Valsartan for Diabetes Prevention

Impaired glucose tolerance is defined as having a fasting plasma glucose level of 100-124 mg/dL or a level of 140-199 mg/dL following an oral glucose tolerance test. Patients with these levels of blood glucose are considered pre-diabetics and numerous clinical trials describe strategies, which include lifestyle changes and pharmacological therapy, that prevent the transition to type 2 diabetes. Patients with pre-diabetes are thought to not only be at risk for the development of diabetes, but for cardiovascular disease. Although there are trials assessing the prevention of diabetes in these patients, as described above, there is little evidence for their efficacy in preventing cardiovascular events.

There is data in the literature suggesting that drugs that target the renin-angiotensin system, such as ACE inhibitors and angiotensin receptor blockers, may prevent both diabetes and cardiovascular events. A new large clinical trial published in the New England Journal of Medicine studied the potential use of valsartan, a angiotensin receptor blocker, in preventing diabetes and cardiovascular events in patients with impaired glucose tolerance.

Eligible patients had impaired glucose tolerance and either one or more cardiovascular risk factors or established cardiovascular disease. 9,306 patients were randomized to receive either placebo or valsartan. All patients were required to undergo lifestyle modification that has previously been demonstrated to prevent progression to diabetes.

Patients were followed for a median of 5 years, where 33.1% of patients in the valsartan group progressed to diabetes in comparison to 36.8% of placebo patients. The hazard ratio for the development of diabetes with valsartan treatment was .86 with a 95% confidence interval of .80 to .92. The authors calculated that diabetes would be prevented in 38 patients for every 1000 treated with valsartan for 5 years. However, valsartan had a negligible effect in reducing cardiovascular events. This may have been due to wide use of other hypertensive and lipid controlling medications in the trial.

Although the trial suggests that valsartan may have a beneficial role in preventing diabetes, a small percentage of patients (38 out of 1000) would benefit from the drug treatment over 5 years. Clinicians need to weigh risks versus benefits before initiating this therapy. It is unclear if valsartan would have a more pronounced role in diabetes prevention if lifestyle modification was not included in the trial. That is, any benefit may have been diluted out by lifestyle modification.

References:

Effect of valsartan on the incidence of diabetes and cardiovascular events. NAVIGATOR Study Group. N Engl J Med. 2010 Apr 22;362(16):1477-90.