Effect of Metformin-Containing Antidiabetic Regimens on All-cause Mortality in Veterans With Type 2 Diabetes Mellitus

• Published in: The American journal of the medical sciences 2008-09, Vol.336 (3), p.241-247
• Main Authors: Mangold, Therese A., Rawls, William N., Wall, Barry M., Gosmanova, Elvira O., Canada, Robert B.
• Format: Article
• Language: English
• Subjects: African Americans - statistics & numerical data; Age Factors; Aged; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Biological and medical sciences; Cause of Death; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - mortality; Drug Therapy, Combination; Epidemiology; European Continental Ancestry Group - statistics & numerical data; Female; General aspects; Glomerular Filtration Rate; Glycated Hemoglobin A - analysis; Humans; Hypoglycemic Agents - therapeutic use; Insulin - therapeutic use; Kaplan-Meier Estimate; Male; Medical sciences; Metformin; Metformin - therapeutic use; Middle Aged; Mortality; Proportional Hazards Models; Public health. Hygiene; Public health. Hygiene-occupational medicine; Sulfonylurea; Sulfonylurea Compounds - therapeutic use; Tennessee; Type 2 diabetes mellitus; United States; Veterans - statistics & numerical data
• ISSN: 0002-9629; 1538-2990
• DOI: 10.1097/MAJ.0b013e31816250e6

There are conflicting reports concerning metformin use and mortality rates in patients with type 2 diabetes (T2DM). The aim of this study was to examine the relationship between metformin use and all-cause mortality in veterans with T2DM. An observational cohort study involving 2206 patients with T2DM was performed using computerized database from the Veterans Affairs Medical Center, Memphis, TN. All-cause mortality was compared among cohorts of metformin and nonmetformin users. Univariate and multivariate Cox regression models were used to estimate hazard ratios (HR) for all-cause mortality after adjusting for age, race, baseline estimated glomerular filtration rate, glycosylated hemoglobin, use of insulin, use of ACE inhibitors or angiotensin II receptor blockers or statins. The average length of follow-up in metformin and nonmetformin users was 62 ± 17 and 61 ± 18months, respectively. The mean age was 63 ± 11 years. Crude mortality rates were similar in both groups: 266 (22%) metformin users and 253 (25.3%) nonmetformin users died. There was a trend for improved survival with metformin use (unadjusted HR 0.85, P=0.07). After multivariate adjustment, metformin users had significantly decreased HR for time to all-cause mortality compared with nonmetformin users (adjusted HR 0.77, P < 0.01). Insulin use was an independent predictor of worsened survival in both univariate and multivariate analyses. In subgroup analysis of patients exposed to insulin, all-cause mortality remained decreased in metformin users (adjusted HR 0.62, P < 0.04). Treatment of T2DM with regimens containing metformin alone or in combination with other hypoglycemic agents was associated with reduced all-cause mortality compared with regimens without metformin.