TY - JOUR
AU - Zoungas S.
AU - Woodward Mark
AU - Visseren F.
AU - Poulter N.
AU - Grobbee D.
AU - Mancia G.
AU - Harrap S.
AU - Heller S.
AU - Marre M.
AU - van der Leeuw J.
AU - van der Graaf Y.
AU - Chalmers J.
AB - <p>
AIMS/HYPOTHESIS: Intensive glucose control reduces the risk of vascular complications while increasing the risk of severe hypoglycaemia at a group level. We sought to estimate individual beneficial and adverse effects of intensive glucose control in patients with type 2 diabetes. METHODS: We performed a post hoc analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, a randomised controlled trial evaluating standard vs intensive glucose control (HbA1c target <!--=6.5% [48 mmol/mol]). In 11,140 participants, we estimated the individual 5 year absolute risk reduction (ARR) for the composite outcome of major micro- and macrovascular events and absolute risk increase (ARI) for severe hypoglycaemia for intensive vs standard glucose control. Predictions were based on competing risks models including clinical characteristics and randomised treatment. RESULTS: Based on these models, 76% of patients had a substantial estimated 5 year ARR for major vascular events (-->1%, 5 year number-needed-to-benefit [NNTB5] &lt;100) and 1% had a small ARR (&lt;0.5%, NNTB5 &gt;200). Similarly, 36% of patients had a substantial estimated ARI for severe hypoglycaemia (5 year number-needed-to-harm [NNTH5] &lt;100) and 29% had a small ARI (NNTH5 &gt;200). When assigning similar or half the weight to severe hypoglycaemia compared with a major vascular event, net benefit was positive in 85% or 99% of patients, respectively. Limiting intensive treatment to the 85% patient subgroup had no significant effect on the overall incidence of major vascular events and severe hypoglycaemia compared with treating all patients. CONCLUSIONS/INTERPRETATION: Taking account of the effects of intensive glucose control on major micro- and macrovascular events and severe hypoglycaemia for individual patients, the estimated net benefit was positive in the majority of the participants in the ADVANCE trial. The estimated individual effects can inform treatment decisions once individual weights assigned to positive and adverse effects have been specified. TRIAL REGISTRATION: ClinicalTrials.gov NCT00145925.
</p>

AD - Department of Vascular Medicine, University Medical Centre Utrecht, PO Box 85500, 3508 GA, Utrecht, the Netherlands.<br/>Department of Vascular Medicine, University Medical Centre Utrecht, PO Box 85500, 3508 GA, Utrecht, the Netherlands. f.l.j.visseren@umcutrecht.nl.<br/>The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia.<br/>The George Institute for Global Health, Nuffield Department of Population Health, University of Oxford, Oxford, UK.<br/>Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, the Netherlands.<br/>The Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia.<br/>University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.<br/>Istituto Auxologico Italiano, University of Milano-Bicocca, Milan, Italy.<br/>Hopital Bichat-Claude Bernard and Universite Paris 7, Paris, France.<br/>International Centre for Circulatory Health, Imperial College, London, UK.
AN - 27586250
BT - Diabetologia
CN - [IF]: 6.671
DP - NLM
ET - 2016/09/03
LA - Eng
LB - AUS<br/>PROF<br/>CDV<br/>FY17
N1 - van der Leeuw, Joep<br/>Visseren, Frank L J<br/>Woodward, Mark<br/>van der Graaf, Yolanda<br/>Grobbee, Diederick E<br/>Harrap, Stephen<br/>Heller, Simon<br/>Mancia, Giuseppe<br/>Marre, Michel<br/>Poulter, Neil<br/>Zoungas, Sophia<br/>Chalmers, John<br/>Diabetologia. 2016 Sep 1.
N2 - <p>
AIMS/HYPOTHESIS: Intensive glucose control reduces the risk of vascular complications while increasing the risk of severe hypoglycaemia at a group level. We sought to estimate individual beneficial and adverse effects of intensive glucose control in patients with type 2 diabetes. METHODS: We performed a post hoc analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, a randomised controlled trial evaluating standard vs intensive glucose control (HbA1c target <!--=6.5% [48 mmol/mol]). In 11,140 participants, we estimated the individual 5 year absolute risk reduction (ARR) for the composite outcome of major micro- and macrovascular events and absolute risk increase (ARI) for severe hypoglycaemia for intensive vs standard glucose control. Predictions were based on competing risks models including clinical characteristics and randomised treatment. RESULTS: Based on these models, 76% of patients had a substantial estimated 5 year ARR for major vascular events (-->1%, 5 year number-needed-to-benefit [NNTB5] &lt;100) and 1% had a small ARR (&lt;0.5%, NNTB5 &gt;200). Similarly, 36% of patients had a substantial estimated ARI for severe hypoglycaemia (5 year number-needed-to-harm [NNTH5] &lt;100) and 29% had a small ARI (NNTH5 &gt;200). When assigning similar or half the weight to severe hypoglycaemia compared with a major vascular event, net benefit was positive in 85% or 99% of patients, respectively. Limiting intensive treatment to the 85% patient subgroup had no significant effect on the overall incidence of major vascular events and severe hypoglycaemia compared with treating all patients. CONCLUSIONS/INTERPRETATION: Taking account of the effects of intensive glucose control on major micro- and macrovascular events and severe hypoglycaemia for individual patients, the estimated net benefit was positive in the majority of the participants in the ADVANCE trial. The estimated individual effects can inform treatment decisions once individual weights assigned to positive and adverse effects have been specified. TRIAL REGISTRATION: ClinicalTrials.gov NCT00145925.
</p>

PY - 2016
SN - 1432-0428 (Electronic)<br/>0012-186X (Linking)
T2 - Diabetologia
TI - Estimation of individual beneficial and adverse effects of intensive glucose control for patients with type 2 diabetes
Y2 - FY17
ER -