REVIEW Effect of Tight Blood Glucose Control Versus Conventional Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review with Meta-Analysis of Randomized Controlled Trials Anna Maria Buehler, 1,2 Alexandre Biasi Cavalcanti, 1 Otavio Berwanger, 1 Mabel Figueiro, 1 L´ ıgia Nasi Laranjeira, 1 Ana Denise Zazula, 1 Bruno Kioshi, 1 Diogo G. Bugano, 1 Eliana Santucci, 1 Grazielle Sbruzzi, 1 Helio Penna Guimaraes, 1 Vitor Oliveira Carvalho 1 & Silvana Auxiliadora Bordin 1 1 Instituto de Ensino e Pesquisa do Hospital do Corac ¸˜ ao (IEP-HCor), S ˜ ao Paulo, Brazil 2 Instituto de Ci ˆ encias Biom ´ edicas da Universidade de S ˜ ao Paulo (ICB I–USP), S ˜ ao Paulo, Brazil Keywords Cardiovascular diseases; Glycemic control; Meta-analysis; Systematic review; Type 2 diabetes mellitus. Correspondence Anna Maria Buehler, R. Ab´ ılio Soares, 250 12 ◦ andar, Para´ ıso, S ˜ ao Paulo, CEP: 04005-000, Brazil. Tel.: 55-11-3053-66-11 Ext 8209; Fax: 55-11-3886-96-45; E-mail: abuehler@hcor.com.br SUMMARY Tight control of blood glucose reduces cardiovascular events and total mortality is conflict- ing. To summarize clinical effects of tight versus conventional glucose control in patients with type 2 diabetes. We systematically searched MEDLINE, EMBASE, Cochrane Library, and ISI Web of Knowledge with no limits of language and time. Further trials were searched from the reference lists of identified studies. We included randomized controlled comparing different levels of blood glucose control intensity in type 2 diabetic patients. Two inde- pendent reviewers extracted data of eligible studies using standard case report forms. We investigated total mortality, cardiovascular and microvascular events, and hypoglycemia in patients with type 2 diabetes. We used random-effects models to obtain relative risks (RR) with 95% confidence intervals (CI). We included 6 trials involving 27,654 patients. There was no significant effect of tight blood glucose control on all-cause mortality (RR 1.03; 95% CI 0.90–1.17) or cardiovascular mortality (RR 1.04; 95% CI 0.83–1.29). Tight glucose control reduced the risk for nonfatal MI (RR 0.85; 95% CI 0.76–0.95), although had no effect on the incidence of nonfatal stroke (RR 1.02; 95% CI 0.88–1.17). For microvascular events, tight glucose control reduced the risk progression of retinopathy (RR 0.80; 95% CI 0.71–0.91), incidence of peripheral neuropathy (RR 0.94; 95% CI 0.89–0.99), and progres- sion of nephropathy (RR 0.55; 95% CI 0.37–0.80), but had not significant effect on the incidence of nephropathy (RR 0.69; 95% CI 0.42–1.14). The risk of severe hypoglycemia increased with tight glucose control (RR 2.39; 95% CI 1.79–3.18). Tight blood glucose con- trol reduces the risk for some macrovascular and microvascular events, without effect on all-cause mortality and cardiovascular mortality. Tight glucose control increases the risk of severe hypoglycemia. Background Type 2 diabetes mellitus is a metabolic disorder characterized by high blood glucose levels as a consequence of insulin resistance and its relative deficiency. It is well known that this metabolic dys- function contributes to atherosclerosis process and endothelium- dependent vasodilation impairment [1,2]. Both macro- and microvascular complications are important causes of morbidity and mortality worldwide [3–7]. Tight blood glucose control has been recommended as a therapeutic strat- egy to decrease the incidence of vascular complications [8]. Ev- idence from randomized controlled trials (RCTs) supports the adoption of tight glucose control for reducing microvascular complications [5,9]. However, evidences regarding cardiovascu- lar events are conflicting [10,11]. Thus, a systematic review is required to summarize and critically appraise the available evidence. This systematic review with meta-analysis of RCTs aimed to ex- amine the effects of tight versus conventional glucose control in total mortality, cardiovascular and microvascular events, and hy- poglycemia in patients with type 2 diabetes. Methods Criteria for Considering Studies for this Review Types of Studies This meta-analysis included all RCTs that studied the ef- fects of tight versus conventional glucose control in total and doi: 10.1111/j.1755-5922.2011.00308.x ª 2011 Blackwell Publishing Ltd Cardiovascular Therapeutics 31 (2013) 147–160 147