Abstract
Objective: We assessed the hypothesis that metformin use significantly decreases risk of all-cause and heart disease (HD) mortality in patients with diabetes mellitus (DM). Methods: Subjects with DM aged ≥30 (n=3612) participating in 1999 -2010 National Health and Nutrition Examination Surveys, who had anti-DM drug therapy information, and were followed up by December 2011 were analyzed. Baseline DM, coronary heart disease (CHD) and heart failure (HF) were defined as a physician-diagnosis of the disease(s). Death from HD was classified using ICD10:I20-I25). Results: Mean (SD) age of 3612 participants was 63.1 (13.02), 83.4% (3056/3612) were under anti-DM therapies, and 20.3% was in metformin monotherapy, 4.9% in metformin combination (MCO), 24.8% in insulin, 45.4% in thiazolidinedione, sulfonylurea, and combinations, and 4.7% in any other antidiabetic drugs therapies. Baseline CHD and HF rates were 11.38% and 9.13%. At the end of follow-up, 1024 died from all-cause (21.86%), and 222 died from HD. Multivariate Cox’s proportional hazard regression analysis indicated that diabetic patients with comorbid HD (CHD and/or HF) had significant higher all-cause mortality than those without. However, these excess mortalities were significantly reduced in patients with metformin therapies than their counterparts without metformin. The hazard ratios (HR, 95%CI) of metformin use versus those without for all-cause mortality was 0.53 (0.38-0.76, p=0.001). Diabetic patients with CHD and with metformin therapies had a significantly lower 10-year all-cause mortality than those without metformin (33% vs. 64%, p<0.001). Similarly, diabetic patients with HF and with metformin therapies had a significantly lower 10-year all-cause mortality than their counterparts (42.8% vs. 73.1%, p<0.001). The effects of metformin on all-cause mortality were positively modified after adjusting dyslipidemia and insulin resistance. In conclusion , metformin significantly increased survival rates from all-cause mortality in diabetic patients with comorbid CHD and/or HF. The mortality risk reduction may be partially explained by an effect of metformin on a reduction of dyslipidemia and insulin resistance.
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