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Food as Medicine: Diet’s Role in Parkinson’s Disease
For 15 years, John Duda, MD, national director of the VA Parkinson’s Disease Research, Education and Clinical Centers, has urged his patients to “keep waiting” for effective treatments to manage both motor and nonmotor symptoms of Parkinson’s disease.
However, Duda, who also serves as director of the Brain Wellness Clinic at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia, Pennsylvania, recognized the persistent lack of effective drugs to address these symptoms. This prompted him to consider what other evidence-based strategies he could use to support his patients. 
“I recognized that nutritional approaches within a broader program that includes medication review, stress management, social connections, adequate sleep, and physical exercise could make a real difference,” he said.
Observational studies have shown an inverse association between dietary patterns and Parkinson’s disease risk, age of onset, symptom severity, and mortality rates — particularly with the Mediterranean diet (MeDi) and the MIND diet, which combines elements of MeDi and the Dietary Approaches to Stop Hypertension (DASH) diet. Although randomized controlled trials are still limited, the epidemiologic evidence supporting dietary interventions is “compelling,” said Duda. 
For example, a cross-sectional study comparing 167 participants with Parkinson’s disease vs 119 controls showed that later age of Parkinson’s disease onset correlated with adherence to the MIND diet in women, with a difference of up to 17.4 years (P < .001) between low and high dietary tertiles. 
The MeDi was correlated with later onset in men, with differences of up to 8.4 years (P = .002). As previously reported, a healthy diet emphasizing vegetables, fruits, nuts, and grains was inversely associated with prodromal features of Parkinson’s disease, including constipation, excessive daytime sleepiness, and depression. In addition, lower rates of Parkinson’s disease have been shown in populations following vegetarian and vegan dietary patterns. 
 
Does Parkinson’s disease Start in the Gut?
Parkinson’s disease is characterized by decreased short-chain fatty acid–producing bacteria and increased pro-inflammatory species linked to intestinal inflammation and alpha-synuclein aggregation. “There are reasons to believe that a-synuclein accumulation may start in the gut,” Duda noted.
Numerous studies implicate gut microbiome dysbiosis as a pathogenic mechanism in Parkinson’s disease, with gastrointestinal symptoms often predating motor symptoms. Dysbiosis might result in a pro-inflammatory state potentially linked to the recurrent gastrointestinal symptoms. Fecal microbiota transplant may restore a healthier gut environment and beneficially affect Parkinson’s disease symptoms, he said.
Some of the benefits conferred by the MeDi and other healthy diets may be mediated by improving the gut microbiome. Duda cited a study that showed that a 14-day ovo-lacto vegetarian diet intervention and a daily fecal enema for 8 days improved not only the microbiome but also Movement Disorder Society Unified Parkinson’s Disease Rating Scale—part III scores. 
Duda also reviewed the role of dietary interventions in addressing common Parkinson’s disease symptoms, such as orthostatic hypotension. He recommended that Parkinson’s disease patients with this condition should avoid eating large meals, increase dietary salt intake, increase fluid intake, and decrease alcohol intake.
Malnutrition affects close to 25% of those with Parkinson’s disease, which is partially attributable to diminished olfaction. Because the experience of taste is largely driven by a sense of smell, patients may be less interested in eating. Duda recommended increasing herbs, spices, and other flavors in food. High caloric–density foods, including nuts, nut butters, and seeds, can boost weight, he said. However, he added, any patient with significant weight loss should consult a nutritionist.
Constipation is one of the most debilitating symptoms of Parkinson’s disease, affecting up to 66% of patients. Duda advised increasing fluid intake, exercise, and dietary fiber and use of stool softeners and laxatives. The MeDi may reduce symptoms of constipation and have a beneficial effect on gut microbiota. 
Coffee may be helpful for sleepiness in Parkinson’s disease and may also confer neuroprotective, motor, and cognitive benefits. As an adjuvant treatment, caffeine may alter levodopa pharmacokinetics, reduce dyskinesia, improve gait in patients with freezing and may even reduce the risk of developing Parkinson’s disease, with a maximum benefit reached at approximately three cups of coffee daily.
 
Problematic Foods
There is also a growing body of evidence regarding the deleterious effects of ultraprocessed foods (UPFs), Duda said. He noted that a recent systematic review and meta-analysis of 28 studies showed that higher UPF intake was significantly associated with an enhanced risk for Parkinson’s disease (relative risk, 1.56; 95% CI, 1.21-2.02). As previously reported, UPFs have been tied to a host of adverse neurologic outcomes, including cognitive decline and stroke.
Although protein is a necessary nutrient, incorporating it into the diet of Parkinson’s disease patients taking levodopa is complicated. Levodopa, a large neutral amino acid (LNAA), competes with other LNAAs for transport to the brain from the small intestine, Duda explained. 
“Some people notice that carbidopa-levodopa doesn’t work as well if taken with a high-protein meal.” He recommended taking carbidopa-levodopa 30 minutes before or 60 minutes after meals.
Rebecca Gilbert, MD, PhD, chief mission officer of the American Parkinson’s Disease Association, said that patients with Parkinson’s disease might want to avoid eating protein during the day, concentrating instead on carbohydrates and vegetables and saving the protein for the evening, which is closer to bedtime. Some evidence also supports the use of protein redistribution diets to enhance the clinical response to levodopa and reduce motor fluctuations. 
 
What About Supplements?
It’s “hard to prove that one specific supplement can be protective against Parkinson’s disease because diet consists of many different components and the whole diet may be worth more than the sum of its parts,” Gilbert said. The evidence for individual supplements “isn’t robust enough to say they prevent or treat Parkinson’s disease.”
Research on the role of specific nutrients in Parkinson’s disease is conflicting, with no clear evidence supporting or refuting their benefits. For example, a study that followed participants for about 30 years showed no link between reduced Parkinson’s disease risk and vitamin B or folate intake. 
On the other hand, there is research suggesting that certain vitamins may help reduce Parkinson’s disease risk, although these nutrients do not operate in isolation. For instance, one recent study showed a connection between vitamins C and E and reduced Parkinson’s disease risk, but factors such as body mass index and coffee consumption appeared to influence the strength of this association.
Consuming polyunsaturated fatty acids along with reducing saturated fatty acid intake has been tied to a reduced risk for Parkinson’s disease. 
Additionally, certain foods may offer protective effects, including green and black tea, with consumption of three or more cups per day associated with a delay in motor symptom onset by 7.7 years. Foods high in nicotine content, such as those from the Solanaceae family — including peppers, tomatoes, tomato juice, and potatoes — have also been linked to potential protective benefits.
Diets rich in antioxidants, including carotenoids, lutein, and vitamins E and C, have been robustly linked to a reduced risk for parkinsonism and progression of parkinsonian symptoms in older adults.
Increasing the intake of dietary flavonoids, particularly tea, berry fruits, apples, red wine, and oranges or orange juice, can reduce Parkinson’s disease risk. One study showed that male participants in the highest quintile of total flavonoid consumption had a 40% lower Parkinson’s disease risk compared with those in the lowest quintile. Another study showed that flavonoid-rich foods were also associated with a lower risk for death in patients with Parkinson’s disease. 
 
Food as Medicine
Although recent research shows that the drug development pipeline for Parkinson’s disease is robust, with a wide variety of approaches being developed and evaluated in phase 1 and 2, investigators note that only a limited number of disease-modifying treatments are transitioning to phase 3.
Duda noted that phytochemicals incorporated into the diet might target some of the same mechanisms that are targets of these drugs in development. 
“Flavonoids have been shown to stabilize alpha-synuclein in vitro,” he said. “Caffeine, curcumin, resveratrol, and eliminating meat and dairy inhibit mTOR [mammalian target of rapamycin], and mTOR inhibition results in increased autophagy that may help clear alpha-synuclein. Genestein, an isoflavone in soybeans, protects dopaminergic neurons by inhibiting microglia activation. Flavonoids inhibit inflammation by inhibiting release of NO [nitric oxide] and pro-inflammatory cytokines,” he noted. 
Ongoing studies of dietary interventions for Parkinson’s disease are exploring various areas, including the potential role of the ketogenic diet in protecting the gut microbiome, optimizing protein intake for muscle preservation and sleep, the effects of psyllium and wheat bran on weight and constipation, and the impact of a gluten-free diet.
 
Practical Tips for Healthy Eating
Gilbert emphasized that there are no medications or interventions currently available that can delay a Parkinson’s disease diagnosis by up to 17 years, as some dietary patterns have been shown to do, and she noted that it’s not possible to replicate the MeDi diet in a pill. However, she recommended a practical approach to eating that includes a diet low in ultraprocessed foods and high in beneficial nutrients. She encouraged people to shop for “real food” and enjoy a variety of colorful fruits and vegetables.
Duda acknowledged that motivating patients to follow a healthy diet can be difficult. As a result, the focus often shifts to making small adjustments and modifications. For example, he suggested that instead of pairing meat with French fries, people could opt for vegetables or add greens to their meals. Similarly, instead of having eggs and bacon for breakfast, they might choose oatmeal.
Preparing whole-food, plant-based meals may take more time than patients are accustomed to, so Duda suggests that, if possible, patients involve loved ones in both the meal preparation and the meal itself. He explained that a healthy meal can become an opportunity for bonding and that the key is educating them about new meal-related concepts. 
Duda reported no relevant financial relationships with the pharmaceutical or food industries. He has received compensation from the Physicians Committee for Responsible Medicine for his lecture delivered at the conference and research grant support from the VA, the National Institutes of Health, the Michael J. Fox Foundation, and the Department of Defense unrelated to this topic. Gilbert reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
For 15 years, John Duda, MD, national director of the VA Parkinson’s Disease Research, Education and Clinical Centers, has urged his patients to “keep waiting” for effective treatments to manage both motor and nonmotor symptoms of Parkinson’s disease.
However, Duda, who also serves as director of the Brain Wellness Clinic at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia, Pennsylvania, recognized the persistent lack of effective drugs to address these symptoms. This prompted him to consider what other evidence-based strategies he could use to support his patients. 
“I recognized that nutritional approaches within a broader program that includes medication review, stress management, social connections, adequate sleep, and physical exercise could make a real difference,” he said.
Observational studies have shown an inverse association between dietary patterns and Parkinson’s disease risk, age of onset, symptom severity, and mortality rates — particularly with the Mediterranean diet (MeDi) and the MIND diet, which combines elements of MeDi and the Dietary Approaches to Stop Hypertension (DASH) diet. Although randomized controlled trials are still limited, the epidemiologic evidence supporting dietary interventions is “compelling,” said Duda. 
For example, a cross-sectional study comparing 167 participants with Parkinson’s disease vs 119 controls showed that later age of Parkinson’s disease onset correlated with adherence to the MIND diet in women, with a difference of up to 17.4 years (P < .001) between low and high dietary tertiles. 
The MeDi was correlated with later onset in men, with differences of up to 8.4 years (P = .002). As previously reported, a healthy diet emphasizing vegetables, fruits, nuts, and grains was inversely associated with prodromal features of Parkinson’s disease, including constipation, excessive daytime sleepiness, and depression. In addition, lower rates of Parkinson’s disease have been shown in populations following vegetarian and vegan dietary patterns. 
 
Does Parkinson’s disease Start in the Gut?
Parkinson’s disease is characterized by decreased short-chain fatty acid–producing bacteria and increased pro-inflammatory species linked to intestinal inflammation and alpha-synuclein aggregation. “There are reasons to believe that a-synuclein accumulation may start in the gut,” Duda noted.
Numerous studies implicate gut microbiome dysbiosis as a pathogenic mechanism in Parkinson’s disease, with gastrointestinal symptoms often predating motor symptoms. Dysbiosis might result in a pro-inflammatory state potentially linked to the recurrent gastrointestinal symptoms. Fecal microbiota transplant may restore a healthier gut environment and beneficially affect Parkinson’s disease symptoms, he said.
Some of the benefits conferred by the MeDi and other healthy diets may be mediated by improving the gut microbiome. Duda cited a study that showed that a 14-day ovo-lacto vegetarian diet intervention and a daily fecal enema for 8 days improved not only the microbiome but also Movement Disorder Society Unified Parkinson’s Disease Rating Scale—part III scores. 
Duda also reviewed the role of dietary interventions in addressing common Parkinson’s disease symptoms, such as orthostatic hypotension. He recommended that Parkinson’s disease patients with this condition should avoid eating large meals, increase dietary salt intake, increase fluid intake, and decrease alcohol intake.
Malnutrition affects close to 25% of those with Parkinson’s disease, which is partially attributable to diminished olfaction. Because the experience of taste is largely driven by a sense of smell, patients may be less interested in eating. Duda recommended increasing herbs, spices, and other flavors in food. High caloric–density foods, including nuts, nut butters, and seeds, can boost weight, he said. However, he added, any patient with significant weight loss should consult a nutritionist.
Constipation is one of the most debilitating symptoms of Parkinson’s disease, affecting up to 66% of patients. Duda advised increasing fluid intake, exercise, and dietary fiber and use of stool softeners and laxatives. The MeDi may reduce symptoms of constipation and have a beneficial effect on gut microbiota. 
Coffee may be helpful for sleepiness in Parkinson’s disease and may also confer neuroprotective, motor, and cognitive benefits. As an adjuvant treatment, caffeine may alter levodopa pharmacokinetics, reduce dyskinesia, improve gait in patients with freezing and may even reduce the risk of developing Parkinson’s disease, with a maximum benefit reached at approximately three cups of coffee daily.
 
Problematic Foods
There is also a growing body of evidence regarding the deleterious effects of ultraprocessed foods (UPFs), Duda said. He noted that a recent systematic review and meta-analysis of 28 studies showed that higher UPF intake was significantly associated with an enhanced risk for Parkinson’s disease (relative risk, 1.56; 95% CI, 1.21-2.02). As previously reported, UPFs have been tied to a host of adverse neurologic outcomes, including cognitive decline and stroke.
Although protein is a necessary nutrient, incorporating it into the diet of Parkinson’s disease patients taking levodopa is complicated. Levodopa, a large neutral amino acid (LNAA), competes with other LNAAs for transport to the brain from the small intestine, Duda explained. 
“Some people notice that carbidopa-levodopa doesn’t work as well if taken with a high-protein meal.” He recommended taking carbidopa-levodopa 30 minutes before or 60 minutes after meals.
Rebecca Gilbert, MD, PhD, chief mission officer of the American Parkinson’s Disease Association, said that patients with Parkinson’s disease might want to avoid eating protein during the day, concentrating instead on carbohydrates and vegetables and saving the protein for the evening, which is closer to bedtime. Some evidence also supports the use of protein redistribution diets to enhance the clinical response to levodopa and reduce motor fluctuations. 
 
What About Supplements?
It’s “hard to prove that one specific supplement can be protective against Parkinson’s disease because diet consists of many different components and the whole diet may be worth more than the sum of its parts,” Gilbert said. The evidence for individual supplements “isn’t robust enough to say they prevent or treat Parkinson’s disease.”
Research on the role of specific nutrients in Parkinson’s disease is conflicting, with no clear evidence supporting or refuting their benefits. For example, a study that followed participants for about 30 years showed no link between reduced Parkinson’s disease risk and vitamin B or folate intake. 
On the other hand, there is research suggesting that certain vitamins may help reduce Parkinson’s disease risk, although these nutrients do not operate in isolation. For instance, one recent study showed a connection between vitamins C and E and reduced Parkinson’s disease risk, but factors such as body mass index and coffee consumption appeared to influence the strength of this association.
Consuming polyunsaturated fatty acids along with reducing saturated fatty acid intake has been tied to a reduced risk for Parkinson’s disease. 
Additionally, certain foods may offer protective effects, including green and black tea, with consumption of three or more cups per day associated with a delay in motor symptom onset by 7.7 years. Foods high in nicotine content, such as those from the Solanaceae family — including peppers, tomatoes, tomato juice, and potatoes — have also been linked to potential protective benefits.
Diets rich in antioxidants, including carotenoids, lutein, and vitamins E and C, have been robustly linked to a reduced risk for parkinsonism and progression of parkinsonian symptoms in older adults.
Increasing the intake of dietary flavonoids, particularly tea, berry fruits, apples, red wine, and oranges or orange juice, can reduce Parkinson’s disease risk. One study showed that male participants in the highest quintile of total flavonoid consumption had a 40% lower Parkinson’s disease risk compared with those in the lowest quintile. Another study showed that flavonoid-rich foods were also associated with a lower risk for death in patients with Parkinson’s disease. 
 
Food as Medicine
Although recent research shows that the drug development pipeline for Parkinson’s disease is robust, with a wide variety of approaches being developed and evaluated in phase 1 and 2, investigators note that only a limited number of disease-modifying treatments are transitioning to phase 3.
Duda noted that phytochemicals incorporated into the diet might target some of the same mechanisms that are targets of these drugs in development. 
“Flavonoids have been shown to stabilize alpha-synuclein in vitro,” he said. “Caffeine, curcumin, resveratrol, and eliminating meat and dairy inhibit mTOR [mammalian target of rapamycin], and mTOR inhibition results in increased autophagy that may help clear alpha-synuclein. Genestein, an isoflavone in soybeans, protects dopaminergic neurons by inhibiting microglia activation. Flavonoids inhibit inflammation by inhibiting release of NO [nitric oxide] and pro-inflammatory cytokines,” he noted. 
Ongoing studies of dietary interventions for Parkinson’s disease are exploring various areas, including the potential role of the ketogenic diet in protecting the gut microbiome, optimizing protein intake for muscle preservation and sleep, the effects of psyllium and wheat bran on weight and constipation, and the impact of a gluten-free diet.
 
Practical Tips for Healthy Eating
Gilbert emphasized that there are no medications or interventions currently available that can delay a Parkinson’s disease diagnosis by up to 17 years, as some dietary patterns have been shown to do, and she noted that it’s not possible to replicate the MeDi diet in a pill. However, she recommended a practical approach to eating that includes a diet low in ultraprocessed foods and high in beneficial nutrients. She encouraged people to shop for “real food” and enjoy a variety of colorful fruits and vegetables.
Duda acknowledged that motivating patients to follow a healthy diet can be difficult. As a result, the focus often shifts to making small adjustments and modifications. For example, he suggested that instead of pairing meat with French fries, people could opt for vegetables or add greens to their meals. Similarly, instead of having eggs and bacon for breakfast, they might choose oatmeal.
Preparing whole-food, plant-based meals may take more time than patients are accustomed to, so Duda suggests that, if possible, patients involve loved ones in both the meal preparation and the meal itself. He explained that a healthy meal can become an opportunity for bonding and that the key is educating them about new meal-related concepts. 
Duda reported no relevant financial relationships with the pharmaceutical or food industries. He has received compensation from the Physicians Committee for Responsible Medicine for his lecture delivered at the conference and research grant support from the VA, the National Institutes of Health, the Michael J. Fox Foundation, and the Department of Defense unrelated to this topic. Gilbert reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
For 15 years, John Duda, MD, national director of the VA Parkinson’s Disease Research, Education and Clinical Centers, has urged his patients to “keep waiting” for effective treatments to manage both motor and nonmotor symptoms of Parkinson’s disease.
However, Duda, who also serves as director of the Brain Wellness Clinic at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia, Pennsylvania, recognized the persistent lack of effective drugs to address these symptoms. This prompted him to consider what other evidence-based strategies he could use to support his patients. 
“I recognized that nutritional approaches within a broader program that includes medication review, stress management, social connections, adequate sleep, and physical exercise could make a real difference,” he said.
Observational studies have shown an inverse association between dietary patterns and Parkinson’s disease risk, age of onset, symptom severity, and mortality rates — particularly with the Mediterranean diet (MeDi) and the MIND diet, which combines elements of MeDi and the Dietary Approaches to Stop Hypertension (DASH) diet. Although randomized controlled trials are still limited, the epidemiologic evidence supporting dietary interventions is “compelling,” said Duda. 
For example, a cross-sectional study comparing 167 participants with Parkinson’s disease vs 119 controls showed that later age of Parkinson’s disease onset correlated with adherence to the MIND diet in women, with a difference of up to 17.4 years (P < .001) between low and high dietary tertiles. 
The MeDi was correlated with later onset in men, with differences of up to 8.4 years (P = .002). As previously reported, a healthy diet emphasizing vegetables, fruits, nuts, and grains was inversely associated with prodromal features of Parkinson’s disease, including constipation, excessive daytime sleepiness, and depression. In addition, lower rates of Parkinson’s disease have been shown in populations following vegetarian and vegan dietary patterns. 
 
Does Parkinson’s disease Start in the Gut?
Parkinson’s disease is characterized by decreased short-chain fatty acid–producing bacteria and increased pro-inflammatory species linked to intestinal inflammation and alpha-synuclein aggregation. “There are reasons to believe that a-synuclein accumulation may start in the gut,” Duda noted.
Numerous studies implicate gut microbiome dysbiosis as a pathogenic mechanism in Parkinson’s disease, with gastrointestinal symptoms often predating motor symptoms. Dysbiosis might result in a pro-inflammatory state potentially linked to the recurrent gastrointestinal symptoms. Fecal microbiota transplant may restore a healthier gut environment and beneficially affect Parkinson’s disease symptoms, he said.
Some of the benefits conferred by the MeDi and other healthy diets may be mediated by improving the gut microbiome. Duda cited a study that showed that a 14-day ovo-lacto vegetarian diet intervention and a daily fecal enema for 8 days improved not only the microbiome but also Movement Disorder Society Unified Parkinson’s Disease Rating Scale—part III scores. 
Duda also reviewed the role of dietary interventions in addressing common Parkinson’s disease symptoms, such as orthostatic hypotension. He recommended that Parkinson’s disease patients with this condition should avoid eating large meals, increase dietary salt intake, increase fluid intake, and decrease alcohol intake.
Malnutrition affects close to 25% of those with Parkinson’s disease, which is partially attributable to diminished olfaction. Because the experience of taste is largely driven by a sense of smell, patients may be less interested in eating. Duda recommended increasing herbs, spices, and other flavors in food. High caloric–density foods, including nuts, nut butters, and seeds, can boost weight, he said. However, he added, any patient with significant weight loss should consult a nutritionist.
Constipation is one of the most debilitating symptoms of Parkinson’s disease, affecting up to 66% of patients. Duda advised increasing fluid intake, exercise, and dietary fiber and use of stool softeners and laxatives. The MeDi may reduce symptoms of constipation and have a beneficial effect on gut microbiota. 
Coffee may be helpful for sleepiness in Parkinson’s disease and may also confer neuroprotective, motor, and cognitive benefits. As an adjuvant treatment, caffeine may alter levodopa pharmacokinetics, reduce dyskinesia, improve gait in patients with freezing and may even reduce the risk of developing Parkinson’s disease, with a maximum benefit reached at approximately three cups of coffee daily.
 
Problematic Foods
There is also a growing body of evidence regarding the deleterious effects of ultraprocessed foods (UPFs), Duda said. He noted that a recent systematic review and meta-analysis of 28 studies showed that higher UPF intake was significantly associated with an enhanced risk for Parkinson’s disease (relative risk, 1.56; 95% CI, 1.21-2.02). As previously reported, UPFs have been tied to a host of adverse neurologic outcomes, including cognitive decline and stroke.
Although protein is a necessary nutrient, incorporating it into the diet of Parkinson’s disease patients taking levodopa is complicated. Levodopa, a large neutral amino acid (LNAA), competes with other LNAAs for transport to the brain from the small intestine, Duda explained. 
“Some people notice that carbidopa-levodopa doesn’t work as well if taken with a high-protein meal.” He recommended taking carbidopa-levodopa 30 minutes before or 60 minutes after meals.
Rebecca Gilbert, MD, PhD, chief mission officer of the American Parkinson’s Disease Association, said that patients with Parkinson’s disease might want to avoid eating protein during the day, concentrating instead on carbohydrates and vegetables and saving the protein for the evening, which is closer to bedtime. Some evidence also supports the use of protein redistribution diets to enhance the clinical response to levodopa and reduce motor fluctuations. 
 
What About Supplements?
It’s “hard to prove that one specific supplement can be protective against Parkinson’s disease because diet consists of many different components and the whole diet may be worth more than the sum of its parts,” Gilbert said. The evidence for individual supplements “isn’t robust enough to say they prevent or treat Parkinson’s disease.”
Research on the role of specific nutrients in Parkinson’s disease is conflicting, with no clear evidence supporting or refuting their benefits. For example, a study that followed participants for about 30 years showed no link between reduced Parkinson’s disease risk and vitamin B or folate intake. 
On the other hand, there is research suggesting that certain vitamins may help reduce Parkinson’s disease risk, although these nutrients do not operate in isolation. For instance, one recent study showed a connection between vitamins C and E and reduced Parkinson’s disease risk, but factors such as body mass index and coffee consumption appeared to influence the strength of this association.
Consuming polyunsaturated fatty acids along with reducing saturated fatty acid intake has been tied to a reduced risk for Parkinson’s disease. 
Additionally, certain foods may offer protective effects, including green and black tea, with consumption of three or more cups per day associated with a delay in motor symptom onset by 7.7 years. Foods high in nicotine content, such as those from the Solanaceae family — including peppers, tomatoes, tomato juice, and potatoes — have also been linked to potential protective benefits.
Diets rich in antioxidants, including carotenoids, lutein, and vitamins E and C, have been robustly linked to a reduced risk for parkinsonism and progression of parkinsonian symptoms in older adults.
Increasing the intake of dietary flavonoids, particularly tea, berry fruits, apples, red wine, and oranges or orange juice, can reduce Parkinson’s disease risk. One study showed that male participants in the highest quintile of total flavonoid consumption had a 40% lower Parkinson’s disease risk compared with those in the lowest quintile. Another study showed that flavonoid-rich foods were also associated with a lower risk for death in patients with Parkinson’s disease. 
 
Food as Medicine
Although recent research shows that the drug development pipeline for Parkinson’s disease is robust, with a wide variety of approaches being developed and evaluated in phase 1 and 2, investigators note that only a limited number of disease-modifying treatments are transitioning to phase 3.
Duda noted that phytochemicals incorporated into the diet might target some of the same mechanisms that are targets of these drugs in development. 
“Flavonoids have been shown to stabilize alpha-synuclein in vitro,” he said. “Caffeine, curcumin, resveratrol, and eliminating meat and dairy inhibit mTOR [mammalian target of rapamycin], and mTOR inhibition results in increased autophagy that may help clear alpha-synuclein. Genestein, an isoflavone in soybeans, protects dopaminergic neurons by inhibiting microglia activation. Flavonoids inhibit inflammation by inhibiting release of NO [nitric oxide] and pro-inflammatory cytokines,” he noted. 
Ongoing studies of dietary interventions for Parkinson’s disease are exploring various areas, including the potential role of the ketogenic diet in protecting the gut microbiome, optimizing protein intake for muscle preservation and sleep, the effects of psyllium and wheat bran on weight and constipation, and the impact of a gluten-free diet.
 
Practical Tips for Healthy Eating
Gilbert emphasized that there are no medications or interventions currently available that can delay a Parkinson’s disease diagnosis by up to 17 years, as some dietary patterns have been shown to do, and she noted that it’s not possible to replicate the MeDi diet in a pill. However, she recommended a practical approach to eating that includes a diet low in ultraprocessed foods and high in beneficial nutrients. She encouraged people to shop for “real food” and enjoy a variety of colorful fruits and vegetables.
Duda acknowledged that motivating patients to follow a healthy diet can be difficult. As a result, the focus often shifts to making small adjustments and modifications. For example, he suggested that instead of pairing meat with French fries, people could opt for vegetables or add greens to their meals. Similarly, instead of having eggs and bacon for breakfast, they might choose oatmeal.
Preparing whole-food, plant-based meals may take more time than patients are accustomed to, so Duda suggests that, if possible, patients involve loved ones in both the meal preparation and the meal itself. He explained that a healthy meal can become an opportunity for bonding and that the key is educating them about new meal-related concepts. 
Duda reported no relevant financial relationships with the pharmaceutical or food industries. He has received compensation from the Physicians Committee for Responsible Medicine for his lecture delivered at the conference and research grant support from the VA, the National Institutes of Health, the Michael J. Fox Foundation, and the Department of Defense unrelated to this topic. Gilbert reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
VA Surpasses Housing Goal for Homeless Veterans in 2024
The US Department of Veterans Affairs (VA) exceeded its 2024 goal to house 41,000 veterans, housing 47,935 veterans—an increase of 16.9% and the highest number housed in a single year since 2019. What’s more, it passed that housing goal a month early.
Ending veteran homelessness has been a priority for VA and the Biden-Harris administration. Since 2022, the VA has permanently housed nearly 134,000 homeless veterans. The number of veterans experiencing homelessness in the US has decreased by over 4% since 2020 and by more than 52% since 2010.
The marked decline in homelessness is largely due to the VA’s change in approach. Transitional housing often has followed a linear stepwise model, designed to foster housing readiness by encouraging sobriety and treatment compliance before moving the veteran to the next stage, from emergency shelter to transitional, and finally, permanent housing. While this method worked for some, it posed challenges for those with serious mental illness, substance addiction, or chronic medical conditions.
The VA began shifting its approach in 2012, adopting what it calls its north star—the evidence-based housing first approach. This strategy prioritizes getting veterans into housing as quickly as possible, skipping the intermediate transitional interventions, and then providing wraparound services such as job training and legal and education assistance. “Permanent housing is a critical tool, rather than a reward, for recovery,” says Shawn Liu, director of communications for the VA Homeless Programs Office, in a 2023 article.
A systematic review of studies from 1992 to 2017, shows that the housing first model leads to quicker exits from homelessness and greater long-term housing stability compared with traditional methods. The VA has also found that doing away with enrollment preconditions helps shorten stays among transitional housing providers, improves rates of permanent housing, and increases access to supportive services when needed.
Evidence suggests that the housing first model may reduce the use of emergency department services, hospitalizations, and hospitalized time compared with traditional treatment methods (although the meta-analysis found “considerable variability” between its examined studies). However, evidence that the Housing First model improves health outcomes associated with mental health, substance abuse, or physical health, remains inconclusive. 
In 2010, a demonstration project in the VA setting compared the housing first model with a treatment‐first program for 177 homeless veterans. The study found that the housing first model reduced time to housing placement from 223 to 35 days, significantly increased housing retention rates (98% vs 86%), and significantly reduced emergency room visits.
Over the past decade, the VA has focused on building on the strengths of the program and identifying areas for improvement, such as increasing the prevalence of recovery-oriented philosophies among service providers. “Nearly 48,000 formerly homeless veterans now have a safe, stable place to call home—and there’s nothing more important than that,” said VA Secretary Denis McDonough. “No veteran should experience homelessness in this nation they swore to defend. We are making real progress in this fight, and we will not rest until veteran homelessness is a thing of the past.”
The US Department of Veterans Affairs (VA) exceeded its 2024 goal to house 41,000 veterans, housing 47,935 veterans—an increase of 16.9% and the highest number housed in a single year since 2019. What’s more, it passed that housing goal a month early.
Ending veteran homelessness has been a priority for VA and the Biden-Harris administration. Since 2022, the VA has permanently housed nearly 134,000 homeless veterans. The number of veterans experiencing homelessness in the US has decreased by over 4% since 2020 and by more than 52% since 2010.
The marked decline in homelessness is largely due to the VA’s change in approach. Transitional housing often has followed a linear stepwise model, designed to foster housing readiness by encouraging sobriety and treatment compliance before moving the veteran to the next stage, from emergency shelter to transitional, and finally, permanent housing. While this method worked for some, it posed challenges for those with serious mental illness, substance addiction, or chronic medical conditions.
The VA began shifting its approach in 2012, adopting what it calls its north star—the evidence-based housing first approach. This strategy prioritizes getting veterans into housing as quickly as possible, skipping the intermediate transitional interventions, and then providing wraparound services such as job training and legal and education assistance. “Permanent housing is a critical tool, rather than a reward, for recovery,” says Shawn Liu, director of communications for the VA Homeless Programs Office, in a 2023 article.
A systematic review of studies from 1992 to 2017, shows that the housing first model leads to quicker exits from homelessness and greater long-term housing stability compared with traditional methods. The VA has also found that doing away with enrollment preconditions helps shorten stays among transitional housing providers, improves rates of permanent housing, and increases access to supportive services when needed.
Evidence suggests that the housing first model may reduce the use of emergency department services, hospitalizations, and hospitalized time compared with traditional treatment methods (although the meta-analysis found “considerable variability” between its examined studies). However, evidence that the Housing First model improves health outcomes associated with mental health, substance abuse, or physical health, remains inconclusive. 
In 2010, a demonstration project in the VA setting compared the housing first model with a treatment‐first program for 177 homeless veterans. The study found that the housing first model reduced time to housing placement from 223 to 35 days, significantly increased housing retention rates (98% vs 86%), and significantly reduced emergency room visits.
Over the past decade, the VA has focused on building on the strengths of the program and identifying areas for improvement, such as increasing the prevalence of recovery-oriented philosophies among service providers. “Nearly 48,000 formerly homeless veterans now have a safe, stable place to call home—and there’s nothing more important than that,” said VA Secretary Denis McDonough. “No veteran should experience homelessness in this nation they swore to defend. We are making real progress in this fight, and we will not rest until veteran homelessness is a thing of the past.”
The US Department of Veterans Affairs (VA) exceeded its 2024 goal to house 41,000 veterans, housing 47,935 veterans—an increase of 16.9% and the highest number housed in a single year since 2019. What’s more, it passed that housing goal a month early.
Ending veteran homelessness has been a priority for VA and the Biden-Harris administration. Since 2022, the VA has permanently housed nearly 134,000 homeless veterans. The number of veterans experiencing homelessness in the US has decreased by over 4% since 2020 and by more than 52% since 2010.
The marked decline in homelessness is largely due to the VA’s change in approach. Transitional housing often has followed a linear stepwise model, designed to foster housing readiness by encouraging sobriety and treatment compliance before moving the veteran to the next stage, from emergency shelter to transitional, and finally, permanent housing. While this method worked for some, it posed challenges for those with serious mental illness, substance addiction, or chronic medical conditions.
The VA began shifting its approach in 2012, adopting what it calls its north star—the evidence-based housing first approach. This strategy prioritizes getting veterans into housing as quickly as possible, skipping the intermediate transitional interventions, and then providing wraparound services such as job training and legal and education assistance. “Permanent housing is a critical tool, rather than a reward, for recovery,” says Shawn Liu, director of communications for the VA Homeless Programs Office, in a 2023 article.
A systematic review of studies from 1992 to 2017, shows that the housing first model leads to quicker exits from homelessness and greater long-term housing stability compared with traditional methods. The VA has also found that doing away with enrollment preconditions helps shorten stays among transitional housing providers, improves rates of permanent housing, and increases access to supportive services when needed.
Evidence suggests that the housing first model may reduce the use of emergency department services, hospitalizations, and hospitalized time compared with traditional treatment methods (although the meta-analysis found “considerable variability” between its examined studies). However, evidence that the Housing First model improves health outcomes associated with mental health, substance abuse, or physical health, remains inconclusive. 
In 2010, a demonstration project in the VA setting compared the housing first model with a treatment‐first program for 177 homeless veterans. The study found that the housing first model reduced time to housing placement from 223 to 35 days, significantly increased housing retention rates (98% vs 86%), and significantly reduced emergency room visits.
Over the past decade, the VA has focused on building on the strengths of the program and identifying areas for improvement, such as increasing the prevalence of recovery-oriented philosophies among service providers. “Nearly 48,000 formerly homeless veterans now have a safe, stable place to call home—and there’s nothing more important than that,” said VA Secretary Denis McDonough. “No veteran should experience homelessness in this nation they swore to defend. We are making real progress in this fight, and we will not rest until veteran homelessness is a thing of the past.”
Pharmacist Advocates for Early Adoption of Quadruple Therapy in HFrEF Treatment
SAN DIEGO — An Air Force pharmacist urged colleagues in the military to advocate for the gold standard of quadruple therapy in patients with heart failure with reduced ejection fraction (HFrEF). “When possible, initiate and optimize quadruple therapy before discharge; don’t leave it for a primary care manager (PCM) to handle,” said Maj. Elizabeth Tesch, PharmD, of Maxwell Air Force Base, Montgomery, Ala., in a presentation here at the Joint Federal Pharmacy Seminar. Tesch also cautioned colleagues about the proper use of IV inotropes and vasodilators in congestive heart failure and warned of the dangers of polypharmacy.
“It’s just as important to use medications that provide a mortality benefit in these patients as it is to remove things that are either harmful or lack trial benefit data,” Tesch said. 
In patients with acute heart failure and systolic blood pressure < 90 mmHg, guidelines recommend using both an inotrope and a vasopressor. “There tends to be better data about 2 of them together vs just cranking up a vasoconstrictor, which we tend to sometimes to do when a patient’s blood pressure is bottoming out,” Tesch explained. “But in these patients specifically, that tends to lead to increased afterload, difficulty with cardiac output, and then increased risk of ischemia. So it tends to be better to use both.”
Ideally, Tesch said, patients stabilize within a couple days. In cases of HFrEF, this is when quadruple therapy can enter the picture. 
Quadruple therapy consists of the “4 pillars”: a sodium-glucose co-transporter 2 inhibitor (SGLT2i), a β blocker, a mineralocorticoid receptor antagonist (MRA), and either an angiotensin receptor neprilysin inhibitor (ARNI), an angiotensin‐converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB). 
Tesch noted that the need for titration varies by drug. β blockers typically will need the most up-titration, often in several steps, followed by ARNIs. MRAs may require only one titration or even not at all, and SGLT2 inhibitors do not require titration. 
“[Clinicians] are most comfortable giving ACE inhibitors, ARBs, and β blockers to patients, she said. But new research suggests there is a 10.3% jump in mortality risk (absolute risk difference) compared to ACEi/ β blocker/ARB therapy. Additionally, a 2022 systematic review linked quadruple therapy to a gain of 5 years of life (ranging from 2.5 to7.5 years) for 70-year-old patients compared to no therapy. 
“I don't know how many times I've had a conversation along the lines of, ‘Hey, can we go ahead and start an SGLT2 on this patient?’ only to hear, ‘We'll give that to the PCM [primary care manager]. That sounds like a PCM thing. You just want to get them out of here, it’s a PCM problem.’”
But quick initiation of treatment is crucial. “We're seeing very real mortality benefit data very quickly in these patients,” Tesch said. 
As for polypharmacy, Tesch highlighted the importance of reducing mediation load when possible. “If they have nothing else wrong, these patients will walk out the door on quadruple therapy and perhaps a diuretic, but they probably have a lot more going on,” she said. “All of us in this room are fully aware of what polypharmacy can do to these patients: increased drug interactions, side effects, higher cost, and decreased patient compliance. This is a problem for the heart failure population that really translates into readmissions and increased mortality. We've got to be able to peel off things that are either harmful or not helping.”
Statins, for example, have questionable benefit in HFrEF without coronary artery disease or hyperlipidemia, she said. Oral iron and vitamin D supplementation also have uncertain benefits in the HFrEF population.
Tesch highlighted a pair of reports – one from 2024 and the other from 2022 – that recommended certain therapies  in heart failure, including the antidepressant citalopram (Celexa), the hypertension/urinary retention drug doxazosin (Cardura), and DPP-4 inhibitors (eg, diabetes/weight-loss drugs such as liraglutide [Saxenda]).
Tesch has no disclosures. 
SAN DIEGO — An Air Force pharmacist urged colleagues in the military to advocate for the gold standard of quadruple therapy in patients with heart failure with reduced ejection fraction (HFrEF). “When possible, initiate and optimize quadruple therapy before discharge; don’t leave it for a primary care manager (PCM) to handle,” said Maj. Elizabeth Tesch, PharmD, of Maxwell Air Force Base, Montgomery, Ala., in a presentation here at the Joint Federal Pharmacy Seminar. Tesch also cautioned colleagues about the proper use of IV inotropes and vasodilators in congestive heart failure and warned of the dangers of polypharmacy.
“It’s just as important to use medications that provide a mortality benefit in these patients as it is to remove things that are either harmful or lack trial benefit data,” Tesch said. 
In patients with acute heart failure and systolic blood pressure < 90 mmHg, guidelines recommend using both an inotrope and a vasopressor. “There tends to be better data about 2 of them together vs just cranking up a vasoconstrictor, which we tend to sometimes to do when a patient’s blood pressure is bottoming out,” Tesch explained. “But in these patients specifically, that tends to lead to increased afterload, difficulty with cardiac output, and then increased risk of ischemia. So it tends to be better to use both.”
Ideally, Tesch said, patients stabilize within a couple days. In cases of HFrEF, this is when quadruple therapy can enter the picture. 
Quadruple therapy consists of the “4 pillars”: a sodium-glucose co-transporter 2 inhibitor (SGLT2i), a β blocker, a mineralocorticoid receptor antagonist (MRA), and either an angiotensin receptor neprilysin inhibitor (ARNI), an angiotensin‐converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB). 
Tesch noted that the need for titration varies by drug. β blockers typically will need the most up-titration, often in several steps, followed by ARNIs. MRAs may require only one titration or even not at all, and SGLT2 inhibitors do not require titration. 
“[Clinicians] are most comfortable giving ACE inhibitors, ARBs, and β blockers to patients, she said. But new research suggests there is a 10.3% jump in mortality risk (absolute risk difference) compared to ACEi/ β blocker/ARB therapy. Additionally, a 2022 systematic review linked quadruple therapy to a gain of 5 years of life (ranging from 2.5 to7.5 years) for 70-year-old patients compared to no therapy. 
“I don't know how many times I've had a conversation along the lines of, ‘Hey, can we go ahead and start an SGLT2 on this patient?’ only to hear, ‘We'll give that to the PCM [primary care manager]. That sounds like a PCM thing. You just want to get them out of here, it’s a PCM problem.’”
But quick initiation of treatment is crucial. “We're seeing very real mortality benefit data very quickly in these patients,” Tesch said. 
As for polypharmacy, Tesch highlighted the importance of reducing mediation load when possible. “If they have nothing else wrong, these patients will walk out the door on quadruple therapy and perhaps a diuretic, but they probably have a lot more going on,” she said. “All of us in this room are fully aware of what polypharmacy can do to these patients: increased drug interactions, side effects, higher cost, and decreased patient compliance. This is a problem for the heart failure population that really translates into readmissions and increased mortality. We've got to be able to peel off things that are either harmful or not helping.”
Statins, for example, have questionable benefit in HFrEF without coronary artery disease or hyperlipidemia, she said. Oral iron and vitamin D supplementation also have uncertain benefits in the HFrEF population.
Tesch highlighted a pair of reports – one from 2024 and the other from 2022 – that recommended certain therapies  in heart failure, including the antidepressant citalopram (Celexa), the hypertension/urinary retention drug doxazosin (Cardura), and DPP-4 inhibitors (eg, diabetes/weight-loss drugs such as liraglutide [Saxenda]).
Tesch has no disclosures. 
SAN DIEGO — An Air Force pharmacist urged colleagues in the military to advocate for the gold standard of quadruple therapy in patients with heart failure with reduced ejection fraction (HFrEF). “When possible, initiate and optimize quadruple therapy before discharge; don’t leave it for a primary care manager (PCM) to handle,” said Maj. Elizabeth Tesch, PharmD, of Maxwell Air Force Base, Montgomery, Ala., in a presentation here at the Joint Federal Pharmacy Seminar. Tesch also cautioned colleagues about the proper use of IV inotropes and vasodilators in congestive heart failure and warned of the dangers of polypharmacy.
“It’s just as important to use medications that provide a mortality benefit in these patients as it is to remove things that are either harmful or lack trial benefit data,” Tesch said. 
In patients with acute heart failure and systolic blood pressure < 90 mmHg, guidelines recommend using both an inotrope and a vasopressor. “There tends to be better data about 2 of them together vs just cranking up a vasoconstrictor, which we tend to sometimes to do when a patient’s blood pressure is bottoming out,” Tesch explained. “But in these patients specifically, that tends to lead to increased afterload, difficulty with cardiac output, and then increased risk of ischemia. So it tends to be better to use both.”
Ideally, Tesch said, patients stabilize within a couple days. In cases of HFrEF, this is when quadruple therapy can enter the picture. 
Quadruple therapy consists of the “4 pillars”: a sodium-glucose co-transporter 2 inhibitor (SGLT2i), a β blocker, a mineralocorticoid receptor antagonist (MRA), and either an angiotensin receptor neprilysin inhibitor (ARNI), an angiotensin‐converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB). 
Tesch noted that the need for titration varies by drug. β blockers typically will need the most up-titration, often in several steps, followed by ARNIs. MRAs may require only one titration or even not at all, and SGLT2 inhibitors do not require titration. 
“[Clinicians] are most comfortable giving ACE inhibitors, ARBs, and β blockers to patients, she said. But new research suggests there is a 10.3% jump in mortality risk (absolute risk difference) compared to ACEi/ β blocker/ARB therapy. Additionally, a 2022 systematic review linked quadruple therapy to a gain of 5 years of life (ranging from 2.5 to7.5 years) for 70-year-old patients compared to no therapy. 
“I don't know how many times I've had a conversation along the lines of, ‘Hey, can we go ahead and start an SGLT2 on this patient?’ only to hear, ‘We'll give that to the PCM [primary care manager]. That sounds like a PCM thing. You just want to get them out of here, it’s a PCM problem.’”
But quick initiation of treatment is crucial. “We're seeing very real mortality benefit data very quickly in these patients,” Tesch said. 
As for polypharmacy, Tesch highlighted the importance of reducing mediation load when possible. “If they have nothing else wrong, these patients will walk out the door on quadruple therapy and perhaps a diuretic, but they probably have a lot more going on,” she said. “All of us in this room are fully aware of what polypharmacy can do to these patients: increased drug interactions, side effects, higher cost, and decreased patient compliance. This is a problem for the heart failure population that really translates into readmissions and increased mortality. We've got to be able to peel off things that are either harmful or not helping.”
Statins, for example, have questionable benefit in HFrEF without coronary artery disease or hyperlipidemia, she said. Oral iron and vitamin D supplementation also have uncertain benefits in the HFrEF population.
Tesch highlighted a pair of reports – one from 2024 and the other from 2022 – that recommended certain therapies  in heart failure, including the antidepressant citalopram (Celexa), the hypertension/urinary retention drug doxazosin (Cardura), and DPP-4 inhibitors (eg, diabetes/weight-loss drugs such as liraglutide [Saxenda]).
Tesch has no disclosures. 
 
AI Tool Identifies Undiagnosed Early-Stage MASLD
SAN DIEGO — according to new research.
Among the patients identified by the algorithm as meeting the criteria for MASLD, only a small percentage had an MASLD-associated diagnostic code.
“A significant portion of patients who meet criteria for MASLD go undiagnosed, which can lead to delays in care and progression to advanced liver disease,” said lead author Ariana Stuart, MD, an internal medicine resident at the University of Washington, Seattle, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
“However, people shouldn’t interpret our findings as a lack of primary care training or management,” she said. “Instead, this study indicates that AI can complement physician workflow and address the limitations of traditional clinical practice.”
 
Developing an MASLD Algorithm
Typically, the identification of MASLD has relied on clinician recognition and descriptions in chart notes, Stuart said. Early-stage disease often goes unnoticed, particularly if patients remain asymptomatic, until cirrhosis develops.
To address this, Stuart and colleagues created a machine learning, natural language processing AI algorithm on the basis of MASLD criteria from AASLD: Hepatic steatosis on imaging and at least one metabolic factor (elevated body mass index, hypertension, prediabetes or diabetes, or dyslipidemia). The model was validated by two physicians, who manually reviewed monthly cohorts generated by the algorithm.
Between December 2023 and May 2024, the researchers used the algorithm to analyze an MASLD cohort from medical centers in the Seattle area. The mean age was 51 years, 44% were women, and 68% were White. Those with alcohol-associated liver disease, metastatic malignancy, and autoimmune, genetic, and infectious causes of liver disease were excluded.
The algorithm identified 957 patients with imaging that matched MASLD criteria.
Among those, 137 patients (17%) identified by the algorithm had an MASLD-associated diagnostic code. For these patients, the mean time from initial imaging with steatosis to diagnosis was 33 days, according to patient records.
An additional 26 patients received an MASLD diagnosis during the study period, with a mean time to diagnosis of 56.2 days.
In terms of patient management, 245 patients (26%) had contact with a gastroenterologist or hepatologist based on documentation of a letter, phone call, or office visit. In addition, 546 patients (57%) were screened for hepatitis C.
After adjusting for an over-inclusion error rate of 12.8% and an overdiagnosis rate of 0.02%, the research team found 697 patients (83%) lacked a relevant diagnosis. After multiple iterations, the algorithm achieved an accuracy of about 88%, Stuart said.
 
Considering Future AI Use
Stuart and colleagues are now testing the algorithm in larger groups and across longer periods.
After that, they intend to implement a quality improvement program to increase awareness for clinicians and primary care providers, as well as train users on how to interpret and move forward with findings of hepatic steatosis in patient records.
For instance, future AI models could flag patients for additional testing, improve chart review, and aid in research efforts around cardiometabolic comorbidities associated with MASLD, she said.
Looking ahead, AI tools such as these represent what’s possible for advancements in research, patient care, and clinical workflows, said Ashley Spann, MD, assistant professor and transplant hepatologist at Vanderbilt University, Nashville, Tennessee, and director of clinical research informatics for Vanderbilt’s Gastroenterology Division.
“AI, in my view, is actually augmented intelligence,” she added. “We need to think about the people and processes involved.”
Spann, who spoke about the use of AI tools in medicine in general, stressed the need for transparency in AI use, careful validation of input-output data, frameworks for machine learning models in medicine, and standardization across institutions.
“What we ultimately need is an infrastructure that supports the simultaneous deployment and evaluation of these models,” she said. “We all need to be on the same page and make sure our models work in multiple settings and make adjustments based on algorithmovigilance afterward.”
Stuart reported no relevant disclosures. Spann serves on Epic’s hepatology steering board, which has focused on how to use AI tools in electronic medical records.
A version of this article appeared on Medscape.com.
SAN DIEGO — according to new research.
Among the patients identified by the algorithm as meeting the criteria for MASLD, only a small percentage had an MASLD-associated diagnostic code.
“A significant portion of patients who meet criteria for MASLD go undiagnosed, which can lead to delays in care and progression to advanced liver disease,” said lead author Ariana Stuart, MD, an internal medicine resident at the University of Washington, Seattle, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
“However, people shouldn’t interpret our findings as a lack of primary care training or management,” she said. “Instead, this study indicates that AI can complement physician workflow and address the limitations of traditional clinical practice.”
 
Developing an MASLD Algorithm
Typically, the identification of MASLD has relied on clinician recognition and descriptions in chart notes, Stuart said. Early-stage disease often goes unnoticed, particularly if patients remain asymptomatic, until cirrhosis develops.
To address this, Stuart and colleagues created a machine learning, natural language processing AI algorithm on the basis of MASLD criteria from AASLD: Hepatic steatosis on imaging and at least one metabolic factor (elevated body mass index, hypertension, prediabetes or diabetes, or dyslipidemia). The model was validated by two physicians, who manually reviewed monthly cohorts generated by the algorithm.
Between December 2023 and May 2024, the researchers used the algorithm to analyze an MASLD cohort from medical centers in the Seattle area. The mean age was 51 years, 44% were women, and 68% were White. Those with alcohol-associated liver disease, metastatic malignancy, and autoimmune, genetic, and infectious causes of liver disease were excluded.
The algorithm identified 957 patients with imaging that matched MASLD criteria.
Among those, 137 patients (17%) identified by the algorithm had an MASLD-associated diagnostic code. For these patients, the mean time from initial imaging with steatosis to diagnosis was 33 days, according to patient records.
An additional 26 patients received an MASLD diagnosis during the study period, with a mean time to diagnosis of 56.2 days.
In terms of patient management, 245 patients (26%) had contact with a gastroenterologist or hepatologist based on documentation of a letter, phone call, or office visit. In addition, 546 patients (57%) were screened for hepatitis C.
After adjusting for an over-inclusion error rate of 12.8% and an overdiagnosis rate of 0.02%, the research team found 697 patients (83%) lacked a relevant diagnosis. After multiple iterations, the algorithm achieved an accuracy of about 88%, Stuart said.
 
Considering Future AI Use
Stuart and colleagues are now testing the algorithm in larger groups and across longer periods.
After that, they intend to implement a quality improvement program to increase awareness for clinicians and primary care providers, as well as train users on how to interpret and move forward with findings of hepatic steatosis in patient records.
For instance, future AI models could flag patients for additional testing, improve chart review, and aid in research efforts around cardiometabolic comorbidities associated with MASLD, she said.
Looking ahead, AI tools such as these represent what’s possible for advancements in research, patient care, and clinical workflows, said Ashley Spann, MD, assistant professor and transplant hepatologist at Vanderbilt University, Nashville, Tennessee, and director of clinical research informatics for Vanderbilt’s Gastroenterology Division.
“AI, in my view, is actually augmented intelligence,” she added. “We need to think about the people and processes involved.”
Spann, who spoke about the use of AI tools in medicine in general, stressed the need for transparency in AI use, careful validation of input-output data, frameworks for machine learning models in medicine, and standardization across institutions.
“What we ultimately need is an infrastructure that supports the simultaneous deployment and evaluation of these models,” she said. “We all need to be on the same page and make sure our models work in multiple settings and make adjustments based on algorithmovigilance afterward.”
Stuart reported no relevant disclosures. Spann serves on Epic’s hepatology steering board, which has focused on how to use AI tools in electronic medical records.
A version of this article appeared on Medscape.com.
SAN DIEGO — according to new research.
Among the patients identified by the algorithm as meeting the criteria for MASLD, only a small percentage had an MASLD-associated diagnostic code.
“A significant portion of patients who meet criteria for MASLD go undiagnosed, which can lead to delays in care and progression to advanced liver disease,” said lead author Ariana Stuart, MD, an internal medicine resident at the University of Washington, Seattle, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
“However, people shouldn’t interpret our findings as a lack of primary care training or management,” she said. “Instead, this study indicates that AI can complement physician workflow and address the limitations of traditional clinical practice.”
 
Developing an MASLD Algorithm
Typically, the identification of MASLD has relied on clinician recognition and descriptions in chart notes, Stuart said. Early-stage disease often goes unnoticed, particularly if patients remain asymptomatic, until cirrhosis develops.
To address this, Stuart and colleagues created a machine learning, natural language processing AI algorithm on the basis of MASLD criteria from AASLD: Hepatic steatosis on imaging and at least one metabolic factor (elevated body mass index, hypertension, prediabetes or diabetes, or dyslipidemia). The model was validated by two physicians, who manually reviewed monthly cohorts generated by the algorithm.
Between December 2023 and May 2024, the researchers used the algorithm to analyze an MASLD cohort from medical centers in the Seattle area. The mean age was 51 years, 44% were women, and 68% were White. Those with alcohol-associated liver disease, metastatic malignancy, and autoimmune, genetic, and infectious causes of liver disease were excluded.
The algorithm identified 957 patients with imaging that matched MASLD criteria.
Among those, 137 patients (17%) identified by the algorithm had an MASLD-associated diagnostic code. For these patients, the mean time from initial imaging with steatosis to diagnosis was 33 days, according to patient records.
An additional 26 patients received an MASLD diagnosis during the study period, with a mean time to diagnosis of 56.2 days.
In terms of patient management, 245 patients (26%) had contact with a gastroenterologist or hepatologist based on documentation of a letter, phone call, or office visit. In addition, 546 patients (57%) were screened for hepatitis C.
After adjusting for an over-inclusion error rate of 12.8% and an overdiagnosis rate of 0.02%, the research team found 697 patients (83%) lacked a relevant diagnosis. After multiple iterations, the algorithm achieved an accuracy of about 88%, Stuart said.
 
Considering Future AI Use
Stuart and colleagues are now testing the algorithm in larger groups and across longer periods.
After that, they intend to implement a quality improvement program to increase awareness for clinicians and primary care providers, as well as train users on how to interpret and move forward with findings of hepatic steatosis in patient records.
For instance, future AI models could flag patients for additional testing, improve chart review, and aid in research efforts around cardiometabolic comorbidities associated with MASLD, she said.
Looking ahead, AI tools such as these represent what’s possible for advancements in research, patient care, and clinical workflows, said Ashley Spann, MD, assistant professor and transplant hepatologist at Vanderbilt University, Nashville, Tennessee, and director of clinical research informatics for Vanderbilt’s Gastroenterology Division.
“AI, in my view, is actually augmented intelligence,” she added. “We need to think about the people and processes involved.”
Spann, who spoke about the use of AI tools in medicine in general, stressed the need for transparency in AI use, careful validation of input-output data, frameworks for machine learning models in medicine, and standardization across institutions.
“What we ultimately need is an infrastructure that supports the simultaneous deployment and evaluation of these models,” she said. “We all need to be on the same page and make sure our models work in multiple settings and make adjustments based on algorithmovigilance afterward.”
Stuart reported no relevant disclosures. Spann serves on Epic’s hepatology steering board, which has focused on how to use AI tools in electronic medical records.
A version of this article appeared on Medscape.com.
FROM AASLD 24
MELD 3.0 Reduces Sex-Based Liver Transplant Disparities
SAN DIEGO — , according to new research.
In particular, women are now more likely to be added to the waitlist for a liver transplant, more likely to receive a transplant, and less likely to fall off the waitlist because of death.
“MELD 3.0 improved access to transplantation for women, and now waitlist mortality and transplant rates for women more closely approximate the rates for men,” said lead author Allison Kwong, MD, assistant professor of medicine and transplant hepatologist at Stanford Medicine in California. 
“Overall transplant outcomes have also improved year over year,” said Kwong, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD). 
 
Changes in MELD and Transplant Numbers
MELD, which estimates liver failure severity and short-term survival in patients with chronic liver disease, has been used since 2002 to determine organ allocation priority for patients in the United States awaiting liver transplantation. Originally, the score incorporated three variables: creatinine, bilirubin, and the international normalized ratio (INR). MELDNa1, or MELD 2.0, was adopted in 2016 to add sodium.
“Under this system, however, there have been sex-based disparities” with women receiving lower priority scores despite similar disease severity, said Kwong. 
“This has been attributed to several factors, such as the creatinine term in the MELD score underestimating renal dysfunction in women, height and body size differences, and differences in disease etiology, and how we’ve assigned exception points historically,” she reported. 
Men have had a lower pretransplant mortality rate and higher deceased donor transplant rates, she added. 
MELD 3.0 was developed to address these gender differences and other determinants of waitlist outcomes. The updated equation added 1.33 points for women, as well as adding other variables, such as albumin, interactions between bilirubin and sodium, and interactions between albumin and creatinine, to increase prediction accuracy. 
To observe the effects of the new system, Kwong and colleagues analyzed OPTN data for patients aged 12 years or older, focusing on the records of more than 20,300 newly registered liver transplant candidates, and about 18,700 transplant recipients, during the 12 months before and 12 months after MELD 3.0 was implemented.
After the switch, 43.7% of newly registered liver transplant candidates were women, compared with 40.4% before the switch. At registration, the median age was 55, both before and after the change in policy, and the median MELD score changed from 23 to 22 after implementation.
In addition, 42.1% of transplants occurred among women after MELD 3.0 implementation, as compared with 37.3% before. Overall, deceased donor transplant rates were similar for men and women after MELD 3.0 implementation.
The 90-day waitlist dropout rate — patients who died or became too sick to receive a transplant — decreased from 13.5% to 9.1% among women, which may be partially attributable to MELD 3.0, said Kwong. 
However, waitlist dropout rates also decreased among men, from 9.8% to 7.4%, probably because of improvements in technology, such as machine perfusion, which have increased the number of available livers, she added.
 
Disparities Continue to Exist
Some disparities still exist. Although the total median MELD score at transplant decreased from 29 to 27, women still had a higher median score of 29 at transplant, compared with a median score of 27 among men.
“This indicates that there may still be differences in transplant access between the sexes,” Kwong said. “There are still body size differences that can affect the probability of transplant, and this would not be addressed by MELD 3.0.”
Additional transplant disparities exist related to other patient characteristics, such as age, race, and ethnicity. 
Future versions of MELD could potentially consider these factors, said session moderator Aleksander Krag, MD, PhD, MBA, professor of clinical medicine at the University of Southern Denmark, Odense, and secretary general of the European Association for the Study of the Liver, 2023-2025.
“There are infinite versions of MELD that can be made,” Kwong said. “It’s still early to see how MELD 3.0 will serve the system, but so far, so good.”
In a comment, Tamar Taddei, MD, professor of medicine in digestive diseases at Yale School of Medicine, New Haven, Connecticut, who comoderated the session, noted the importance of using a MELD score that considers sex-based differences.
This study brings MELD 3.0 to its fruition by reducing the disparities experienced by women who were underserved by the previous scoring systems, she said. 
It was lovely to see that MELD 3.0 reduced the disparities with transplants, and also that the waitlist dropout was reduced — for both men and women,” Taddei said. “This change is a no-brainer.”
Kwong, Krag, and Taddei reported no relevant disclosures.
A version of this article appeared on Medscape.com.
SAN DIEGO — , according to new research.
In particular, women are now more likely to be added to the waitlist for a liver transplant, more likely to receive a transplant, and less likely to fall off the waitlist because of death.
“MELD 3.0 improved access to transplantation for women, and now waitlist mortality and transplant rates for women more closely approximate the rates for men,” said lead author Allison Kwong, MD, assistant professor of medicine and transplant hepatologist at Stanford Medicine in California. 
“Overall transplant outcomes have also improved year over year,” said Kwong, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD). 
 
Changes in MELD and Transplant Numbers
MELD, which estimates liver failure severity and short-term survival in patients with chronic liver disease, has been used since 2002 to determine organ allocation priority for patients in the United States awaiting liver transplantation. Originally, the score incorporated three variables: creatinine, bilirubin, and the international normalized ratio (INR). MELDNa1, or MELD 2.0, was adopted in 2016 to add sodium.
“Under this system, however, there have been sex-based disparities” with women receiving lower priority scores despite similar disease severity, said Kwong. 
“This has been attributed to several factors, such as the creatinine term in the MELD score underestimating renal dysfunction in women, height and body size differences, and differences in disease etiology, and how we’ve assigned exception points historically,” she reported. 
Men have had a lower pretransplant mortality rate and higher deceased donor transplant rates, she added. 
MELD 3.0 was developed to address these gender differences and other determinants of waitlist outcomes. The updated equation added 1.33 points for women, as well as adding other variables, such as albumin, interactions between bilirubin and sodium, and interactions between albumin and creatinine, to increase prediction accuracy. 
To observe the effects of the new system, Kwong and colleagues analyzed OPTN data for patients aged 12 years or older, focusing on the records of more than 20,300 newly registered liver transplant candidates, and about 18,700 transplant recipients, during the 12 months before and 12 months after MELD 3.0 was implemented.
After the switch, 43.7% of newly registered liver transplant candidates were women, compared with 40.4% before the switch. At registration, the median age was 55, both before and after the change in policy, and the median MELD score changed from 23 to 22 after implementation.
In addition, 42.1% of transplants occurred among women after MELD 3.0 implementation, as compared with 37.3% before. Overall, deceased donor transplant rates were similar for men and women after MELD 3.0 implementation.
The 90-day waitlist dropout rate — patients who died or became too sick to receive a transplant — decreased from 13.5% to 9.1% among women, which may be partially attributable to MELD 3.0, said Kwong. 
However, waitlist dropout rates also decreased among men, from 9.8% to 7.4%, probably because of improvements in technology, such as machine perfusion, which have increased the number of available livers, she added.
 
Disparities Continue to Exist
Some disparities still exist. Although the total median MELD score at transplant decreased from 29 to 27, women still had a higher median score of 29 at transplant, compared with a median score of 27 among men.
“This indicates that there may still be differences in transplant access between the sexes,” Kwong said. “There are still body size differences that can affect the probability of transplant, and this would not be addressed by MELD 3.0.”
Additional transplant disparities exist related to other patient characteristics, such as age, race, and ethnicity. 
Future versions of MELD could potentially consider these factors, said session moderator Aleksander Krag, MD, PhD, MBA, professor of clinical medicine at the University of Southern Denmark, Odense, and secretary general of the European Association for the Study of the Liver, 2023-2025.
“There are infinite versions of MELD that can be made,” Kwong said. “It’s still early to see how MELD 3.0 will serve the system, but so far, so good.”
In a comment, Tamar Taddei, MD, professor of medicine in digestive diseases at Yale School of Medicine, New Haven, Connecticut, who comoderated the session, noted the importance of using a MELD score that considers sex-based differences.
This study brings MELD 3.0 to its fruition by reducing the disparities experienced by women who were underserved by the previous scoring systems, she said. 
It was lovely to see that MELD 3.0 reduced the disparities with transplants, and also that the waitlist dropout was reduced — for both men and women,” Taddei said. “This change is a no-brainer.”
Kwong, Krag, and Taddei reported no relevant disclosures.
A version of this article appeared on Medscape.com.
SAN DIEGO — , according to new research.
In particular, women are now more likely to be added to the waitlist for a liver transplant, more likely to receive a transplant, and less likely to fall off the waitlist because of death.
“MELD 3.0 improved access to transplantation for women, and now waitlist mortality and transplant rates for women more closely approximate the rates for men,” said lead author Allison Kwong, MD, assistant professor of medicine and transplant hepatologist at Stanford Medicine in California. 
“Overall transplant outcomes have also improved year over year,” said Kwong, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD). 
 
Changes in MELD and Transplant Numbers
MELD, which estimates liver failure severity and short-term survival in patients with chronic liver disease, has been used since 2002 to determine organ allocation priority for patients in the United States awaiting liver transplantation. Originally, the score incorporated three variables: creatinine, bilirubin, and the international normalized ratio (INR). MELDNa1, or MELD 2.0, was adopted in 2016 to add sodium.
“Under this system, however, there have been sex-based disparities” with women receiving lower priority scores despite similar disease severity, said Kwong. 
“This has been attributed to several factors, such as the creatinine term in the MELD score underestimating renal dysfunction in women, height and body size differences, and differences in disease etiology, and how we’ve assigned exception points historically,” she reported. 
Men have had a lower pretransplant mortality rate and higher deceased donor transplant rates, she added. 
MELD 3.0 was developed to address these gender differences and other determinants of waitlist outcomes. The updated equation added 1.33 points for women, as well as adding other variables, such as albumin, interactions between bilirubin and sodium, and interactions between albumin and creatinine, to increase prediction accuracy. 
To observe the effects of the new system, Kwong and colleagues analyzed OPTN data for patients aged 12 years or older, focusing on the records of more than 20,300 newly registered liver transplant candidates, and about 18,700 transplant recipients, during the 12 months before and 12 months after MELD 3.0 was implemented.
After the switch, 43.7% of newly registered liver transplant candidates were women, compared with 40.4% before the switch. At registration, the median age was 55, both before and after the change in policy, and the median MELD score changed from 23 to 22 after implementation.
In addition, 42.1% of transplants occurred among women after MELD 3.0 implementation, as compared with 37.3% before. Overall, deceased donor transplant rates were similar for men and women after MELD 3.0 implementation.
The 90-day waitlist dropout rate — patients who died or became too sick to receive a transplant — decreased from 13.5% to 9.1% among women, which may be partially attributable to MELD 3.0, said Kwong. 
However, waitlist dropout rates also decreased among men, from 9.8% to 7.4%, probably because of improvements in technology, such as machine perfusion, which have increased the number of available livers, she added.
 
Disparities Continue to Exist
Some disparities still exist. Although the total median MELD score at transplant decreased from 29 to 27, women still had a higher median score of 29 at transplant, compared with a median score of 27 among men.
“This indicates that there may still be differences in transplant access between the sexes,” Kwong said. “There are still body size differences that can affect the probability of transplant, and this would not be addressed by MELD 3.0.”
Additional transplant disparities exist related to other patient characteristics, such as age, race, and ethnicity. 
Future versions of MELD could potentially consider these factors, said session moderator Aleksander Krag, MD, PhD, MBA, professor of clinical medicine at the University of Southern Denmark, Odense, and secretary general of the European Association for the Study of the Liver, 2023-2025.
“There are infinite versions of MELD that can be made,” Kwong said. “It’s still early to see how MELD 3.0 will serve the system, but so far, so good.”
In a comment, Tamar Taddei, MD, professor of medicine in digestive diseases at Yale School of Medicine, New Haven, Connecticut, who comoderated the session, noted the importance of using a MELD score that considers sex-based differences.
This study brings MELD 3.0 to its fruition by reducing the disparities experienced by women who were underserved by the previous scoring systems, she said. 
It was lovely to see that MELD 3.0 reduced the disparities with transplants, and also that the waitlist dropout was reduced — for both men and women,” Taddei said. “This change is a no-brainer.”
Kwong, Krag, and Taddei reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM AASLD 24
‘Watershed Moment’: Semaglutide Shown to Be Effective in MASH
SAN DIEGO — according to interim results from a phase 3 trial.
At 72 weeks, a 2.4-mg once-weekly subcutaneous dose of semaglutide demonstrated superiority, compared with placebo, for the two primary endpoints: Resolution of steatohepatitis with no worsening of fibrosis and improvement in liver fibrosis with no worsening of steatohepatitis.
“It’s been a long journey. I’ve been working with GLP-1s for 16 years, and it’s great to be able to report the first GLP-1 receptor agonist to demonstrate efficacy in a phase 3 trial for MASH,” said lead author Philip Newsome, MD, PhD, director of the Roger Williams Institute of Liver Studies at King’s College London in England.
“There were also improvements in a slew of other noninvasive markers,” said Newsome, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
Although already seen in a broader context, “it’s nice to see a demonstration of the cardiometabolic benefits in the context of MASH and a reassuring safety profile,” he added.
 
Interim ESSENCE Trial Analysis
ESSENCE (NCT04822181) is an ongoing multicenter, phase 3 randomized, double-blind, placebo-controlled outcome trial studying semaglutide for the potential treatment of MASH.
The trial includes 1200 participants with biopsy-defined MASH and fibrosis, stages F2 and F3, who were randomized 2:1 to a once-weekly subcutaneous injection of 2.4 mg of semaglutide or placebo for 240 weeks. After initiation, the semaglutide dosage was increased every 4 weeks up to 16 weeks when the full dose (2.4 mg) was reached.
In a planned interim analysis, the trial investigators evaluated the primary endpoints at week 72 for the first 800 participants, with biopsies taken at weeks 1 and 72.
A total of 534 people were randomized to the semaglutide group, including 169 with F2 fibrosis and 365 with F3 fibrosis. Among the 266 participants randomized to placebo, 81 had F2 fibrosis and 185 had F3 fibrosis.
At baseline, the patient characteristics were similar between the groups (mean age, 56 years; body mass index, 34.6). A majority of participants also were White (67.5%), women (57.1%), had type 2 diabetes (55.9%), F3 fibrosis (68.8%), and enhanced liver fibrosis (ELF) scores around 10 (55.5%).
For the first primary endpoint, 62.9% of those in the semaglutide group and 34.1% of those in the placebo group reached resolution of steatohepatitis with no worsening of fibrosis. This represented an estimated difference in responder proportions (EDP) of 28.9%.
In addition, 37% of those in the semaglutide group and 22.5% of those in the placebo group met the second primary endpoint of improvement in liver fibrosis with no worsening of steatohepatitis (EDP, 14.4%).
Among the secondary endpoints, combined resolution of steatohepatitis with a one-stage improvement in liver fibrosis occurred in 32.8% of the semaglutide group and 16.2% of the placebo group (EDP, 16.6%).
In additional analyses, Newsome and colleagues found 20%-40% improvements in liver enzymes and noninvasive fibrosis markers, such as ELF and vibration-controlled transient elastography liver stiffness.
Weight loss was also significant, with a 10.5% reduction in the semaglutide group compared with a 2% reduction in the placebo group.
Cardiometabolic risk factors improved as well, with changes in blood pressure measurements, hemoglobin A1c scores, and cholesterol values.
Although not considered statistically significant, patients in the semaglutide group also reported greater reductions in body pain.
In a safety analysis of 1195 participants at 96 weeks, adverse events, severe adverse events, and discontinuations were similar in both groups. Not surprisingly, gastrointestinal side effects were more commonly reported in the semaglutide group, Newsome said.
 
Highly Anticipated Results
After Newsome’s presentation, attendees applauded.
Rohit Loomba, MD, a gastroenterologist at the University of California, San Diego, who was not involved with the study, called the results the “highlight of the meeting.”
This sentiment was echoed by Naga Chalasani, MD, AGAF, a gastroenterologist at Indiana University Medical Center, Indianapolis, who called the results a “watershed moment in the MASH field” with “terrific data.”
 
Based on questions after the presentation, Newsome indicated that future ESSENCE reports would look at certain aspects of the results, such as the 10% weight loss among those in the semaglutide group, as well as the mechanisms of histological and fibrosis improvement.
“We know from other GLP-1 trials that more weight loss occurs in those who don’t have type 2 diabetes, and we’re still running those analyses,” he said. “Weight loss is clearly a major contributor to MASH improvement, but there seem to be some weight-independent effects here, which are likely linked to insulin sensitivity or inflammation. We look forward to presenting those analyses in due course.”
 
In a comment, Kimberly Ann Brown, MD, AGAF, chief of gastroenterology and hepatology at Henry Ford Health System in Detroit, Michigan, AASLD Foundation chair, and comoderator of the late-breaking abstract session, spoke about the highly anticipated presentation.
“This study was really the pinnacle of this meeting. We’ve all been waiting for this data, in large part because many of our patients are already using these medications,” Brown said. “Seeing the benefit for the liver, as well as lipids and other cardiovascular measures, is so important. Having this confirmatory study will hopefully lead to the availability of the medication for this indication among our patients.”
Newsome reported numerous disclosures, including consultant relationships with pharmaceutical companies, such as Novo Nordisk, Boehringer Ingelheim, and Madrigal Pharmaceuticals. Loomba has research grant relationships with numerous companies, including Hanmi, Gilead, Galmed Pharmaceuticals, Galectin Therapeutics, Eli Lilly, Bristol-Myers Squibb, and Boehringer Ingelheim. Chalasani has consultant relationships with Ipsen, Pfizer, Merck, Altimmune, GSK, Madrigal Pharmaceuticals, and Zydus. Brown reported no relevant disclosures.
A version of this article appeared on Medscape.com.
SAN DIEGO — according to interim results from a phase 3 trial.
At 72 weeks, a 2.4-mg once-weekly subcutaneous dose of semaglutide demonstrated superiority, compared with placebo, for the two primary endpoints: Resolution of steatohepatitis with no worsening of fibrosis and improvement in liver fibrosis with no worsening of steatohepatitis.
“It’s been a long journey. I’ve been working with GLP-1s for 16 years, and it’s great to be able to report the first GLP-1 receptor agonist to demonstrate efficacy in a phase 3 trial for MASH,” said lead author Philip Newsome, MD, PhD, director of the Roger Williams Institute of Liver Studies at King’s College London in England.
“There were also improvements in a slew of other noninvasive markers,” said Newsome, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
Although already seen in a broader context, “it’s nice to see a demonstration of the cardiometabolic benefits in the context of MASH and a reassuring safety profile,” he added.
 
Interim ESSENCE Trial Analysis
ESSENCE (NCT04822181) is an ongoing multicenter, phase 3 randomized, double-blind, placebo-controlled outcome trial studying semaglutide for the potential treatment of MASH.
The trial includes 1200 participants with biopsy-defined MASH and fibrosis, stages F2 and F3, who were randomized 2:1 to a once-weekly subcutaneous injection of 2.4 mg of semaglutide or placebo for 240 weeks. After initiation, the semaglutide dosage was increased every 4 weeks up to 16 weeks when the full dose (2.4 mg) was reached.
In a planned interim analysis, the trial investigators evaluated the primary endpoints at week 72 for the first 800 participants, with biopsies taken at weeks 1 and 72.
A total of 534 people were randomized to the semaglutide group, including 169 with F2 fibrosis and 365 with F3 fibrosis. Among the 266 participants randomized to placebo, 81 had F2 fibrosis and 185 had F3 fibrosis.
At baseline, the patient characteristics were similar between the groups (mean age, 56 years; body mass index, 34.6). A majority of participants also were White (67.5%), women (57.1%), had type 2 diabetes (55.9%), F3 fibrosis (68.8%), and enhanced liver fibrosis (ELF) scores around 10 (55.5%).
For the first primary endpoint, 62.9% of those in the semaglutide group and 34.1% of those in the placebo group reached resolution of steatohepatitis with no worsening of fibrosis. This represented an estimated difference in responder proportions (EDP) of 28.9%.
In addition, 37% of those in the semaglutide group and 22.5% of those in the placebo group met the second primary endpoint of improvement in liver fibrosis with no worsening of steatohepatitis (EDP, 14.4%).
Among the secondary endpoints, combined resolution of steatohepatitis with a one-stage improvement in liver fibrosis occurred in 32.8% of the semaglutide group and 16.2% of the placebo group (EDP, 16.6%).
In additional analyses, Newsome and colleagues found 20%-40% improvements in liver enzymes and noninvasive fibrosis markers, such as ELF and vibration-controlled transient elastography liver stiffness.
Weight loss was also significant, with a 10.5% reduction in the semaglutide group compared with a 2% reduction in the placebo group.
Cardiometabolic risk factors improved as well, with changes in blood pressure measurements, hemoglobin A1c scores, and cholesterol values.
Although not considered statistically significant, patients in the semaglutide group also reported greater reductions in body pain.
In a safety analysis of 1195 participants at 96 weeks, adverse events, severe adverse events, and discontinuations were similar in both groups. Not surprisingly, gastrointestinal side effects were more commonly reported in the semaglutide group, Newsome said.
 
Highly Anticipated Results
After Newsome’s presentation, attendees applauded.
Rohit Loomba, MD, a gastroenterologist at the University of California, San Diego, who was not involved with the study, called the results the “highlight of the meeting.”
This sentiment was echoed by Naga Chalasani, MD, AGAF, a gastroenterologist at Indiana University Medical Center, Indianapolis, who called the results a “watershed moment in the MASH field” with “terrific data.”
 
Based on questions after the presentation, Newsome indicated that future ESSENCE reports would look at certain aspects of the results, such as the 10% weight loss among those in the semaglutide group, as well as the mechanisms of histological and fibrosis improvement.
“We know from other GLP-1 trials that more weight loss occurs in those who don’t have type 2 diabetes, and we’re still running those analyses,” he said. “Weight loss is clearly a major contributor to MASH improvement, but there seem to be some weight-independent effects here, which are likely linked to insulin sensitivity or inflammation. We look forward to presenting those analyses in due course.”
 
In a comment, Kimberly Ann Brown, MD, AGAF, chief of gastroenterology and hepatology at Henry Ford Health System in Detroit, Michigan, AASLD Foundation chair, and comoderator of the late-breaking abstract session, spoke about the highly anticipated presentation.
“This study was really the pinnacle of this meeting. We’ve all been waiting for this data, in large part because many of our patients are already using these medications,” Brown said. “Seeing the benefit for the liver, as well as lipids and other cardiovascular measures, is so important. Having this confirmatory study will hopefully lead to the availability of the medication for this indication among our patients.”
Newsome reported numerous disclosures, including consultant relationships with pharmaceutical companies, such as Novo Nordisk, Boehringer Ingelheim, and Madrigal Pharmaceuticals. Loomba has research grant relationships with numerous companies, including Hanmi, Gilead, Galmed Pharmaceuticals, Galectin Therapeutics, Eli Lilly, Bristol-Myers Squibb, and Boehringer Ingelheim. Chalasani has consultant relationships with Ipsen, Pfizer, Merck, Altimmune, GSK, Madrigal Pharmaceuticals, and Zydus. Brown reported no relevant disclosures.
A version of this article appeared on Medscape.com.
SAN DIEGO — according to interim results from a phase 3 trial.
At 72 weeks, a 2.4-mg once-weekly subcutaneous dose of semaglutide demonstrated superiority, compared with placebo, for the two primary endpoints: Resolution of steatohepatitis with no worsening of fibrosis and improvement in liver fibrosis with no worsening of steatohepatitis.
“It’s been a long journey. I’ve been working with GLP-1s for 16 years, and it’s great to be able to report the first GLP-1 receptor agonist to demonstrate efficacy in a phase 3 trial for MASH,” said lead author Philip Newsome, MD, PhD, director of the Roger Williams Institute of Liver Studies at King’s College London in England.
“There were also improvements in a slew of other noninvasive markers,” said Newsome, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
Although already seen in a broader context, “it’s nice to see a demonstration of the cardiometabolic benefits in the context of MASH and a reassuring safety profile,” he added.
 
Interim ESSENCE Trial Analysis
ESSENCE (NCT04822181) is an ongoing multicenter, phase 3 randomized, double-blind, placebo-controlled outcome trial studying semaglutide for the potential treatment of MASH.
The trial includes 1200 participants with biopsy-defined MASH and fibrosis, stages F2 and F3, who were randomized 2:1 to a once-weekly subcutaneous injection of 2.4 mg of semaglutide or placebo for 240 weeks. After initiation, the semaglutide dosage was increased every 4 weeks up to 16 weeks when the full dose (2.4 mg) was reached.
In a planned interim analysis, the trial investigators evaluated the primary endpoints at week 72 for the first 800 participants, with biopsies taken at weeks 1 and 72.
A total of 534 people were randomized to the semaglutide group, including 169 with F2 fibrosis and 365 with F3 fibrosis. Among the 266 participants randomized to placebo, 81 had F2 fibrosis and 185 had F3 fibrosis.
At baseline, the patient characteristics were similar between the groups (mean age, 56 years; body mass index, 34.6). A majority of participants also were White (67.5%), women (57.1%), had type 2 diabetes (55.9%), F3 fibrosis (68.8%), and enhanced liver fibrosis (ELF) scores around 10 (55.5%).
For the first primary endpoint, 62.9% of those in the semaglutide group and 34.1% of those in the placebo group reached resolution of steatohepatitis with no worsening of fibrosis. This represented an estimated difference in responder proportions (EDP) of 28.9%.
In addition, 37% of those in the semaglutide group and 22.5% of those in the placebo group met the second primary endpoint of improvement in liver fibrosis with no worsening of steatohepatitis (EDP, 14.4%).
Among the secondary endpoints, combined resolution of steatohepatitis with a one-stage improvement in liver fibrosis occurred in 32.8% of the semaglutide group and 16.2% of the placebo group (EDP, 16.6%).
In additional analyses, Newsome and colleagues found 20%-40% improvements in liver enzymes and noninvasive fibrosis markers, such as ELF and vibration-controlled transient elastography liver stiffness.
Weight loss was also significant, with a 10.5% reduction in the semaglutide group compared with a 2% reduction in the placebo group.
Cardiometabolic risk factors improved as well, with changes in blood pressure measurements, hemoglobin A1c scores, and cholesterol values.
Although not considered statistically significant, patients in the semaglutide group also reported greater reductions in body pain.
In a safety analysis of 1195 participants at 96 weeks, adverse events, severe adverse events, and discontinuations were similar in both groups. Not surprisingly, gastrointestinal side effects were more commonly reported in the semaglutide group, Newsome said.
 
Highly Anticipated Results
After Newsome’s presentation, attendees applauded.
Rohit Loomba, MD, a gastroenterologist at the University of California, San Diego, who was not involved with the study, called the results the “highlight of the meeting.”
This sentiment was echoed by Naga Chalasani, MD, AGAF, a gastroenterologist at Indiana University Medical Center, Indianapolis, who called the results a “watershed moment in the MASH field” with “terrific data.”
 
Based on questions after the presentation, Newsome indicated that future ESSENCE reports would look at certain aspects of the results, such as the 10% weight loss among those in the semaglutide group, as well as the mechanisms of histological and fibrosis improvement.
“We know from other GLP-1 trials that more weight loss occurs in those who don’t have type 2 diabetes, and we’re still running those analyses,” he said. “Weight loss is clearly a major contributor to MASH improvement, but there seem to be some weight-independent effects here, which are likely linked to insulin sensitivity or inflammation. We look forward to presenting those analyses in due course.”
 
In a comment, Kimberly Ann Brown, MD, AGAF, chief of gastroenterology and hepatology at Henry Ford Health System in Detroit, Michigan, AASLD Foundation chair, and comoderator of the late-breaking abstract session, spoke about the highly anticipated presentation.
“This study was really the pinnacle of this meeting. We’ve all been waiting for this data, in large part because many of our patients are already using these medications,” Brown said. “Seeing the benefit for the liver, as well as lipids and other cardiovascular measures, is so important. Having this confirmatory study will hopefully lead to the availability of the medication for this indication among our patients.”
Newsome reported numerous disclosures, including consultant relationships with pharmaceutical companies, such as Novo Nordisk, Boehringer Ingelheim, and Madrigal Pharmaceuticals. Loomba has research grant relationships with numerous companies, including Hanmi, Gilead, Galmed Pharmaceuticals, Galectin Therapeutics, Eli Lilly, Bristol-Myers Squibb, and Boehringer Ingelheim. Chalasani has consultant relationships with Ipsen, Pfizer, Merck, Altimmune, GSK, Madrigal Pharmaceuticals, and Zydus. Brown reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM AASLD 24
Canadian Scientists Keep Watchful Eye on H5N1 Human Case
Now that Canada has confirmed its first human case of highly pathogenic avian influenza (HPAI) linked to H5N1, virologists and infectious disease experts are urging caution around surveillance, infection control, and the potential for spread among mammals and humans.
 Public health officials at the National Microbiology Laboratory in Winnipeg, Manitoba, Canada, confirmed that the virus strain is related to the ones circulating among poultry in British Columbia.
So far, the case appears to be isolated, and no additional infections have been detected among the teen’s family, friends, or healthcare workers. But Canadian and American scientists who have studied the genetic sequence of the virus have found mutations that could make it easier to infect humans. Even if this strain remains contained after the teen’s case resolves, the mere fact that mutations have occurred could be a cause for concern about future strains.
“HPAI is one of those diseases that scientists, public health specialists, animal health specialists, and physicians have been watching closely for 20 years due to its epidemic and pandemic potential, including impacts to agriculture, food security, and financial security,” Isaac Bogoch, MD, associate professor of medicine at the University of Toronto and infectious disease specialist with the University Health Network, Toronto, Ontario, Canada, said in an interview.
“The last couple of years have been notable in that the H5N1 outbreak among wild birds and migratory birds has been larger, and the spillover to dairy cows and humans in the US is obviously concerning,” he said. “As we see more viral reassortment and more mammals are impacted, the more opportunities there are for this to go awry.”
 
Current H5N1 Outlook
Canadian public health officials and virologists are still unsure how the teen in British Columbia became infected, Bogoch said. The case has prompted concern due to the disease severity and need for hospitalization, while other cases across North America have remained mild.
The United States has reported 53 human cases as of November 21, according to the Centers for Disease Control and Prevention. In all but one case, the infections occurred among dairy or poultry workers, primarily in California, Colorado, and Washington. In all these cases, patients have reported mild symptoms, including mild respiratory issues and conjunctivitis. None have been hospitalized.
In Canada, the teen was infected with a strain of the virus circulating in wild birds. This strain has also been found in poultry outbreaks in British Columbia and Washington during the past month. So far, the risk for infection remains low for the public, according to the Public Health Agency of Canada.
“This detection was picked up via hospital-based influenza surveillance, confirming that human influenza surveillance in British Columbia and Canada is effective at detecting avian influenza A (H5N1),” Theresa Tam, MD, Canada’s chief public health officer, said in a statement. “We must continue to remain vigilant in our efforts to prevent the spread of avian influenza between animals and to humans.”
For now, Canadian virologists are watching developments closely and urging caution among those who encounter wild or migratory birds but not recommending major changes overall.
“The fact that we have a first human case in Canada is not at all surprising, given what is happening in the US and Europe, as well as what is happening in domestic bird flocks in British Columbia,” said Brian Ward, MD, professor of medicine at McGill University, researcher with McGill’s JD MacLean Centre for Tropical Diseases, and co-director of McGill’s Vaccine Study Centre, Montreal, Quebec, Canada.
“Millions of migratory waterfowl are flying over Canada right now, many of which may be carrying or infected with the virus,” he said. “The bottom line is that increasing evidence of mammal-to-mammal spread among dairy cows, elephant seals, and mink and ermine farms is worrisome, but we don’t need to sound the sirens yet.”
 
Future Outbreak Measures
Looking ahead, though, the developing situation feels more threatening than benign, given the ongoing spread among dairy cattle in the United States, said Bogoch. “It’s difficult to get the genie back in the bottle. I had hoped to see the cases slow down this year, but we just haven’t seen that.”
The fact that surveillance measures such as wastewater sampling have been scaled back in some areas of Canada is cause for concern, Bogoch added.
“We have great foundations for surveillance and action; we just need to make sure they are supported adequately, that groups communicate (across too many silos), and that there are quick responses,” said Scott Weese, DVM, professor of pathobiology at the Ontario Veterinary College and director of the University of Guelph’s Centre for Public Health and Zoonoses in Ontario.
“With cattle in the US, I think it’s highlighted what can happen if the initial response is not very aggressive. There could have been a lot more proactive response to H5N1 in dairy cattle, but there are so many competing interests and unwillingness to take necessary steps that the virus continues to spread,” he said. “Hopefully we’ve learned from that. However, as is often the case, the science is sometimes the easy part. Getting people to take the required actions is the challenge.”
On a personal level, masks and social distancing work well against influenza virus, including both seasonal and avian strains, said Ward. On a broader level, healthcare providers can monitor patients and support testing, where appropriate.
“The most important thing for people to know is that there is going to be another pandemic. It might or might not be due to a variant of H5N1, but it will come at some time,” said Allison McGeer, MD, professor of laboratory medicine and pathobiology at the University of Toronto and an infectious disease specialist with the Sinai Health System, Toronto.
Healthcare providers should follow ongoing updates to public health guidance, support surveillance where possible, and work with hospital leadership and infection control officials to ensure that pandemic plans are in place, she said.
“They may not be needed in the next few months, but they will be needed,” McGeer said. “We know a lot more about influenza than we did about SARS-CoV-2, so we have more tools to mitigate the impact, but we need to have them ready and know how to use them effectively.”
A version of this article appeared on Medscape.com.
Now that Canada has confirmed its first human case of highly pathogenic avian influenza (HPAI) linked to H5N1, virologists and infectious disease experts are urging caution around surveillance, infection control, and the potential for spread among mammals and humans.
 Public health officials at the National Microbiology Laboratory in Winnipeg, Manitoba, Canada, confirmed that the virus strain is related to the ones circulating among poultry in British Columbia.
So far, the case appears to be isolated, and no additional infections have been detected among the teen’s family, friends, or healthcare workers. But Canadian and American scientists who have studied the genetic sequence of the virus have found mutations that could make it easier to infect humans. Even if this strain remains contained after the teen’s case resolves, the mere fact that mutations have occurred could be a cause for concern about future strains.
“HPAI is one of those diseases that scientists, public health specialists, animal health specialists, and physicians have been watching closely for 20 years due to its epidemic and pandemic potential, including impacts to agriculture, food security, and financial security,” Isaac Bogoch, MD, associate professor of medicine at the University of Toronto and infectious disease specialist with the University Health Network, Toronto, Ontario, Canada, said in an interview.
“The last couple of years have been notable in that the H5N1 outbreak among wild birds and migratory birds has been larger, and the spillover to dairy cows and humans in the US is obviously concerning,” he said. “As we see more viral reassortment and more mammals are impacted, the more opportunities there are for this to go awry.”
 
Current H5N1 Outlook
Canadian public health officials and virologists are still unsure how the teen in British Columbia became infected, Bogoch said. The case has prompted concern due to the disease severity and need for hospitalization, while other cases across North America have remained mild.
The United States has reported 53 human cases as of November 21, according to the Centers for Disease Control and Prevention. In all but one case, the infections occurred among dairy or poultry workers, primarily in California, Colorado, and Washington. In all these cases, patients have reported mild symptoms, including mild respiratory issues and conjunctivitis. None have been hospitalized.
In Canada, the teen was infected with a strain of the virus circulating in wild birds. This strain has also been found in poultry outbreaks in British Columbia and Washington during the past month. So far, the risk for infection remains low for the public, according to the Public Health Agency of Canada.
“This detection was picked up via hospital-based influenza surveillance, confirming that human influenza surveillance in British Columbia and Canada is effective at detecting avian influenza A (H5N1),” Theresa Tam, MD, Canada’s chief public health officer, said in a statement. “We must continue to remain vigilant in our efforts to prevent the spread of avian influenza between animals and to humans.”
For now, Canadian virologists are watching developments closely and urging caution among those who encounter wild or migratory birds but not recommending major changes overall.
“The fact that we have a first human case in Canada is not at all surprising, given what is happening in the US and Europe, as well as what is happening in domestic bird flocks in British Columbia,” said Brian Ward, MD, professor of medicine at McGill University, researcher with McGill’s JD MacLean Centre for Tropical Diseases, and co-director of McGill’s Vaccine Study Centre, Montreal, Quebec, Canada.
“Millions of migratory waterfowl are flying over Canada right now, many of which may be carrying or infected with the virus,” he said. “The bottom line is that increasing evidence of mammal-to-mammal spread among dairy cows, elephant seals, and mink and ermine farms is worrisome, but we don’t need to sound the sirens yet.”
 
Future Outbreak Measures
Looking ahead, though, the developing situation feels more threatening than benign, given the ongoing spread among dairy cattle in the United States, said Bogoch. “It’s difficult to get the genie back in the bottle. I had hoped to see the cases slow down this year, but we just haven’t seen that.”
The fact that surveillance measures such as wastewater sampling have been scaled back in some areas of Canada is cause for concern, Bogoch added.
“We have great foundations for surveillance and action; we just need to make sure they are supported adequately, that groups communicate (across too many silos), and that there are quick responses,” said Scott Weese, DVM, professor of pathobiology at the Ontario Veterinary College and director of the University of Guelph’s Centre for Public Health and Zoonoses in Ontario.
“With cattle in the US, I think it’s highlighted what can happen if the initial response is not very aggressive. There could have been a lot more proactive response to H5N1 in dairy cattle, but there are so many competing interests and unwillingness to take necessary steps that the virus continues to spread,” he said. “Hopefully we’ve learned from that. However, as is often the case, the science is sometimes the easy part. Getting people to take the required actions is the challenge.”
On a personal level, masks and social distancing work well against influenza virus, including both seasonal and avian strains, said Ward. On a broader level, healthcare providers can monitor patients and support testing, where appropriate.
“The most important thing for people to know is that there is going to be another pandemic. It might or might not be due to a variant of H5N1, but it will come at some time,” said Allison McGeer, MD, professor of laboratory medicine and pathobiology at the University of Toronto and an infectious disease specialist with the Sinai Health System, Toronto.
Healthcare providers should follow ongoing updates to public health guidance, support surveillance where possible, and work with hospital leadership and infection control officials to ensure that pandemic plans are in place, she said.
“They may not be needed in the next few months, but they will be needed,” McGeer said. “We know a lot more about influenza than we did about SARS-CoV-2, so we have more tools to mitigate the impact, but we need to have them ready and know how to use them effectively.”
A version of this article appeared on Medscape.com.
Now that Canada has confirmed its first human case of highly pathogenic avian influenza (HPAI) linked to H5N1, virologists and infectious disease experts are urging caution around surveillance, infection control, and the potential for spread among mammals and humans.
 Public health officials at the National Microbiology Laboratory in Winnipeg, Manitoba, Canada, confirmed that the virus strain is related to the ones circulating among poultry in British Columbia.
So far, the case appears to be isolated, and no additional infections have been detected among the teen’s family, friends, or healthcare workers. But Canadian and American scientists who have studied the genetic sequence of the virus have found mutations that could make it easier to infect humans. Even if this strain remains contained after the teen’s case resolves, the mere fact that mutations have occurred could be a cause for concern about future strains.
“HPAI is one of those diseases that scientists, public health specialists, animal health specialists, and physicians have been watching closely for 20 years due to its epidemic and pandemic potential, including impacts to agriculture, food security, and financial security,” Isaac Bogoch, MD, associate professor of medicine at the University of Toronto and infectious disease specialist with the University Health Network, Toronto, Ontario, Canada, said in an interview.
“The last couple of years have been notable in that the H5N1 outbreak among wild birds and migratory birds has been larger, and the spillover to dairy cows and humans in the US is obviously concerning,” he said. “As we see more viral reassortment and more mammals are impacted, the more opportunities there are for this to go awry.”
 
Current H5N1 Outlook
Canadian public health officials and virologists are still unsure how the teen in British Columbia became infected, Bogoch said. The case has prompted concern due to the disease severity and need for hospitalization, while other cases across North America have remained mild.
The United States has reported 53 human cases as of November 21, according to the Centers for Disease Control and Prevention. In all but one case, the infections occurred among dairy or poultry workers, primarily in California, Colorado, and Washington. In all these cases, patients have reported mild symptoms, including mild respiratory issues and conjunctivitis. None have been hospitalized.
In Canada, the teen was infected with a strain of the virus circulating in wild birds. This strain has also been found in poultry outbreaks in British Columbia and Washington during the past month. So far, the risk for infection remains low for the public, according to the Public Health Agency of Canada.
“This detection was picked up via hospital-based influenza surveillance, confirming that human influenza surveillance in British Columbia and Canada is effective at detecting avian influenza A (H5N1),” Theresa Tam, MD, Canada’s chief public health officer, said in a statement. “We must continue to remain vigilant in our efforts to prevent the spread of avian influenza between animals and to humans.”
For now, Canadian virologists are watching developments closely and urging caution among those who encounter wild or migratory birds but not recommending major changes overall.
“The fact that we have a first human case in Canada is not at all surprising, given what is happening in the US and Europe, as well as what is happening in domestic bird flocks in British Columbia,” said Brian Ward, MD, professor of medicine at McGill University, researcher with McGill’s JD MacLean Centre for Tropical Diseases, and co-director of McGill’s Vaccine Study Centre, Montreal, Quebec, Canada.
“Millions of migratory waterfowl are flying over Canada right now, many of which may be carrying or infected with the virus,” he said. “The bottom line is that increasing evidence of mammal-to-mammal spread among dairy cows, elephant seals, and mink and ermine farms is worrisome, but we don’t need to sound the sirens yet.”
 
Future Outbreak Measures
Looking ahead, though, the developing situation feels more threatening than benign, given the ongoing spread among dairy cattle in the United States, said Bogoch. “It’s difficult to get the genie back in the bottle. I had hoped to see the cases slow down this year, but we just haven’t seen that.”
The fact that surveillance measures such as wastewater sampling have been scaled back in some areas of Canada is cause for concern, Bogoch added.
“We have great foundations for surveillance and action; we just need to make sure they are supported adequately, that groups communicate (across too many silos), and that there are quick responses,” said Scott Weese, DVM, professor of pathobiology at the Ontario Veterinary College and director of the University of Guelph’s Centre for Public Health and Zoonoses in Ontario.
“With cattle in the US, I think it’s highlighted what can happen if the initial response is not very aggressive. There could have been a lot more proactive response to H5N1 in dairy cattle, but there are so many competing interests and unwillingness to take necessary steps that the virus continues to spread,” he said. “Hopefully we’ve learned from that. However, as is often the case, the science is sometimes the easy part. Getting people to take the required actions is the challenge.”
On a personal level, masks and social distancing work well against influenza virus, including both seasonal and avian strains, said Ward. On a broader level, healthcare providers can monitor patients and support testing, where appropriate.
“The most important thing for people to know is that there is going to be another pandemic. It might or might not be due to a variant of H5N1, but it will come at some time,” said Allison McGeer, MD, professor of laboratory medicine and pathobiology at the University of Toronto and an infectious disease specialist with the Sinai Health System, Toronto.
Healthcare providers should follow ongoing updates to public health guidance, support surveillance where possible, and work with hospital leadership and infection control officials to ensure that pandemic plans are in place, she said.
“They may not be needed in the next few months, but they will be needed,” McGeer said. “We know a lot more about influenza than we did about SARS-CoV-2, so we have more tools to mitigate the impact, but we need to have them ready and know how to use them effectively.”
A version of this article appeared on Medscape.com.
Oxidative Stress Marker May Signal Fracture Risk in T2D
TOPLINE:
Elevated levels of plasma F2-isoprostanes, a reliable marker of oxidative stress, are associated with an increased risk for fractures in older ambulatory patients with type 2 diabetes (T2D) independently of bone density.
METHODOLOGY:
- Patients with T2D face an increased risk for fractures at any given bone mineral density; oxidative stress levels (reflected in circulating F2-isoprostanes), which are elevated in T2D, are associated with other T2D complications, and may weaken bone integrity.
- Researchers analyzed data from an observational cohort study to investigate the association between the levels of circulating F2-isoprostanes and the risk for clinical fractures in older patients with T2D.
- The data included 703 older ambulatory adults (baseline age, 70-79 years; about half White individuals and half Black individuals ; about half men and half women) from the Health, Aging and Body Composition Study, of whom 132 had T2D.
- Plasma F2-isoprostane levels were measured using baseline serum samples; bone turnover markers were also measured including procollagen type 1 N-terminal propeptide, osteocalcin, and C-terminal telopeptide of type 1 collagen.
- Incident clinical fractures were tracked over a follow-up period of up to 17.3 years, with fractures verified through radiology reports.
TAKEAWAY:
- Overall, 25.8% patients in the T2D group and 23.5% adults in the non-diabetes group reported an incident clinical fracture during a mean follow-up period of 6.2 and 8.0 years, respectively.
- In patients with T2D, the risk for incident clinical fracture increased by 93% for every standard deviation increase in the log F2-isoprostane serum levels (hazard ratio [HR], 1.93; 95% CI, 1.26-2.95; P = .002) independently of baseline bone density, medication use, and other risk factors, with no such association reported in individuals without T2D (HR, 0.98; 95% CI, 0.81-1.18; P = .79).
- In the T2D group, elevated plasma F2-isoprostane levels were also associated with a decrease in total hip bone mineral density over 4 years (r = −0.28; P = .008), but not in the non-diabetes group.
- No correlation was found between plasma F2-isoprostane levels and circulating advanced glycoxidation end-products, bone turnover markers, or A1c levels in either group.
IN PRACTICE:
“Oxidative stress in T2D may play an important role in the decline of bone quality and not just bone quantity,” the authors wrote.
SOURCE:
This study was led by Bowen Wang, PhD, Rensselaer Polytechnic Institute, Troy, New York. It was published online in The Journal of Clinical Endocrinology & Metabolism.
LIMITATIONS:
This study was conducted in a well-functioning elderly population with only White and Black participants, which may limit the generalizability of the findings to other age groups or less healthy populations. Additionally, the study did not assess prevalent vertebral fracture risk due to the small sample size.
DISCLOSURES:
This study was supported by the US National Institute on Aging and the Intramural Research Program of the US National Institutes of Health and the Dr and Ms Sands and Sands Family for Orthopaedic Research. The authors reported no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Elevated levels of plasma F2-isoprostanes, a reliable marker of oxidative stress, are associated with an increased risk for fractures in older ambulatory patients with type 2 diabetes (T2D) independently of bone density.
METHODOLOGY:
- Patients with T2D face an increased risk for fractures at any given bone mineral density; oxidative stress levels (reflected in circulating F2-isoprostanes), which are elevated in T2D, are associated with other T2D complications, and may weaken bone integrity.
- Researchers analyzed data from an observational cohort study to investigate the association between the levels of circulating F2-isoprostanes and the risk for clinical fractures in older patients with T2D.
- The data included 703 older ambulatory adults (baseline age, 70-79 years; about half White individuals and half Black individuals ; about half men and half women) from the Health, Aging and Body Composition Study, of whom 132 had T2D.
- Plasma F2-isoprostane levels were measured using baseline serum samples; bone turnover markers were also measured including procollagen type 1 N-terminal propeptide, osteocalcin, and C-terminal telopeptide of type 1 collagen.
- Incident clinical fractures were tracked over a follow-up period of up to 17.3 years, with fractures verified through radiology reports.
TAKEAWAY:
- Overall, 25.8% patients in the T2D group and 23.5% adults in the non-diabetes group reported an incident clinical fracture during a mean follow-up period of 6.2 and 8.0 years, respectively.
- In patients with T2D, the risk for incident clinical fracture increased by 93% for every standard deviation increase in the log F2-isoprostane serum levels (hazard ratio [HR], 1.93; 95% CI, 1.26-2.95; P = .002) independently of baseline bone density, medication use, and other risk factors, with no such association reported in individuals without T2D (HR, 0.98; 95% CI, 0.81-1.18; P = .79).
- In the T2D group, elevated plasma F2-isoprostane levels were also associated with a decrease in total hip bone mineral density over 4 years (r = −0.28; P = .008), but not in the non-diabetes group.
- No correlation was found between plasma F2-isoprostane levels and circulating advanced glycoxidation end-products, bone turnover markers, or A1c levels in either group.
IN PRACTICE:
“Oxidative stress in T2D may play an important role in the decline of bone quality and not just bone quantity,” the authors wrote.
SOURCE:
This study was led by Bowen Wang, PhD, Rensselaer Polytechnic Institute, Troy, New York. It was published online in The Journal of Clinical Endocrinology & Metabolism.
LIMITATIONS:
This study was conducted in a well-functioning elderly population with only White and Black participants, which may limit the generalizability of the findings to other age groups or less healthy populations. Additionally, the study did not assess prevalent vertebral fracture risk due to the small sample size.
DISCLOSURES:
This study was supported by the US National Institute on Aging and the Intramural Research Program of the US National Institutes of Health and the Dr and Ms Sands and Sands Family for Orthopaedic Research. The authors reported no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Elevated levels of plasma F2-isoprostanes, a reliable marker of oxidative stress, are associated with an increased risk for fractures in older ambulatory patients with type 2 diabetes (T2D) independently of bone density.
METHODOLOGY:
- Patients with T2D face an increased risk for fractures at any given bone mineral density; oxidative stress levels (reflected in circulating F2-isoprostanes), which are elevated in T2D, are associated with other T2D complications, and may weaken bone integrity.
- Researchers analyzed data from an observational cohort study to investigate the association between the levels of circulating F2-isoprostanes and the risk for clinical fractures in older patients with T2D.
- The data included 703 older ambulatory adults (baseline age, 70-79 years; about half White individuals and half Black individuals ; about half men and half women) from the Health, Aging and Body Composition Study, of whom 132 had T2D.
- Plasma F2-isoprostane levels were measured using baseline serum samples; bone turnover markers were also measured including procollagen type 1 N-terminal propeptide, osteocalcin, and C-terminal telopeptide of type 1 collagen.
- Incident clinical fractures were tracked over a follow-up period of up to 17.3 years, with fractures verified through radiology reports.
TAKEAWAY:
- Overall, 25.8% patients in the T2D group and 23.5% adults in the non-diabetes group reported an incident clinical fracture during a mean follow-up period of 6.2 and 8.0 years, respectively.
- In patients with T2D, the risk for incident clinical fracture increased by 93% for every standard deviation increase in the log F2-isoprostane serum levels (hazard ratio [HR], 1.93; 95% CI, 1.26-2.95; P = .002) independently of baseline bone density, medication use, and other risk factors, with no such association reported in individuals without T2D (HR, 0.98; 95% CI, 0.81-1.18; P = .79).
- In the T2D group, elevated plasma F2-isoprostane levels were also associated with a decrease in total hip bone mineral density over 4 years (r = −0.28; P = .008), but not in the non-diabetes group.
- No correlation was found between plasma F2-isoprostane levels and circulating advanced glycoxidation end-products, bone turnover markers, or A1c levels in either group.
IN PRACTICE:
“Oxidative stress in T2D may play an important role in the decline of bone quality and not just bone quantity,” the authors wrote.
SOURCE:
This study was led by Bowen Wang, PhD, Rensselaer Polytechnic Institute, Troy, New York. It was published online in The Journal of Clinical Endocrinology & Metabolism.
LIMITATIONS:
This study was conducted in a well-functioning elderly population with only White and Black participants, which may limit the generalizability of the findings to other age groups or less healthy populations. Additionally, the study did not assess prevalent vertebral fracture risk due to the small sample size.
DISCLOSURES:
This study was supported by the US National Institute on Aging and the Intramural Research Program of the US National Institutes of Health and the Dr and Ms Sands and Sands Family for Orthopaedic Research. The authors reported no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
US Alcohol-Related Deaths Double Over 2 Decades, With Notable Age and Gender Disparities
TOPLINE:
US alcohol-related mortality rates increased from 10.7 to 21.6 per 100,000 between 1999 and 2020, with the largest rise of 3.8-fold observed in adults aged 25-34 years. Women experienced a 2.5-fold increase, while the Midwest region showed a similar rise in mortality rates.
METHODOLOGY:
- Analysis utilized the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research to examine alcohol-related mortality trends from 1999 to 2020.
- Researchers analyzed data from a total US population of 180,408,769 people aged 25 to 85+ years in 1999 and 226,635,013 people in 2020.
- International Classification of Diseases, Tenth Revision, codes were used to identify deaths with alcohol attribution, including mental and behavioral disorders, alcoholic organ damage, and alcohol-related poisoning.
TAKEAWAY:
- Overall mortality rates increased from 10.7 (95% CI, 10.6-10.8) per 100,000 in 1999 to 21.6 (95% CI, 21.4-21.8) per 100,000 in 2020, representing a significant twofold increase.
- Adults aged 55-64 years demonstrated both the steepest increase and highest absolute rates in both 1999 and 2020.
- American Indian and Alaska Native individuals experienced the steepest increase and highest absolute rates among all racial groups.
- The West region maintained the highest absolute rates in both 1999 and 2020, despite the Midwest showing the largest increase.
IN PRACTICE:
“Individuals who consume large amounts of alcohol tend to have the highest risks of total mortality as well as deaths from cardiovascular disease. Cardiovascular disease deaths are predominantly due to myocardial infarction and stroke. To mitigate these risks, health providers may wish to implement screening for alcohol use in primary care and other healthcare settings. By providing brief interventions and referrals to treatment, healthcare providers would be able to achieve the early identification of individuals at risk of alcohol-related harm and offer them the support and resources they need to reduce their alcohol consumption,” wrote the authors of the study.
SOURCE:
The study was led by Alexandra Matarazzo, BS, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton. It was published online in The American Journal of Medicine.
LIMITATIONS:
According to the authors, the cross-sectional nature of the data limits the study to descriptive analysis only, making it suitable for hypothesis generation but not hypothesis testing. While the validity and generalizability within the United States are secure because of the use of complete population data, potential bias and uncontrolled confounding may exist because of different population mixes between the two time points.
DISCLOSURES:
The authors reported no relevant conflicts of interest. One coauthor disclosed serving as an independent scientist in an advisory role to investigators and sponsors as Chair of Data Monitoring Committees for Amgen and UBC, to the Food and Drug Administration, and to Up to Date. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
US alcohol-related mortality rates increased from 10.7 to 21.6 per 100,000 between 1999 and 2020, with the largest rise of 3.8-fold observed in adults aged 25-34 years. Women experienced a 2.5-fold increase, while the Midwest region showed a similar rise in mortality rates.
METHODOLOGY:
- Analysis utilized the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research to examine alcohol-related mortality trends from 1999 to 2020.
- Researchers analyzed data from a total US population of 180,408,769 people aged 25 to 85+ years in 1999 and 226,635,013 people in 2020.
- International Classification of Diseases, Tenth Revision, codes were used to identify deaths with alcohol attribution, including mental and behavioral disorders, alcoholic organ damage, and alcohol-related poisoning.
TAKEAWAY:
- Overall mortality rates increased from 10.7 (95% CI, 10.6-10.8) per 100,000 in 1999 to 21.6 (95% CI, 21.4-21.8) per 100,000 in 2020, representing a significant twofold increase.
- Adults aged 55-64 years demonstrated both the steepest increase and highest absolute rates in both 1999 and 2020.
- American Indian and Alaska Native individuals experienced the steepest increase and highest absolute rates among all racial groups.
- The West region maintained the highest absolute rates in both 1999 and 2020, despite the Midwest showing the largest increase.
IN PRACTICE:
“Individuals who consume large amounts of alcohol tend to have the highest risks of total mortality as well as deaths from cardiovascular disease. Cardiovascular disease deaths are predominantly due to myocardial infarction and stroke. To mitigate these risks, health providers may wish to implement screening for alcohol use in primary care and other healthcare settings. By providing brief interventions and referrals to treatment, healthcare providers would be able to achieve the early identification of individuals at risk of alcohol-related harm and offer them the support and resources they need to reduce their alcohol consumption,” wrote the authors of the study.
SOURCE:
The study was led by Alexandra Matarazzo, BS, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton. It was published online in The American Journal of Medicine.
LIMITATIONS:
According to the authors, the cross-sectional nature of the data limits the study to descriptive analysis only, making it suitable for hypothesis generation but not hypothesis testing. While the validity and generalizability within the United States are secure because of the use of complete population data, potential bias and uncontrolled confounding may exist because of different population mixes between the two time points.
DISCLOSURES:
The authors reported no relevant conflicts of interest. One coauthor disclosed serving as an independent scientist in an advisory role to investigators and sponsors as Chair of Data Monitoring Committees for Amgen and UBC, to the Food and Drug Administration, and to Up to Date. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
US alcohol-related mortality rates increased from 10.7 to 21.6 per 100,000 between 1999 and 2020, with the largest rise of 3.8-fold observed in adults aged 25-34 years. Women experienced a 2.5-fold increase, while the Midwest region showed a similar rise in mortality rates.
METHODOLOGY:
- Analysis utilized the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research to examine alcohol-related mortality trends from 1999 to 2020.
- Researchers analyzed data from a total US population of 180,408,769 people aged 25 to 85+ years in 1999 and 226,635,013 people in 2020.
- International Classification of Diseases, Tenth Revision, codes were used to identify deaths with alcohol attribution, including mental and behavioral disorders, alcoholic organ damage, and alcohol-related poisoning.
TAKEAWAY:
- Overall mortality rates increased from 10.7 (95% CI, 10.6-10.8) per 100,000 in 1999 to 21.6 (95% CI, 21.4-21.8) per 100,000 in 2020, representing a significant twofold increase.
- Adults aged 55-64 years demonstrated both the steepest increase and highest absolute rates in both 1999 and 2020.
- American Indian and Alaska Native individuals experienced the steepest increase and highest absolute rates among all racial groups.
- The West region maintained the highest absolute rates in both 1999 and 2020, despite the Midwest showing the largest increase.
IN PRACTICE:
“Individuals who consume large amounts of alcohol tend to have the highest risks of total mortality as well as deaths from cardiovascular disease. Cardiovascular disease deaths are predominantly due to myocardial infarction and stroke. To mitigate these risks, health providers may wish to implement screening for alcohol use in primary care and other healthcare settings. By providing brief interventions and referrals to treatment, healthcare providers would be able to achieve the early identification of individuals at risk of alcohol-related harm and offer them the support and resources they need to reduce their alcohol consumption,” wrote the authors of the study.
SOURCE:
The study was led by Alexandra Matarazzo, BS, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton. It was published online in The American Journal of Medicine.
LIMITATIONS:
According to the authors, the cross-sectional nature of the data limits the study to descriptive analysis only, making it suitable for hypothesis generation but not hypothesis testing. While the validity and generalizability within the United States are secure because of the use of complete population data, potential bias and uncontrolled confounding may exist because of different population mixes between the two time points.
DISCLOSURES:
The authors reported no relevant conflicts of interest. One coauthor disclosed serving as an independent scientist in an advisory role to investigators and sponsors as Chair of Data Monitoring Committees for Amgen and UBC, to the Food and Drug Administration, and to Up to Date. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Side Effects of GLP-1 Drugs: What Doctors Should Know
Just a few years after some TikTok videos spiked the demand, one in eight US adults has tried Ozempic (semaglutide) or another drug in its class. Glucagon-like peptide 1 (GLP-1) receptor agonist medications have revolutionized obesity medicine.
But they’re not without problems. In the early days of the social media craze, news reports often featured patients whose gastrointestinal side effects sent them to the emergency room (ER).
“It happened a lot then. Patients didn’t want to complain because they were losing weight, and they wound up in the ER with extreme constipation or a small bowel obstruction,” said Caroline Apovian, MD, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.
“But that’s not really happening now,” she added.
Research backs up her assertion: A recent clinical review of studies found that many patients still experience side effects, but only at a mild to moderate level, while the dosage increases — and the unpleasantness tapers with time. Roughly 7% of patients discontinue the medications due to these symptoms.
Here’s what the latest research shows about GLP-1s’ side effects.
 
Most Common: Gastrointestinal Issues
Depending on the symptom and the specific drug, anywhere from one third to one half of patients will experience some kind of stomach trouble.
- In that clinical review, which looked at studies of three GLP-1 medications — semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Saxenda, Victoza), and tirzepatide (Mounjaro, Zepbound) — semaglutide users fared comparatively worse.
- Nausea was reported most frequently — 44.2% of semaglutide users dealt with it, compared with 40.2% for liraglutide and 31% for tirzepatide. Diarrhea, constipation, and vomiting also struck one quarter to one third of semaglutide patients, and slightly fewer for the other two medications.
Apovian finds that careful dosage helps her patients avoid the worst effects.
“We don’t know who’s going to do well and who’s not,” she said. “We start slowly, and usually things go OK.”
If a patient does react poorly, she’ll hold off on increasing the dosage until they acclimate and advise using over-the-counter meds like MiraLAX to address the symptoms.
Few documented severe adverse gastro events appeared in the data, affecting less than 1% of liraglutide and tirzepatide patients and 2.6% of semaglutide users. The majority of these events were gallbladder-related.
 
Questions About Causation: Depression and Suicidality
About a year ago, a study used 18 years’ worth of data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to examine how often patients reported suicidal ideation and/or depression while using GLP-1 medications. Compared with metformin and insulin, researchers found disproportionate reporting by patients using semaglutide and liraglutide. Other GLP-1 medications didn’t show this effect. The researchers pointed out: These statistics don’t show causation — there’s no clear reason why those two medications were linked to more reports.
Further research has been more reassuring:
- Another study also used FAERS but looked only at data from 2018 to 2022, when usage of these drugs was ramping up, and found no link between suicidal or self-injurious behaviors and GLP-1.
- A recent cohort study, which looked at data from nearly 300,000 people, found that GLP-1 users aren’t at increased risk for death by suicide.
- Both the FDA and the European Medicines Agency have issued statements that the evidence doesn’t support a causal association.
There are several factors at play here. People with obesity and diabetes are more likely to have depression to begin with. And more importantly, even if there is a link, causality remains unclear. For instance, patients who lose weight via bariatric surgery are at increased risk for depression, substance abuse, and self-harm. These symptoms may be related to the weight loss itself, not the medications.
“Some people use food as something other than nutrition. They use food to soothe other psychological issues,” Apovian said. “When that’s taken away, the psychological issues are still there.”
In her practice, she’s seen the risk for mental health issues rise with more substantial weight loss — 50-100 pounds.
This lack of clarity regarding causation means it’s important to perform a detailed patient history before prescribing, so you can monitor more closely with preexisting psychiatric disorders.
 
Possible Link: Ocular Symptoms
Here, too, the research isn’t definitive but leans toward no clear association. Several studies have looked for a link between GLP-1 and vision-related issues:
- One examined FAERS data and network pharmacology and found semaglutide and lixisenatide were significantly associated with adverse events like blurred vision, visual impairment, and diabetic retinopathy.
- This summer, a cohort study of almost 17,000 people with diabetes or overweight/obesity suggested a link between semaglutide and nonarteritic anterior ischemic optic neuropathy (NAION), a common cause of blindness due to optic nerve damage. The study found “a substantially increased risk of NAION among individuals prescribed semaglutide relative to those prescribed other medications to treat type 2 diabetes and obesity or overweight.”
- But this month, another cohort study with 135,000 participants looked at NAION in people with type 2 diabetes, obesity, or both. It compared results with common non-GLP-1 medications and found just the opposite: No increased risk for NAION.
One drawback with all these studies is that they’re based on large databases rather than randomized controlled trials (RCTs). When researchers focused on RCTs in a 2023 meta-analysis, they found a significant association with only one form of GLP-1, albiglutide — which was withdrawn from the market in 2017. The other six FDA-approved drugs didn’t show a statistically significant link.
 
Possible Trouble: Pulmonary Aspiration Under Sedation
Earlier this month, the FDA updated labeling for semaglutide, liraglutide, and tirzepatide to include a warning about the risk for aspiration during surgery. While there are no published studies, several case reports have appeared.
GLP-1 medications delay gastric emptying, so even though a patient may have fasted before surgery as usual, some food or liquid may remain. In response to this possibility, a group of professional medical societies issued guidelines for using these medications during the perioperative period. They include:
- Consideration of dosage, symptoms, and other medical conditions: The risk is higher during the escalation phase, and in general, higher doses mean higher risk.
- Potential discontinuation of GLP-1 usage when assessment shows an elevated risk.
- Assessment on the day of the procedure for possible delayed gastric emptying.
- Preoperative dietary modifications, which might include switching to a liquid diet.
Rare: Serious Effects
And then there are the outliers, the frightening issues that make headlines. On their own, none of these are common enough to affect consideration of GLP-1 use:
- Studies in rats suggested an increased risk for thyroid cancer, but subsequent research has found no evidence.
- Colonic ischemia in association with tirzepatide.
- Acute pancreatitis leading to death in association with semaglutide.
- Speaking of pancreatitis, that clinical review of studies did find that both liraglutide and semaglutide led to an elevated risk for pancreatitis, bowel obstruction, and gastroparesis. But the numbers were so small as to be insignificant — for instance, just 0.2% of patients experienced pancreatitis.
Benefits Outweigh Risks
When you lay out these side effects against the countless known benefits of weight loss and blood sugar management — the lower risk for high blood pressure, heart disease, stroke, metabolic syndrome, fatty liver disease, several cancers, and more — the advantages of GLP-1 drugs seem clear. Ultimately, of course, it’s the patient’s decision whether to begin and continue taking any medication for a chronic disease.
Apovian recommends having in-depth conversations before you write that first prescription – she compares the situation to using an antihypertensive drug. If your patient understands potential side effects, they’re more likely to maintain long-term compliance.
“We educate our patients how to use these drugs, indefinitely, if you want to maintain a lower, healthier body weight,” she said. “I don’t see patients who stop using them, but they’re out there. These are people desperate to lose weight, who aren’t given the education to understand we’re treating a disease. It’s not a matter of willpower.”
And once a patient starts taking a GLP-1, monitor them closely, with in-person visits rather than telehealth, while increasing the dosage. If they experience side effects, stay at that level until they ease. And if the patient has a good weight-loss response at a lower dose, stay there. Just because you can go higher, it doesn’t mean you should.
 
A version of this article first appeared on Medscape.com.
Just a few years after some TikTok videos spiked the demand, one in eight US adults has tried Ozempic (semaglutide) or another drug in its class. Glucagon-like peptide 1 (GLP-1) receptor agonist medications have revolutionized obesity medicine.
But they’re not without problems. In the early days of the social media craze, news reports often featured patients whose gastrointestinal side effects sent them to the emergency room (ER).
“It happened a lot then. Patients didn’t want to complain because they were losing weight, and they wound up in the ER with extreme constipation or a small bowel obstruction,” said Caroline Apovian, MD, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.
“But that’s not really happening now,” she added.
Research backs up her assertion: A recent clinical review of studies found that many patients still experience side effects, but only at a mild to moderate level, while the dosage increases — and the unpleasantness tapers with time. Roughly 7% of patients discontinue the medications due to these symptoms.
Here’s what the latest research shows about GLP-1s’ side effects.
 
Most Common: Gastrointestinal Issues
Depending on the symptom and the specific drug, anywhere from one third to one half of patients will experience some kind of stomach trouble.
- In that clinical review, which looked at studies of three GLP-1 medications — semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Saxenda, Victoza), and tirzepatide (Mounjaro, Zepbound) — semaglutide users fared comparatively worse.
- Nausea was reported most frequently — 44.2% of semaglutide users dealt with it, compared with 40.2% for liraglutide and 31% for tirzepatide. Diarrhea, constipation, and vomiting also struck one quarter to one third of semaglutide patients, and slightly fewer for the other two medications.
Apovian finds that careful dosage helps her patients avoid the worst effects.
“We don’t know who’s going to do well and who’s not,” she said. “We start slowly, and usually things go OK.”
If a patient does react poorly, she’ll hold off on increasing the dosage until they acclimate and advise using over-the-counter meds like MiraLAX to address the symptoms.
Few documented severe adverse gastro events appeared in the data, affecting less than 1% of liraglutide and tirzepatide patients and 2.6% of semaglutide users. The majority of these events were gallbladder-related.
 
Questions About Causation: Depression and Suicidality
About a year ago, a study used 18 years’ worth of data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to examine how often patients reported suicidal ideation and/or depression while using GLP-1 medications. Compared with metformin and insulin, researchers found disproportionate reporting by patients using semaglutide and liraglutide. Other GLP-1 medications didn’t show this effect. The researchers pointed out: These statistics don’t show causation — there’s no clear reason why those two medications were linked to more reports.
Further research has been more reassuring:
- Another study also used FAERS but looked only at data from 2018 to 2022, when usage of these drugs was ramping up, and found no link between suicidal or self-injurious behaviors and GLP-1.
- A recent cohort study, which looked at data from nearly 300,000 people, found that GLP-1 users aren’t at increased risk for death by suicide.
- Both the FDA and the European Medicines Agency have issued statements that the evidence doesn’t support a causal association.
There are several factors at play here. People with obesity and diabetes are more likely to have depression to begin with. And more importantly, even if there is a link, causality remains unclear. For instance, patients who lose weight via bariatric surgery are at increased risk for depression, substance abuse, and self-harm. These symptoms may be related to the weight loss itself, not the medications.
“Some people use food as something other than nutrition. They use food to soothe other psychological issues,” Apovian said. “When that’s taken away, the psychological issues are still there.”
In her practice, she’s seen the risk for mental health issues rise with more substantial weight loss — 50-100 pounds.
This lack of clarity regarding causation means it’s important to perform a detailed patient history before prescribing, so you can monitor more closely with preexisting psychiatric disorders.
 
Possible Link: Ocular Symptoms
Here, too, the research isn’t definitive but leans toward no clear association. Several studies have looked for a link between GLP-1 and vision-related issues:
- One examined FAERS data and network pharmacology and found semaglutide and lixisenatide were significantly associated with adverse events like blurred vision, visual impairment, and diabetic retinopathy.
- This summer, a cohort study of almost 17,000 people with diabetes or overweight/obesity suggested a link between semaglutide and nonarteritic anterior ischemic optic neuropathy (NAION), a common cause of blindness due to optic nerve damage. The study found “a substantially increased risk of NAION among individuals prescribed semaglutide relative to those prescribed other medications to treat type 2 diabetes and obesity or overweight.”
- But this month, another cohort study with 135,000 participants looked at NAION in people with type 2 diabetes, obesity, or both. It compared results with common non-GLP-1 medications and found just the opposite: No increased risk for NAION.
One drawback with all these studies is that they’re based on large databases rather than randomized controlled trials (RCTs). When researchers focused on RCTs in a 2023 meta-analysis, they found a significant association with only one form of GLP-1, albiglutide — which was withdrawn from the market in 2017. The other six FDA-approved drugs didn’t show a statistically significant link.
 
Possible Trouble: Pulmonary Aspiration Under Sedation
Earlier this month, the FDA updated labeling for semaglutide, liraglutide, and tirzepatide to include a warning about the risk for aspiration during surgery. While there are no published studies, several case reports have appeared.
GLP-1 medications delay gastric emptying, so even though a patient may have fasted before surgery as usual, some food or liquid may remain. In response to this possibility, a group of professional medical societies issued guidelines for using these medications during the perioperative period. They include:
- Consideration of dosage, symptoms, and other medical conditions: The risk is higher during the escalation phase, and in general, higher doses mean higher risk.
- Potential discontinuation of GLP-1 usage when assessment shows an elevated risk.
- Assessment on the day of the procedure for possible delayed gastric emptying.
- Preoperative dietary modifications, which might include switching to a liquid diet.
Rare: Serious Effects
And then there are the outliers, the frightening issues that make headlines. On their own, none of these are common enough to affect consideration of GLP-1 use:
- Studies in rats suggested an increased risk for thyroid cancer, but subsequent research has found no evidence.
- Colonic ischemia in association with tirzepatide.
- Acute pancreatitis leading to death in association with semaglutide.
- Speaking of pancreatitis, that clinical review of studies did find that both liraglutide and semaglutide led to an elevated risk for pancreatitis, bowel obstruction, and gastroparesis. But the numbers were so small as to be insignificant — for instance, just 0.2% of patients experienced pancreatitis.
Benefits Outweigh Risks
When you lay out these side effects against the countless known benefits of weight loss and blood sugar management — the lower risk for high blood pressure, heart disease, stroke, metabolic syndrome, fatty liver disease, several cancers, and more — the advantages of GLP-1 drugs seem clear. Ultimately, of course, it’s the patient’s decision whether to begin and continue taking any medication for a chronic disease.
Apovian recommends having in-depth conversations before you write that first prescription – she compares the situation to using an antihypertensive drug. If your patient understands potential side effects, they’re more likely to maintain long-term compliance.
“We educate our patients how to use these drugs, indefinitely, if you want to maintain a lower, healthier body weight,” she said. “I don’t see patients who stop using them, but they’re out there. These are people desperate to lose weight, who aren’t given the education to understand we’re treating a disease. It’s not a matter of willpower.”
And once a patient starts taking a GLP-1, monitor them closely, with in-person visits rather than telehealth, while increasing the dosage. If they experience side effects, stay at that level until they ease. And if the patient has a good weight-loss response at a lower dose, stay there. Just because you can go higher, it doesn’t mean you should.
 
A version of this article first appeared on Medscape.com.
Just a few years after some TikTok videos spiked the demand, one in eight US adults has tried Ozempic (semaglutide) or another drug in its class. Glucagon-like peptide 1 (GLP-1) receptor agonist medications have revolutionized obesity medicine.
But they’re not without problems. In the early days of the social media craze, news reports often featured patients whose gastrointestinal side effects sent them to the emergency room (ER).
“It happened a lot then. Patients didn’t want to complain because they were losing weight, and they wound up in the ER with extreme constipation or a small bowel obstruction,” said Caroline Apovian, MD, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.
“But that’s not really happening now,” she added.
Research backs up her assertion: A recent clinical review of studies found that many patients still experience side effects, but only at a mild to moderate level, while the dosage increases — and the unpleasantness tapers with time. Roughly 7% of patients discontinue the medications due to these symptoms.
Here’s what the latest research shows about GLP-1s’ side effects.
 
Most Common: Gastrointestinal Issues
Depending on the symptom and the specific drug, anywhere from one third to one half of patients will experience some kind of stomach trouble.
- In that clinical review, which looked at studies of three GLP-1 medications — semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Saxenda, Victoza), and tirzepatide (Mounjaro, Zepbound) — semaglutide users fared comparatively worse.
- Nausea was reported most frequently — 44.2% of semaglutide users dealt with it, compared with 40.2% for liraglutide and 31% for tirzepatide. Diarrhea, constipation, and vomiting also struck one quarter to one third of semaglutide patients, and slightly fewer for the other two medications.
Apovian finds that careful dosage helps her patients avoid the worst effects.
“We don’t know who’s going to do well and who’s not,” she said. “We start slowly, and usually things go OK.”
If a patient does react poorly, she’ll hold off on increasing the dosage until they acclimate and advise using over-the-counter meds like MiraLAX to address the symptoms.
Few documented severe adverse gastro events appeared in the data, affecting less than 1% of liraglutide and tirzepatide patients and 2.6% of semaglutide users. The majority of these events were gallbladder-related.
 
Questions About Causation: Depression and Suicidality
About a year ago, a study used 18 years’ worth of data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to examine how often patients reported suicidal ideation and/or depression while using GLP-1 medications. Compared with metformin and insulin, researchers found disproportionate reporting by patients using semaglutide and liraglutide. Other GLP-1 medications didn’t show this effect. The researchers pointed out: These statistics don’t show causation — there’s no clear reason why those two medications were linked to more reports.
Further research has been more reassuring:
- Another study also used FAERS but looked only at data from 2018 to 2022, when usage of these drugs was ramping up, and found no link between suicidal or self-injurious behaviors and GLP-1.
- A recent cohort study, which looked at data from nearly 300,000 people, found that GLP-1 users aren’t at increased risk for death by suicide.
- Both the FDA and the European Medicines Agency have issued statements that the evidence doesn’t support a causal association.
There are several factors at play here. People with obesity and diabetes are more likely to have depression to begin with. And more importantly, even if there is a link, causality remains unclear. For instance, patients who lose weight via bariatric surgery are at increased risk for depression, substance abuse, and self-harm. These symptoms may be related to the weight loss itself, not the medications.
“Some people use food as something other than nutrition. They use food to soothe other psychological issues,” Apovian said. “When that’s taken away, the psychological issues are still there.”
In her practice, she’s seen the risk for mental health issues rise with more substantial weight loss — 50-100 pounds.
This lack of clarity regarding causation means it’s important to perform a detailed patient history before prescribing, so you can monitor more closely with preexisting psychiatric disorders.
 
Possible Link: Ocular Symptoms
Here, too, the research isn’t definitive but leans toward no clear association. Several studies have looked for a link between GLP-1 and vision-related issues:
- One examined FAERS data and network pharmacology and found semaglutide and lixisenatide were significantly associated with adverse events like blurred vision, visual impairment, and diabetic retinopathy.
- This summer, a cohort study of almost 17,000 people with diabetes or overweight/obesity suggested a link between semaglutide and nonarteritic anterior ischemic optic neuropathy (NAION), a common cause of blindness due to optic nerve damage. The study found “a substantially increased risk of NAION among individuals prescribed semaglutide relative to those prescribed other medications to treat type 2 diabetes and obesity or overweight.”
- But this month, another cohort study with 135,000 participants looked at NAION in people with type 2 diabetes, obesity, or both. It compared results with common non-GLP-1 medications and found just the opposite: No increased risk for NAION.
One drawback with all these studies is that they’re based on large databases rather than randomized controlled trials (RCTs). When researchers focused on RCTs in a 2023 meta-analysis, they found a significant association with only one form of GLP-1, albiglutide — which was withdrawn from the market in 2017. The other six FDA-approved drugs didn’t show a statistically significant link.
 
Possible Trouble: Pulmonary Aspiration Under Sedation
Earlier this month, the FDA updated labeling for semaglutide, liraglutide, and tirzepatide to include a warning about the risk for aspiration during surgery. While there are no published studies, several case reports have appeared.
GLP-1 medications delay gastric emptying, so even though a patient may have fasted before surgery as usual, some food or liquid may remain. In response to this possibility, a group of professional medical societies issued guidelines for using these medications during the perioperative period. They include:
- Consideration of dosage, symptoms, and other medical conditions: The risk is higher during the escalation phase, and in general, higher doses mean higher risk.
- Potential discontinuation of GLP-1 usage when assessment shows an elevated risk.
- Assessment on the day of the procedure for possible delayed gastric emptying.
- Preoperative dietary modifications, which might include switching to a liquid diet.
Rare: Serious Effects
And then there are the outliers, the frightening issues that make headlines. On their own, none of these are common enough to affect consideration of GLP-1 use:
- Studies in rats suggested an increased risk for thyroid cancer, but subsequent research has found no evidence.
- Colonic ischemia in association with tirzepatide.
- Acute pancreatitis leading to death in association with semaglutide.
- Speaking of pancreatitis, that clinical review of studies did find that both liraglutide and semaglutide led to an elevated risk for pancreatitis, bowel obstruction, and gastroparesis. But the numbers were so small as to be insignificant — for instance, just 0.2% of patients experienced pancreatitis.
Benefits Outweigh Risks
When you lay out these side effects against the countless known benefits of weight loss and blood sugar management — the lower risk for high blood pressure, heart disease, stroke, metabolic syndrome, fatty liver disease, several cancers, and more — the advantages of GLP-1 drugs seem clear. Ultimately, of course, it’s the patient’s decision whether to begin and continue taking any medication for a chronic disease.
Apovian recommends having in-depth conversations before you write that first prescription – she compares the situation to using an antihypertensive drug. If your patient understands potential side effects, they’re more likely to maintain long-term compliance.
“We educate our patients how to use these drugs, indefinitely, if you want to maintain a lower, healthier body weight,” she said. “I don’t see patients who stop using them, but they’re out there. These are people desperate to lose weight, who aren’t given the education to understand we’re treating a disease. It’s not a matter of willpower.”
And once a patient starts taking a GLP-1, monitor them closely, with in-person visits rather than telehealth, while increasing the dosage. If they experience side effects, stay at that level until they ease. And if the patient has a good weight-loss response at a lower dose, stay there. Just because you can go higher, it doesn’t mean you should.
 
A version of this article first appeared on Medscape.com.
 


