A lifestyle intervention did not reduce cardiovascular outcomes in overweight or obese patients with type 2 diabetes

The Look AHEAD trial randomized more than 5,000 overweight and obese type 2 diabetics to intensive lifestyle intervention (ILI) or diabetes support and education (DSE) and found that the intensive group reduced weight, hemoglobin A1c (HbA1c) and some cardiovascular (CV) risk factors, but not the primary outcome of CV-related death, myocardial infarction, stroke or angina hospitalization.

The study was published in the July 11 New England Journal of Medicine. The following commentary by Donald A. Smith, MD, MPH, FACP, was published in the ACP Journal Club section of the Oct. 15 Annals of Internal Medicine.

There are many possible reasons that the superb trial by the Look AHEAD research group found no reduction in CV ischemic events at 10 years, a finding that conflicts with the results of at least 1 previous observational study. For example, the DSE group steadily lost 4 kg over 10 years. The initial 7-kg between-group difference in weight in the first year was not maintained and was reduced to approximately 2.5 kg over the final 5 years. Accordingly, differences between the ILI and DSE groups in HbA1c (7.33% vs. 7.44%) and systolic blood pressure (126 vs. 127 mm Hg) over the course of the study were small.

Further, mean baseline low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides already met Adult Treatment Panel III lipid guidelines. Baseline statin use (44% in both groups) increased less in the ILI group (71% vs. 74% at 10 y), producing LDL cholesterol levels that were 1.2 mg/dL lower in the DSE group than in the ILI group over 10 years. On the other hand, identical baseline HDL cholesterol levels of 43.5 mg/dL increased to 48.7 vs. 47.8 mg/dL in the ILI and DSE groups, respectively.

Although a significant effect might have been seen with longer follow-up or more aggressive and persistent weight loss, the benefits are unlikely to approach those seen with the potent risk factor–lowering medications currently available. The results of Look AHEAD suggest that, rather than expecting CV event reduction, patients with obesity and diabetes should make lifestyle changes for the important quality-of-life benefits already reported in this trial.