CHICAGO

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CHICAGO

• Carotid intima-media tHICkness in Atherosclerosis
  using pioGlitazOne trial

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CHICAGO Background and rationale

• Even in the presence of optimal cardiovascular
  (CV) risk factor control (?LDL-C and ?BP),
  individuals with T2DM remain at high risk for CV
  events
• Thiazolidinediones have shown favorable effects
  on systemic inflammation, coagulation, lipids,
  and endothelial function
• Carotid intima-media thickness (CIMT) is a highly
  validated surrogate endpoint to detect future CV
  disease risk

CHICAGO compared the long-term effects of
pioglitazone vs glimepiride on CIMT progression
in ethnically and racially diverse,
urban patients with T2DM
Mazzone T et al. JAMA. 2006.
T2DM type 2 diabetes mellitus
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CHICAGO Study design
N 462 with T2DM
Pioglitazone 1545 mg(n 232)
Glimepiride 14 mg(n 230)
Double-blindComparator-controlled
Primary endpointChange in mean posterior-wall
CIMT in right and left common carotid arteries
Follow-up 18 months
Primary CIMT analysis n 175Intention-to-treat
(ITT) analysis n 230
Primary CIMT analysis n 186ITT analysis n
228
Initial dose based on sulfonylurea use and
titrated to achieve fasting plasma glucose (FPG)
140 mg/dLBaseline 1 qualifying CIMT image
Mazzone T et al. JAMA. 2006.
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CHICAGO Baseline demographics
Mazzone T et al. JAMA. 2006.
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CHICAGO Medical history
Mazzone T et al. JAMA. 2006.
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CHICAGO Baseline CV medications
Mazzone T et al. JAMA. 2006.
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CHICAGO Baseline risk factors
NR not reported
Mazzone T et al. JAMA. 2006.
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CHICAGO Treatment effect on posterior wall CIMT
0.016
0.012
Change from baseline (least-square means, mm)
0.008
P 0.02
0.004
0
-0.004
-0.008
-0.012
Week 72
Week 48
Week 24
Baseline
Glimepiride
Pioglitazone

Mazzone T et al. JAMA. 2006.
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CHICAGO Treatment effect on posterior wall CIMT
in prespecified subgroups
Favorspioglitazone
Favorsglimepiride
-0.04
-0.03
-0.02
-0.01
0
0.01
0.02
Treatment-group difference in posterior wall
CIMT(mean change, mm)
Mazzone T et al. JAMA. 2006.
Within 7 days of 1st study drug dose
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CHICAGO Treatment effect on glucose control
0.2



0
A1C change from baseline (least square means, )
-0.2
-0.4
-0.6
72
48
24
Baseline
60
40
32
16
Week
Glimepiride
Pioglitazone
P 0.04 P 0.01 P 0.002 (treatment-group
difference)
Mazzone T et al. JAMA. 2006.
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CHICAGO Treatment effect on HDL-C
8


6

HDL-C change from baseline (least square means,
mg/dL)
4
6.45 mg/dL(95 CI 4.977.93)
2
0
-2
24
48
72
Baseline
Week
Glimepiride (n 206)
Pioglitazone (n 201)
P lt 0.001 (treatment-group difference) HDL-C
mg/dL (SE) Glimepiride 47.6 (0.91), Pioglitazone
47.1 (0.90)
Mazzone T et al. JAMA. 2006. Courtesy of SM
Haffner, MD.
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CHICAGO Adverse events
Mazzone T et al. JAMA. 2006.
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CHICAGO Summary

• In an ethnically and racially diverse patient
  population with T2DM, treatment with pioglitazone
  demonstrated clinical benefits
• Progression of carotid atherosclerosis was
  retarded vs sulfonylurea (P 0.02)
• Benefits observed across all prespecified
  subgroups age, gender, SBP, diabetes duration,
  BMI, A1C, statin use
• Edema and weight gain were higher in TZD group
• CIMT may be preferred for assessing
  treatment-related changes in carotid
  atherosclerosis

Mazzone T et al. JAMA. 2006. Bernard S et al.
Diabetes Care. 2005281158-62.
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CHICAGO Implications

• Compared with previous trial cohorts, patients in
  CHICAGO were well-treated at baseline and had
  near-optimal risk factor control
• Mean LDL-C 113.8 mg/dL (pioglitazone) and 111.3
  mg/dL (glimepiride)
• 130.1/78.3 mm Hg (pioglitazone) and 128.7/77.1 mm
  Hg (glimepiride)
• Slowed atherosclerosis progression is consistent
  with clinical endpoint data reported in
  PROactive
• Additional data will contribute to the overall
  understanding and clinical significance of
  CHICAGO results

PROspective pioglitAzone Clinical Trial In
macroVascular Events
Mazzone T et al. JAMA. 2006.Dormandy JA et al.
Lancet. 20053661279-89.