Early glycemic control key after metformin initiation
medwireNews: Patients with type 2 diabetes who experience a large reduction in glycated hemoglobin (HbA1c) levels within 6 months of starting metformin therapy have a lower risk for adverse outcomes than those who do not achieve early glycemic control, study results suggest.
Lowering HbA1c levels to below 7% “has been a recommended target in treatment guidelines for more than a decade” for most patients with type 2 diabetes, but “it remains debated whether even tighter glucose control (such as HbA1c<6.5%) may be more beneficial or harmful,” say the study authors.
Compared with 11,849 metformin initiators who achieved a target HbA1c below 6.5% after 6 months of metformin therapy, 6578 patients with HbA1c levels of 6.5–6.99% had a 1.18-fold increased risk for acute myocardial infarction, stroke, or death over a median follow-up of 2.6 years after adjustment for factors including demographics, baseline HbA1c, diabetic complications, and medication use.
And the risk for the combined outcome event “gradually increased with rising levels of HbA1c,” report Reimar Thomsen (Aarhus University Hospital, Denmark) and colleagues.
Indeed, 3035 patients with HbA1c levels of 7.0–7.49% had a 1.23-fold increased risk for adverse outcomes compared with those achieving levels below 6.5%, whereas those with HbA1c levels of 7.5–7.99% (n=1434) and 8% and above (n=1856) had a 1.34- and 1.59-fold increased risk, respectively.
The team also observed an association between the magnitude of HbA1c change and outcome. Participants with an HbA1c reduction of 4 percentage points had a 20% reduced risk for the composite outcome relative to those with no reduction in HbA1c levels after adjustment for confounders.
And those with a decrease in HbA1c levels of 3, 2, and 1 percentage points had a corresponding reduction in the risk for adverse outcomes of 2%, 8%, and 1%.
“[T]hese 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,” write the authors in Diabetes Care.
While Thomsen and colleagues were able to account for “a range of possible confounders,” they caution that data on smoking was not available, and note that over the course of the study – conducted from 2000 until 2012 – guidelines changed from recommending lifestyle modification to emphasizing early drug treatment.
Therefore, it is likely that patients had high HbA1c levels at the beginning of the study “primarily as a result of late initiation of medical therapy, and that HbA1c measurements from recent years more reliably reflect baseline glycemic control in newly diagnosed type 2 diabetes,” they believe.
Nonetheless, the researchers conclude that: “Whereas causality is difficult to prove in our observational study design, these results provide an early prediction tool for identification of patient subgroups with type 2 diabetes that have increased risk for cardiovascular complications and death.”
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