Macrovascular Complication Is Unaffected by Glucose Control Intensity in Diabetes

Macrovascular complication risk does not increase with intensive glucose control therapy among individuals with type 2 diabetes, according to a study published in Diabetes/Metabolism Research and Reviews. However, younger patients (age <61 years) with hemoglobin A1c (HbA1c) levels lower than 7% may be less likely to experience macrovascular events with intensive treatment, while older individuals with HBA1c levels of 9% or higher may be less likely to benefit from intensive treatment, the report suggests.

Researchers included participants who had previously been enrolled in the ACCORD (ClinicalTrials.gov Identifier: NCT00000620) and observational follow-up ACCORDION studies in the investigation — 10,251 participants with type 2 diabetes who had known cardiovascular disease (CVD) or were at high risk for CVD were randomly assigned to intensive glucose control (n=5128; HbA1c target <6% [42 mmol/mol]) or standard glucose control (n=5123; HbA1c target of 7-7.9% [53-63 mmol/mol]) treatment. Due to the excess mortality of patients in the high-intensity glucose control group, all patients were treated by the standard intensity glucose control regulations after a mean of 3.7 years, and the intensive glucose control arm was stopped. The subsequent observational study ACCORDION followed 8601 of the surviving patients from ACCORD for an average 7.7 years. The primary outcomes were CVD events, including nonfatal stroke, nonfatal myocardial infarction, death from cardiovascular causes, and hospitalizations due to heart failure.

Participants treated with intensive glucose therapy and standard glucose therapy experienced a similar percentage of cardiovascular events — 16.0% (n=822) and 16.4% (n=840) experienced a single CVD event, 3.7% (n=189) and 4.2% (n=214) experienced 2 CVD events, 1.0% (n=52) and 0.8% (n=40) had 3 events, and 0.02% (n=1) in both arms experienced 4 cardiovascular events, respectively. The study’s mean follow-up duration was 7.7 years and investigators did not observe evidence of a treatment effect, which was indicated by a rate difference of 0.0 per 100 person-years when comparing the intensive vs standard interventions. However, the investigators did note a statistically insignificantly association between intensive glucose control and lower event rates in younger patients with HbA1clevels less than 7% and higher event rates in older patients with HbA1c levels greater than or equal to 9%.

 “[T]here was no evidence of an effect of intensive glucose control in patients at high cardiovascular risk on the cumulative burden of macrovascular disease, defined as the total of the first occurrence of each of nonfatal stroke, non-fatal myocardial infarction, hospitalization for heart failure and cardiovascular death,” according to the researchers. “In line with the drive towards individualized treatment in current guidelines, these results can help to define subgroups of patients in whom intensive glucose control may offer limited benefits or carry increased risks, or in whom the risk of macrovascular disease is associated with other easily identifiable characteristics regardless of treatment.”

Study limitations include a relatively short intensive treatment duration, high cardiovascular disease risk among participants, and the absence of new glucose-lowering agents.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.