March 22nd, 2012
Uncertainty Over the Clinical Importance of the Diabetes Risk of Diuretics and Statins
With all of the hullaballoo about statins and diabetes last week I wanted to point out a paper that was published online this week in Circulation: Cardiovascular Quality and Outcomes. This study examined the long-term effects of incident diabetes on cardiovascular outcomes in patients enrolled in ALLHAT. As you may remember, this trial included more than 20,000 subjects and compared different strategies to treat hypertension. They reported that chlorthalidone therapy was associated with a lower risk of clinical cardiovascular outcomes than amlodipine and lisinopril. As expected, incident diabetes was higher in the chlorthalidone group, a known adverse effect of thiazide diuretics.
In this study the authors show that incident diabetes in the chlorthalidone group conferred less risk of CHD outcomes than incident diabetes for those on lisinopril or amlodipine. In other words, although more subjects developed diabetes in the chlorthalidone group, incident diabetes was more benign in this group. The follow-up period was almost 7 years. They conclude that concerns about incident diabetes in those treated with thiazide diuretics should not inhibit its use. While I am sure that this study will not put to rest concerns about thiazide-associated incident diabetes, it does raise questions about whether the blood glucose elevation in these patients really confers much risk. And the outcomes in this study – the outcomes that patients actually experience – did favor the diuretic group. This may have relevance for the statin story – in which the trials show strong benefits for outcomes that patients’ experience – and there is uncertainty about the clinical importance of the elevation in blood glucose. The FDA expressed the same uncertainty.