significant (P<0.01), but no statistically significant difference existed between two groups (P>0.05), it demonstrated two groups had similar effect in decreasing the level of HbA1c.2. Comparision of difference of HbA1c level between first-treatment group and secondary-treatment group: Among FAS population, the endpoint of the first-treatment groups of benfluorex group and metformin group decreased by -1.50±1.29 and -1.31±1.35 respectively compared with baseline after 16-week treatment, no statistically significant difference existed between two groups (P>0.05). Among FAS population, the endpoint of the secondary-treatment groups of metformin group (n=35) and benfluorex group(n=32) decreased by -1.13±1.87 and -1.37±1.75 respectively compared with baseline after 16-week treatment, no statistically significance existed between two groups (P>0.05). PPS population had similar results with FAS.3. Comparision of FPG, PPG and insulin levels between benfluorex group and metformin group: Among FAS population, FPG or PPG levels of benfluorex group and metformin group decreased significantly after 16-week treatment (P<0.01), while insulin levels of benfluorex group and metformin group had no statistically siginificant difference (P>0.05), no statistically significant difference existed between two groups (P>0.05).4. Comparision of TG level: TG levels of benfluorex group and metformin group decreased from2.18 mmol/L and 1.99 mmol/L to 1.93 mmol/L and 1.75 mmol/L respectively after 16-week treatment. The difference of TG levels between pretreatment and posttreatment in benfluorex group was proved statistically significant (P<0.01), while the difference in metformin group was nonsignificant (P>0.05), no statistically significant difference existed between two groups (P>0.05). The difference of LDL-C levels between pretreatment and posttreatment in benfluorex group was proved significant (P<0.01), no statistically significant difference existed between two groups (P>0.05).5. Comparision of IRI: IRIs of benfluorex group and metformin group decreased from 5.31±7.04 and 4.63±4.15 to 3.11±3.00 and 2.73±2.09 respectively after 16-week treatment. The difference of IRIs between pretreatment and posttreatment in benfluorex group was proved statistically significant (P<0.01), and the difference in metformin group was also statistically significant (P<0.05), no statistically significant difference existed between two groups (P>0.05).6. Safety evaluation: Of the 70 adverse events in trial between two groups, 32(26.67%) occured in metformin group, while 38(31.67%) occured in benfluorex group. Of the 61 adverse reaction cases, 29(24.17%) occured in metformin group, while 23 (26.67%) occured in benfluorex group. No statistically difference existed between two groups (P>0.05). ConclusionBenfluorex and metformin have similar effect of decreasing HbA1c,FPG and PPG in treatment of type 2 diabetic patients, and they both have no effect on insulin level, but both two groups can improve IR; the decreased extent of blood lipid was nonsignificant between two groups. Ulike metformin, benfluorex can lower serum TG and LDL-C levels significantly and improve hypolipemia symptom. The difference of incidences of adverse event was nonsignificant between two groups. Therefore, our results demonstrate that benfluorex and metformin have similar efficacy and safty profiles either in the treatment or in the IRI improvement of type 2 diabetic patients, in addition benfluorex have more advantage than metformin in treating type 2 diabetic patients with hyperlipemia. |
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