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Sulphonylurea–metformin combination therapy, cardiovascular disease and all‐cause mortality: the Fremantle Diabetes Study
Author(s) -
Sillars B.,
Davis W. A.,
Hirsch I. B.,
Davis T. M. E.
Publication year - 2010
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2010.01230.x
Subject(s) - medicine , metformin , diabetes mellitus , type 2 diabetes , proportional hazards model , cause of death , cohort , disease , cohort study , mortality rate , insulin , endocrinology
Aim: To determine whether combination of metformin–sulphonylurea is associated with an increased risk of cardiovascular disease (CVD) and mortality in an urban community‐based cohort of type 2 patients. Methods: We studied 1271 (98.2%) of 1294 type 2 participants in the observational Fremantle Diabetes Study (mean age 64.2 years, 48.8% males) who had detailed diabetes‐specific therapy recorded at baseline and complete follow‐up data. Mortality and hospital discharge data were collected over 13 174 patient‐years (mean ± SD: 10.4 ± 3.9 years). Cox proportional hazards modelling was used to determine whether baseline diabetes treatments were independently associated with cardiovascular mortality, hospitalization for/death from CVD or all‐cause mortality after adjustment for other explanatory variables. Results: During follow‐up, 523 deaths occurred (41.1%) of which 269 (51.4%) were attributed to CVD. Hospitalization for CVD as principal diagnosis occurred at least once for 481 (37.8%) participants. In Kaplan–Meier analyses, there were significant differences in cardiovascular mortality, hospitalization for/death from CVD and all‐cause mortality between diabetes therapy groups (p < 0.001). Compared with diet and metformin monotherapy, those treated with metformin–sulphonylurea had higher cardiovascular and all‐cause mortality (p ≤ 0.024). Insulin users had significantly higher cardiovascular mortality, hospitalization for/death from CVD and all‐cause mortality than those on combination therapy (p ≤ 0.016). After adjustment for significant variables in the most parsimonious models, diabetes treatment was not independently associated with any of the three study endpoints (p ≥ 0.49). Conclusions: Combination metformin–sulphonylurea appears as safe as other blood glucose‐lowering therapies used for type 2 diabetes.