Mortality Rates in Trials of Subjects With Type 2 Diabetes

BACKGROUND: In randomized controlled trials (RCTs) of subjects with type 2 diabetes mellitus, mortality rates vary substantially. We sought to examine the inclusion and exclusion criteria of these RCTs to explore relationships with mortality. METHODS AND RESULTS: MEDLINE database was searched from August 1980 through March 2011. Selection criterion included published RCTs of adults with type 2 diabetes mellitus of at least 1000 patients, reporting all-cause mortality and having follow-up duration of at least 1 year. Twenty-two trials were eligible. Annualized mortality rates were derived. Inclusion and exclusion criteria were tabulated for each trial. Trials were categorized in 4 groups according to annual mortality rates: <1, ≥1 to <2, ≥2 to <4, and ≥4 per 100 patient-years. The analysis cohort included 91842 patients and 6837 deaths. Mortality rates ranged from 0.28 to 8.24 per 100 patient-years. Patients enrolled in the highest mortality category were more likely to be older and had longer diabetes duration and higher blood pressure. The selection for hypertension was common in the low- as well as high-mortality trials. Although the mortality rates were higher in RCTs with prior cardiovascular morbidity, the selection for chronic kidney disease—defined by either higher serum creatinine or lower estimated glomerular filtration rate and/or the presence of proteinuria—was associated with the highest mortality rates. CONCLUSIONS: In this analysis of RCTs of type 2 diabetes mellitus, a 29-fold difference in annualized mortality was observed. In these RCTs, selection for renal disease, defined by either decline in renal function or presence of proteinuria, portends important mortality risk. (J Am Heart Assoc. 2012;1:8-15.) CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00303979