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

Pernille Kähler; Berit Grevstad; Thomas Almdal; Christian Gluud; Jørn Wetterslev; Allan Vaag; Bianca Hemmingsen

doi:10.1136/bmjopen-2014-004806

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

Pernille Kähler, Berit Grevstad, Thomas Almdal, Christian Gluud, Jørn Wetterslev, Allan Vaag, Bianca Hemmingsen

Department of Clinical Medicine

21 Citations (Scopus)

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.

Original language	English
Article number	e004806
Journal	B M J Open
Volume	4
Issue number	8
Pages (from-to)	1-21
Number of pages	21
ISSN	2044-6055
DOIs	https://doi.org/10.1136/bmjopen-2014-004806
Publication status	Published - 2014

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10.1136/bmjopen-2014-004806

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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. / Kähler, Pernille; Grevstad, Berit; Almdal, Thomas et al.

In: B M J Open, Vol. 4, No. 8, e004806, 2014, p. 1-21.

Research output: Contribution to journal › Journal article › Research › peer-review

Kähler, P, Grevstad, B, Almdal, T, Gluud, C, Wetterslev, J, Vaag, A & Hemmingsen, B 2014, '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', B M J Open, vol. 4, no. 8, e004806, pp. 1-21. https://doi.org/10.1136/bmjopen-2014-004806

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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.",

author = "Pernille K{\"a}hler and Berit Grevstad and Thomas Almdal and Christian Gluud and J{\o}rn Wetterslev and Allan Vaag and Bianca Hemmingsen",

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T1 - Targeting intensive versus conventional glycaemic control for type 1 diabetes mellitus

T2 - a systematic review with meta-analyses and trial sequential analyses of randomised clinical trials

AU - Kähler, Pernille

AU - Grevstad, Berit

AU - Almdal, Thomas

AU - Gluud, Christian

AU - Wetterslev, Jørn

AU - Vaag, Allan

AU - Hemmingsen, Bianca

N1 - 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.

PY - 2014

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N2 - 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.

AB - 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.

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DO - 10.1136/bmjopen-2014-004806

M3 - Journal article

C2 - 25138801

SN - 2044-6055

VL - 4

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EP - 21

JO - BMJ Open

JF - BMJ Open

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M1 - e004806

ER -

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

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