Summary
In this study we evaluated the relationships between plasma metformin levels, measured by reversed-phase high-performance liquid chromatography, and serum lipid levels in 20 metformintreated, type II diabetic patients. Mean fasting plasma metformin concentration was 490 ± 188 ng/ml. No correlation was found between daily dose of drug and lipid parameters. A significant correlation emerged between circulating metformin concentration and serum triglycerides (r=−0.574, p<0.01), HDL-cholesterol (r=0.583, p<0.01) and HDL2-cholesterol (r=0.670, p<0.05). Multiple linear regression analysis showed that the correlation between plasma metformin concentration and serum triglycerides still remained significant after correction for other clinical and metabolic parameters. Total cholesterol and HDL3-cholesterol were not correlated with metformin concentrations. These results demonstrate the clinical usefulness of measuring plasma metforminc concentrations and indicate that some effects of metformin on lipid metabolism depend on the drug plasma levels.
Similar content being viewed by others
References
Benzi L., Marchetti P., Cecchetti P., Navalesi R.: Determination of metformin and phenformin in plasma and urine by reversed-phase high-performance liquid chromatography — J. Chromatogr. biomed. Appl.375, 184–189, 1986.
Czyzyk A.: The use of biguanide derivatives in the treatment of diabetes. In: Diabetes. Excerpta Med. Foundation, Amsterdam, 1977, p. 422–450.
Descovich G., Montaguti U., Ceredi C., Cocuzza E., Sirtori C. R.: Long-term treatment with metformin in a large cohort of hyperlipidemic patients — Artery4, 348–359, 1978.
Fedele D., Tiengo A., Nosadini R., Marchiori E., Briani G., Garotti M. C., Muggeo M.: Hypolipidemic effects of metformin in hyperprebetalipoproteinemia — Diabète et Métabol.2, 127–131, 1976.
Ferlito S., Spina E., Del Campo E., Romano F., Modica L.: Effect of metformin on plasma lipoprotein lipase — Arch. Sci. med. (Torino)137, 739–743, 1980.
Fielding C. J.: The endothelium, triglyceride-rich lipoproteins and atherosclerosis. Insight from cell biology and lipid metabolism — Diabetes30 (Suppl. 2), 19–23, 1981.
Gidez L. I., Miller G. J., Burstein M., Eder H. A.: Analysis of plasma HDL subclasses by precipitation procedure. In: Report of the HDL Methodology Workshop. NIH Publication no 82-1661, Bethesda/MD, 1979; pp. 328–340.
Gidez L. I., Miller G. J., Burstein M., Slagle S., Eder H. A.: Separation and quantitation of subclasses of human plasma high density lipoproteins by a simple precipitation procedure — J. Lipid Res.23, 1206–1223, 1982.
Glickman R. M., Khorana J., Kilgore A.: Localization of apoprotein B in intestinal epithelial cells — Science193, 1254–1259, 1976.
Gofman J. W., Young W., Tandy R.: Ischemic heart disease, atherosclerosis and longevity — Circulation34, 679–697, 1966.
Gustafson A., Björntorp P., Fahlen M.: Metformin administration in hyperlipidaemic states — Acta med. scand.190, 491–494, 1971.
Hermann L. S.: Metformin: a review of its pharmacological properties and therapeutic use — Diabète et Métabol.5, 233–245, 1979.
Kissebah A. H., Adams P. W., Tulloch B. R., Wynn C.: The effect of phenethylbiguanide on plasma free fatty acid (FFA) and triglyceride turnover in maturity-onset diabetics. In:Hoet J. J., Lefebvre P., Butterfield W. J. H., Vallance-Owen J. (Eds): VIII Congr. Int. Diabetes Fed. Excerpta Medica, Amsterdam-Princeton-London-Geneva-Tokyo, 1973; p. 213, abstract # 473.
Lintz W., Berger W., Aenishaenslin W., Kutova V., Baerlocher C., Kapp J. P., Beckmann R.: Butylbiguanide concentration in plasma, liver and intestine after intravenous and oral administration in man — Europ. J. clin. Pharmacol.7, 433–439, 1974.
Marchetti P., Benzi L., Cecchetti P., Boni C., Ciociaro D., Ciccarone A. M., Giannarelli R., Di Cianni G., Zappella A., Navalesi R.: Plasma biguanide levels are related with blood metabolites in diabetic patients — Clin. Pharmacol. Ther.41, 450–456, 1987.
Marquié G.: Effect of metformin on lipid metabolism in the rabbit aortic wall — Atherosclerosis30, 166–175, 1978.
Patsch J. R., Gotto A. M. Jr., Olivecrona T., Eisenberg S.: Formation of high density lipoprotein-like particles during lipolysis of very low density lipoproteinsin vitro — Proc. nat. Acad. Sci. (Wash.)75, 4519–4523, 1978.
Schäfer G.: Biguanides: a review of history, pharmacodynamics and therapy — Diabète et Métabol.9, 148–163, 1983.
Sirtori C. R., Catapano A., Ghiselli G. C., Innocenti A. L., Rodriguez J.: Metformin: an antiatherosclerotic agent modifying very low density lipoproteins in rabbits — Atherosclerosis26, 79–89, 1977.
Sirtori C. R., Catapano A., Ghiselli G. C., Shore B., Shore V.: Effects of metformin on lipoprotein composition in rabbits and man — Prot. biol. Fluids25, 379–383, 1978.
Sirtori C. R., Franceschini G., Gianfranceschi G., Sirtori M., Montanari G., Bosisio E., Mantero E., Bandioli A.: Metformin improves peripheral vascular flow in nonhyperlipidemic patients with arterial disease — J. cardiovasc. Pharmacol.6, 914–923, 1984.
Sirtori C. R., Tremoli E., Sirtori M., Conti F., Paoletti R.: Treatment of hypertriglyceridemia with metformin — Atherosclerosis26, 583–587, 1977.
Stout R. W., Brunzell J. D., Porte D. Jr., Bierman E. L.: Effect of phenformin on lipid transport in hypertriglyceridemia — Metabolism,23, 815–820, 1974.
Weisweiler P., Drosner M., Schwandt P.: Dietary effects on very low-density lipoproteins in type II (non-insulin-dependent) diabetes mellitus — Diabetologia23, 101–103, 1982.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Marchetti, P., Benzi, L., Cerri, M. et al. Effect of plasma metformin concentrations on serum lipid levels in type II diabetic patients. Acta diabet. lat 25, 55–62 (1988). https://doi.org/10.1007/BF02581246
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02581246