Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomised controlled trials

Intensive glucose control is understood to prevent complications in adults with type 2 diabetes. We aimed to more precisely estimate the effects of more intensive glucose control, compared with less intensive glucose control, on the risk of microvascular events. In this meta-analysis, we obtained de...

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Published in:	The lancet. Diabetes & endocrinology Vol. 5; no. 6; p. 431
Main Authors:	Zoungas, Sophia, Arima, Hisatomi, Gerstein, Hertzel C, Holman, Rury R, Woodward, Mark, Reaven, Peter, Hayward, Rodney A, Craven, Timothy, Coleman, Ruth L, Chalmers, John
Format:	Journal Article
Language:	English
Published:	England 01.06.2017
Subjects:	Blood Glucose - drug effects Diabetes Complications - epidemiology Diabetes Complications - pathology Diabetes Complications - prevention & control Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - pathology Diabetic Nephropathies - prevention & control Eye Diseases - etiology Eye Diseases - prevention & control Female Glomerular Filtration Rate - drug effects Humans Hypoglycemic Agents - therapeutic use Male Middle Aged Models, Theoretical Proportional Hazards Models Randomized Controlled Trials as Topic Risk Assessment
ISSN:	2213-8595, 2213-8595
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Abstract	Intensive glucose control is understood to prevent complications in adults with type 2 diabetes. We aimed to more precisely estimate the effects of more intensive glucose control, compared with less intensive glucose control, on the risk of microvascular events. In this meta-analysis, we obtained de-identified individual participant data from large-scale randomised controlled trials assessing the effects of more intensive glucose control versus less intensive glucose control in adults with type 2 diabetes, with at least 1000 patient-years of follow-up in each treatment group and a minimum of 2 years average follow-up on randomised treatment. The prespecified and standardised primary outcomes were kidney events (a composite of end-stage kidney disease, renal death, development of an estimated glomerular filtration rate <30 mL/min per 1·73m , or development of overt diabetic nephropathy), eye events (a composite of requirement for retinal photocoagulation therapy or vitrectomy, development of proliferative retinopathy, or progression of diabetic retinopathy), and nerve events (a composite of new loss of vibratory sensation, ankle reflexes, or light touch). We used a random-effects model to calculate overall estimates of effect. We included four trials (ACCORD, ADVANCE, UKPDS, and VADT) with 27 049 participants. 1626 kidney events, 795 eye events, and 7598 nerve events were recorded during the follow-up period (median 5·0 years, IQR 4·5-5·0). Compared with less intensive glucose control, more intensive glucose control resulted in an absolute difference of -0·90% (95% CI -1·22 to -0·58) in mean HbA at completion of follow-up. The relative risk was reduced by 20% for kidney events (hazard ratio 0·80, 95% CI 0·72 to 0·88; p<0·0001) and by 13% for eye events (0·87, 0·76 to 1·00; p=0·04), but was not reduced for nerve events (0·98, 0·87 to 1·09; p=0·68). More intensive glucose control over 5 years reduced both kidney and eye events. Glucose lowering remains important for the prevention of long-term microvascular complications in adults with type 2 diabetes. None.
AbstractList	Intensive glucose control is understood to prevent complications in adults with type 2 diabetes. We aimed to more precisely estimate the effects of more intensive glucose control, compared with less intensive glucose control, on the risk of microvascular events.BACKGROUNDIntensive glucose control is understood to prevent complications in adults with type 2 diabetes. We aimed to more precisely estimate the effects of more intensive glucose control, compared with less intensive glucose control, on the risk of microvascular events.In this meta-analysis, we obtained de-identified individual participant data from large-scale randomised controlled trials assessing the effects of more intensive glucose control versus less intensive glucose control in adults with type 2 diabetes, with at least 1000 patient-years of follow-up in each treatment group and a minimum of 2 years average follow-up on randomised treatment. The prespecified and standardised primary outcomes were kidney events (a composite of end-stage kidney disease, renal death, development of an estimated glomerular filtration rate <30 mL/min per 1·73m2, or development of overt diabetic nephropathy), eye events (a composite of requirement for retinal photocoagulation therapy or vitrectomy, development of proliferative retinopathy, or progression of diabetic retinopathy), and nerve events (a composite of new loss of vibratory sensation, ankle reflexes, or light touch). We used a random-effects model to calculate overall estimates of effect.METHODSIn this meta-analysis, we obtained de-identified individual participant data from large-scale randomised controlled trials assessing the effects of more intensive glucose control versus less intensive glucose control in adults with type 2 diabetes, with at least 1000 patient-years of follow-up in each treatment group and a minimum of 2 years average follow-up on randomised treatment. The prespecified and standardised primary outcomes were kidney events (a composite of end-stage kidney disease, renal death, development of an estimated glomerular filtration rate <30 mL/min per 1·73m2, or development of overt diabetic nephropathy), eye events (a composite of requirement for retinal photocoagulation therapy or vitrectomy, development of proliferative retinopathy, or progression of diabetic retinopathy), and nerve events (a composite of new loss of vibratory sensation, ankle reflexes, or light touch). We used a random-effects model to calculate overall estimates of effect.We included four trials (ACCORD, ADVANCE, UKPDS, and VADT) with 27 049 participants. 1626 kidney events, 795 eye events, and 7598 nerve events were recorded during the follow-up period (median 5·0 years, IQR 4·5-5·0). Compared with less intensive glucose control, more intensive glucose control resulted in an absolute difference of -0·90% (95% CI -1·22 to -0·58) in mean HbA1c at completion of follow-up. The relative risk was reduced by 20% for kidney events (hazard ratio 0·80, 95% CI 0·72 to 0·88; p<0·0001) and by 13% for eye events (0·87, 0·76 to 1·00; p=0·04), but was not reduced for nerve events (0·98, 0·87 to 1·09; p=0·68).FINDINGSWe included four trials (ACCORD, ADVANCE, UKPDS, and VADT) with 27 049 participants. 1626 kidney events, 795 eye events, and 7598 nerve events were recorded during the follow-up period (median 5·0 years, IQR 4·5-5·0). Compared with less intensive glucose control, more intensive glucose control resulted in an absolute difference of -0·90% (95% CI -1·22 to -0·58) in mean HbA1c at completion of follow-up. The relative risk was reduced by 20% for kidney events (hazard ratio 0·80, 95% CI 0·72 to 0·88; p<0·0001) and by 13% for eye events (0·87, 0·76 to 1·00; p=0·04), but was not reduced for nerve events (0·98, 0·87 to 1·09; p=0·68).More intensive glucose control over 5 years reduced both kidney and eye events. Glucose lowering remains important for the prevention of long-term microvascular complications in adults with type 2 diabetes.INTERPRETATIONMore intensive glucose control over 5 years reduced both kidney and eye events. Glucose lowering remains important for the prevention of long-term microvascular complications in adults with type 2 diabetes.None.FUNDINGNone. Intensive glucose control is understood to prevent complications in adults with type 2 diabetes. We aimed to more precisely estimate the effects of more intensive glucose control, compared with less intensive glucose control, on the risk of microvascular events. In this meta-analysis, we obtained de-identified individual participant data from large-scale randomised controlled trials assessing the effects of more intensive glucose control versus less intensive glucose control in adults with type 2 diabetes, with at least 1000 patient-years of follow-up in each treatment group and a minimum of 2 years average follow-up on randomised treatment. The prespecified and standardised primary outcomes were kidney events (a composite of end-stage kidney disease, renal death, development of an estimated glomerular filtration rate <30 mL/min per 1·73m , or development of overt diabetic nephropathy), eye events (a composite of requirement for retinal photocoagulation therapy or vitrectomy, development of proliferative retinopathy, or progression of diabetic retinopathy), and nerve events (a composite of new loss of vibratory sensation, ankle reflexes, or light touch). We used a random-effects model to calculate overall estimates of effect. We included four trials (ACCORD, ADVANCE, UKPDS, and VADT) with 27 049 participants. 1626 kidney events, 795 eye events, and 7598 nerve events were recorded during the follow-up period (median 5·0 years, IQR 4·5-5·0). Compared with less intensive glucose control, more intensive glucose control resulted in an absolute difference of -0·90% (95% CI -1·22 to -0·58) in mean HbA at completion of follow-up. The relative risk was reduced by 20% for kidney events (hazard ratio 0·80, 95% CI 0·72 to 0·88; p<0·0001) and by 13% for eye events (0·87, 0·76 to 1·00; p=0·04), but was not reduced for nerve events (0·98, 0·87 to 1·09; p=0·68). More intensive glucose control over 5 years reduced both kidney and eye events. Glucose lowering remains important for the prevention of long-term microvascular complications in adults with type 2 diabetes. None.
Author	Gerstein, Hertzel C Reaven, Peter Zoungas, Sophia Coleman, Ruth L Woodward, Mark Hayward, Rodney A Holman, Rury R Arima, Hisatomi Craven, Timothy Chalmers, John
Author_xml	– sequence: 1 givenname: Sophia surname: Zoungas fullname: Zoungas, Sophia email: szoungas@georgeinstitute.org.au organization: The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia. Electronic address: szoungas@georgeinstitute.org.au – sequence: 2 givenname: Hisatomi surname: Arima fullname: Arima, Hisatomi organization: The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia; Department of Preventive Medicine and Public Health, Fukuoka University, Fukuoka, Japan – sequence: 3 givenname: Hertzel C surname: Gerstein fullname: Gerstein, Hertzel C organization: Department of Medicine and Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada – sequence: 4 givenname: Rury R surname: Holman fullname: Holman, Rury R organization: Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK – sequence: 5 givenname: Mark surname: Woodward fullname: Woodward, Mark organization: The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia; The George Institute for Global Health, University of Oxford, Oxford, UK; Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA – sequence: 6 givenname: Peter surname: Reaven fullname: Reaven, Peter organization: Phoenix VA Health Care System, Phoenix, AZ, USA – sequence: 7 givenname: Rodney A surname: Hayward fullname: Hayward, Rodney A organization: Ann Arbor VA Health Care System, Ann Arbor, MI, USA – sequence: 8 givenname: Timothy surname: Craven fullname: Craven, Timothy organization: Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA – sequence: 9 givenname: Ruth L surname: Coleman fullname: Coleman, Ruth L organization: Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK – sequence: 10 givenname: John surname: Chalmers fullname: Chalmers, John organization: The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia
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CorporateAuthor	Collaborators on Trials of Lowering Glucose (CONTROL) group
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PublicationTitle	The lancet. Diabetes & endocrinology
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Snippet	Intensive glucose control is understood to prevent complications in adults with type 2 diabetes. We aimed to more precisely estimate the effects of more...
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SubjectTerms	Blood Glucose - drug effects Diabetes Complications - epidemiology Diabetes Complications - pathology Diabetes Complications - prevention & control Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - pathology Diabetic Nephropathies - prevention & control Eye Diseases - etiology Eye Diseases - prevention & control Female Glomerular Filtration Rate - drug effects Humans Hypoglycemic Agents - therapeutic use Male Middle Aged Models, Theoretical Proportional Hazards Models Randomized Controlled Trials as Topic Risk Assessment
Title	Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomised controlled trials
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