Effect of combined secretagogue/biguanide treatment on mortality in type 2 diabetic patients with and without ischemic heart disease

Background: The aim of this investigation was the assessment of the association of combined secretagogue/biguanide treatment with mortality in type 2 diabetic patients with and without ischemic heart disease (IHD). Methods: A retrospective observational cohort study was performed on a consecutive series of 1108 non insulin-treated diabetic outpatients, with a mean follow-up of 28.0 +/- 6.5 months. Information on all-cause mortality was obtained by the City of Florence Registry Office. Results: Patients treated with combinations of insulin secretagogues and biguanides at enrolment showed a significantly higher yearly mortality rate when compared with the rest of the sample (3.6% vs. 6.2% yearly; p < 0.05); this was confirmed at multivariate analysis (OR [95% CI] 1.618[ 1.044; 2.512]). When patients with IHD were analyzed separately, combined therapy was associated with a significantly higher mortality (hazard ratio 2.262[1.005; 5.102]). Conversely, among patients without a previous diagnosis of IHD, a non significant trend toward an increase of mortality was observed in those on combined therapy. Conclusions: The present study shows that the increase of mortality associated with combinations of biguanides and insulin secretagogues is evident only in patients with IHD. It can be speculated that biguanides could enhance the well-known effects of sulphonylureas on ischemic preconditioning in patients with IHD, aggravating the damage determined by ischemia. (c) 2007 Elsevier Ireland Ltd. All rights reserved.