A preclinical study shows a common antidiabetic drug significantly reduces stroke size and brain swelling, offering new possibilities for stroke treatment.
Summary: Researchers at Huntington Medical Research Institutes (HMRI) have demonstrated that the antidiabetic drug empagliflozin significantly reduces stroke size and brain swelling in preclinical models, with acute treatment reducing stroke size by 74%. Presented at the American Heart Association Scientific Sessions, the findings highlight empagliflozin’s potential for both preventative and acute stroke care, though further research is needed to confirm its efficacy in clinical settings.
Key Takeaways:
- Significant Reduction in Stroke Size: Acute treatment with empagliflozin reduced stroke size by 74% in preclinical models, while chronic treatment also showed notable benefits, highlighting the drug’s potential for reducing brain damage caused by ischemic strokes.
- Potential Mechanisms Identified: Researchers hypothesize that empagliflozin’s effectiveness is linked to preserving mitochondrial function and reducing oxidative stress, though further investigation is required to confirm these mechanisms.
- Future Implications for Stroke Care: While still experimental, empagliflozin could be used preventatively for high-risk individuals or acutely during stroke to limit damage, representing a promising avenue for improving stroke outcomes.
Researchers from Huntington Medical Research Institutes (HMRI) presented findings at the American Heart Association Scientific Sessions showing that the antidiabetic drug empagliflozin significantly reduces stroke size and brain swelling in preclinical models, offering potential new strategies for stroke treatment.
In pilot studies, HMRI’s team of cardiovascular researchers, led by Robert A. Kloner, MD, PhD, chief science officer, chair of cardiovascular research, and professor of medicine (clinical scholar) at Keck School of Medicine of the University of Southern California, and Wangde Dai, MD, associate professor of cardiovascular research, showed a dramatic reduction in stroke size using empagliflozin, a common antidiabetic drug.
Strokes are rising at alarming rates. Over a span of 29 years, from 1990 to 2019, the absolute number of incident strokes increased by 70%. HMRI’s investigators aim to improve lives through novel scientific discoveries that reduce the size and severity of heart attacks and strokes, addressing this increasingly urgent public health crisis.
When a person experiences a stroke, brain cells die either from blocked blood flow (ischemic stroke) or a ruptured blood vessel in the brain (hemorrhagic stroke). Every year in the United States, about 795,000 people experience a new or recurrent stroke; of those, 87% are ischemic, and 13% are hemorrhagic. A stroke-based study from 2017– 2020 estimates that 9.4 million Americans ages 20 and older have been diagnosed with a stroke. The global stroke epidemic is associated with increasing mortality, morbidity, and disabilities that can be detrimental to the survivor’s quality of life.
Scientists administered empagliflozin (EMPA), a sodium-glucose co-transporter-2 inhibitor, into a chronic treatment group for seven days before the experimental preclinical stroke model. They observed a significant reduction in the size of cerebral infarctions in stroke models. In the acute treatment group, EMPA was given intravenously 10 minutes prior to the middle cerebral artery occlusion and one minute before reperfusion. The acute treatment reduced the size of the stroke by 74%. EMPA also reduced the swelling of the brain due to stroke.
EMPA started as an antidiabetic drug and now has cardiovascular indications as well. “We know that diabetes is a risk factor for stroke, but the exact mechanism as to why empagliflozin was so powerful in reducing stroke size remains to be determined,” says Kloner in a release. “We hypothesize that it preserves the function of the mitochondria, the energy factories of the cells, and reduces reactive oxygen species or free radical damage.”
When patients enter the hospital with symptoms of a stroke, imaging procedures help physicians determine if a stroke is present—providing information on the type of stroke, size, and area of the brain affected. Some common therapies for ischemic strokes may include thrombolytic drugs to dissolve the clot, usually given within the first three hours of the onset of symptoms, or blood clot removal via thrombectomy. Hemorrhagic strokes may require potential surgery.
The financial burden of stroke on the healthcare system in the US is $34 to $40 billion annually, according to a release from HMRI. This includes direct costs, such as hospital stays, outpatient visits, and home health care, as well as indirect costs, such as lost wages and premature death.
“Even with modern approaches to treatment for stroke, death rates remain high and are increasing—and the subsequent disability costs are intolerable,” says Kloner in a release. “There is an urgent need for new approaches that will better preserve brain cells in the setting of ischemic stroke and reduce the size of the stroke, also known as cerebral infarction.”
While their work currently remains experimental, HMRI’s researchers are hopeful. In the future, they speculate that EMPA could be administered preventatively for people with a high risk of stroke and acutely in the setting of stroke to reduce its size. However, more research is needed at the preclinical and clinical stages.
HMRI’s cardiovascular researchers will continue their studies on stroke to determine whether EMPA is effective after the onset of a stroke. They will also explore whether EMPA’s effect on reducing stroke size will improve neurological function long-term after a stroke.
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