Metformin use may not influence SGLT2 inhibitor effect
medwireNews: Post-hoc analysis of the VERTIS-CV trial indicates that the cardiovascular effects of ertugliflozin are unaffected by whether people are also taking metformin.
And a second presentation – a mediation analysis – indicated that the benefits of ertugliflozin may be largely related to changes in volume status and blood concentration and formation.
Both analyses were reported at the virtual ESC Congress 2021. In the first, presenter Francesco Cosentino (Karolinska Institute, Stockholm, Sweden) noted that the recent shift from a glucose-focused approach toward early use of medications with cardiorenal benefits “has raised a lively debate on the need to use metformin as [a] first-line drug.”
He added that many people recruited to cardiovascular outcomes trials are not using metformin at enrollment – 24% in the case of VERTIS-CV, with around three-quarters of these people taking just one glucose-lowering agent, with this most often being insulin.
These people had a significantly longer duration of type 2 diabetes, poorer kidney function, and more frequently had heart failure than those who were taking metformin at enrollment.
In the previously reported primary findings, ertugliflozin had no significant effect on the overall major adverse cardiovascular events endpoint, nor on cardiovascular death, but it did significantly reduce the risk for the key secondary endpoint of heart failure hospitalization and for two renal outcomes.
None of these relationships between intervention and outcomes were affected by whether the participants were taking metformin, reported Cosentino.
The second analysis, presented by Matthew Segar (University of Texas Southwestern Medical Center, Dallas, USA), looked at changes in biomarkers during ertugliflozin treatment, to identify pathways that might explain ertugliflozin’s positive effects on heart failure and renal outcomes.
Looking at early biomarker changes (the first recorded change), the researchers found that the top four potential mediators were hematocrit, hemoglobin, high-density lipoprotein cholesterol, and serum albumin.
And looking at average changes across the whole of follow-up, they found hemoglobin, serum albumin, serum uric acid, and hematocrit to be the most prominent mediators.
Segar said this suggests potential mechanisms of benefit not just for ertugliflozin, but also for the sodium-glucose cotransporter (SGLT)2 inhibitor class as a whole.
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