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Starting metformin reduces risks for CV events, death in type 2 diabetes

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April 20, 2017

The risks for cardiovascular events and death are decreased 6 months after metformin initiation among adults with type 2 diabetes who experience a large initial HbA1c reduction and reach HbA1c less than 6.5%, according to findings from researchers in Denmark.

Reimar Wernich Thomsen, MD, PhD, consultant and clinical associate professor in the department of clinical epidemiology at Aarhus University Hospital in Denmark, and colleagues evaluated data from patient registries in Northern Denmark on all adults (mean age, 62.5 years; 55% men) with type 2 diabetes who initiated metformin (n = 24,752) between 2000 and 2012 to determine the effect of metformin on HbA1c level and effect of HbA1c reduction on subsequent risk for CV events or death.

Reimar Thomsen
Reimar Wernich Thomsen

Participants were classified by HbA1c level reached (< 6.5% or higher) 6 months after metformin initiation. Rates of acute myocardial infarction, stroke or death, controlling for baseline HbA1c and other confounding factors, were examined by Cox regression. Follow-up was a median 2.6 years.

Overall, researchers identified 439 incident MIs, 594 strokes and 1,845 deaths. Participants who reached HbA1c levels of less than 6.5% had the lowest risk for CV events or death at 180 days after metformin initiation compared with participants with HbA1c at least 8%, who had the highest risk.

Compared with HbA1c less than 6.5%, the risk for the composite endpoint increased with rising levels of early achieved HbA1c. The greatest outcome risk reductions were associated with large HbA1c reductions among participants with a high baseline HbA1c (ie, > 9%).

“Among patients with type 2 diabetes who initiate their first metformin treatment, achievement of good early glycemic control and large HbA1c reduction predicts decreased risk of CV outcomes and death,” Thomsen told Endocrine Today. “Poor early glycemic response provides an important prediction tool for identification of patient subgroups with type 2 diabetes who have increased risk for CV complications and death. Studies that can clarify whether this association is caused by better early glucose-lowering therapy (eg, more intensive therapy or better patient adherence) or by a different pathological trajectory/milder variant of type 2 diabetes in those patients who are rapid glycemic responders [are needed].” – by Amber Cox

For more information:

Reimar Wernich Thomsen, MD, PhD, can be reached at Aarhus University Hospital, Department of Clinical Epidemiology, 8200 Aarhus N, Denmark; email:

Disclosure: Thomsen reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.