medwireNews: Metformin status at the time of initial dipeptidyl peptidase (DPP) 4 inhibitor use may influence the effect these agents have on cardiovascular outcomes, be it positive or negative, suggest results of a hypothesis-generating meta-analysis.
Discussing their findings, the authors note that metformin use is unlikely to be the only difference between these subgroups and suggest that its use may indicate other baseline differences such as rates of chronic kidney disease or congestive heart failure, which should be accounted for in future analyses.
Matthew Crowley (Duke University School of Medicine, Durham, North Carolina, USA) and colleagues analysed data from three multinational trials examining the effects of the DPP-4 inhibitors sitagliptin, alogliptin, or saxagliptin versus placebo on cardiovascular outcomes in patients with type 2 diabetes.
They found that, overall, DPP-4 inhibition had a neutral effect on the risk for the composite outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (plus unstable angina hospitalization in one study) during a median follow-up period of 1.5 to 3 years.
However, when the study participants were grouped according to baseline metformin use, the researchers observed a trend toward improved cardiovascular outcomes with DPP-4 inhibition in individuals who were using metformin at baseline (prevalent users), at a nonsignificant hazard ratio (HR) of 0.92.
By contrast, baseline metformin nonusers showed a trend toward an increased risk for cardiovascular events, with a nonsignificant HR of 1.10 reported.
Further analysis revealed that the effect DPP-4 inhibition had on cardiovascular risk differed significantly between prevalent metformin users and baseline nonusers.
This suggests that “the cardiovascular effects of DPP-4 [inhibitor] agents may differ depending on whether these medications are coprescribed with metformin,” Crowley et al write in Diabetes Care.
Crowley and team conclude: “This hypothesis-generating analysis suggests that there is residual uncertainty as to whether DPP-4 [inhibitors] are associated with cardiovascular neutrality, benefit, or even harm, depending on how these medications are used in clinical practice.”
They add: “Future research should further examine metformin’s moderating effects on individual DPP-4 [inhibitor] agents and also explore how metformin may interact with other novel medication classes, such as [glucagon-like peptide]-1 receptor agonists and sodium–glucose cotransporter 2 inhibitors.”
By Laura Cowen
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