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

4. Comparison
If standard glucose control, discontinued gliclazide and
switched to different SU if required

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