A meta-analysis of five trials has shown that more intensive glucose control in type 2 diabetes leads to fewer heart attacks and heart disease events — but has no significant effect on stroke or mortality from all causes. The findings are reported in an Article in this week's diabetes special issue of The Lancet, written by Dr Kausik Ray, University of Cambridge, UK, and colleagues.
To date, individual studies of intensive glucose control have failed to show consistent benefits on cardiovascular events and some have even suggested possible harm. The authors say this could be because each trial was underpowered to show clinical benefit. This meta-analysis combined five large trials, with the authors hoping to provide definitive evidence of a significant benefit of more intensive glucose control compared with standard care.
The five studies looked at more than 33,000 patients and provided information on 1,497 heart attacks, 2,318 events of coronary heart disease, 1,127 strokes, and 2,892 deaths. The mean haemoglobin A1c concentration* (HbA1c) was assessed in the patients. More intensive glucose control was achieved in the studies using additional medications and/or higher doses as shown by the lower levels of HbA1c which were achieved. HbA1c is used to indicate the average plasma glucose concentration of the preceding two to three months. In general, the reference range (that found in healthy persons who do not have diabetes), is about 4%—5.9%. Patients with diabetes usually have HbA1c levels above 6.5%
The researchers found that HbA1c was 0.9% lower in those patients given more intense treatment than those given standard treatment (6.6% vs 7.5%). Increased intensity of treatment resulted in a 17% reduction in non-fatal heart attacks, and a 15% reduction in events of coronary heart disease (fatal and non-fatal heart attacks). However, increased intensity treatment had no effect on stroke rates or all-cause mortality.
The authors say: "Our findings provide reassurance about the effectiveness of glycaemic control for cardiovascular risk reduction, but we have not proven a clear benefit to all-cause mortality. By contrast, strong evidence suggests that lipid-lowering treatment and blood pressure reduction does benefit all-cause mortality, which reinforces the crucial importance of these treatments to reduce cardiovascular events and all-cause mortality in individuals with type 2 diabetes. The optimum methods to achieve glycaemic control need to be established, and guidelines drawn up with specific recommendations for reduction of HbA1c concentration in a range of patient populations."
They conclude: "Overall, intensive compared with standard glycaemic control significantly reduces coronary events without an increased risk of death. However, the optimum mechanism, speed, and extent of HbA1c reduction might be different in differing populations."
In an accompanying Comment, Dr Theodore Mazzone, University of Illinois at Chicago, USA, says: "Intensive glucose-control efforts might need to be started sooner after onset of diabetes, and extended follow-up could be required. The benefit of glucose control on coronary heart disease in type 2 diabetes will certainly not be as great as that produced by blood pressure control or statin treatment. However, on the basis of current information, and the urgent need to address residual risk of coronary heart disease in a rapidly expanding population with type 2 diabetes, it is premature to conclude that glucose control has no part to play."
Dr Kausik Ray, University of Cambridge, UK T) +44 (0) 1223 740893 / +44 (0) 1223 741398 / +44 (0) 7960 181754 E) kkr25@medschl.cam.ac.uk
Dr Theodore Mazzone, University of Illinois at Chicago, USA T) +1 312 996-7989 E) tmazzone@uic.edu
For full Article and Comment see: http://press.thelancet.com/intensive.pdf
Journal
The Lancet