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A diabetes drug could help lower the risk of heart failure in certain patients.
A new study published in Nature Medicine analyzed how SGLT2 inhibitor dapagliflozin, a medication used to treat type 2 diabetes, could help prevent heart failure in people with rare genetic variants linked to cardiomyopathy (a progressive disease of the heart muscle).
Using data from the DECLARE-TIMI 58 trial, researchers from Harvard Medical School, Mass General Brigham and MIT looked at more than 12,000 adults who had type 2 diabetes and increased cardiovascular risk.
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About 121 participants carried inherited gene variants that could raise their chances of developing cardiomyopathy.
After a median 4.2-year follow-up, dapagliflozin was found to lower hospitalization for heart failure more in individuals with the variants than in those without.
While dapagliflozin lowered heart failure hospitalization in both groups, the reduction was about eight times stronger in carriers of the genetic variant.
Among the 82% of carriers without a prior history of heart failure, 12.8% developed heart failure in the placebo group, while no heart-failure events were observed among carriers receiving dapagliflozin.
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Co-lead study author Shinwan Kany, MD, a visiting scientist at the Cardiovascular Research Center with Mass General Brigham Heart and Vascular Institute and the Broad Institute, commented on how these findings could shape preventive care.
“Historically, identifying a genetic variant for cardiomyopathy mostly meant telling a patient they were at high risk and not having a specific preventive therapy to offer,” he said in a press release. “These data show we do have tools to lower risk in these individuals.”
As this was an analysis of a larger randomized trial, the results require further confirmation, according to experts. The narrow sample size of carriers also poses a limitation.
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“These findings are very encouraging because they suggest we may be entering an era where heart failure prevention becomes more precise and more genetically informed,” Andrew Freeman, MD, a cardiologist at National Jewish Health, told Fox News Digital.
Freeman, who was not involved in the study, called the research “important and provocative.”
Participants with no history of heart failure who took dapagliflozin were less likely to develop the condition, a finding that “raises the possibility that SGLT2 inhibitors may be especially useful as preventive therapy in genetically high-risk individuals,” the doctor said.
“This should be viewed as an exciting hypothesis-generating finding, not yet a practice-changing mandate for all patients with these genetic variants,” Freeman cautioned.
SGLT2 inhibitors are already “foundational” cardiovascular and kidney-protective medications, the doctor noted.
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“They reduce heart failure hospitalization across a broad range of patients, including those with diabetes, chronic kidney disease and established heart failure,” he said. “What this study adds is the possibility that genetic information may help identify a subgroup of people who derive especially large benefit from early treatment.”
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Genetic testing for cardiomyopathy is often used for diagnosis, family screening and risk stratification, Freeman said.
If future clinical trials confirm the findings, cardiologists could eventually use genetic screening to identify high-risk patients, monitor them more closely, and begin treatments such as SGLT2 inhibitors before heart failure symptoms appear, according to the cardiologist.
Heart failure does not always begin when symptoms appear, Freeman noted. In some patients, risk may be present years earlier due to inherited genetics.
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Preventive cardiology could identify high-risk patients earlier, before they develop symptoms such as shortness of breath, fluid retention or the need for hospitalization.
The decision to medicate should always be discussed with a clinician, Freeman advised, especially for those with a personal or family history of cardiovascular events.
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