Large, early HbA1c reduction lowered risk for CVD events, death

A study of patients with type 2 diabetes showed that after initiation of treatment with metformin, achievement of good early glycemic control and large HbA1c reduction were important predictors of decreased risk of cardiovascular outcomes and death.

“Previous studies have pointed towards some benefit for early intensive glycemic control on cardiovascular outcomes, in particular myocardial infarction, but the exact association is disputed,” Reimar W. Thomsen, PhD, of the department of clinical epidemiology for the Institute of Clinical Medicine at Aarhus University Hospital in Aarhus, Denmark, told Medical Economics. “The definitive relationship between early achieved HbA1c level after glucose-lowering drug start, or the magnitude of early HbA1c reduction achieved, and subsequent long-term risk of CVD outcomes and death in a real-world setting has never been investigated thoroughly.”

The study, published in Diabetes Care, included all metformin initiators with HbA1c test in Northern Demark from 2000-2012 (n=24,752). Six months after metformin initiation, the researchers classified patients by whether or not they achieved an HbA1c of 6.5% and by the magnitude of HbA1c change from baseline. The median age of patients was 62.5 years and the median follow-up was 2.6 years.

“We found that risk for a combined measure of death, myocardial infarction and stroke gradually increased with rising levels of achieved HbA1c, compared to a stringent target of <6.5%,” Thomsen said. “Individual outcome events followed a similar pattern.”

Specifically, compared with an HbA1c of less than 6.5%, the hazard ratio for a combined outcome event was 1.18 (95% CI, 1.07-1.30) for a target HbA1c of 6.5% to 6.99%, increased to 1.23 (95% CI, 1.09-1.40) for 7.0% to 7.49%, to 1.34 for 7.5% to 7.99% (95% CI, 1.14-1.57), and was 1.59  for an HbA1c of 8% or greater (95% CI, 1.37-1.84).

“A large reduction of HbA1c from baseline also predicted reduced risk of adverse outcomes,” Thomsen said. “Of importance, we observed this association between good glycemic control and beneficial outcomes also in elderly people with type 2 diabetes.”

Based on these results, the researchers are not able to say if the decreased risk for cardiovascular outcomes and mortality seen in the study was related to more intensive and compliant early glucose-lowering therapy, or if rapid glycemic responders to therapy may have had a milder variant of type 2 diabetes than patients who were poor responders, Thomsen explained.

“No matter what, poor early glycemic response provides an important prediction tool for doctors in identifying patients who have increased risk for cardiovascular complications and death,” he said.