Letter to the Editor

Abstract

We thank Dr. Bell for his interest in our paper. He states that metformin has never been shown to decrease sympathetic activity (SA) in humans, citing the work of Gudbjörnsdottir showing no effect of metformin on muscle sympathetic nerve activity or on norepinephrine (NE) spillover in nondiabetic, insulin-resistant men ( 1. Gudbjörnsdottir S. Friberg P. Elam M. Attvall S. Lönnroth P. Wallin B.G. The effect of metformin and insulin on sympathetic nerve activity, norepinephrine spillover and blood pressure in obese, insulin resistant, normoglycemic, hypertensive men. Blood Press. 1994; 3: 394-403 Crossref PubMed Scopus (73) Google Scholar ). We have discussed the limitations of that study in detail ( 2. Anabtawi A. Miles J.M. Metformin: nonglycemic effects and potential novel indications. Endocr Pract. 2016; 22: 999-1007 Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar , 3. Miles J.M. Rule A.D. Borlaug B.A. Use of metformin in diseases of aging. Curr Diab Rep. 2014; 14: 490 Crossref PubMed Scopus (32) Google Scholar ), including the fact that myocardial SA was not measured. This is important because regional and systemic SA are known to diverge in some situations ( 4. Patel J.N. Eisenhofer G. Coppack S.W. Miles J.M. Norepinephrine spillover in forearm and subcutaneous adipose tissue before and after eating. J Clin Endocrinol Metab. 1999; 84: 2815-2819 PubMed Google Scholar ). In our review, we conclude that metformin lowers blood pressure when it is given to people with elevated blood pressure. We also cite studies showing a reduction in circulating NE concentrations ( 5. Giugliano D. De Rosa N. Di Maro G. et al. Metformin improves glucose, lipid metabolism, and reduces blood pressure in hypertensive, obese women. Diabetes Care. 1993; 16: 1387-1390 Crossref PubMed Scopus (201) Google Scholar ) and an increase in R-R variability ( 6. Manzella D. Grella R. Esposito K. Giugliano D. Barbagallo M. Paolisso G. Blood pressure and cardiac autonomic nervous system in obese type 2 diabetic patients: effect of metformin administration. Am J Hypertens. 2004; 17: 223-227 Crossref PubMed Scopus (69) Google Scholar ) in people treated with metformin as at least indirect evidence of decreased SA. Taking these points together, it seems premature to exclude an effect of metformin on SA.