article203

VADT

"Intensive Glucose Control in Type 2 Diabetes". The New England Journal of Medicine. 2009. 360:129-139. PubMed • Full text • PDF

Clinical Question

Does intensive glucose control reduce the rate of major cardiovascular events among patients with long-standing type 2 diabetes?

Bottom Line

Intensive glucose control in patients with poorly controlled type 2 diabetes did not significantly reduce the rate of major cardiovascular events, death, or microvascular complications, except for a reduction in the progression of albuminuria.

Major Points

Guidelines

As of the last knowledge update for this summary, no specific guidelines have been generated based on this trial. However, guidelines generally suggest individualized glucose targets for patients with type 2 diabetes, taking into account the risk of hypoglycemia, patient preference, and disease duration.

Design

- Multicenter, open-label, randomized, controlled trial
- N=1791 military veterans with type 2 diabetes and suboptimal response to therapy
- Intensive therapy (n=891); Standard therapy (n=900)
- Setting: 20 VA medical centers in the U.S.
- Enrollment: 2000-2003
- Follow-up: median 5.6 years
- Analysis: Intention-to-treat
- Primary outcome: Time to the first major cardiovascular event

Population

- Inclusion criteria: Military veterans with type 2 diabetes and suboptimal response to therapy, glycated hemoglobin level >7.5%
- Exclusion criteria: Recent cardiovascular event, advanced heart failure, limited life expectancy, BMI >40, creatinine >1.6 mg/dL, and alanine aminotransferase >3× upper limit of normal
- Baseline characteristics: Mean age 60.4 years, 11.5 years since diabetes diagnosis, 40% had a cardiovascular event, 72% had hypertension

Interventions

- Intensive therapy group: Goal glycated hemoglobin level reduction of 1.5% compared to the standard-therapy group
- Standard therapy group: Less aggressive glycemic targets
- Similar treatment for other cardiovascular risk factors

Outcomes

- Primary Outcome: No significant difference in the time to the first occurrence of a major cardiovascular event between groups (HR 0.88; 95% CI 0.74 to 1.05; P=0.14)
- Secondary Outcomes: No significant difference in any of the individual components of the primary outcome or in all-cause death (HR 1.07; 95% CI 0.81 to 1.42; P=0.62)
- Adverse Events: Higher rate of hypoglycemia in the intensive-therapy group (24.1%) compared to standard-therapy group (17.6%, P=0.05)

Criticisms

- Primarily male veteran population may limit generalizability to other groups
- Lack of double-blind design may have introduced bias
- Potential for newer agents to have different effects not considered in the trial protocol

Funding

- Veterans Affairs Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, pharmaceutical and other supplies and financial assistance from GlaxoSmithKline, Novo Nordisk, Roche Diagnostics, Sanofi-Aventis, Amylin, and Kos Pharmaceuticals.