medwireNews: Findings from the SAVOR-TIMI 53 trial suggest that metformin treatment reduces cardiovascular and all-cause mortality but not nonfatal cardiovascular disease (CVD) events, but a meta-analysis points to wider benefits.
The SAVOR-TIMI 53 analysis, reported in Circulation by Brian Bergmark (Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA) and colleagues, involved 12,156 people with type 2 diabetes who were randomly assigned to receive saxagliptin or placebo.
The 74% of participants with metformin exposure had a significant 32% reduced risk for cardiovascular death and a 25% reduced risk for all-cause mortality. But the risk for the composite endpoint of cardiovascular death, myocardial infarction, or ischemic stroke was reduced by only a nonsignificant 8%.
The reduced risk for all-cause mortality associated with metformin did not apply to the 13% of patients with prior heart failure or the 11% with at least moderate chronic kidney disease, the researchers note. They stress the need for randomized trial data in these subgroups, in light of the cardioprotective effect of newer medication classes.
The team also performed a meta-analysis of an additional 25 studies, giving a total 815,639 patients, which confirmed the protective association of metformin treatment with all-cause mortality, at a 26% risk reduction.
Another meta-analysis, published in Cardiovascular Diabetology by Zhujun Shen (Peking Union Medical College Hospital, Beijing, China) and co-workers, also looks at the effects of metformin on CVD risk.
This analysis included 40 studies and 1,066,408 patients with existing coronary artery disease, and found a significant 19% reduction in the risk for cardiovascular mortality (from 11 studies) and a 33% reduction in the risk for all-cause mortality (from 21 studies). The protective effect against all-cause mortality was consistent for patients with pre-existing myocardial infarction and, contrary to the SAVOR-TIMI 53 findings, in those with heart failure.
Across 21 studies, there was a significant association between metformin use and a reduced risk for CVD events, at a 17% reduction, but this applied only to people with type 2 diabetes; there was no association in the four studies reporting on people without diabetes. There was also no effect in patients with pre-existing myocardial infarction.
As Bergmark and colleagues conclude: “In the rapidly evolving field of cardiovascular risk reduction for patients with diabetes, rigorous testing of the first line antihyperglycemic agent, metformin, is needed.”
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