Sulphonylurea-metformin combination therapy, cardiovascular disease and all-cause mortality: the Fremantle Diabetes Study

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.