Aims/hypothesis. This study analysed cause-specific mortality in Type II (non-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 analyses were adjusted for age, sex, duration of diabetes, study area, year of inclusion and fasting blood
glucose at inclusion.
Results. We included 169 patients taking sulphonylurea and metformin in combination 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 mortality was 1.63 (95 % confidence interval
1.27–2.09) in patients taking sulphonylurea and metformin combination vs those using sulphonylurea alone. For mortality from
ischaemic heart disease and stroke the adjusted odds ratios were 1.73 (95 % confidence interval 1.17–2.55) and 2.33 (95 %
confidence interval 1.17–4.63), respectively.
Conclusion/interpretation. There was a higher cardiovascular mortality in Type 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 mortality. It is feasible that the increased mortality was secondary to a more aggressive type of diabetes
in the patients using sulphonylurea and metformin in combination. Combination therapy is known to promote additional blood
glucose reduction but there is as yet no evidence that a sulphonylurea and metformin combination is more beneficial on micro-
or macrovascular disease than sulphonylurea or metformin alone. [Diabetologia (2000) 43: 558–560]
Keywords Type II diabetes - pharmacoepidemiology - sulphonylurea - metformin - combination treatment - mortality.
Received: 6 December 1999 and in revised form: 7 February 2000