Kinetics and mechanism of the reaction of metformin with methylglyoxal Sinan Battah, Naila Ahmed, Paul J. Thornalley * Department of Biological and Chemical Sciences, University of Essex, Central Campus, Wivenhoe Park, Colchester, Essex CO4 3SQ, UK Abstract We examined the rate of reaction of methylglyoxal with metformin, forming hydroimidazolone, triazepinone and other adducts at pH 7.4 and 37 jC in an initial rate study. Metformin was not an efficient scavenger of methylglyoxal. Mechanisms other than the scavenging of methylglyoxal were probably responsible for decreased methylglyoxal concentration in diabetic subjects on metformin therapy—the lifting of insulin resistance, for example. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Metformin; Methylglyoxal; Glycation; Hydroimidazolone; Triazepinone 1. Introduction Metformin is a drug used in the therapy of type 2 diabetes mellitus. It decreased blood glucose levels by increasing hepatic and peripheral tissue sensitivity to insulin [1]. It was also found recently to decrease the blood plasma concentration of methylglyoxal [2]. Metformin has been proposed as a scavenger of methylglyoxal in vivo where a triazepinone adduct was formed [3]. 2. Results and discussion The reaction of methylglyoxal and metformin was associated with an initial rapid increase in absorbance at 225 nm and formation of early stage adducts. Purification of 0531-5131/02 D 2002 Elsevier Science B.V. All rights reserved. PII:S0531-5131(02)00889-0 Abbreviations: MALDI, matrix-assisted laser desorption ionisation. * Corresponding author. Tel./fax: +44-1206-873010. E-mail address: thorp@essex.ac.uk (P.J. Thornalley). International Congress Series 1245 (2002) 355 – 356