Ozempic and other GLP1 agonists are associated with a reduced risk of developing cirrhosis and cancer liver in people with type 2 diabetes and chronic liver disease, according to a nationwide study from the Karolinska Institutet in Sweden.
The results of research were published in Gut magazine.
Liver: here's what the new research says
GLP1 agonists such as Ozempic reduce blood sugar levels and are primarily used to treat type 2 diabetes. However, because the drug also reduces appetite, it is now increasingly used to treat obesity and has become a popular slimming drug.
Results from early clinical trials also suggest that GLP1 agonists may reduce the risk of liver damage. Therefore, researchers from Karolinska Institutet included all people in Sweden with chronic liver disease and type 2 diabetes in a registry-based study. They then compared the risk of severe liver damage in those who had been treated with GLP1 agonists and those who had not. The findings show that those who took the drug for a long period of time had a lower risk of later developing more severe forms of liver disease such as cirrhosis and liver cancer.
According to the researchers, this suggests that GLP1 agonists could be an effective treatment to avoid serious liver disease in people with concomitant type 2 diabetes.
“Fatty liver disease is estimated to affect up to one in five people in Sweden, many of whom have type 2 diabetes, and around one in twenty develops severe liver disease,” says first author Axel Wester, assistant professor at the Department of Medicine, Huddinge, Karolinska Institutet. “Our findings are interesting because there are currently no drugs approved to reduce this risk.”
Many of the people involved in the study stopped taking GLP1 agonists, resulting in a lack of protective effect. However, those who continued taking the drugs for a period of ten years were half as likely to develop serious liver disease.
“The results need to be confirmed in clinical studies, but it will take many years before these studies are completed,” says Axel Wester. “Therefore, we use existing registry data to try to say something about the effect of the drugs before that.”
One limitation of the method is that it cannot control for factors for which there is no data, such as blood tests to describe the severity of liver disease in more detail. However, researchers have recently created a new database called HERALD where they have access to blood samples from patients in the Stockholm region.
“As a next step, we will study the effect of GLP1 agonists in this database,” says the study's last author Hannes Hagström, consultant in hepatology at the Karolinska University Hospital and adjunct professor at the Department of Medicine, Huddinge, Karolinska Institutet.
“If we obtained similar results, it would further strengthen the hypothesis that GLP1 agonists could be used to reduce the risk of serious liver disease.”
In a study published in the journal Hepatology, a research team from Karolinska Institutet shows that people with fatty liver disease are expected to live almost three years less than the general population.
People diagnosed with so-called fatty liver are at greater risk of developing cardiovascular disease and losing life expectancy than the general population. These patients have a shorter expected survival of approximately 2.8 years, based on data collected from a large number of Swedish patients. However, the risk of death after a heart attack or stroke is still comparable to that of people without f. fat.
The results of the study are important because they can be used to facilitate communication between healthcare professionals and patients with f. fat.
“It will be easier to communicate about the patient's expected survival and the importance of the best possible treatment, which will hopefully also improve the patient's prognosis. Furthermore, the findings indicate that it will not be necessary to examine the liver to see if heart attack or stroke patients have f. fat,” says postdoc Ying Shang at the Department of Medicine, Huddinge, Karolinska Institutet, the first author of the study.
In this national population-based cohort, extensive data linkages between national registers were collected. By analyzing a very large group of fatty liver patients (>10,000), the researchers were able to identify all patients with fatty liver in Sweden and compare them with the general population.
“In my research group, there are several ongoing projects, in which we study better ways to identify which patients with f. fat are at greater risk of developing serious complications such as cardiovascular disease, death, cirrhosis and cancer,” says Hannes Hagström from the Department of Medicine, Huddinge, one of the authors of the study.
Children and young people whose mothers had a BMI above 30 at the start of pregnancy are at increased risk of fatty liver disease. This is demonstrated in a study based on registries from Karolinska Institutet and Harvard University published in the Journal of Hepatology. As obesity rates increase even among women of childbearing age, more and more young people are at risk of developing F. fat, researchers say.
“The findings are important because obesity is becoming more common at younger ages and f. fat due to overweight is increasing in the world. If the tendency towards obesity and fatty liver disease can be 'inherited,' it may have public health consequences,” says the study's lead author, Dr. Hannes Hagström, associate professor at the Department of Medicine, Huddinge, Karolinska Institutet.
Through the so-called ESPRESSO study, in which liver biopsies were collected from all pathology departments in Sweden, the researchers identified all children and young adults born after 1992 who, after tissue sampling, were diagnosed with steatosis non-alcoholic liver disease (NAFLD). , for a total of 165 individuals.
The children had an average age of 12 years, just over 60% were male, and nearly half had fatty liver with fibrosis. The control group consisted of children and youth without fatty liver matched for sex and age.
From the Swedish medical birth register, the researchers then retrieved in
formation on the mother's BMI (body mass index) during the early stages of pregnancy. Children of obese mothers (BMI greater than 30) were three times more likely to be diagnosed with fatty liver disease than children of mothers with normal BMI during pregnancy.
The increased risk was observed even after accounting for other important factors such as education, smoking and country of birth.
Previous animal research has shown that obesity in the mother can lead to changes in the fetus that are thought to lead to a change in behavior with increased food intake, but such research in humans is lacking. The limitations of the new study are mainly the lack of data on food intake, type of diet and physical activity, as such information is not available in Swedish registers.
“We cannot say for sure whether the finding is a biological effect of maternal obesity on the growing fetus, or whether there are socio-economic explanations such as increased energy intake and an unhealthy lifestyle after birth. But in any case, pregnant women or expectant mothers with obesity should receive advice on how to reduce the risk of the baby developing fatty liver disease later in life,” says Dr. Hannes Hagström.
The occurrence of fatty liver disease in children is unknown in Sweden, but in the United States it is estimated at 5-10%. It is mainly in line with the incidence of obesity, which is also the main risk factor for non-alcoholic fatty liver disease.
“Other research has shown that being overweight early in life increases the risk of fatty liver disease, but our study is the first to investigate the effect of obesity across generations. Swedish registries offer unique opportunities to follow patients over a long period of time,” says the study's last author Jonas F. Ludvigsson, pediatrician and professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
Fatty liver often causes no discomfort, and many people suffer from it without knowing it, but the disease can sometimes lead to liver inflammation and liver cirrhosis. The amount of fat stored in the liver can be reduced with weight loss and good habits such as physical activity.
The children had an average age of 12 years, just over 60% were male, and nearly half had fatty liver with fibrosis. The control group consisted of children and youth without fatty liver matched for sex and age.
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