EFFECT OF BENFLUOREX IN ADDITION TO INSULIN THERAPY IN OBESE TYPE-II DIABETIC-PATIENTS WITH SECONDARY FAILURE TO CONVENTIONAL ORAL TREATMENT

Benfluorex hydrochloride is a hypolipidaemic and anti-hyperglycaemic d rug, Its anti-hyperglycaemic effects are mediated through modification of insulin action rather than stimulation of insulin secretion by the B-cell, Aim of the study: to evaluate the effects of 3-month treatmen t with benfluorex (B) in an insulin-resistant population of 20 obese ( Body Mass Index (BMI) 34.4+/-5.4 kg/m(2)) insulin-treated (daily dose 69.4+/-37.0 U/day) Type II diabetic patients with secondary failure to conventional oral treatment, Parameters were glycaemic control, insul in requirement, peripheral insulin resistance and lipids. Methods: the study was designed in a randomized double blind placebo (P) controlle d fashion, using stratification for degree of obesity and known durati on of diabetes, Insulin resistance was measured using the euglycaemic hyperinsulinaemic clamp technique at an insulin infusion rate of 0.10 U/kg/h. Results: mean fasting plasma glucose did not significantly cha nge (10.87+/-3.76 to 9.30+/-2.66 mmol/l (mean+/-SD)) in the placebo gr oup and decreased from 9.68+/-1.75 to 6.68+/-1.69 mmol/l in the benflu orex group (p=0.001), HbA(1c) levels did not change after P (8.67+/-1. 53 to 8.95+/-1.25 mmol/l (NS)) and decreased after B (7.13+/-0.94 to 6 .56 to 0.60 mmol/l (p=0.026)). The change was different between groups (p<0.001). Daily insulin requirements were not significantly modified , Similar differences between P and B treatment were observed for fast ing C-peptide (p=0.039) and fasting insulin (p=0.020) with high levels in the placebo treated group and low levels in the benfluorex treated group, Clamp results however showed no significant differences in ins ulin-mediated glucose disposal. Mean glucose infusion rates (GIR) duri ng steady state euglycaemia in the last 30 min of each clamp yielded 3 .63+/-1.93 and 4.03+/-2.56 mg/kg/min for P treatment respectively 4.34 +/-2.18 and 4.93+/-1.80 mg/kg/min for B treatment, Apolipoprotein-B (a po-B) levels and LDL-cholesterol levels decreased in the B group compa red with P (p=0.050 and p=0.018). Conclusions: benfluorex improves gly caemic control in poorly controlled, obese insulin-treated Type II dia betic patients, As no differences in peripheral insulin action nor in daily insulin requirements were observed these observations suggest ot her mechanisms such as a reduction in hepatic glucose production durin g the night. The observed reduction in LDL-cholesterol and apo-B exten ds the hypolipidaemic effect of benfluorex.