Tag: 7/11/25

Categories : Neurodegenerative DiseasesTags :

Empagliflozin and Nasal Insulin Improve Brain Health in Early Alzheimer’s Disease

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A clinical trial from Wake Forest University School of Medicine shows that two widely available medications, the diabetes drug empagliflozin (Jardiance) and intranasal insulin, safely improve brain health in people with mild cognitive impairment and early Alzheimer’s disease. The study, published in Alzheimer’s & Dementia, marks the first time empagliflozin has been tested in non-diabetic patients with Alzheimer’s disease. The results show promising effects on memory, brain health and brain blood flow.

The research addresses a critical treatment gap for patients with Alzheimer’s disease. While recently approved anti-amyloid drugs represent progress, their benefits are modest, and they’re unavailable to many patients due to side effects and medical contraindications. They also don’t address the upstream metabolic and vascular problems that drive disease progression or help restore brain function after damage occurs.

“Our study suggests that targeting metabolism can change the course of Alzheimer’s disease,” said Suzanne Craft, PhD, lead investigator and professor of medicine and director of the Wake Forest Alzheimer’s Disease Research Center. “For the first time, we found that empagliflozin, an established diabetes and heart medication, reduced markers of brain injury while restoring blood flow in critical brain regions. We also confirmed that delivering insulin directly to the brain with a newly validated device enhances cognition, neurovascular health and immune function. Together, these findings highlight metabolism as a powerful new frontier in Alzheimer’s treatment.”

The four-week trial enrolled 47 older adults (average age 70) with mild cognitive impairment or early Alzheimer’s disease. Participants were randomly assigned to receive intranasal insulin alone, empagliflozin alone, both medications together or a placebo. 

Both medications were safe and well-tolerated. Treatment-related side effects were mild and similar across all groups. Participants found the nasal insulin device highly feasible to use (4.6 out of 5.0), and compliance rates exceeded 97% for both medications throughout the study.

The results revealed different benefits for each medication. Intranasal insulin improved performance on sensitive cognitive tests that detect early memory and thinking changes. Brain imaging showed insulin treatment increased the structural integrity of white matter connections and changed blood flow patterns in memory-critical regions. The treatment also reduced plasma GFAP, a marker of astrocyte (support cells that maintain healthy connections between blood vessels and brain cells) dysfunction that’s elevated in Alzheimer’s disease. 

Empagliflozin had different effects. The medication significantly lowered cerebrospinal fluid tau, a protein that forms toxic tangles in the brain in patients with Alzheimer’s disease. It also reduced neurogranin and vascular markers linked to disease progression and changed blood flow in key brain regions. Empagliflozin also increased HDL cholesterol, showing its beneficial metabolic effects work even in non-diabetic patients.

Both medications influenced multiple immune and inflammatory proteins in cerebrospinal fluid and blood. The changes suggest the drugs help activate protective immune responses while reducing harmful inflammation. Intranasal insulin particularly affected proteins involved in the nasal-olfactory plexus, a newly discovered pathway that connects the brain’s waste-clearance system to immune systems throughout the body.

The medications work differently but target overlapping problems. Empagliflozin, originally developed for diabetes, improves how the body processes glucose and sodium. That leads to better insulin sensitivity and vascular health throughout the body and brain. The drug also reduces oxidative stress and inflammation while improving how mitochondria produce energy in cells.

Intranasal insulin uses a precision delivery device to send insulin directly into the brain through the nose, bypassing the bloodstream. Once there, insulin activates receptors throughout the brain that keep synapses healthy, support blood vessel function, maintain white matter integrity, and regulate immune responses. Previous studies showed that lower doses of intranasal insulin preserved brain glucose metabolism and slowed white matter damage over 12 months.

The trial used higher insulin doses than previous studies (160 IU daily versus 40-80 IU) delivered through a cartridge pump system developed by Aptar Pharma and validated in earlier brain imaging studies. This device provides precise, reliable delivery to brain regions involved in memory and cognition. Empagliflozin was given at the standard 10 mg daily dose used for cardiovascular conditions in non-diabetic adults.

People with Alzheimer’s disease often have insulin resistance in the brain alongside vascular problems that reduce blood flow and nutrient delivery. These metabolic and vascular disruptions speed up the accumulation of amyloid plaques and tau tangles while preventing the brain from clearing these toxic proteins. Both medications tested in this trial target these upstream problems. 

“We plan to build on these promising results with larger, longer studies in people with early and preclinical Alzheimer’s disease,” Craft said. “Because empagliflozin or intranasal insulin improved tau tangles, cognition, neurovascular health and immune function, we believe these treatments could offer real therapeutic potential, either on their own or in combination with other Alzheimer’s therapies.”

The complementary effects of the two medications could make them valuable additions to combination therapy approaches. Since both drugs are already FDA-approved for other conditions with well-established safety profiles, they could reach patients faster than entirely new medications would.

Source: Wake Forest University School of Medicine

Categories : Medical Research & TechnologyTags :

Solving Africa’s Hidden Snakebite Problem with a New Universal Antivenom

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Photo by Nivedh P on Unsplash

In Sub-Saharan Africa, more than 300 000 people are bitten by venomous snakes annually, 3000 of whom die – but with the underreporting that goes hand in hand with the lack of healthcare infrastructure, the real number could be as much as five times higher. Many more face amputations. Even if patients manage to make it to a clinic or hospital in time, there is no guarantee that there will be any anti-venom available to treat them. As a South African case study shows, just having antivenom in the right place is a problem even in Western Cape’s relatively well-developed healthcare system, with antivenom’s three-year shelf life and cold chain failures posing a major problem for rural healthcare centres.

But now, scientists have developed a new kind of antivenom that is effective for 17 different snake species, including mambas, cobras and a rinkhals. The study, published in Nature, makes use of a nanobody-based cocktail that targets common mechanisms across venoms – and which is also more effective at preventing the tissue damage that leads to amputations.

A huge obstacle to creating broad-spectrum antivenoms is the enormous diversity of venomous snakes and the complexity of their venoms – a single species’ venom may contain 100 toxins from multiple different protein families. Listen to our podcast to hear a deep dive into Africa’s snakebite burden and how the international team of researchers accomplished their feat:

Categories : Cardiovascular Disease Metabolic DisordersTags :

Waist-to-Height Ratio Better than BMI at Predicting Cardiovascular Risk

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Photo by Andres Ayrton on Pexels

The ratio of a person’s waist measurement compared to their height is more reliable than body mass index (BMI) at predicting heart disease risk, according to new research from UPMC and University of Pittsburgh physician-scientists. 

This finding, published out now in The Lancet Regional Health—Americas, could reshape how clinicians and the public assess cardiovascular risk, especially for people who don’t meet the classic definition of obesity. 

The team analysed data from 2721 adults who had participated in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). The individuals had no cardiovascular disease at baseline and were followed for more than five years. 

“Higher BMI, waist circumference and waist-to-height ratio at baseline were all associated with higher risk of developing future cardiovascular disease – until we adjusted for other classic risk factors, such as age, sex, smoking, exercise, diabetes, hypertension and cholesterol,” said lead author Thiago Bosco Mendes, clinical instructor of medicine at Pitt and obesity medicine fellow at UPMC. “When we did that, only waist-to-height ratio held as a predictor.” 

Much of that predictive power is concentrated among individuals with a BMI under 30, which is below the classic threshold for obesity, who may not realise they are at risk for cardiovascular disease.  

BMI doesn’t account for fat distribution or distinguish between harmful, visceral fat and protective, subcutaneous fat. By contrast, waist-to-height ratio (WHtR), calculated by dividing waist circumference by height, directly reflects central obesity, which is more closely linked to heart disease. That means that people with a BMI lower than 30, but a WHtR over 0.5, may be at higher risk of future coronary artery calcification, a key marker of cardiovascular disease, even in the absence of other risk factors. 

“Using waist-to-height ratio as a cardiovascular screening tool could lead to earlier identification and intervention for at-risk patients who might otherwise be missed,” said senior author Marcio Bittencourt, associate professor of medicine at Pitt and cardiologist at UPMC. “It’s a simple and powerful way to spot heart disease risk early, even if a patient’s weight, cholesterol and blood pressure all seem normal.” 

Source: University of Pittsburgh School of Medicine

Categories : Exercise Metabolic DisordersTags :

Weightlifting Beats Running for Glycaemic Control, Researchers Find

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Study shows that resistance training outperforms endurance exercise in improving insulin sensitivity in obesity and Type 2 diabetes models.

Photo by Jonathan Borba on Unsplash

Running may help burn calories, but when it comes to preventing diabetes and obesity, pumping iron might have the edge, according to preclinical findings from Virginia Tech scientists at the Fralin Biomedical Research Institute at VTC.

The research, published in the Journal of Sport and Health Science, compared the effects of endurance and resistance exercise in mice fed a high-fat diet, a widely used model of obesity, hyperglycaemia, and Type 2 diabetes.

A team led by exercise medicine researcher Zhen Yan found that while both running and weightlifting helped the body clear excess sugar from the blood, resistance training was more effective in reducing subcutaneous and visceral fat, improving glucose tolerance, and lowering insulin resistance – key factors in preventing and managing diabetes.

“We all want to live a long, healthy life,” said Prof Yan, director of the Center for Exercise Medicine Research. “We all know the benefits of regular exercise. There is plenty of evidence in humans that both endurance exercise, such as running, and resistance exercise, such as weightlifting, are effective in promoting insulin sensitivity.” 

But while both support metabolic function, a rigorous side-by-side comparison was lacking. Is one type of exercise better than the other? 

What they did

To conduct the first direct, controlled comparison, members of the research team built something that had not previously existed: a mouse model of weightlifting.

In this model, mice lived in specially designed cages where food was accessed through a hinged, weighted lid. To eat, the mice had to lift the lid while wearing a small shoulder collar, causing a squat-like movement that engaged the muscle contractions people use during resistance exercise. The load was gradually increased over several days, mimicking progressive strength training.

For the endurance group, mice were given open access to a running wheel, an established model of aerobic exercise. Control groups included sedentary mice on either a normal or high-fat diet.

Over eight weeks, the researchers monitored weight gain, body composition, and fat distribution. They tested exercise capacity with treadmill runs, assessed heart and muscle function, and measured how well the mice regulated blood sugar. They also analyzed skeletal muscle tissue to study insulin signaling at the molecular level.

Using their novel model of resistance exercise, team members were able to directly compare how the two training styles affect obesity, blood glucose, and insulin sensitivity in a way that closely mirrors human exercise.

“Our data showed that both running and weightlifting reduce fat in the abdomen and under the skin and improve blood glucose maintenance with better insulin signaling in skeletal muscle,” Yan said. “Importantly, weightlifting outperforms running in these health benefits.”

Why this matters

Diabetes and obesity are major public health challenges, fuelled by sedentary lifestyles and high-fat diets. The findings underscore decades of clinical trials showing that endurance, resistance, and high-intensity interval training all reduce HbA1c while also lowering body mass index, blood pressure, and improving quality of life.

The new Virginia Tech study, which also involves collaborators from the University of Virginia, helps fill a critical gap by directly comparing voluntary running and weightlifting in a controlled, preclinical model of diet-induced obesity.

“The findings also bring good news for people who, for any number of reasons, cannot engage in endurance-type exercise,” Yan said. “Weight training has equal, if not better, anti-diabetes benefits.”

The researchers also saw changes in skeletal muscle signaling pathways that could inform new drug therapies for Type 2 diabetes.

Interestingly, the benefits of resistance training were not explained by changes in muscle mass or exercise performance, suggesting unique metabolic mechanisms at play.

Yan said the study underscores the idea that, while popular drug interventions like GLP-1 agonists can help with diabetes management and weight loss, they do not replace the unique, accessible, and comprehensive benefits of a well-balanced exercise programme. 

“The take-home message is that you should do both endurance and resistance exercise, if possible, to get the most health benefit,” said Yan, who is also a professor in the Department of Human Nutrition, Foods, and Exercise in the College of Agriculture and Life Sciences at Virginia Tech. 

Source: Virginia Tech