Sulphonylurea-metformin combination therapy, cardiovascular disease and all-cause mortality: the Fremantle Diabetes Study.
OBJECTIVE
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 < or = 0.024). Insulin users had significantly higher cardiovascular mortality, hospitalization for/death from CVD and all-cause mortality than those on combination therapy (p < or = 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 > or = 0.49).


CONCLUSIONS
Combination metformin-sulphonylurea appears as safe as other blood glucose-lowering therapies used for type 2 diabetes.
Sillars
B
B
University of Western Australia, Nedlands, Australia.
Davis
W A
WA
Hirsch
I B
IB
Davis
T M E
TM
D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000401:mortality*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000401:mortality*; D003925:Diabetic Angiopathies / Q000139:chemically induced / Q000401:mortality; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D053208:Kaplan-Meier Estimate; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects*
D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D008687:Metformin