Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes

Anushka Patel, Stephen MacMahon, John Chalmers, Bruce Neal, Laurent Billot, Mark Woodward, Michel Marre, Mark Cooper, Paul Glasziou, Diederick Grobbee, Pavel Hamet, Stephen Harrap, Simon Heller, Lisheng Liu, Giuseppe Mancia, Carl Erik Mogensen, Changyu Pan, Neil Poulter, Anthony Rodgers, Bryan Williams & 5 others Severine Bompoint, Bastiaan E. de Galan, Rohina Joshi, Florence Travert, ADVANCE Collaborative Group

Research output: Contribution to journalArticleResearchpeer-review

4855 Citations (Scopus)

Abstract

Background: In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain.

Methods: We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately.

Results: After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P

Conclusions: A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT00145925.).

Original languageEnglish
Pages (from-to)2560-2572
Number of pages13
JournalNew England Journal of Medicine
Volume358
Issue number24
DOIs
Publication statusPublished - 12 Jun 2008
Externally publishedYes

Cite this

Patel, A., MacMahon, S., Chalmers, J., Neal, B., Billot, L., Woodward, M., ... ADVANCE Collaborative Group (2008). Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. New England Journal of Medicine, 358(24), 2560-2572. https://doi.org/10.1056/NEJMoa0802987
Patel, Anushka ; MacMahon, Stephen ; Chalmers, John ; Neal, Bruce ; Billot, Laurent ; Woodward, Mark ; Marre, Michel ; Cooper, Mark ; Glasziou, Paul ; Grobbee, Diederick ; Hamet, Pavel ; Harrap, Stephen ; Heller, Simon ; Liu, Lisheng ; Mancia, Giuseppe ; Mogensen, Carl Erik ; Pan, Changyu ; Poulter, Neil ; Rodgers, Anthony ; Williams, Bryan ; Bompoint, Severine ; de Galan, Bastiaan E. ; Joshi, Rohina ; Travert, Florence ; ADVANCE Collaborative Group. / Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. In: New England Journal of Medicine. 2008 ; Vol. 358, No. 24. pp. 2560-2572.
@article{48dfa934c6e44f49a09c6d62a00fbd63,
title = "Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes",
abstract = "Background: In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain.Methods: We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5{\%} or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately.Results: After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5{\%}) than in the standard-control group (7.3{\%}). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1{\%}, vs. 20.0{\%} with standard control; hazard ratio, 0.90; 95{\%} confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4{\%} vs. 10.9{\%}; hazard ratio, 0.86; 95{\%} CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1{\%} vs. 5.2{\%}; hazard ratio, 0.79; 95{\%} CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95{\%} CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95{\%} CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95{\%} CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7{\%}, vs. 1.5{\%} in the standard-control group; hazard ratio, 1.86; 95{\%} CI, 1.42 to 2.40; PConclusions: A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5{\%} yielded a 10{\%} relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21{\%} relative reduction in nephropathy. (ClinicalTrials.gov number, NCT00145925.).",
author = "Anushka Patel and Stephen MacMahon and John Chalmers and Bruce Neal and Laurent Billot and Mark Woodward and Michel Marre and Mark Cooper and Paul Glasziou and Diederick Grobbee and Pavel Hamet and Stephen Harrap and Simon Heller and Lisheng Liu and Giuseppe Mancia and Mogensen, {Carl Erik} and Changyu Pan and Neil Poulter and Anthony Rodgers and Bryan Williams and Severine Bompoint and {de Galan}, {Bastiaan E.} and Rohina Joshi and Florence Travert and {ADVANCE Collaborative Group}",
year = "2008",
month = "6",
day = "12",
doi = "10.1056/NEJMoa0802987",
language = "English",
volume = "358",
pages = "2560--2572",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "MASSACHUSETTS MEDICAL SOC",
number = "24",

}

Patel, A, MacMahon, S, Chalmers, J, Neal, B, Billot, L, Woodward, M, Marre, M, Cooper, M, Glasziou, P, Grobbee, D, Hamet, P, Harrap, S, Heller, S, Liu, L, Mancia, G, Mogensen, CE, Pan, C, Poulter, N, Rodgers, A, Williams, B, Bompoint, S, de Galan, BE, Joshi, R, Travert, F & ADVANCE Collaborative Group 2008, 'Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes' New England Journal of Medicine, vol. 358, no. 24, pp. 2560-2572. https://doi.org/10.1056/NEJMoa0802987

Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. / Patel, Anushka; MacMahon, Stephen; Chalmers, John; Neal, Bruce; Billot, Laurent; Woodward, Mark; Marre, Michel; Cooper, Mark; Glasziou, Paul; Grobbee, Diederick; Hamet, Pavel; Harrap, Stephen; Heller, Simon; Liu, Lisheng; Mancia, Giuseppe; Mogensen, Carl Erik; Pan, Changyu; Poulter, Neil; Rodgers, Anthony; Williams, Bryan; Bompoint, Severine; de Galan, Bastiaan E.; Joshi, Rohina; Travert, Florence; ADVANCE Collaborative Group.

In: New England Journal of Medicine, Vol. 358, No. 24, 12.06.2008, p. 2560-2572.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes

AU - Patel, Anushka

AU - MacMahon, Stephen

AU - Chalmers, John

AU - Neal, Bruce

AU - Billot, Laurent

AU - Woodward, Mark

AU - Marre, Michel

AU - Cooper, Mark

AU - Glasziou, Paul

AU - Grobbee, Diederick

AU - Hamet, Pavel

AU - Harrap, Stephen

AU - Heller, Simon

AU - Liu, Lisheng

AU - Mancia, Giuseppe

AU - Mogensen, Carl Erik

AU - Pan, Changyu

AU - Poulter, Neil

AU - Rodgers, Anthony

AU - Williams, Bryan

AU - Bompoint, Severine

AU - de Galan, Bastiaan E.

AU - Joshi, Rohina

AU - Travert, Florence

AU - ADVANCE Collaborative Group

PY - 2008/6/12

Y1 - 2008/6/12

N2 - Background: In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain.Methods: We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately.Results: After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; PConclusions: A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT00145925.).

AB - Background: In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain.Methods: We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately.Results: After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; PConclusions: A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT00145925.).

U2 - 10.1056/NEJMoa0802987

DO - 10.1056/NEJMoa0802987

M3 - Article

VL - 358

SP - 2560

EP - 2572

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 24

ER -

Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. New England Journal of Medicine. 2008 Jun 12;358(24):2560-2572. https://doi.org/10.1056/NEJMoa0802987