• Pernille Kähler, Berit Grevstad, Thomas Almdal, Christian Gluud, Jørn Wetterslev, Søren Søgaard Lund, Allan Vaag, and Bianca Hemmingsen.
• Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
• BMJ Open. 2014 Jan 1;4(8):e004806.

ObjectiveTo assess the benefits and harms of targeting intensive versus conventional glycaemic control in patients with type 1 diabetes mellitus.DesignA systematic review with meta-analyses and trial sequential analyses of randomised clinical trials.Data SourcesThe Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded and LILACS to January 2013.Study SelectionRandomised clinical trials that prespecified different targets of glycaemic control in participants at any age with type 1 diabetes mellitus were included.Data ExtractionTwo authors independently assessed studies for inclusion and extracted data.Results18 randomised clinical trials included 2254 participants with type 1 diabetes mellitus. All trials had high risk of bias. There was no statistically significant effect of targeting intensive glycaemic control on all-cause mortality (risk ratio 1.16, 95% CI 0.65 to 2.08) or cardiovascular mortality (0.49, 0.19 to 1.24). Targeting intensive glycaemic control reduced the relative risks for the composite macrovascular outcome (0.63, 0.41 to 0.96; p=0.03), and nephropathy (0.37, 0.27 to 0.50; p<0.00001. The effect estimates of retinopathy, ketoacidosis and retinal photocoagulation were not consistently statistically significant between random and fixed effects models. The risk of severe hypoglycaemia was significantly increased with intensive glycaemic targets (1.40, 1.01 to 1.94). Trial sequential analyses showed that the amount of data needed to demonstrate a relative risk reduction of 10% were, in general, inadequate.ConclusionsThere was no significant effect towards improved all-cause mortality when targeting intensive glycaemic control compared with conventional glycaemic control. However, there may be beneficial effects of targeting intensive glycaemic control on the composite macrovascular outcome and on nephropathy, and detrimental effects on severe hypoglycaemia. Notably, the data for retinopathy and ketoacidosis were inconsistent. There was a severe lack of reporting on patient relevant outcomes, and all trials had poor bias control.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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