Randomized Trial of the Effects of Insulin and Metformin on Myocardial Injury and Stress in Diabetes Mellitus: A Post Hoc Exploratory Analysis

Background Subclinical myocardial injury, as measured by high‐sensitivity cardiac troponin T (hsTnT), and myocardial stress, as measured by N‐terminal pro‐B‐type natriuretic peptide ( NT ‐pro BNP ), are related to glycemic control in patients with type 2 diabetes mellitus, and are strong predictors of adverse cardiovascular outcomes. We sought to determine whether antihyperglycemic therapy improves measures of myocardial injury and myocardial stress in patients with type 2 diabetes mellitus. Methods and Results We randomized, in a 2×2 factorial fashion, 438 patients with type 2 diabetes mellitus to insulin glargine, metformin, the combination, or placebo and measured changes in NT ‐pro BNP and hsTnT after 12 weeks of therapy. At baseline, the median (Q1–Q3) plasma concentration was 35.4 (15.7–86.3) ng/L for NT ‐pro BNP and 6.7 (4.6–10.1) ng/L for hsTnT. The adjusted (95% confidence interval) change in NT ‐pro BNP concentration was 20.7% (7.9–35.0) in the insulin arm compared with 0.13% (−10.8 to 12.5) in the no‐insulin arm ( P =0.03 for comparison). These changes were not related to changes in fasting or postprandial glucose, glycated hemoglobin, weight, blood pressure, or inflammation. In the metformin arm, the adjusted change in NT ‐pro BNP was 7.8% (−3.7 to 20.7) compared with 13.0% (0.72–26.8) in the no‐metformin arm ( P =0.58). No significant changes in hsTnT concentrations were observed for any of the treatment arms. Conclusions Insulin glargine was associated with a significant 20.7% increase in NT ‐pro BNP , a marker of myocardial stress, after 12 weeks of therapy. No change in hsTnT, a marker of myocardial injury, was observed. The changes were independent of substantial improvements in glucose control. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00366301.