TY - JOUR
T1 - Estimation of individual beneficial and adverse effects of intensive glucose control for patients with type 2 diabetes
AU - van der Leeuw, Joep
AU - Visseren, Frank L.J.
AU - Woodward, Mark
AU - van der Graaf, Yolanda
AU - Grobbee, Diederick E.
AU - Harrap, Stephen
AU - Heller, Simon
AU - Mancia, Giuseppe
AU - Marre, Michel
AU - Poulter, Neil
AU - Zoungas, Sophia
AU - Chalmers, John
N1 - Funding Information:
The ADVANCE trial was funded by grants from the National Health and Medical Research Council of Australia and Servier International.
Publisher Copyright:
© 2016, The Author(s).
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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] <100) and 1% had a small ARR (<0.5%, NNTB5 >200). Similarly, 36% of patients had a substantial estimated ARI for severe hypoglycaemia (5 year number-needed-to-harm [NNTH5] <100) and 29% had a small ARI (NNTH5 >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
AB - 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] <100) and 1% had a small ARR (<0.5%, NNTB5 >200). Similarly, 36% of patients had a substantial estimated ARI for severe hypoglycaemia (5 year number-needed-to-harm [NNTH5] <100) and 29% had a small ARI (NNTH5 >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
KW - Glycaemic target
KW - Hypoglycaemia
KW - Net benefit
KW - Personalised medicine
KW - Type 2 diabetes
KW - Vascular complications
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U2 - 10.1007/s00125-016-4082-5
DO - 10.1007/s00125-016-4082-5
M3 - Article
C2 - 27586250
AN - SCOPUS:84984856925
VL - 59
SP - 2603
EP - 2612
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 12
ER -