In a post hoc analysis of the SAVOR-TIMI 53 trial of patients with diabetes at high risk for CVD, patients taking metformin had lower rates of mortality than those not taking it.
However, metformin use did not significantly affect the trial’s primary endpoint of CV death, MI or ischemic stroke, and was most effective in patients without prior HF.
As Healio previously reported, in the main results of SAVOR-TIMI 53, the dipeptidyl peptidase IV (DPP-IV) inhibitor saxagliptin (Onglyza, AstraZeneca) did not differ from placebo in CV death, MI or ischemic stroke.
For the present study, the researchers analyzed 12,156 patients from the cohort (13% with prior HF, 11% with moderate or severe chronic kidney disease) whose metformin use status was known; 74% had used metformin.
Brian A. Bergmark, MD, interventional cardiologist at Brigham and Women’s Hospital, and colleagues used inverse probability of treatment weighting to estimate the association between metformin exposure and outcomes.
The researchers found that the metformin and no-metformin groups did not differ in CV death/MI/ischemic stroke (inverse probability of treatment weighting HR = 0.92; 95% CI, 0.76-1.11), but the metformin group had lower risk for all-cause mortality (inverse probability of treatment weighting HR = 0.75; 95% CI, 0.59-0.95).
There was no interaction by saxagliptin vs. placebo treatment arm and metformin exposure for all-cause mortality or CV death/MI/ischemic stroke.
Metformin use was not linked to lower all-cause mortality risk in patients with prior HF, but it was in patients without prior HF (P for interaction = .001), whereas there was no heterogeneity by chronic kidney disease status (P for interaction = .141), Bergmark and colleagues wrote.
“If a potential causal relationship is to be posited, it would be helpful for there to be a biologically plausible mechanism for decreased mortality in the absence of reduction in MI or ischemic stroke. At present, no single mechanism of this nature exists,” the researchers wrote. “It is also true, however, that metformin appears to have pleotropic effects, including restoration of endothelial nitric oxide synthase function in the setting of obesity, and favorable modification of myocardial energy metabolism. ... These findings emphasize the need for an adequately powered randomized trial in these high-risk patients.” – by Erik Swain
Disclosures: The original SAVOR-TIMI 53 study was funded by AstraZeneca and Bristol-Myers Squibb. Bergmark reports he received grant support from Abbott Vascular and MedImmune and consultant fees from Abbott Vascular, Daiichi Sankyo, Janssen Pharmaceuticals and Quark Pharmaceuticals. Please see the study for all other authors’ relevant financial disclosures.