MEFORMIN, PLASMA-GLUCOSE AND FREE FATTY-ACIDS IN TYPE-II DIABETIC OUT-PATIENTS - RESULTS OF A CLINICAL-STUDY

Abnormalities in free fatty acid (FFA) metabolism are an intrinsic fea ture of type II diabetes mellitus and may even play a role in the deve lopment of glycaemic imbalance. This study investigated whether the an ti-diabetic drug metformin can reduce FFA levels in clinical practice and whether this correlates with its anti-diabetic effect. For 6 month s metformin was added to sulfonylurea therapy in 68 type II diabetic o utpatients with poor glycaemic control, being administered before meal s and at bed-time. Basal and daily area-under-the-curve (AUG) glucose levels dropped (both P < 0.0005) like basal and daily AUC FFA levels ( P < 0.004 and P < 0.001 respectively) reductions were all correlated ( P < 0.001 and P < 0.003 respectively). Reductions in fasting and daily AUC glucose correlated more closely with body fat distribution, expre ssed by waist-hip ratio (WHR) (P < 0.006 and P < 0.004 respectively), than with the body mass index (BMI) (P < 0.02 and P < 0.04 respectivel y). Similarly fasting and daily AUC FFA correlated with WHR (P < 0.007 and P < 0.01 respectively) but not with BMI (both P = ns). Subdividin g male and female diabetic patients into groups with low and high WHRs , fasting and daily AUC glucose were reduced in men (P < 0.01 and P < 0.02) and in women (P < 0.02 and P < 0.04 respectively) with low WHRs less than in men and in women with higher WHRs (for each gender P < 0. 0001 and P < 0.0002 respectively). Decreases in fasting and daily AUC FFA, which did not reach significance in either men or women with low WHRs, were statistically significant in men (P < 0.03 and P < 0.01 res pectively) and in women (P < 0.02 and P < 0.005 respectively) with hig h WHRs. These findings suggest that an improvement in FFA plasma level s might contribute to metformin's anti-diabetic activity which appears to be more marked in patients with high WHRs. Moreover adding a bed-t ime dosage to the standard administration at meal times seems to be an effective therapeutical strategy. (C) 1997 Elsevier Science Ireland L td.