Achieving Low HbA1c Levels Benefited Metformin Initiators

As achieved glycated hemoglobin A1c levels increased, the risk for a combined cardiovascular event increased.

New results published in Diabetes Care suggest that a large, initial reduction in hemoglobin A1c (HbA1c) and achievement of low HbA1c levels 6 months after metformin initiation lowered the risk for cardiovascular events and death in patients with type 2 diabetes. 

The population-based cohort study included 24,752 individuals (median age, 62.5; 55% men) with type 2 diabetes who initiated first-time ever metformin treatment. All metformin initiators had HbA1c tests in Northern Denmark between 2000 and 2012.


Six months after initiation, the researchers classified patients according to achieved HbA1c level and magnitude of HbA1c change from pretreatment baseline.

After controlling for baseline HbA1c and other confounders, researchers examined rates of myocardial infarction, stroke, and death.

During follow-up (median 2.6 years), the risk for a combined outcome event increased as achieved HbA1c levels increased. Specifically, compared with a target HbA1c of <6.5%, the adjusted hazard ratio (HR) for an HbA1c of 6.5% to 6.99% was 1.18 (95% CI, 1.07-1.30); for 7% to 7.49% it was 1.23 (95% CI, 1.09-1.40); for 7.5% to 7.99% it was 1.34 (95% CI, 1.14-1.57); and for ≥8% it was 1.59 (95% CI, 1.37-1.84).

Results did not differ for individual outcome events and were robust by age group and other patient characteristics, according to the researchers.

In addition, the researchers analyzed the impact of absolute reductions of HbA1c compared with no HbA1c change, and reported the following:

  • -4 absolute reduction: HR, 0.80 (95% CI, 0.65-0.97)
  • -3 absolute reduction: HR, 0.98 (95% CI, 0.80-1.20)
  • -2 absolute reduction: HR, 0.92 (95% CI, 0.78-1.08)
  • -1 absolute reduction: HR, 0.99 (95% CI, 0.89-1.10)

“In conclusion,” the researchers wrote, “these real-world data provide evidence that not only achievement of early glycemic control but also the magnitude of HbA1c reduction predicts decreased risk of cardiovascular outcomes and mortality in metformin initiators, independent of baseline HbA1c levels at treatment initiation.”

Although the observational study design made causality difficult to prove, results provided an early prediction tool for identifying patient subgroups with type 2 diabetes that have increased risk for cardiovascular complications and death, the researchers wrote.


Two researchers report either being a current or former employee of Novo Nordisk, which partly funded the study in the form of a research grant. The other researchers report no relevant financial disclosures.

Related Articles


Svensson E, Baggesen LM, Johnsen SP, et al. Early glycemic control and magnitude of HbA1c reduction predict cardiovascular events and mortality: Population-based cohort study of 24,752 metformin initiators. Diabetes Care. 2017. doi:10.2337/dc16-2271