METFORMIN INCREASES CIRCULATING TUMOR-NECROSIS-FACTOR-ALPHA LEVELS INNONOBESE NONDIABETIC PATIENTS WITH CORONARY HEART-DISEASE

Metformin reduces insulin resistance and hyperinsulinaemia, as well as lipid levels and body weight. The mechanisms behind these effects are likely to involve intracellular insulin signalling, Recent evidence i mplicates tumour necrosis factor-alpha (TNF-alpha) as a modulatory fac tor on insulin resistance, The present investigation was undertaken to clarify whether metformin affects TNF-alpha and soluble TNF receptor levels. Sixty non-diabetic men with coronary heart disease were treate d with diet and lifestyle advice and lovastatin 40 mg/day during a 4-w eek run-in period, During this period TNF-alpha and soluble TNF recept or p75 remained unchanged, whereas soluble TNF receptor p55 increased by 8% (P < 0.05), Twelve weeks of metformin treatment increased TNF-al pha by 33% (P < 0.05), This effect was-restricted to non-obese patient s in whom TNF-alpha increased by 68% (P < 0.01). Soluble TNF receptors p55 and p75 remained unchanged in the whole group, whereas soluble TN F receptor p55 increased by 11% (P < 0.05) in non-obese patients. Sinc e metformin reduces insulin resistance both in obese and non-obese sub jects but increases TNF-alpha levels only in the latter, it is conclud ed that the drug does not exert its effect on insulin resistance throu gh regulation of circulating TNF-alpha levels. (C) 1997 Academic Press Limited.