Intensive Glucose Control in Diabetics with an Acute Myocardial Infarction Does not Improve Mortality and Increases Risk of Hypoglycemia-A Meta-Regression Analysis

Objectives: Some early trials comparing intensive glucose control in type 2 diabetics with an acute myocardial infarction (MI) reported a decrease in mortality over a short period of follow up leading to a presumption of improved survival with intensive glucose control. Later data refuted this hypothesis. The 2009 ACC/AHA focused update on ST elevation MI gave a weak recommendation for the use of an insulin based regimen to achieve and maintain blood glucose less than 180 mg/dL. We decided to assess the validity of this recommendation. Methods: The authors searched the Pub-Med, Cochrane CENTRAL and EMBASE databases for randomized controlled trials from 1965 through 2011. Trials included were direct head-to-head comparisons of an intensive blood glucose control strategy using pharmacological means (insulin in most cases) with a less intensive regimen. The primary outcome assessed was the risk of all -cause mortality in the two groups at the end of follow up. Also assessed was the rate of hypoglycemia. The methodological quality of the studies was assessed. Event rates were compared using a forest plot of relative risk (RR; 95% confidence interval [CI]) using a random effects model (Mantel-Haenszel) assuming inter-study heterogeneity. Statistical analysis was done with Review Manager V5.1 and SYSTAT. Meta-regression was done with duration of therapy as covariate. Results: Three studies (total N = 2113) met the inclusion/exclusion criteria. Mortality was not different between the groups (RR 0.94, 95% CI of 0.66-1.34; p=0.73.). Rate of hypoglycemia was significantly higher in the intensive glucose control group (RR 13.40, 95% CI 3.69-48.61; p<0.01), with a 12% absolute risk increase and a number needed to harm (NNH) of 9 (95% CI 6.89.8)- even without achieving target glycemic control. Neither did intensive control improve CHF, arrhythmias and reinfarction rates. Meta regression revealed that mortality with intensive glycemic control was worse with increased duration of therapy (p=0.001, for trend). Conclusions: This systematic review suggests limited benefit of intensive glycemic control in type 2 diabetics with an MI, with a significant risk of serious hypoglycemia.