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Targeting intensive versus conventional glycaemic control for type 1 diabetes mellitus: a systematic review with meta-analyses and trial sequential analyses of randomised clinical trials
  1. Pernille Kähler1,
  2. Berit Grevstad1,
  3. Thomas Almdal2,
  4. Christian Gluud1,3,
  5. Jørn Wetterslev1,
  6. Allan Vaag4,
  7. Bianca Hemmingsen1
  1. 1Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  2. 2Department of Medicine F, Gentofte Hospital, Gentofte, Denmark
  3. 3Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  4. 4Department of Endocrinology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  1. Correspondence to Pernille Kähler; pernille_kahler{at}yahoo.dk

Abstract

Objective To assess the benefits and harms of targeting intensive versus conventional glycaemic control in patients with type 1 diabetes mellitus.

Design A systematic review with meta-analyses and trial sequential analyses of randomised clinical trials.

Data sources The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded and LILACS to January 2013.

Study selection Randomised clinical trials that prespecified different targets of glycaemic control in participants at any age with type 1 diabetes mellitus were included.

Data extraction Two authors independently assessed studies for inclusion and extracted data.

Results 18 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.

Conclusions There 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.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

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