Increased mortality in Type I diabetic patients using sulphonylurea and metformin in combination: a population-based observational study

Aims/hypothesis. This study analysed cause-specific mortality in Type II (n on-insulin-dependent) diabetic patients using either sulphonylurea alone or in combination with metformin. Methods. Patients were followed from the first day they were taking either the combination or sulphonylurea alone. Odds ratios by Cox regression analy ses were adjusted for age, sex, duration of diabetes, study area, year of i nclusion and fasting blood glucose at inclusion. Results. We included 169 patients taking sulphonylurea and metformin in com bination and 741 patients taking only sulphonylurea. Mean (range) follow-up time was 6.1 (0.1-13.0) years. The adjusted odds ratio for overall mortali ty was 1.63 (95 % confidence interval 1.27-2.09) in patients taking sulphon ylurea and metformin combination vs those using sulphonylurea alone. For mo rtality from ischaemic heart disease and stroke the adjusted odds ratios we re 1.73 (95 % confidence interval 1.17-2.55) and 2.33 (95 % confidence inte rval 1.17-4.63), respectively. Conclusion/interpretation. There was a higher cardiovascular mortality in T ype II diabetic patients taking sulphonylurea and metformin in combination than in those taking only sulphonylurea. Hence, it cannot be excluded that this kind of combination therapy possibly increases cardiovascular mortalit y. It is feasible that the increased mortality was secondary to a more aggr essive type of diabetes in the patients using sulphonylurea and metformin i n combination. Combination therapy is known to promote additional blood glu cose reduction but there is as yet no evidence that a sulphonylurea and met formin combination is more beneficial on micro- or macrovascular disease th an sulphonylurea or metformin alone.