Glucose Control May Not Reduce Risk of Heart Failure

According to John McMurray, MD, of the University of Glasgow in Glasgow, Scotland, and colleagues, the thiazolidinediones – may actually increase the risk for heart failure.

The findings appear to contradict epidemiological evidence that has suggested a link between blood glucose, as measured by glycated hemoglobin (HbA1c) levels, and heart failure. The reason for the apparent contradiction is "uncertain," but the researchers argued there are several possible explanations, including insufficient duration of treatment or follow-up, treatment too late in the disease course, and off-target toxicity of some treatments.

As well, they noted, it may be that hyperglycemia does not directly cause heart failure in diabetic patients, but instead is a marker of some other factor.

The findings come from a meta-analysis of eight randomized controlled trials that compared standard treatment with more aggressive glycemic control.

All told, the studies included 37,229 patients, although the study size varied sharply, from 153 to 11,140. Follow-up averaged from 2.3 to 10.1 years.

• Overall, participants given more intensive glucose-lowering regimens, had a weighted mean HbA1c concentration that was 0.9% lower than those offered conventional treatment.
• There were 1,469 episodes of heart failure, including 107 deaths.
• The overall event rate did not differ between groups -- 8.0 per 1,000 person-years of follow-up – although event rates varied markedly among the trials.
• With meta-analytic pooling, intensive glucose control did not significantly increase the overall occurrence of heart failure. The odds ratio was 1.20, with a 95% confidence interval from 0.96 to 1.48.

However, in a prespecified analysis, the researchers broke out the four trials in which a large proportion of patients were treated with thiazolidinediones and found an increased risk of heart failure associated with intensive glycemic control. The odds ratio for heart failure, given intensive control, was 1.33, with a 95% confidence interval from 1.02 to 1.72, they reported.

Conversely, in the subgroup of trials that mainly used other anti-diabetic drugs -- sulfonylureas, metformin, or insulin – intensive treatment had little effect. The odds ratio for heart failure was 0.96, with a 95% confidence interval from 0.81 to 1.13.

The researchers cautioned that the eight studies were conducted over a 13-year period during which diabetes management "has changed significantly." They added that they did not have patient-level data and can't say anything about the relative benefits or harms of specific treatment regimens.

As well, potential modifiers of the effect – such things as age and duration of disease – could not be measured because of the small number of trials in the meta-analysis, the researchers noted.

Practice Pearls:

·         Note that for the subgroup treated with thiazolidinediones, the risk of heart failure was actually increased.

·         Explain that a meta-analysis of eight randomized trials found that tight glycemic control did not decrease the risk of heart failure in patients with type 2 diabetes.

Castagno D, et al "Intensive glycemic control has no impact on the risk of heart failure in type 2 diabetic patients: Evidence from a 37,229 patient meta-analysis" Am Heart J 2011; 162: 938-948.e2.