Mortality in type 2 diabetic subjects prescribed metformin and sulphonylurea drugs in combination: cohort study.
BACKGROUND
In the UK Prospective Diabetes Study, treatment with sulphonylurea and metformin in combination was associated with increased mortality. We compared mortality in subjects treated either with metformin or sulphonylurea drugs alone, or in combination.


METHODS
Cohort study in 263 general practices in the United Kingdom. Subjects were aged >/=30 years. Outcome was survival from first prescription of oral hypoglycaemic drugs till death from any cause. Transfer to metformin and sulphonylurea in combination was modelled as a time-dependent covariate. Hazard ratios were adjusted for age, sex, year of treatment, presence of coronary heart disease or prescription of cardiovascular drugs. Analyses were also stratified by propensity score.


RESULTS
There were 8488 subjects who were initially prescribed sulphonylureas with a total of 20 783 person years of follow-up and 1157 deaths. The crude mortality rate was 58.56 per 1000 person years during suphonlyurea as sole treatment. In 1868 subjects who were prescribed additional metformin, the mortality rate was 39.75 per 1000. The adjusted hazard ratio was 1.06 (95% confidence interval 0.85 to 1.31, P = 0.616). There were 3099 subjects initially treated with metformin with a total of 7306 person years of follow-up and 176 deaths. During metformin-only treatment, the mortality rate was 25.48 per 1000. After addition of sulphonylurea in 867 subjects, mortality was 19.35 per 1000. The adjusted hazard ratio was 0.95 (0.64 to 1.40, P = 0.801).


CONCLUSIONS
In this large non-randomized study, there was no evidence of increased mortality risk following prescription of sulphonylurea and metformin in combination, as compared to either drug prescribed singly.
Gulliford
Martin
M
Department of Public Health Sciences, King's College London, London, UK. martin.gulliford@kcl.ac.uk
Latinovic
Radoslav
R
D000328:Adult; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000401:mortality*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D016016:Proportional Hazards Models; D013453:Sulfonylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects
D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D008687:Metformin