The Pharmaceutical Journal
Vol 278 No 7436 p96
27 January 2007

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ACE inhibitors and ARBs least likely to lead to development of diabetes

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are the antihypertensive drugs least associated with developing diabetes, according to research published in The Lancet last week (2007;369:201).

William Elliott and Peter Meyer, of the department of preventive medicine, Rush University Medical Centre, Chicago, explain that the propensity for some antihypertensive drugs to lower glucose tolerance and precipitate diabetes has been known for many years. Some long-term clinical trials of antihypertensive drugs have shown differences in the rates of new cases of diabetes between treatment groups but meta-analyses have been hindered by the lack of comparability between trials as well as the absence of trials comparing ACE inhibitors with ARBs, they say.

The researchers therefore used network meta-analysis — a new statistical technique that allows direct and indirect comparisons to be undertaken even when two of the strategies have not been directly compared — to assess the relative odds of developing diabetes during long-term treatment with an initial class of antihypertensive drug. An initial diuretic was used as the standard of comparison.

They analysed data from 22 trials up to September 2006 involving 143,153 participants who did not have diabetes at randomisation. The researchers found that an initial ARB (odds ratio 0.57, 95 per cent confidence interval 0.46–0.72; P<0.0001) or ACE inhibitor (0.67, 0.56–0.80; P<0.0001) was least associated with new diabetes, followed by a calcium-channel blocker (0.75, 0.62–0.90; P=0.002) or placebo (0.77, 0.63–0.94; P=0.009) and then a beta-blocker (0.90, 0.75–1.09; P=0.30) or diuretic (standard of comparison).

The researchers acknowledge that the existing studies are not powered to detect an increased risk of cardiovascular events in patients who develop diabetes and say that future research is likely to provide better quality data to help establish the importance of glycaemic effects of antihypertensive drugs.