Meformin, plasma glucose and free fatty acids in type II diabetic out-patients: results of a clinical study

Abstract

Abnormalities in free fatty acid (FFA) metabolism are an intrinsic feature of type II diabetes mellitus and may even play a role in the development of glycaemic imbalance. This study investigated whether the anti-diabetic drug metformin can reduce FFA levels in clinical practice and whether this correlates with its anti-diabetic effect. For 6 months metformin was added to sulfonylurea therapy in 68 type II diabetic outpatients with poor glycaemic control, being administered before meals and at bed-time. Basal and daily area-under-the-curve (AUC) 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, expressed 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 respectively). Similarly fasting and daily AUC FFA correlated with WHR ( P<0.007 and P<0.01 respectively) but not with BMI (both P=ns). Subdividing 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 respectively) and in women ( P<0.02 and P<0.005 respectively) with high WHRs. These findings suggest that an improvement in FFA plasma levels might contribute to metformin's anti-diabetic activity which appears to be more marked in patients with high WHRs. Moreover adding a bed-time dosage to the standard administration at meal times seems to be an effective therapeutical strategy.