Combination therapy with sulfonylureas and metformin and the prevention of death in type 2 diabetes: a nested case-control study.
OBJECTIVE
To determine whether combination of sulfonylureas and metformin increases the risk of death from any cause in patients with type 2 diabetes.


METHODS
A nested case-control study was conducted within a population-based cohort from the UK General Practice Research Database (GPRD). The cohort included patients over the age of 40 who were prescribed a first oral hypoglycaemic agent between 1 January 1988 and 30 June 2008. Cases included all patients who deceased during follow-up. Up to 10 controls were matched to each case on year of birth, date of cohort entry (+/-1 year) and duration of follow-up. Conditional logistic regression was used to estimate rate ratios (RRs) of death from any cause associated with the use of combination of sulfonylureas and metformin, relative to sulfonylurea monotherapy.


RESULTS
The cohort comprised 84 231 users of oral hypoglycaemic agents, of whom 14 996 died from any cause during a mean of 4.3 years of follow-up (mortality rate 4.1 per 100 per year). Patients currently exposed to a combination of sulfonylureas and metformin were at a decreased risk of death from any cause compared to patients exposed to sulfonylurea monotherapy (adjusted RR: 0.77, 95%CI: 0.70, 0.85). Similar results were obtained for patients currently exposed to metformin monotherapy (adjusted RR: 0.70, 95%CI: 0.64, 0.75) when compared to sulfonylurea monotherapy. Patients had to be exposed to the combination therapy for at least 4 months prior to index date to experience a lower risk of mortality compared to sulfonylurea monotherapy.


CONCLUSIONS
The combination of sulfonylureas and metformin does not increase the risk of death. In contrast, it may moderately reduce this risk compared to sulfonylurea monotherapy.
Azoulay
Laurent
L
Division of Clinical Epidemiology, SMBD-Jewish General Hospital, Montreal, Quebec, Canada.
Schneider-Lindner
Verena
V
Dell'aniello
Sophie
S
Schiffrin
Alicia
A
Suissa
Samy
S
D016022:Case-Control Studies; D015331:Cohort Studies; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000401:mortality*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D012306:Risk; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology
D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D008687:Metformin