Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial.
BACKGROUND
Hyperglycaemia is associated with increased risk of cardiovascular complications in people with type 2 diabetes. We investigated whether reduction of blood glucose concentration decreases the rate of microvascular complications in people with type 2 diabetes.


METHODS
ACCORD was a parallel-group, randomised trial done in 77 clinical sites in North America. People with diabetes, high HbA(1c) concentrations (>7.5%), and cardiovascular disease (or >or=2 cardiovascular risk factors) were randomly assigned by central randomisation to intensive (target haemoglobin A(1c) [HbA(1c)] of <6.0%) or standard (7.0-7.9%) glycaemic therapy. In this analysis, the prespecified composite outcomes were: dialysis or renal transplantation, high serum creatinine (>291.7 micromol/L), or retinal photocoagulation or vitrectomy (first composite outcome); or peripheral neuropathy plus the first composite outcome (second composite outcome). 13 prespecified secondary measures of kidney, eye, and peripheral nerve function were also assessed. Investigators and participants were aware of treatment group assignment. Analysis was done for all patients who were assessed for microvascular outcomes, on the basis of treatment assignment, irrespective of treatments received or compliance to therapies. ACCORD is registered with ClinicalTrials.gov, number NCT00000620.


RESULTS
10 251 patients were randomly assigned, 5128 to the intensive glycaemia control group and 5123 to standard group. Intensive therapy was stopped before study end because of higher mortality in that group, and patients were transitioned to standard therapy. At transition, the first composite outcome was recorded in 443 of 5107 patients in the intensive group versus 444 of 5108 in the standard group (HR 1.00, 95% CI 0.88-1.14; p=1.00), and the second composite outcome was noted in 1591 of 5107 versus 1659 of 5108 (0.96, 0.89-1.02; p=0.19). Results were similar at study end (first composite outcome 556 of 5119 vs 586 of 5115 [HR 0.95, 95% CI 0.85-1.07, p=0.42]; and second 1956 of 5119 vs 2046 of 5115, respectively [0.95, 0.89-1.01, p=0.12]). Intensive therapy did not reduce the risk of advanced measures of microvascular outcomes, but delayed the onset of albuminuria and some measures of eye complications and neuropathy. Seven secondary measures at study end favoured intensive therapy (p<0.05).


CONCLUSIONS
Microvascular benefits of intensive therapy should be weighed against the increase in total and cardiovascular disease-related mortality, increased weight gain, and high risk for severe hypoglycaemia.


BACKGROUND
US National Institutes of Health; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Eye Institute; Centers for Disease Control and Prevention; and General Clinical Research Centers.
Ismail-Beigi
Faramarz
F
Department of Medicine, Division of Clinical and Molecular Endocrinology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4951, USA. faramarz.ismail-beigi@case.edu
Craven
Timothy
T
Banerji
Mary Ann
MA
Basile
Jan
J
Calles
Jorge
J
Cohen
Robert M
RM
Cuddihy
Robert
R
Cushman
William C
WC
Genuth
Saul
S
Grimm
Richard H
RH
Hamilton
Bruce P
BP
Hoogwerf
Byron
B
Karl
Diane
D
Katz
Lois
L
Krikorian
Armand
A
O'Connor
Patrick
P
Pop-Busui
Rodica
R
Schubart
Ulrich
U
Simmons
Debra
D
Taylor
Harris
H
Thomas
Abraham
A
Weiss
Daniel
D
Hramiak
Irene
I
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D003928:Diabetic Nephropathies / Q000517:prevention & control; D003929:Diabetic Neuropathies / Q000517:prevention & control; D003930:Diabetic Retinopathy / Q000517:prevention & control; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008055:Lipids / Q000097:blood; D008875:Middle Aged
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008055:Lipids