Association between first-line monotherapy with sulphonylurea versus metformin and risk of all-cause mortality and cardiovascular events: a retrospective, observational study.
OBJECTIVE
To evaluate the risk of all-cause mortality and major adverse cardiovascular events (MACE) for patients exposed to first-line monotherapy with sulphonylurea or metformin.


METHODS
Data were from the Clinical Practice Research Datalink (CPRD). Patients with type 2 diabetes were selected if initiated with metformin or sulphonylurea monotherapy as their first-line glucose-lowering regimen 2000-2012. The primary endpoint was all-cause mortality; the secondary endpoint was MACE (myocardial infarction or stroke). Times to endpoints were compared using Cox proportional hazards models. Additional analyses were performed on subsets matched directly on key characteristics and by propensity score.


RESULTS
In the main analysis, 76 811 patients were prescribed metformin monotherapy (mean follow-up 2.9 years) and 15 687 sulphonylurea monotherapy (mean follow-up 3.1 years). A total of 2604 patients were included in each arm of the directly matched cohorts and 8836 in the propensity-matched. With respect to all-cause mortality, using all three analytical approaches the hazard ratio (HR) was significantly increased for sulphonylurea compared with metformin: adjusted HR = 1.580 (95% CI 1.483-1.684) for the main analysis, 1.902 (1.733-2.088) for those matched on propensity score, and 1.272 (1.021-1.584) for the directly matched cohort analysis. For MACE, the respective HRs were 1.196 (1.090-1.313), 1.202 (1.001-1.442) and 0.814 (0.578-1.148), respectively.


CONCLUSIONS
All-cause mortality was significantly increased in patients prescribed sulphonylurea compared with metformin monotherapy. Whilst residual confounding and confounding by indication may remain, this study indicates that first-line treatment with sulphonylurea monotherapy should be reconsidered.
Global Epidemiology, Pharmatelligence, Cardiff, UK.
C Ll
CL
Morgan
J
J
Mukherjee
S
S
Jenkins-Jones
S E
SE
Holden
C J
CJ
Currie
D000075202:Contraindications; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000401:mortality / Q000517:prevention & control; D018579:Patient Selection; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D020521:Stroke / Q000139:chemically induced* / Q000401:mortality / Q000517:prevention & control; D013453:Sulfonylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D006113:United Kingdom / Q000453:epidemiology
D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D008687:Metformin
MACE; first-line therapy; metformin; mortality; myocardial infarction; stroke; sulphonylurea