ACCORD Age Discord: Differing Responses to Diabetes Therapy

Marlene Busko

November 13, 2013

Response to standard or intensive glucose-lowering strategies appears to differ by age in individuals with type 2 diabetes, a new analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial illustrates

Cardiovascular mortality increased in the trial in middle-aged adults who received intensive vs standard glucose-lowering therapy, but this was not true for older adults. However, severe hypoglycemia occurred more often in the older individuals.

"This paper shows, first of all, that older people can tolerate diabetes therapy better than people who are middle-aged," second author Jeff D. Williamson, MD, from Wake Forest School of Medicine, Winston-Salem, North Carolina, told Medscape Medical News. "In ACCORD, we see that for a given goal, the benefit overall is often greater in older people than in younger people, although the side effects are also greater in older people than in younger people," he noted.

However, there is still a great deal to learn to be able to identify in clinical practice which elderly patients can tolerate more intensive therapy and which cannot, Dr. Williamson added. He and his colleagues report the new findings in their study published online October 29 in Diabetes Care.

Young vs Old, Intense vs Standard Therapy

As widely reported, the blood glucose lowering part of ACCORD compared an intensive-glucose-control strategy that had a target HbA1c below 6.0% with a standard strategy and target HbA1c of 7% to 7.9% in patients with type 2 diabetes and cardiovascular risk factors. Participants were recruited from 2001 to 2005, but the trial was stopped in 2008 after a mean of 3.7 years instead of 5 years due to higher mortality in the intensive-glucose-control arm.

Since little is known about the different responses to therapy among older vs younger adults with diabetes, the researchers aimed to analyze data from ACCORD to investigate this.

Specifically, they compared standard vs intensive glucose control in adults who were 65 to 89 years old at study entry with adults who were 40 to 64 years old at study entry to determine the impact and tolerability of the 2 strategies on attained glucose control, adverse events, major cardiovascular outcomes, and death.

The younger subgroup was composed of 6776 participants and the older subgroup was composed of 3475 participants (1888 aged 65 to 69, 1054 aged 70 to 74, 486 aged 75 to 79, and 47 aged 80 and older). About 40% of the younger group and 25% of the older group were women.

Among participants who received intensive therapy, older individuals attained the same median HbA1c level (around 6.4%) as younger individuals. Similarly, among participants who received standard therapy, older ones attained a comparable but slightly lower median HbA1c level than younger ones (7.5% and 7.6%, respectively).

Older and younger participants in the intensive-glucose-control arm were about 3 times more likely to have severe hypoglycemia compared with their same-age counterparts in the standard-glucose-control arm. However, older individuals experienced higher absolute rates of severe hypoglycemia.

The annualized rates of severe hypoglycemia were 4.45% and 1.36% in the intensive-glucose-control and the standard-glucose-control arms, respectively, for older individuals and were 2.45% and 0.80%, respectively, for the younger individuals.

In the younger group, intensive therapy conferred an increased risk for cardiovascular mortality compared with standard therapy (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.17 – 2.50). This was not true for the older group (HR, 0.97; 95% CI, 0.70 – 1.36). However, there was little evidence to suggest that older individuals who received intensive therapy had a benefit in terms of cardiovascular disease.

Age Alone Should Not Determine HbA1c Target

The results should be viewed as hypothesis-generating, since they are tertiary analyses of subgroups of the ACCORD trial, Dr. Williamson cautioned.

"While we have shown that similar glycemic levels can be reached in ambulatory, community-dwelling older and younger adults, the frequency of serious adverse events associated with intensive targets was consistently higher within the older subgroup," he and his colleagues summarize.

"The increased risk of hypoglycemia in older vs younger adults, regardless of whether they were in intensive or standard therapy, also suggests the need to individualize therapy in older adults with type 2 diabetes."

This agrees with "the recent 2012 ADA consensus report, [which] emphasizes a need to stratify targets based on comorbid illness and functional status, among other factors, rather than on age alone," they observe.

Dr. Williamson reports no relevant financial relationships. Disclosures for the coauthors are listed with the article.

Diabetes Care. Published online October 29, 2013. Abstract

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