ADVANCE - Type 2 diabetes - vascular risk with intervention
1. Intensive Blood Glucose
Control and Vascular
Outcomes in Patients with
Type 2 Diabetes
N Eng J Med 358;24 2560 - 2572
ADVANCE Collaborative Group
Taz Babiker
2. Population
Patients with type 2 diabetes aged ≥ 30 years at
diagnosis
Aged ≥ 55
History of major macrovascular disease, OR
At least one other risk factor for vascular disease
Excluded if:
Definite indication for any of the study treatments
Contraindication to any of the study treatments
Definite indication for long-term insulin
Median duration of follow up 5.0 years
3. Intervention
6 week run in period
Fixed combination of perindopril and indapamide
Random assignment to either perindopril or indapamide
or placebo
Random assignment to intensive (HbA1c < 6.5%) vs
standard glucose control
Gliclazide MR ± metformin, thiazolidinediones, acarbose
or insulin
Regular follow up
5. Outcome
Primary outcomes – composite of macrovascular and
microvascular events
Death from cardiovascular causes
Nonfatal MI
Nonfatal stroke
New or worsening nephropathy
Doubling of serum creatinine
Renal replacement therapy
Death due to renal disease
Retinopathy
6. Outcome
HbA1c 6.5% vs 7.3% ?significant
Systolic BP 135.5 vs 137.9 mmHg (p<0.001)
Weight 0.7 kg greater in intensive group (p<0.001)
Major macro/microvascular event: 18.1 vs 20.0% (hazard
ratio 0.90, p=0.01)
In a 5 yr period, an event would be averted in 1 in 52
participants
Sig reduction in major microvascular but not major
macrovascular events
No evidence of interaction between BP and glucose
intervention
7. Outcome
Death: 8.9% vs 9.6% (p=0.28)
Reduction in renal events
new/worsening nephropathy (HR 0.79, p=0.006)
New-onset microalbuminuria (HR 0.91, p=0.02)
Macroalbuminuria 2.9% vs 4.1% (HR 0.70, p<0.001)
Reduced RRT or death from renal causes – 0.4% vs
0.6%, HR 0.64, p=0.09)
Increased severe hypoglycaemia (BM < 2.8) and minor
hypos in intensive group
8. Discussion
ACCORD – excess mortality in intensive arm led to
premature termination
ADVANCE – no sig difference in mortality from any
cause/CV causes
Not enough statistical power to achieve expected
improvement in CV risk with intensive group
Lower BP explains some but no more than 25-33% of
the relative risk reduction
Hinweis der Redaktion
21% relative risk reduction in risk of new or worsening nephropathy