The New England Journal of Medicine has published the results of two studies that aimed to assess the efficacy of medication on the incidence of diabetes and cardiovascular events. The results of these studies have been reported in the general media (BBC).
Although the results are published as two papers the study was a single trial that investigated to interventions. The first intervention compared the effect of valsartan (Diovan®) to placebo. The second intervention compared nateglinide (Starlix®) to placebo.
The study recruited 9,306 participants in 40 countries and followed them for a median period of 5 years for incidence of diabetes. Participants had impaired fasting plasma (glucose between 5.3mmol/L and 7.0mmol/L) and also a risk factor for or overt cardiovascular disease. Treatment was randomly assigned in a 2-by-2 factorial design such that patients could have been taking 2 placebos, only one of the active treatments or both of the active treatments.
The primary outcome measure was either incidence of diabetes or a composite of cardiovascular events including death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospital admission for heart failure, arterial revascularisation or hospital admission for unstable angina.
Nateglinide provided no benefit over placebo in prevention of diabetes (Hazard Ratio 1.07, 95%CI 1.00-1.15, p=0.05) or cardiovascular events (HR 0.94, 95%CI 0.82-1.09, p=0.43). Valsartan provided no benefit over placebo on prevention of cardiovascular events (HR 0.96, 95%CI 0.86-1.07, p=0.43) but did provide a modest benefit in progression to diabetes (HR 0.86, 95%CI 0.80-0.92, p<0.001).
The authors conclude that treatment with "nateglinide for 5 years did not reduce the incidence of diabetes or the co-primary composite cardiovascular outcomes" and that "use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events".
The paper notes that the reduction in diabetes observed with valsartan equates to 38 fewer cases of diabetes per 1,000 patients every 5 years. In addition, the risk reduction observed is less than that seen with alternative strategies including lifestyle modification, metformin and rosiglitazone. The authors therefore note that "lifestyle modification should remain the primary intervention to reduce the risk of diabetes in the general population".
Action: Clinicians should be aware of these studies. Individuals with impaired fasting glucose should be encouraged to make lifestyle modifications to prevent or delay progression to diabetes.