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Allergens Present in Most ‘Hypoallergenic’ Baby Cleansers, Study Finds
TOPLINE:
METHODOLOGY:
- Many baby cleansers are marketed as “hypoallergenic,” but these claims are not validated.
- This study assessed the potential allergens and marketing claims in best-selling baby cleansers.
- The researchers collected ingredients and marketing claims of the top 50 best-selling baby body wash products sold on Amazon on April 4, 2023.
- Ingredient lists were checked for potential allergens using the 2020 American Contact Dermatitis Society (ACDS) core allergen series, which lists 90 common allergens for adults and children.
TAKEAWAY:
- In the 50 cleansers tested, 10 allergens were identified. Overall, 94% of the cleansers contained at least one allergen, averaging 2.9 allergens per product; cocamidopropyl betaine (72%), fragrance (64%), and sodium benzoate (54%) were the most common allergens.
- All cleansers had at least five marketing claims, with an average of 10.9 claims per product; the most common claims were “paraben-free” (88%), “phthalate-free” (84%), “tear-free” (74%), and “hypoallergenic” or “allergy-tested” (74%).
- There was no significant difference in the number of allergens in the cleansers marketed as “hypoallergenic” or “allergy tested” compared with cleansers that did not have these claims (P = .843).
- Fewer allergens were found in cleansers endorsed by the National Eczema Association (P = .004) or labeled “synthetic fragrance-free” (P = .003).
- There was a positive correlation between a greater number of allergens and an increased number of marketing claims (r = 0.547, P < .001) and a negative correlation between cost and number of allergens (r = −0.450, P = .001).
IN PRACTICE:
Because marketing claims like “hypoallergenic” may be misleading, “clinicians should counsel parents to carefully examine cleanser ingredients or consider selecting cleansers” endorsed by the National Eczema Association or another international eczema organization, especially for infants and children with a history of atopic dermatitis, the authors wrote.
SOURCE:
The study, led by Sasan D. Noveir, BA, from the University of California, Los Angeles, and coauthors from the division of dermatology at UCLA, was published online in Pediatric Dermatology.
LIMITATIONS:
The study only evaluated top-selling products from a single online source at a specific time, which may limit generalizability. Potential allergens not included in the ACDS core series may be present.
DISCLOSURES:
The study did not disclose any funding source. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Many baby cleansers are marketed as “hypoallergenic,” but these claims are not validated.
- This study assessed the potential allergens and marketing claims in best-selling baby cleansers.
- The researchers collected ingredients and marketing claims of the top 50 best-selling baby body wash products sold on Amazon on April 4, 2023.
- Ingredient lists were checked for potential allergens using the 2020 American Contact Dermatitis Society (ACDS) core allergen series, which lists 90 common allergens for adults and children.
TAKEAWAY:
- In the 50 cleansers tested, 10 allergens were identified. Overall, 94% of the cleansers contained at least one allergen, averaging 2.9 allergens per product; cocamidopropyl betaine (72%), fragrance (64%), and sodium benzoate (54%) were the most common allergens.
- All cleansers had at least five marketing claims, with an average of 10.9 claims per product; the most common claims were “paraben-free” (88%), “phthalate-free” (84%), “tear-free” (74%), and “hypoallergenic” or “allergy-tested” (74%).
- There was no significant difference in the number of allergens in the cleansers marketed as “hypoallergenic” or “allergy tested” compared with cleansers that did not have these claims (P = .843).
- Fewer allergens were found in cleansers endorsed by the National Eczema Association (P = .004) or labeled “synthetic fragrance-free” (P = .003).
- There was a positive correlation between a greater number of allergens and an increased number of marketing claims (r = 0.547, P < .001) and a negative correlation between cost and number of allergens (r = −0.450, P = .001).
IN PRACTICE:
Because marketing claims like “hypoallergenic” may be misleading, “clinicians should counsel parents to carefully examine cleanser ingredients or consider selecting cleansers” endorsed by the National Eczema Association or another international eczema organization, especially for infants and children with a history of atopic dermatitis, the authors wrote.
SOURCE:
The study, led by Sasan D. Noveir, BA, from the University of California, Los Angeles, and coauthors from the division of dermatology at UCLA, was published online in Pediatric Dermatology.
LIMITATIONS:
The study only evaluated top-selling products from a single online source at a specific time, which may limit generalizability. Potential allergens not included in the ACDS core series may be present.
DISCLOSURES:
The study did not disclose any funding source. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Many baby cleansers are marketed as “hypoallergenic,” but these claims are not validated.
- This study assessed the potential allergens and marketing claims in best-selling baby cleansers.
- The researchers collected ingredients and marketing claims of the top 50 best-selling baby body wash products sold on Amazon on April 4, 2023.
- Ingredient lists were checked for potential allergens using the 2020 American Contact Dermatitis Society (ACDS) core allergen series, which lists 90 common allergens for adults and children.
TAKEAWAY:
- In the 50 cleansers tested, 10 allergens were identified. Overall, 94% of the cleansers contained at least one allergen, averaging 2.9 allergens per product; cocamidopropyl betaine (72%), fragrance (64%), and sodium benzoate (54%) were the most common allergens.
- All cleansers had at least five marketing claims, with an average of 10.9 claims per product; the most common claims were “paraben-free” (88%), “phthalate-free” (84%), “tear-free” (74%), and “hypoallergenic” or “allergy-tested” (74%).
- There was no significant difference in the number of allergens in the cleansers marketed as “hypoallergenic” or “allergy tested” compared with cleansers that did not have these claims (P = .843).
- Fewer allergens were found in cleansers endorsed by the National Eczema Association (P = .004) or labeled “synthetic fragrance-free” (P = .003).
- There was a positive correlation between a greater number of allergens and an increased number of marketing claims (r = 0.547, P < .001) and a negative correlation between cost and number of allergens (r = −0.450, P = .001).
IN PRACTICE:
Because marketing claims like “hypoallergenic” may be misleading, “clinicians should counsel parents to carefully examine cleanser ingredients or consider selecting cleansers” endorsed by the National Eczema Association or another international eczema organization, especially for infants and children with a history of atopic dermatitis, the authors wrote.
SOURCE:
The study, led by Sasan D. Noveir, BA, from the University of California, Los Angeles, and coauthors from the division of dermatology at UCLA, was published online in Pediatric Dermatology.
LIMITATIONS:
The study only evaluated top-selling products from a single online source at a specific time, which may limit generalizability. Potential allergens not included in the ACDS core series may be present.
DISCLOSURES:
The study did not disclose any funding source. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
During Global GLP-1 Shortage, Doctors Prioritize Certain Patients
Glucagon-like peptide 1 (GLP-1) receptor agonists are the latest blockbuster drugs — thanks to their potent ability to help patients lose weight. But
Semaglutide for weight loss (Wegovy) has launched in eight countries, namely, Denmark, Germany, Iceland, Norway, the United Arab Emirates, the United Kingdom, the United States, and Switzerland, and was released in Japan in February. Semaglutide for type 2 diabetes (Ozempic) is approved in 82 countries and often is prescribed off-label to treat obesity.
The dual glucose-dependent insulinotropic polypeptide/GLP-1 agonist tirzepatide — sold as Mounjaro for type 2 diabetes — started rolling out in 2022. It’s approved for chronic weight management in the European Union and the United Kingdom, sold in the United States as the weight loss drug Zepbound, and is currently under review in China.
As shortages continue, some governments are asking clinicians not to prescribe the drugs for obesity and instead reserve them for people with type 2 diabetes. But governments are limited in how to enforce this request, and some providers disagree with the guidance. Here’s a look at various countries’ approaches to handling these blockbuster drugs.
Sweden
Ylva Trolle Lagerros, MD, said it’s common for the Swedish Medicines Agency to post guidance for drugs on their website, and occasionally, the agency will send letters to physicians if a drug is recalled or found to have new side effects. In December, Dr. Lagerros, along with physicians throughout Sweden, received a letter at her home address requesting that they not prescribe GLP-1 receptor agonists to people for weight loss alone, over concerns the drugs wouldn’t be available for patients with type 2 diabetes.
Given the shortages, Dr. Lagerros, an obesity medicine specialist and associate professor at the Karolinska Institutet in Stockholm, Sweden, expected the guidance but said it was reinforced with the letters mailed to physicians’ homes.
“It’s not forbidden to go off-label. It is a right you have as a physician, but we are clearly told not to,” said Dr. Lagerros, who is also a senior physician at the Center for Obesity in Stockholm, Sweden’s largest obesity clinic.
Providers are being forced to prioritize some patients above others, she added.
“Yes, GLP-1 [agonists] are good for people with type 2 diabetes, but given this global shortage, I think the people who are most severely sick should be prioritized,” she said. “With this principle, we are walking away from that, saying only people with type 2 diabetes should get it.”
Dr. Lagerros said she does not prescribe Ozempic, the only injectable GLP-1 currently available in Sweden, off-label because she works closely with the government on national obesity guidelines and feels unable to, but she understands why some of her colleagues at other clinics do.
In Sweden, some companies are importing and selling Wegovy, which is typically not available, at different price points, said Dr. Lagerros. She said she knows of at least three telehealth apps operating in Sweden through which patients are prescribed semaglutide for weight loss without being seen by a doctor.
“That adds to the ethical problem that if you prescribe it as a diabetes medication, the patient doesn’t have to pay, but if you prescribe it as an obesity medication, the patient has to pay a lot of money,” Dr. Lagerros said.
United Kingdom
Last summer, health officials in the United Kingdom took a similar approach to Sweden’s, urging providers to stop prescribing appetite-suppressing medications for weight loss due to shortages for patients with diabetes. The notice also asked providers to hold off on writing new prescriptions for GLP-1 agonists, as well as the drug Trulicity, for patients with type 2 diabetes.
In the United Kingdom, Wegovy, Mounjaro, and Saxenda, an oral semaglutide, have been approved for weight loss and are covered by the National Health System. People must have a body mass index (BMI) of 30 or more with one weight-related condition, or a BMI of at least 35, to qualify for Wegovy. Because Ozempic, only approved for treating type 2 diabetes, is used off-label but is not specifically indicated for weight loss, physicians typically use the same parameters when prescribing it off-label as they do Wegovy.
Naresh Dr. Kanumilli, MD, a general practitioner and diabetes specialist in the Northenden Group Practice in Manchester, England, said he believes GLP-1 agonists should not be used off-label for weight loss.
“The global shortage was probably exacerbated because a lot of the drugs were going toward obesity when they should be going to diabetes,” he said.
Dr. Kanumilli, who is also a National Health Service England Clinical Network lead for diabetes, said he hopes more doctors in the United Kingdom offer their patients other drugs for weight loss before reaching for Wegovy.
He said doctors in the United Kingdom are allowing patients to jump from a metformin-only regimen to GLP-1 plus metformin, without trying an intermediate group of drugs called sodium-glucose transport protein 2 inhibitors. “We want to reinforce that these drugs should be tried prior to GLP-1 agonists [for obesity treatment],” he said.
United States
Despite widespread shortages, the US government has not asked clinicians to reserve GLP-1 agonists for patients with type 2 diabetes, but patients are experiencing additional restrictions related to cost and insurance coverage.
In the United States, where these types of medications already cost more than they do in other countries, private insurers rarely cover the drugs for obesity. Medicare is forbidden to cover any type of weight loss drug, although proposed legislation could change that.
According to August 2023 data from KFF, formerly The Kaiser Family Foundation, a month’s supply of a 1.7-mg or 2.4-mg dose of Wegovy costs an average of $1349 in the United States, which is considerably higher than other countries. In Germany, that same supply runs about $328. In the Netherlands, it’s $296. A 1-month supply of Rybelsus or Ozempic costs about four times as much in the United States as it does in the Netherlands. Eli Lilly’s list price for 1 month of Mounjaro in the United States is $1069.08 compared to about $319 in Japan, according to the report.
On the rare occasion a private insurer in the United States does cover a GLP-1 agonist prescribed for weight loss — only about 27% of insurance companies did in 2023 — people may need to prove other interventions, including lifestyle changes, did not produce results.
Beverly Tchang, MD, an assistant professor of clinical medicine at Weill Comprehensive Weight Control Center in New York, said she takes a patient-by-patient approach when considering prescribing these medications.
The BMI thresholds for Wegovy are 27 if a person has at least one weight-related comorbidity, and 30 if they do not, in the United States. Dr. Tchang said these rules are strict, but some exceptions are made for ethnicities such as those of South or East Asian descent where a BMI of 25 can be used as they have a lower threshold for overweight or obesity.
If Dr. Tchang feels a patient would benefit from significant weight loss, she is comfortable prescribing the drugs for weight loss to a patient who doesn’t have type 2 diabetes.
“Most people I see would benefit from that 10%-15% or more weight loss threshold, so I often do reach for the tirzepatide and semaglutide,” she said.
For patients who need to lose closer to 5% of their body weight to manage or prevent comorbidities, Dr. Tchang said she would likely try another medication that does not produce as extreme results.
Canada
The Canadian government has not directed clinicians to reserve GLP-1 agonists for certain patients. Instead, access is limited by cost, said Ehud Ur, MD, a professor of medicine at the University of British Columbia and consulting endocrinologist at St. Paul’s Hospital in Vancouver, British Columbia, Canada.
About 67% of Canadians have private insurance, according to The Commonwealth Fund. Most private insurers cover GLP-1 agonists for weight loss, but Canada’s public healthcare system only covers the drugs for type 2 diabetes, not for weight loss alone.
He agreed that people with type 2 diabetes should not be favored over those with obesity for prescriptions of GLP-1 agonists. Rather, he said, physicians should focus on what is the best treatment is for each patient. For some people with obesity, these medications can elicit the same weight loss as surgery, which no other medication currently can.
Dr. Ur said some clinicians in Canada prescribe GLP-1 agonists to people who do not need to lose a significant amount of weight, but the drugs are also being taken by people who do.
“The drive for the drugs is largely due to their efficacy,” he said. “You have physicians that have more confidence in this drug than they have for any other antiobesity agent, so you have a big drive for prescriptions.”
What Are the Alternatives?
In the face of shortages, physicians including Dr. Lagerros, Dr. Tchang, and Dr. Ur are resorting to other drugs when necessary to get patients the care they need.
“We have been in the business of treating obesity for decades,” Dr. Tchang said. “Before the GLP-1s were invented.”
Dr. Lagerros does not believe all her patients need GLP-1 agonists but does want them more widely available for those who overeat because they are unable to control their appetite, who she said are prime candidates for the drugs.
“I’m telling my patients, ‘yes, we don’t have semaglutide right now, but we just have to hang in there and work with what we have right now,’” she said.
A version of this article appeared on Medscape.com.
Glucagon-like peptide 1 (GLP-1) receptor agonists are the latest blockbuster drugs — thanks to their potent ability to help patients lose weight. But
Semaglutide for weight loss (Wegovy) has launched in eight countries, namely, Denmark, Germany, Iceland, Norway, the United Arab Emirates, the United Kingdom, the United States, and Switzerland, and was released in Japan in February. Semaglutide for type 2 diabetes (Ozempic) is approved in 82 countries and often is prescribed off-label to treat obesity.
The dual glucose-dependent insulinotropic polypeptide/GLP-1 agonist tirzepatide — sold as Mounjaro for type 2 diabetes — started rolling out in 2022. It’s approved for chronic weight management in the European Union and the United Kingdom, sold in the United States as the weight loss drug Zepbound, and is currently under review in China.
As shortages continue, some governments are asking clinicians not to prescribe the drugs for obesity and instead reserve them for people with type 2 diabetes. But governments are limited in how to enforce this request, and some providers disagree with the guidance. Here’s a look at various countries’ approaches to handling these blockbuster drugs.
Sweden
Ylva Trolle Lagerros, MD, said it’s common for the Swedish Medicines Agency to post guidance for drugs on their website, and occasionally, the agency will send letters to physicians if a drug is recalled or found to have new side effects. In December, Dr. Lagerros, along with physicians throughout Sweden, received a letter at her home address requesting that they not prescribe GLP-1 receptor agonists to people for weight loss alone, over concerns the drugs wouldn’t be available for patients with type 2 diabetes.
Given the shortages, Dr. Lagerros, an obesity medicine specialist and associate professor at the Karolinska Institutet in Stockholm, Sweden, expected the guidance but said it was reinforced with the letters mailed to physicians’ homes.
“It’s not forbidden to go off-label. It is a right you have as a physician, but we are clearly told not to,” said Dr. Lagerros, who is also a senior physician at the Center for Obesity in Stockholm, Sweden’s largest obesity clinic.
Providers are being forced to prioritize some patients above others, she added.
“Yes, GLP-1 [agonists] are good for people with type 2 diabetes, but given this global shortage, I think the people who are most severely sick should be prioritized,” she said. “With this principle, we are walking away from that, saying only people with type 2 diabetes should get it.”
Dr. Lagerros said she does not prescribe Ozempic, the only injectable GLP-1 currently available in Sweden, off-label because she works closely with the government on national obesity guidelines and feels unable to, but she understands why some of her colleagues at other clinics do.
In Sweden, some companies are importing and selling Wegovy, which is typically not available, at different price points, said Dr. Lagerros. She said she knows of at least three telehealth apps operating in Sweden through which patients are prescribed semaglutide for weight loss without being seen by a doctor.
“That adds to the ethical problem that if you prescribe it as a diabetes medication, the patient doesn’t have to pay, but if you prescribe it as an obesity medication, the patient has to pay a lot of money,” Dr. Lagerros said.
United Kingdom
Last summer, health officials in the United Kingdom took a similar approach to Sweden’s, urging providers to stop prescribing appetite-suppressing medications for weight loss due to shortages for patients with diabetes. The notice also asked providers to hold off on writing new prescriptions for GLP-1 agonists, as well as the drug Trulicity, for patients with type 2 diabetes.
In the United Kingdom, Wegovy, Mounjaro, and Saxenda, an oral semaglutide, have been approved for weight loss and are covered by the National Health System. People must have a body mass index (BMI) of 30 or more with one weight-related condition, or a BMI of at least 35, to qualify for Wegovy. Because Ozempic, only approved for treating type 2 diabetes, is used off-label but is not specifically indicated for weight loss, physicians typically use the same parameters when prescribing it off-label as they do Wegovy.
Naresh Dr. Kanumilli, MD, a general practitioner and diabetes specialist in the Northenden Group Practice in Manchester, England, said he believes GLP-1 agonists should not be used off-label for weight loss.
“The global shortage was probably exacerbated because a lot of the drugs were going toward obesity when they should be going to diabetes,” he said.
Dr. Kanumilli, who is also a National Health Service England Clinical Network lead for diabetes, said he hopes more doctors in the United Kingdom offer their patients other drugs for weight loss before reaching for Wegovy.
He said doctors in the United Kingdom are allowing patients to jump from a metformin-only regimen to GLP-1 plus metformin, without trying an intermediate group of drugs called sodium-glucose transport protein 2 inhibitors. “We want to reinforce that these drugs should be tried prior to GLP-1 agonists [for obesity treatment],” he said.
United States
Despite widespread shortages, the US government has not asked clinicians to reserve GLP-1 agonists for patients with type 2 diabetes, but patients are experiencing additional restrictions related to cost and insurance coverage.
In the United States, where these types of medications already cost more than they do in other countries, private insurers rarely cover the drugs for obesity. Medicare is forbidden to cover any type of weight loss drug, although proposed legislation could change that.
According to August 2023 data from KFF, formerly The Kaiser Family Foundation, a month’s supply of a 1.7-mg or 2.4-mg dose of Wegovy costs an average of $1349 in the United States, which is considerably higher than other countries. In Germany, that same supply runs about $328. In the Netherlands, it’s $296. A 1-month supply of Rybelsus or Ozempic costs about four times as much in the United States as it does in the Netherlands. Eli Lilly’s list price for 1 month of Mounjaro in the United States is $1069.08 compared to about $319 in Japan, according to the report.
On the rare occasion a private insurer in the United States does cover a GLP-1 agonist prescribed for weight loss — only about 27% of insurance companies did in 2023 — people may need to prove other interventions, including lifestyle changes, did not produce results.
Beverly Tchang, MD, an assistant professor of clinical medicine at Weill Comprehensive Weight Control Center in New York, said she takes a patient-by-patient approach when considering prescribing these medications.
The BMI thresholds for Wegovy are 27 if a person has at least one weight-related comorbidity, and 30 if they do not, in the United States. Dr. Tchang said these rules are strict, but some exceptions are made for ethnicities such as those of South or East Asian descent where a BMI of 25 can be used as they have a lower threshold for overweight or obesity.
If Dr. Tchang feels a patient would benefit from significant weight loss, she is comfortable prescribing the drugs for weight loss to a patient who doesn’t have type 2 diabetes.
“Most people I see would benefit from that 10%-15% or more weight loss threshold, so I often do reach for the tirzepatide and semaglutide,” she said.
For patients who need to lose closer to 5% of their body weight to manage or prevent comorbidities, Dr. Tchang said she would likely try another medication that does not produce as extreme results.
Canada
The Canadian government has not directed clinicians to reserve GLP-1 agonists for certain patients. Instead, access is limited by cost, said Ehud Ur, MD, a professor of medicine at the University of British Columbia and consulting endocrinologist at St. Paul’s Hospital in Vancouver, British Columbia, Canada.
About 67% of Canadians have private insurance, according to The Commonwealth Fund. Most private insurers cover GLP-1 agonists for weight loss, but Canada’s public healthcare system only covers the drugs for type 2 diabetes, not for weight loss alone.
He agreed that people with type 2 diabetes should not be favored over those with obesity for prescriptions of GLP-1 agonists. Rather, he said, physicians should focus on what is the best treatment is for each patient. For some people with obesity, these medications can elicit the same weight loss as surgery, which no other medication currently can.
Dr. Ur said some clinicians in Canada prescribe GLP-1 agonists to people who do not need to lose a significant amount of weight, but the drugs are also being taken by people who do.
“The drive for the drugs is largely due to their efficacy,” he said. “You have physicians that have more confidence in this drug than they have for any other antiobesity agent, so you have a big drive for prescriptions.”
What Are the Alternatives?
In the face of shortages, physicians including Dr. Lagerros, Dr. Tchang, and Dr. Ur are resorting to other drugs when necessary to get patients the care they need.
“We have been in the business of treating obesity for decades,” Dr. Tchang said. “Before the GLP-1s were invented.”
Dr. Lagerros does not believe all her patients need GLP-1 agonists but does want them more widely available for those who overeat because they are unable to control their appetite, who she said are prime candidates for the drugs.
“I’m telling my patients, ‘yes, we don’t have semaglutide right now, but we just have to hang in there and work with what we have right now,’” she said.
A version of this article appeared on Medscape.com.
Glucagon-like peptide 1 (GLP-1) receptor agonists are the latest blockbuster drugs — thanks to their potent ability to help patients lose weight. But
Semaglutide for weight loss (Wegovy) has launched in eight countries, namely, Denmark, Germany, Iceland, Norway, the United Arab Emirates, the United Kingdom, the United States, and Switzerland, and was released in Japan in February. Semaglutide for type 2 diabetes (Ozempic) is approved in 82 countries and often is prescribed off-label to treat obesity.
The dual glucose-dependent insulinotropic polypeptide/GLP-1 agonist tirzepatide — sold as Mounjaro for type 2 diabetes — started rolling out in 2022. It’s approved for chronic weight management in the European Union and the United Kingdom, sold in the United States as the weight loss drug Zepbound, and is currently under review in China.
As shortages continue, some governments are asking clinicians not to prescribe the drugs for obesity and instead reserve them for people with type 2 diabetes. But governments are limited in how to enforce this request, and some providers disagree with the guidance. Here’s a look at various countries’ approaches to handling these blockbuster drugs.
Sweden
Ylva Trolle Lagerros, MD, said it’s common for the Swedish Medicines Agency to post guidance for drugs on their website, and occasionally, the agency will send letters to physicians if a drug is recalled or found to have new side effects. In December, Dr. Lagerros, along with physicians throughout Sweden, received a letter at her home address requesting that they not prescribe GLP-1 receptor agonists to people for weight loss alone, over concerns the drugs wouldn’t be available for patients with type 2 diabetes.
Given the shortages, Dr. Lagerros, an obesity medicine specialist and associate professor at the Karolinska Institutet in Stockholm, Sweden, expected the guidance but said it was reinforced with the letters mailed to physicians’ homes.
“It’s not forbidden to go off-label. It is a right you have as a physician, but we are clearly told not to,” said Dr. Lagerros, who is also a senior physician at the Center for Obesity in Stockholm, Sweden’s largest obesity clinic.
Providers are being forced to prioritize some patients above others, she added.
“Yes, GLP-1 [agonists] are good for people with type 2 diabetes, but given this global shortage, I think the people who are most severely sick should be prioritized,” she said. “With this principle, we are walking away from that, saying only people with type 2 diabetes should get it.”
Dr. Lagerros said she does not prescribe Ozempic, the only injectable GLP-1 currently available in Sweden, off-label because she works closely with the government on national obesity guidelines and feels unable to, but she understands why some of her colleagues at other clinics do.
In Sweden, some companies are importing and selling Wegovy, which is typically not available, at different price points, said Dr. Lagerros. She said she knows of at least three telehealth apps operating in Sweden through which patients are prescribed semaglutide for weight loss without being seen by a doctor.
“That adds to the ethical problem that if you prescribe it as a diabetes medication, the patient doesn’t have to pay, but if you prescribe it as an obesity medication, the patient has to pay a lot of money,” Dr. Lagerros said.
United Kingdom
Last summer, health officials in the United Kingdom took a similar approach to Sweden’s, urging providers to stop prescribing appetite-suppressing medications for weight loss due to shortages for patients with diabetes. The notice also asked providers to hold off on writing new prescriptions for GLP-1 agonists, as well as the drug Trulicity, for patients with type 2 diabetes.
In the United Kingdom, Wegovy, Mounjaro, and Saxenda, an oral semaglutide, have been approved for weight loss and are covered by the National Health System. People must have a body mass index (BMI) of 30 or more with one weight-related condition, or a BMI of at least 35, to qualify for Wegovy. Because Ozempic, only approved for treating type 2 diabetes, is used off-label but is not specifically indicated for weight loss, physicians typically use the same parameters when prescribing it off-label as they do Wegovy.
Naresh Dr. Kanumilli, MD, a general practitioner and diabetes specialist in the Northenden Group Practice in Manchester, England, said he believes GLP-1 agonists should not be used off-label for weight loss.
“The global shortage was probably exacerbated because a lot of the drugs were going toward obesity when they should be going to diabetes,” he said.
Dr. Kanumilli, who is also a National Health Service England Clinical Network lead for diabetes, said he hopes more doctors in the United Kingdom offer their patients other drugs for weight loss before reaching for Wegovy.
He said doctors in the United Kingdom are allowing patients to jump from a metformin-only regimen to GLP-1 plus metformin, without trying an intermediate group of drugs called sodium-glucose transport protein 2 inhibitors. “We want to reinforce that these drugs should be tried prior to GLP-1 agonists [for obesity treatment],” he said.
United States
Despite widespread shortages, the US government has not asked clinicians to reserve GLP-1 agonists for patients with type 2 diabetes, but patients are experiencing additional restrictions related to cost and insurance coverage.
In the United States, where these types of medications already cost more than they do in other countries, private insurers rarely cover the drugs for obesity. Medicare is forbidden to cover any type of weight loss drug, although proposed legislation could change that.
According to August 2023 data from KFF, formerly The Kaiser Family Foundation, a month’s supply of a 1.7-mg or 2.4-mg dose of Wegovy costs an average of $1349 in the United States, which is considerably higher than other countries. In Germany, that same supply runs about $328. In the Netherlands, it’s $296. A 1-month supply of Rybelsus or Ozempic costs about four times as much in the United States as it does in the Netherlands. Eli Lilly’s list price for 1 month of Mounjaro in the United States is $1069.08 compared to about $319 in Japan, according to the report.
On the rare occasion a private insurer in the United States does cover a GLP-1 agonist prescribed for weight loss — only about 27% of insurance companies did in 2023 — people may need to prove other interventions, including lifestyle changes, did not produce results.
Beverly Tchang, MD, an assistant professor of clinical medicine at Weill Comprehensive Weight Control Center in New York, said she takes a patient-by-patient approach when considering prescribing these medications.
The BMI thresholds for Wegovy are 27 if a person has at least one weight-related comorbidity, and 30 if they do not, in the United States. Dr. Tchang said these rules are strict, but some exceptions are made for ethnicities such as those of South or East Asian descent where a BMI of 25 can be used as they have a lower threshold for overweight or obesity.
If Dr. Tchang feels a patient would benefit from significant weight loss, she is comfortable prescribing the drugs for weight loss to a patient who doesn’t have type 2 diabetes.
“Most people I see would benefit from that 10%-15% or more weight loss threshold, so I often do reach for the tirzepatide and semaglutide,” she said.
For patients who need to lose closer to 5% of their body weight to manage or prevent comorbidities, Dr. Tchang said she would likely try another medication that does not produce as extreme results.
Canada
The Canadian government has not directed clinicians to reserve GLP-1 agonists for certain patients. Instead, access is limited by cost, said Ehud Ur, MD, a professor of medicine at the University of British Columbia and consulting endocrinologist at St. Paul’s Hospital in Vancouver, British Columbia, Canada.
About 67% of Canadians have private insurance, according to The Commonwealth Fund. Most private insurers cover GLP-1 agonists for weight loss, but Canada’s public healthcare system only covers the drugs for type 2 diabetes, not for weight loss alone.
He agreed that people with type 2 diabetes should not be favored over those with obesity for prescriptions of GLP-1 agonists. Rather, he said, physicians should focus on what is the best treatment is for each patient. For some people with obesity, these medications can elicit the same weight loss as surgery, which no other medication currently can.
Dr. Ur said some clinicians in Canada prescribe GLP-1 agonists to people who do not need to lose a significant amount of weight, but the drugs are also being taken by people who do.
“The drive for the drugs is largely due to their efficacy,” he said. “You have physicians that have more confidence in this drug than they have for any other antiobesity agent, so you have a big drive for prescriptions.”
What Are the Alternatives?
In the face of shortages, physicians including Dr. Lagerros, Dr. Tchang, and Dr. Ur are resorting to other drugs when necessary to get patients the care they need.
“We have been in the business of treating obesity for decades,” Dr. Tchang said. “Before the GLP-1s were invented.”
Dr. Lagerros does not believe all her patients need GLP-1 agonists but does want them more widely available for those who overeat because they are unable to control their appetite, who she said are prime candidates for the drugs.
“I’m telling my patients, ‘yes, we don’t have semaglutide right now, but we just have to hang in there and work with what we have right now,’” she said.
A version of this article appeared on Medscape.com.
Neurologists Read Signs to Diagnose Functional Neurological Disorders
They have gone by many different names over the centuries: hysteria, psychosomatic illnesses, psychogenic neurological disorders, conversion disorders, dissociative neurological symptom disorders. The terminology may change, but functional neurological disorders by any other name are still real and serious yet treatable phenomena.
Functional neurological disorders, or FNDs, live at the crossroads of neurology and psychiatry, and they are as much a product of the body as they are of the brain, say neurologists who specialize in treating these complex and clinically challenging conditions.
“Whether they’re easily recognized or not depends on someone’s training and experience in this regard,” said Mark Hallett, MD, of the Human Motor Control Section of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland.
“The difficulty has been that there hasn’t been very good education about functional disorders over the last 50 years or so,” he said in an interview.
However, with training and experience, clinicians can learn to identify these common and disabling conditions, Dr. Hallett said.
Varying Definitions
The Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) labels FND as “conversion disorder,” and lists diagnostic criteria that include “one or more symptoms of altered voluntary motor or sensory function; clinical findings provide evidence of incompatibility between the symptom and recognized neurological or medical conditions; the symptom or deficit is not better explained by another medical or mental disorder;” and “the symptom or deficit causes clinically significant distress or impairment in social, occupational, or other important areas of functioning or warrants medical evaluation.”
Dr. Hallett offers his own definition of FND, which includes the following characteristics:
- A neurological disorder, characterized by almost any type of neurological symptom
- Not voluntarily produced
- Caused by a brain network dysfunction that does not exclude the possibility of normal function
- Sometimes due in part to a psychological cause, and not explained by other neurological pathology that may or may not be present
- Symptoms may be inconsistent (variable) or incompatible (incongruent) with other known neurological disorders or human anatomy and physiology.
The two most common types of FND are psychogenic nonepileptic seizures and functional movement disorders, but patients may also have functional sensory, visual, auditory, speech, and urologic disorders, and even functional coma.
Dr. Hallett cited studies showing that an estimated 9% of neurology hospital admission are for FNDS, and that among patients in neurology clinics 5.4% had a diagnosis of FND, and 30% had an FND as part of the diagnosis.
Women comprise between 60% and 75% of the population with FNDs.
Diagnosis
FND is not, as once thought, a diagnosis of exclusion, but is based on signs and symptoms, which may be either inconsistent or irreversible and may occur in the absence of a stressor, said Sara Finkelstein, MD, MSc, of the Functional Neurological Disorder Unit in the Department of Neurology at Massachusetts General Hospital in Boston.
She emphasized that there are several diagnostic pitfalls that clinicians need to be aware of.
For example, “just because a patient has a psychiatric history does not mean that they have a functional neurological disorder,” she said in an interview.
Clinicians may also make unwarranted assumptions about a given patient, excluding an FND diagnosis in, say, a young woman with symptoms of anxiety. Alternatively, clinicians may either include or exclude a diagnosis based on personality factors or on a prior stressor, neither of which alone are sufficiently diagnostic.
Additionally, a clinician may be tempted to make the diagnosis of an FND based on the absence of findings on standard exams rather than on rule-in signs and symptoms, she emphasized.
Functional seizures
A definitive diagnosis can depend on the type of disorder.
“Many functional seizures have some clinical manifestations that are apparent, but as seizures are intermittent the doctor may not see one, and it may depend upon someone taking a video of the person with the seizure perhaps, or bringing them into a hospital and watching them until they do have the seizure,” Dr. Hallett said.
There are some manifestations that indicate the likelihood that a seizure has a functional origin, and when there is uncertainty EEG can help to nail down a diagnosis, he added.
Dr. Finkelstein noted that exam signs with good reliability for functional seizures include eye closure or resistance to opening; duration longer than 2 minutes; stopping and starting; asynchronous limb movements; patient maintenance of awareness during a generalized event; and ictal weeping.
Differential diagnoses included migraine with complex aura, dissociation related to posttraumatic stress disorder, or anxiety.
Functional movement disorders
Dr. Finkelstein cautioned that when evaluating patients for potential functional movement disorders, it’s important to not jump to conclusions.
For example, the amplitude of tremor can vary in Parkinson’s disease and essential tremor as well as in functional tremor. The clinician should not read too much into the observation that a patient’s tremor gets worse with increasing stress as stress can exacerbate most tremor types, she said.
One sign that tremor could be functional (dystonic tremor) is irregularity of amplitude and frequency, she noted.
When assessing patients with gait disorder, it’s important to understand that there is no single sign that is specially characteristic for a given disorder, and just because a patient has a “bizarre” gait, it doesn’t necessarily signal a functional disorder.
“A dystonic gait may improve with an alternate motor pattern or be inconsistent over time,” Dr. Finkelstein said.
Treatment
In a comprehensive review published in The Lancet: Neurology in 2022, Dr. Hallett and colleagues said that good doctor-patient communications and understanding of each patient’s needs and goals are essential for effective treatment of all FNDs.
“Neurologists have traditionally avoided taking responsibility for people with FND, although are often most appropriate to engage patients in treatment. Explaining the diagnosis with clarity, confidence, using the principles of a ‘rule in’ process, is a key step in treatment,” they wrote.
Treatment can take several forms, depending on the FND, and may include physiotherapy for patients with functional movement disorders and psychological therapy for patients with functional seizures.
“With increasing evidence-based treatment, the diagnosis of FND should be seen as a process of looking for potentially reversible cause of disability and distress whether or not an individual has abnormalities on conventional laboratory or radiological testing,” Dr. Hallett and colleagues concluded.
This article was based on interviews and from presentations by Dr. Hallett and Dr. Finkelstein at a 2023 meeting of the Indiana Neurological Society. Dr. Hallett and Dr. Finkelstein declared no conflicts of interest.
They have gone by many different names over the centuries: hysteria, psychosomatic illnesses, psychogenic neurological disorders, conversion disorders, dissociative neurological symptom disorders. The terminology may change, but functional neurological disorders by any other name are still real and serious yet treatable phenomena.
Functional neurological disorders, or FNDs, live at the crossroads of neurology and psychiatry, and they are as much a product of the body as they are of the brain, say neurologists who specialize in treating these complex and clinically challenging conditions.
“Whether they’re easily recognized or not depends on someone’s training and experience in this regard,” said Mark Hallett, MD, of the Human Motor Control Section of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland.
“The difficulty has been that there hasn’t been very good education about functional disorders over the last 50 years or so,” he said in an interview.
However, with training and experience, clinicians can learn to identify these common and disabling conditions, Dr. Hallett said.
Varying Definitions
The Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) labels FND as “conversion disorder,” and lists diagnostic criteria that include “one or more symptoms of altered voluntary motor or sensory function; clinical findings provide evidence of incompatibility between the symptom and recognized neurological or medical conditions; the symptom or deficit is not better explained by another medical or mental disorder;” and “the symptom or deficit causes clinically significant distress or impairment in social, occupational, or other important areas of functioning or warrants medical evaluation.”
Dr. Hallett offers his own definition of FND, which includes the following characteristics:
- A neurological disorder, characterized by almost any type of neurological symptom
- Not voluntarily produced
- Caused by a brain network dysfunction that does not exclude the possibility of normal function
- Sometimes due in part to a psychological cause, and not explained by other neurological pathology that may or may not be present
- Symptoms may be inconsistent (variable) or incompatible (incongruent) with other known neurological disorders or human anatomy and physiology.
The two most common types of FND are psychogenic nonepileptic seizures and functional movement disorders, but patients may also have functional sensory, visual, auditory, speech, and urologic disorders, and even functional coma.
Dr. Hallett cited studies showing that an estimated 9% of neurology hospital admission are for FNDS, and that among patients in neurology clinics 5.4% had a diagnosis of FND, and 30% had an FND as part of the diagnosis.
Women comprise between 60% and 75% of the population with FNDs.
Diagnosis
FND is not, as once thought, a diagnosis of exclusion, but is based on signs and symptoms, which may be either inconsistent or irreversible and may occur in the absence of a stressor, said Sara Finkelstein, MD, MSc, of the Functional Neurological Disorder Unit in the Department of Neurology at Massachusetts General Hospital in Boston.
She emphasized that there are several diagnostic pitfalls that clinicians need to be aware of.
For example, “just because a patient has a psychiatric history does not mean that they have a functional neurological disorder,” she said in an interview.
Clinicians may also make unwarranted assumptions about a given patient, excluding an FND diagnosis in, say, a young woman with symptoms of anxiety. Alternatively, clinicians may either include or exclude a diagnosis based on personality factors or on a prior stressor, neither of which alone are sufficiently diagnostic.
Additionally, a clinician may be tempted to make the diagnosis of an FND based on the absence of findings on standard exams rather than on rule-in signs and symptoms, she emphasized.
Functional seizures
A definitive diagnosis can depend on the type of disorder.
“Many functional seizures have some clinical manifestations that are apparent, but as seizures are intermittent the doctor may not see one, and it may depend upon someone taking a video of the person with the seizure perhaps, or bringing them into a hospital and watching them until they do have the seizure,” Dr. Hallett said.
There are some manifestations that indicate the likelihood that a seizure has a functional origin, and when there is uncertainty EEG can help to nail down a diagnosis, he added.
Dr. Finkelstein noted that exam signs with good reliability for functional seizures include eye closure or resistance to opening; duration longer than 2 minutes; stopping and starting; asynchronous limb movements; patient maintenance of awareness during a generalized event; and ictal weeping.
Differential diagnoses included migraine with complex aura, dissociation related to posttraumatic stress disorder, or anxiety.
Functional movement disorders
Dr. Finkelstein cautioned that when evaluating patients for potential functional movement disorders, it’s important to not jump to conclusions.
For example, the amplitude of tremor can vary in Parkinson’s disease and essential tremor as well as in functional tremor. The clinician should not read too much into the observation that a patient’s tremor gets worse with increasing stress as stress can exacerbate most tremor types, she said.
One sign that tremor could be functional (dystonic tremor) is irregularity of amplitude and frequency, she noted.
When assessing patients with gait disorder, it’s important to understand that there is no single sign that is specially characteristic for a given disorder, and just because a patient has a “bizarre” gait, it doesn’t necessarily signal a functional disorder.
“A dystonic gait may improve with an alternate motor pattern or be inconsistent over time,” Dr. Finkelstein said.
Treatment
In a comprehensive review published in The Lancet: Neurology in 2022, Dr. Hallett and colleagues said that good doctor-patient communications and understanding of each patient’s needs and goals are essential for effective treatment of all FNDs.
“Neurologists have traditionally avoided taking responsibility for people with FND, although are often most appropriate to engage patients in treatment. Explaining the diagnosis with clarity, confidence, using the principles of a ‘rule in’ process, is a key step in treatment,” they wrote.
Treatment can take several forms, depending on the FND, and may include physiotherapy for patients with functional movement disorders and psychological therapy for patients with functional seizures.
“With increasing evidence-based treatment, the diagnosis of FND should be seen as a process of looking for potentially reversible cause of disability and distress whether or not an individual has abnormalities on conventional laboratory or radiological testing,” Dr. Hallett and colleagues concluded.
This article was based on interviews and from presentations by Dr. Hallett and Dr. Finkelstein at a 2023 meeting of the Indiana Neurological Society. Dr. Hallett and Dr. Finkelstein declared no conflicts of interest.
They have gone by many different names over the centuries: hysteria, psychosomatic illnesses, psychogenic neurological disorders, conversion disorders, dissociative neurological symptom disorders. The terminology may change, but functional neurological disorders by any other name are still real and serious yet treatable phenomena.
Functional neurological disorders, or FNDs, live at the crossroads of neurology and psychiatry, and they are as much a product of the body as they are of the brain, say neurologists who specialize in treating these complex and clinically challenging conditions.
“Whether they’re easily recognized or not depends on someone’s training and experience in this regard,” said Mark Hallett, MD, of the Human Motor Control Section of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland.
“The difficulty has been that there hasn’t been very good education about functional disorders over the last 50 years or so,” he said in an interview.
However, with training and experience, clinicians can learn to identify these common and disabling conditions, Dr. Hallett said.
Varying Definitions
The Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) labels FND as “conversion disorder,” and lists diagnostic criteria that include “one or more symptoms of altered voluntary motor or sensory function; clinical findings provide evidence of incompatibility between the symptom and recognized neurological or medical conditions; the symptom or deficit is not better explained by another medical or mental disorder;” and “the symptom or deficit causes clinically significant distress or impairment in social, occupational, or other important areas of functioning or warrants medical evaluation.”
Dr. Hallett offers his own definition of FND, which includes the following characteristics:
- A neurological disorder, characterized by almost any type of neurological symptom
- Not voluntarily produced
- Caused by a brain network dysfunction that does not exclude the possibility of normal function
- Sometimes due in part to a psychological cause, and not explained by other neurological pathology that may or may not be present
- Symptoms may be inconsistent (variable) or incompatible (incongruent) with other known neurological disorders or human anatomy and physiology.
The two most common types of FND are psychogenic nonepileptic seizures and functional movement disorders, but patients may also have functional sensory, visual, auditory, speech, and urologic disorders, and even functional coma.
Dr. Hallett cited studies showing that an estimated 9% of neurology hospital admission are for FNDS, and that among patients in neurology clinics 5.4% had a diagnosis of FND, and 30% had an FND as part of the diagnosis.
Women comprise between 60% and 75% of the population with FNDs.
Diagnosis
FND is not, as once thought, a diagnosis of exclusion, but is based on signs and symptoms, which may be either inconsistent or irreversible and may occur in the absence of a stressor, said Sara Finkelstein, MD, MSc, of the Functional Neurological Disorder Unit in the Department of Neurology at Massachusetts General Hospital in Boston.
She emphasized that there are several diagnostic pitfalls that clinicians need to be aware of.
For example, “just because a patient has a psychiatric history does not mean that they have a functional neurological disorder,” she said in an interview.
Clinicians may also make unwarranted assumptions about a given patient, excluding an FND diagnosis in, say, a young woman with symptoms of anxiety. Alternatively, clinicians may either include or exclude a diagnosis based on personality factors or on a prior stressor, neither of which alone are sufficiently diagnostic.
Additionally, a clinician may be tempted to make the diagnosis of an FND based on the absence of findings on standard exams rather than on rule-in signs and symptoms, she emphasized.
Functional seizures
A definitive diagnosis can depend on the type of disorder.
“Many functional seizures have some clinical manifestations that are apparent, but as seizures are intermittent the doctor may not see one, and it may depend upon someone taking a video of the person with the seizure perhaps, or bringing them into a hospital and watching them until they do have the seizure,” Dr. Hallett said.
There are some manifestations that indicate the likelihood that a seizure has a functional origin, and when there is uncertainty EEG can help to nail down a diagnosis, he added.
Dr. Finkelstein noted that exam signs with good reliability for functional seizures include eye closure or resistance to opening; duration longer than 2 minutes; stopping and starting; asynchronous limb movements; patient maintenance of awareness during a generalized event; and ictal weeping.
Differential diagnoses included migraine with complex aura, dissociation related to posttraumatic stress disorder, or anxiety.
Functional movement disorders
Dr. Finkelstein cautioned that when evaluating patients for potential functional movement disorders, it’s important to not jump to conclusions.
For example, the amplitude of tremor can vary in Parkinson’s disease and essential tremor as well as in functional tremor. The clinician should not read too much into the observation that a patient’s tremor gets worse with increasing stress as stress can exacerbate most tremor types, she said.
One sign that tremor could be functional (dystonic tremor) is irregularity of amplitude and frequency, she noted.
When assessing patients with gait disorder, it’s important to understand that there is no single sign that is specially characteristic for a given disorder, and just because a patient has a “bizarre” gait, it doesn’t necessarily signal a functional disorder.
“A dystonic gait may improve with an alternate motor pattern or be inconsistent over time,” Dr. Finkelstein said.
Treatment
In a comprehensive review published in The Lancet: Neurology in 2022, Dr. Hallett and colleagues said that good doctor-patient communications and understanding of each patient’s needs and goals are essential for effective treatment of all FNDs.
“Neurologists have traditionally avoided taking responsibility for people with FND, although are often most appropriate to engage patients in treatment. Explaining the diagnosis with clarity, confidence, using the principles of a ‘rule in’ process, is a key step in treatment,” they wrote.
Treatment can take several forms, depending on the FND, and may include physiotherapy for patients with functional movement disorders and psychological therapy for patients with functional seizures.
“With increasing evidence-based treatment, the diagnosis of FND should be seen as a process of looking for potentially reversible cause of disability and distress whether or not an individual has abnormalities on conventional laboratory or radiological testing,” Dr. Hallett and colleagues concluded.
This article was based on interviews and from presentations by Dr. Hallett and Dr. Finkelstein at a 2023 meeting of the Indiana Neurological Society. Dr. Hallett and Dr. Finkelstein declared no conflicts of interest.
FROM THE INDIANA NEUROLOGICAL SOCIETY’S FUNCTIONAL NEUROLOGICAL DISORDERS CONFERENCE
Diet and Exercise in a Pill Are Real: How Mimetics Work
If couch-potato lab mice had beach-body dreams and if they could speak, they might tell you they’re thrilled by advances in the science of exercise and calorie-restriction (CR) mimetics.
In recent studies conducted at research centers across the United States, mice have chowed down, fattened up, exercised only if they felt like it, and still managed to lose body fat, improve their blood lipids, increase muscle power, avoid blood sugar problems, and boost heart function.
How did these mice get so lucky? They were given mimetics, experimental drugs that “mimic” the effects of exercise and calorie reduction in the body without the need to break a sweat or eat less.
“The mice looked like they’d done endurance training,” said Thomas Burris, PhD, chair of the Department of Pharmacodynamics at the University of Florida, Gainesville, Florida, and coauthor of a September 2023 study of the exercise mimetic SLU-PP-332, published in The Journal of Pharmacology and Experimental Therapeutics.
Meanwhile, the CR mimetic mannoheptulose (MH) “was incredibly effective at stopping the negative effects of a high-fat diet in mice,” said Donald K. Ingram, PhD, an adjunct professor at Louisiana State University’s Pennington Biomedical Research Center, Baton Rouge, Louisiana, who began studying CR mimetics at the National Institute on Aging in the 1980s. In a 2022 study published in Nutrients, MH also increased insulin sensitivity.
These “have your cake and eat it, too” drugs aren’t on the market for human use — but they’re edging closer. Several have moved into human trials with encouraging results. The National Institutes of Health and the pharmaceutical industry are taking notice, anteing up big research dollars. At the earliest, one could win US Food and Drug Administration (FDA) approval in 4-5 years, Dr. Burris said.
The medical appeal is clear: Mimetics could one day prevent and treat serious conditions such as age- and disease-related muscle loss, diabetes, heart failure, and even neurodegenerative disorders like Parkinson’s disease and Alzheimer’s disease, said the scientists studying them.
The commercial appeal is unavoidable: Mimetics have the potential to help nondieters avoid weight gain and allow dieters to build and/or preserve more calorie-burning muscle — a boon because losing weight can reduce muscle, especially with rapid loss.
How do these drugs work? What’s their downside? Like the “miracle” glucagon-like peptide 1 (GLP-1) weight-loss drugs that are now ubiquitous, are mimetics an effective pharmaceutical way to replicate two of society’s biggest lifestyle sticking points — diet and exercise?
It’s possible…
CR Mimetics: The Healthspan Drug?
From nematodes and fruit flies to yeast, Labrador Retrievers, and people, plenty of research shows that reducing calorie intake may improve health and prolong life. By how much? Cutting calories by 25% for 2 years slowed the pace of aging 2%-3% in the landmark CALERIE study of 197 adults, according to a 2023 study in Nature Aging. Sounds small, but the researchers said that equals a 10%-15% lower risk for an early death — on par with the longevity bonus you’d get from quitting smoking.
Trouble is low-cal living isn’t easy. “Diets work,” said George Roth, PhD, of GeroScience, Inc., in Pylesville, MD, who began studying CR at the National Institute on Aging in the 1980s with Ingram. “But it’s hard to sustain.”
That’s where CR mimetics come in. They activate the same health-promoting genes switched on by dieting, fasting, and extended periods of hunger, Dr. Roth said. The end result isn’t big weight loss. Instead, CR mimetics may keep us healthier and younger as we age. “Calorie restriction shifts metabolic processes in the body to protect against damage and stress,” he said.
Dr. Roth and Dr. Ingram are currently focused on the CR mimetic mannoheptulose (MH), a sugar found in unripe avocados. “It works at the first step in carbohydrate metabolism in cells throughout the body, so less energy goes through that pathway,” he said. “Glucose metabolism is reduced by 10%-15%. It’s the closest thing to actually eating less food.”
Their 2022 study found that while mice on an all-you-can-eat high-fat diet gained weight and body fat and saw blood lipids increase while insulin sensitivity decreased, mice that also got MH avoided these problems. A 2023 human study in Nutrients coauthored by Dr. Roth and Dr. Ingram found that a group consuming freeze-dried avocado had lower insulin levels than a placebo group.
Other researchers are looking at ways to stimulate the CR target nicotinamide adenine dinucleotide (NAD+). NAD+ assists sirtuins — a group of seven enzymes central to the beneficial effects of CR on aging — but levels drop with age. University of Colorado researchers are studying the effects of nicotinamide riboside (NR), an NAD+ precursor, in older adults with a $2.5 million National Institute on Aging grant. Small, preliminary human studies have found the compound reduced indicators of insulin resistance in the brain, in a January 2023 study in Aging Cell, and reduced blood pressure and arterial stiffness in a 2018 study published in Nature Communications.
Another NAD+ precursor, nicotinamide mononucleotide, reduced low-density lipoprotein cholesterol, diastolic blood pressure, and body weight in a Harvard Medical School study of 30 midlife and older adults with overweight and obesity, published in August 2023 in The Journal of Clinical Endocrinology & Metabolism. And in an April 2022 study published in Hepatology of people with nonalcoholic fatty liver disease, a proprietary supplement that included NR didn’t reduce liver fat but had a significant (vs placebo) reduction in ceramide and the liver enzyme alanine aminotransferase, a marker of inflammation.
“I think it was a pretty interesting result,” said lead researcher Leonard Guarente, PhD, professor of biology at Massachusetts Institute of Technology and founder of the supplement company Elysium. “Fatty liver progressively damages the liver. This has the potential to slow that down.”
Exercise Mimetics: Fitness in a Pill?
Physical activity builds muscle and fitness, helps keeps bones strong, sharpens thinking and memory, guards against depression, and helps discourage a slew of health concerns from weight gain and high blood pressure to diabetes and heart disease. Muscle becomes more dense, more powerful and may even burn more calories, said Dr. Burris. The problem: That pesky part about actually moving. Fewer than half of American adults get recommended amounts of aerobic exercise and fewer than a quarter fit in strength training, according to the Centers for Disease Control and Prevention.
Enter the exercise mimetics. Unlike CR mimetics, exercise mimetics affect mitochondria — the tiny power plants in muscle and every other cell in the body. They switch on genes that encourage the growth of more mitochondria and encourage them to burn fatty acids, not just glucose, for fuel.
In mice, this can keep them from gaining weight, increase insulin sensitivity, and boost exercise endurance. “We can use a drug to activate the same networks that are activated by physical activity,” said Ronald Evans, PhD, professor and director of the Gene Expression Laboratory at the Salk Institute for Biological Studies in La Jolla, California.
Among notable mimetics moving into human studies is ASP0367, a drug in a class called PPAR delta modulators first developed in Evans’ lab. ASP0367 was licensed to the pharmaceutical company Mitobridge, later acquired by Astellas. Astellas is currently running a phase 2/3 human trial of the investigational drug in people with the rare genetic disorder primary mitochondrial myopathy.
At the University of Florida, Dr. Burris and team hope to soon move the exercise mimetic SLU-PP-332 into human studies. “It targets a receptor called ERR that I’ve been working on since the 1980s,” Dr. Burris said. “We knew from genetic studies that ERR has a role in exercise’s effects on mitochondrial function in muscle.” The calorie mimetics he’s studying also activate genes for making more mitochondria and driving them to burn fatty acids. “This generates a lot of energy,” he said. In a January 2024 study in Circulation, Dr. Burris found the drug restores heart function in mice experiencing heart failure. “Very little heart function was lost,” he said. It’s had no serious side effects.
The Future of Exercise and CR Pills
The field has hit some bumps. Some feel inevitable — such as otherwise healthy people misusing the drugs. GW1516, an early experimental exercise mimetic studied by Dr. Evans and abandoned because it triggered tumor growth in lab studies, is used illegally by elite athletes as a performance-enhancing drug despite warnings from the US Anti-Doping Agency. Dr. Burris worries that future CR mimetics could be misused the same way.
But he and others see plenty of benefits in future, FDA-approved drugs. Exercise mimetics like SLU-PP-332 might one day be given to people alongside weight-loss drugs, such as Mounjaro (tirzepatide) or Ozempic (semaglutide) to prevent muscle loss. “SLU-PP-332 doesn’t affect hunger or food intake the way those drugs do,” he said. “It changes muscle.”
Mimetics may one day help older adults and people with muscle disorders rebuild muscle even when they cannot exercise and to delay a range of age-related diseases without onerous dieting. “The chance to intervene and provide a longer healthspan and lifespan — that’s been the moon shot,” Dr. Roth said.
Dr. Guarente noted that CR mimetics may work best for people who aren’t carrying extra pounds but want the health benefits of slashing calories without sacrificing meals and snacks. “Fat is still going to be a problem for joints, cholesterol, inflammation,” he said. “Calorie mimetics are not a panacea for obesity but could help preserve overall health and vitality.”
And what about the billion-dollar question: What happens when these drugs become available to a general public that has issues with actual exercise and healthy diet?
Evans sees only positives. “Our environment is designed to keep people sitting down and consuming high-calorie foods,” he said. “In the absence of people getting motivated to exercise — and there’s no evidence the country is moving in that direction on its own — a pill is an important option to have.”
A version of this article appeared on Medscape.com.
If couch-potato lab mice had beach-body dreams and if they could speak, they might tell you they’re thrilled by advances in the science of exercise and calorie-restriction (CR) mimetics.
In recent studies conducted at research centers across the United States, mice have chowed down, fattened up, exercised only if they felt like it, and still managed to lose body fat, improve their blood lipids, increase muscle power, avoid blood sugar problems, and boost heart function.
How did these mice get so lucky? They were given mimetics, experimental drugs that “mimic” the effects of exercise and calorie reduction in the body without the need to break a sweat or eat less.
“The mice looked like they’d done endurance training,” said Thomas Burris, PhD, chair of the Department of Pharmacodynamics at the University of Florida, Gainesville, Florida, and coauthor of a September 2023 study of the exercise mimetic SLU-PP-332, published in The Journal of Pharmacology and Experimental Therapeutics.
Meanwhile, the CR mimetic mannoheptulose (MH) “was incredibly effective at stopping the negative effects of a high-fat diet in mice,” said Donald K. Ingram, PhD, an adjunct professor at Louisiana State University’s Pennington Biomedical Research Center, Baton Rouge, Louisiana, who began studying CR mimetics at the National Institute on Aging in the 1980s. In a 2022 study published in Nutrients, MH also increased insulin sensitivity.
These “have your cake and eat it, too” drugs aren’t on the market for human use — but they’re edging closer. Several have moved into human trials with encouraging results. The National Institutes of Health and the pharmaceutical industry are taking notice, anteing up big research dollars. At the earliest, one could win US Food and Drug Administration (FDA) approval in 4-5 years, Dr. Burris said.
The medical appeal is clear: Mimetics could one day prevent and treat serious conditions such as age- and disease-related muscle loss, diabetes, heart failure, and even neurodegenerative disorders like Parkinson’s disease and Alzheimer’s disease, said the scientists studying them.
The commercial appeal is unavoidable: Mimetics have the potential to help nondieters avoid weight gain and allow dieters to build and/or preserve more calorie-burning muscle — a boon because losing weight can reduce muscle, especially with rapid loss.
How do these drugs work? What’s their downside? Like the “miracle” glucagon-like peptide 1 (GLP-1) weight-loss drugs that are now ubiquitous, are mimetics an effective pharmaceutical way to replicate two of society’s biggest lifestyle sticking points — diet and exercise?
It’s possible…
CR Mimetics: The Healthspan Drug?
From nematodes and fruit flies to yeast, Labrador Retrievers, and people, plenty of research shows that reducing calorie intake may improve health and prolong life. By how much? Cutting calories by 25% for 2 years slowed the pace of aging 2%-3% in the landmark CALERIE study of 197 adults, according to a 2023 study in Nature Aging. Sounds small, but the researchers said that equals a 10%-15% lower risk for an early death — on par with the longevity bonus you’d get from quitting smoking.
Trouble is low-cal living isn’t easy. “Diets work,” said George Roth, PhD, of GeroScience, Inc., in Pylesville, MD, who began studying CR at the National Institute on Aging in the 1980s with Ingram. “But it’s hard to sustain.”
That’s where CR mimetics come in. They activate the same health-promoting genes switched on by dieting, fasting, and extended periods of hunger, Dr. Roth said. The end result isn’t big weight loss. Instead, CR mimetics may keep us healthier and younger as we age. “Calorie restriction shifts metabolic processes in the body to protect against damage and stress,” he said.
Dr. Roth and Dr. Ingram are currently focused on the CR mimetic mannoheptulose (MH), a sugar found in unripe avocados. “It works at the first step in carbohydrate metabolism in cells throughout the body, so less energy goes through that pathway,” he said. “Glucose metabolism is reduced by 10%-15%. It’s the closest thing to actually eating less food.”
Their 2022 study found that while mice on an all-you-can-eat high-fat diet gained weight and body fat and saw blood lipids increase while insulin sensitivity decreased, mice that also got MH avoided these problems. A 2023 human study in Nutrients coauthored by Dr. Roth and Dr. Ingram found that a group consuming freeze-dried avocado had lower insulin levels than a placebo group.
Other researchers are looking at ways to stimulate the CR target nicotinamide adenine dinucleotide (NAD+). NAD+ assists sirtuins — a group of seven enzymes central to the beneficial effects of CR on aging — but levels drop with age. University of Colorado researchers are studying the effects of nicotinamide riboside (NR), an NAD+ precursor, in older adults with a $2.5 million National Institute on Aging grant. Small, preliminary human studies have found the compound reduced indicators of insulin resistance in the brain, in a January 2023 study in Aging Cell, and reduced blood pressure and arterial stiffness in a 2018 study published in Nature Communications.
Another NAD+ precursor, nicotinamide mononucleotide, reduced low-density lipoprotein cholesterol, diastolic blood pressure, and body weight in a Harvard Medical School study of 30 midlife and older adults with overweight and obesity, published in August 2023 in The Journal of Clinical Endocrinology & Metabolism. And in an April 2022 study published in Hepatology of people with nonalcoholic fatty liver disease, a proprietary supplement that included NR didn’t reduce liver fat but had a significant (vs placebo) reduction in ceramide and the liver enzyme alanine aminotransferase, a marker of inflammation.
“I think it was a pretty interesting result,” said lead researcher Leonard Guarente, PhD, professor of biology at Massachusetts Institute of Technology and founder of the supplement company Elysium. “Fatty liver progressively damages the liver. This has the potential to slow that down.”
Exercise Mimetics: Fitness in a Pill?
Physical activity builds muscle and fitness, helps keeps bones strong, sharpens thinking and memory, guards against depression, and helps discourage a slew of health concerns from weight gain and high blood pressure to diabetes and heart disease. Muscle becomes more dense, more powerful and may even burn more calories, said Dr. Burris. The problem: That pesky part about actually moving. Fewer than half of American adults get recommended amounts of aerobic exercise and fewer than a quarter fit in strength training, according to the Centers for Disease Control and Prevention.
Enter the exercise mimetics. Unlike CR mimetics, exercise mimetics affect mitochondria — the tiny power plants in muscle and every other cell in the body. They switch on genes that encourage the growth of more mitochondria and encourage them to burn fatty acids, not just glucose, for fuel.
In mice, this can keep them from gaining weight, increase insulin sensitivity, and boost exercise endurance. “We can use a drug to activate the same networks that are activated by physical activity,” said Ronald Evans, PhD, professor and director of the Gene Expression Laboratory at the Salk Institute for Biological Studies in La Jolla, California.
Among notable mimetics moving into human studies is ASP0367, a drug in a class called PPAR delta modulators first developed in Evans’ lab. ASP0367 was licensed to the pharmaceutical company Mitobridge, later acquired by Astellas. Astellas is currently running a phase 2/3 human trial of the investigational drug in people with the rare genetic disorder primary mitochondrial myopathy.
At the University of Florida, Dr. Burris and team hope to soon move the exercise mimetic SLU-PP-332 into human studies. “It targets a receptor called ERR that I’ve been working on since the 1980s,” Dr. Burris said. “We knew from genetic studies that ERR has a role in exercise’s effects on mitochondrial function in muscle.” The calorie mimetics he’s studying also activate genes for making more mitochondria and driving them to burn fatty acids. “This generates a lot of energy,” he said. In a January 2024 study in Circulation, Dr. Burris found the drug restores heart function in mice experiencing heart failure. “Very little heart function was lost,” he said. It’s had no serious side effects.
The Future of Exercise and CR Pills
The field has hit some bumps. Some feel inevitable — such as otherwise healthy people misusing the drugs. GW1516, an early experimental exercise mimetic studied by Dr. Evans and abandoned because it triggered tumor growth in lab studies, is used illegally by elite athletes as a performance-enhancing drug despite warnings from the US Anti-Doping Agency. Dr. Burris worries that future CR mimetics could be misused the same way.
But he and others see plenty of benefits in future, FDA-approved drugs. Exercise mimetics like SLU-PP-332 might one day be given to people alongside weight-loss drugs, such as Mounjaro (tirzepatide) or Ozempic (semaglutide) to prevent muscle loss. “SLU-PP-332 doesn’t affect hunger or food intake the way those drugs do,” he said. “It changes muscle.”
Mimetics may one day help older adults and people with muscle disorders rebuild muscle even when they cannot exercise and to delay a range of age-related diseases without onerous dieting. “The chance to intervene and provide a longer healthspan and lifespan — that’s been the moon shot,” Dr. Roth said.
Dr. Guarente noted that CR mimetics may work best for people who aren’t carrying extra pounds but want the health benefits of slashing calories without sacrificing meals and snacks. “Fat is still going to be a problem for joints, cholesterol, inflammation,” he said. “Calorie mimetics are not a panacea for obesity but could help preserve overall health and vitality.”
And what about the billion-dollar question: What happens when these drugs become available to a general public that has issues with actual exercise and healthy diet?
Evans sees only positives. “Our environment is designed to keep people sitting down and consuming high-calorie foods,” he said. “In the absence of people getting motivated to exercise — and there’s no evidence the country is moving in that direction on its own — a pill is an important option to have.”
A version of this article appeared on Medscape.com.
If couch-potato lab mice had beach-body dreams and if they could speak, they might tell you they’re thrilled by advances in the science of exercise and calorie-restriction (CR) mimetics.
In recent studies conducted at research centers across the United States, mice have chowed down, fattened up, exercised only if they felt like it, and still managed to lose body fat, improve their blood lipids, increase muscle power, avoid blood sugar problems, and boost heart function.
How did these mice get so lucky? They were given mimetics, experimental drugs that “mimic” the effects of exercise and calorie reduction in the body without the need to break a sweat or eat less.
“The mice looked like they’d done endurance training,” said Thomas Burris, PhD, chair of the Department of Pharmacodynamics at the University of Florida, Gainesville, Florida, and coauthor of a September 2023 study of the exercise mimetic SLU-PP-332, published in The Journal of Pharmacology and Experimental Therapeutics.
Meanwhile, the CR mimetic mannoheptulose (MH) “was incredibly effective at stopping the negative effects of a high-fat diet in mice,” said Donald K. Ingram, PhD, an adjunct professor at Louisiana State University’s Pennington Biomedical Research Center, Baton Rouge, Louisiana, who began studying CR mimetics at the National Institute on Aging in the 1980s. In a 2022 study published in Nutrients, MH also increased insulin sensitivity.
These “have your cake and eat it, too” drugs aren’t on the market for human use — but they’re edging closer. Several have moved into human trials with encouraging results. The National Institutes of Health and the pharmaceutical industry are taking notice, anteing up big research dollars. At the earliest, one could win US Food and Drug Administration (FDA) approval in 4-5 years, Dr. Burris said.
The medical appeal is clear: Mimetics could one day prevent and treat serious conditions such as age- and disease-related muscle loss, diabetes, heart failure, and even neurodegenerative disorders like Parkinson’s disease and Alzheimer’s disease, said the scientists studying them.
The commercial appeal is unavoidable: Mimetics have the potential to help nondieters avoid weight gain and allow dieters to build and/or preserve more calorie-burning muscle — a boon because losing weight can reduce muscle, especially with rapid loss.
How do these drugs work? What’s their downside? Like the “miracle” glucagon-like peptide 1 (GLP-1) weight-loss drugs that are now ubiquitous, are mimetics an effective pharmaceutical way to replicate two of society’s biggest lifestyle sticking points — diet and exercise?
It’s possible…
CR Mimetics: The Healthspan Drug?
From nematodes and fruit flies to yeast, Labrador Retrievers, and people, plenty of research shows that reducing calorie intake may improve health and prolong life. By how much? Cutting calories by 25% for 2 years slowed the pace of aging 2%-3% in the landmark CALERIE study of 197 adults, according to a 2023 study in Nature Aging. Sounds small, but the researchers said that equals a 10%-15% lower risk for an early death — on par with the longevity bonus you’d get from quitting smoking.
Trouble is low-cal living isn’t easy. “Diets work,” said George Roth, PhD, of GeroScience, Inc., in Pylesville, MD, who began studying CR at the National Institute on Aging in the 1980s with Ingram. “But it’s hard to sustain.”
That’s where CR mimetics come in. They activate the same health-promoting genes switched on by dieting, fasting, and extended periods of hunger, Dr. Roth said. The end result isn’t big weight loss. Instead, CR mimetics may keep us healthier and younger as we age. “Calorie restriction shifts metabolic processes in the body to protect against damage and stress,” he said.
Dr. Roth and Dr. Ingram are currently focused on the CR mimetic mannoheptulose (MH), a sugar found in unripe avocados. “It works at the first step in carbohydrate metabolism in cells throughout the body, so less energy goes through that pathway,” he said. “Glucose metabolism is reduced by 10%-15%. It’s the closest thing to actually eating less food.”
Their 2022 study found that while mice on an all-you-can-eat high-fat diet gained weight and body fat and saw blood lipids increase while insulin sensitivity decreased, mice that also got MH avoided these problems. A 2023 human study in Nutrients coauthored by Dr. Roth and Dr. Ingram found that a group consuming freeze-dried avocado had lower insulin levels than a placebo group.
Other researchers are looking at ways to stimulate the CR target nicotinamide adenine dinucleotide (NAD+). NAD+ assists sirtuins — a group of seven enzymes central to the beneficial effects of CR on aging — but levels drop with age. University of Colorado researchers are studying the effects of nicotinamide riboside (NR), an NAD+ precursor, in older adults with a $2.5 million National Institute on Aging grant. Small, preliminary human studies have found the compound reduced indicators of insulin resistance in the brain, in a January 2023 study in Aging Cell, and reduced blood pressure and arterial stiffness in a 2018 study published in Nature Communications.
Another NAD+ precursor, nicotinamide mononucleotide, reduced low-density lipoprotein cholesterol, diastolic blood pressure, and body weight in a Harvard Medical School study of 30 midlife and older adults with overweight and obesity, published in August 2023 in The Journal of Clinical Endocrinology & Metabolism. And in an April 2022 study published in Hepatology of people with nonalcoholic fatty liver disease, a proprietary supplement that included NR didn’t reduce liver fat but had a significant (vs placebo) reduction in ceramide and the liver enzyme alanine aminotransferase, a marker of inflammation.
“I think it was a pretty interesting result,” said lead researcher Leonard Guarente, PhD, professor of biology at Massachusetts Institute of Technology and founder of the supplement company Elysium. “Fatty liver progressively damages the liver. This has the potential to slow that down.”
Exercise Mimetics: Fitness in a Pill?
Physical activity builds muscle and fitness, helps keeps bones strong, sharpens thinking and memory, guards against depression, and helps discourage a slew of health concerns from weight gain and high blood pressure to diabetes and heart disease. Muscle becomes more dense, more powerful and may even burn more calories, said Dr. Burris. The problem: That pesky part about actually moving. Fewer than half of American adults get recommended amounts of aerobic exercise and fewer than a quarter fit in strength training, according to the Centers for Disease Control and Prevention.
Enter the exercise mimetics. Unlike CR mimetics, exercise mimetics affect mitochondria — the tiny power plants in muscle and every other cell in the body. They switch on genes that encourage the growth of more mitochondria and encourage them to burn fatty acids, not just glucose, for fuel.
In mice, this can keep them from gaining weight, increase insulin sensitivity, and boost exercise endurance. “We can use a drug to activate the same networks that are activated by physical activity,” said Ronald Evans, PhD, professor and director of the Gene Expression Laboratory at the Salk Institute for Biological Studies in La Jolla, California.
Among notable mimetics moving into human studies is ASP0367, a drug in a class called PPAR delta modulators first developed in Evans’ lab. ASP0367 was licensed to the pharmaceutical company Mitobridge, later acquired by Astellas. Astellas is currently running a phase 2/3 human trial of the investigational drug in people with the rare genetic disorder primary mitochondrial myopathy.
At the University of Florida, Dr. Burris and team hope to soon move the exercise mimetic SLU-PP-332 into human studies. “It targets a receptor called ERR that I’ve been working on since the 1980s,” Dr. Burris said. “We knew from genetic studies that ERR has a role in exercise’s effects on mitochondrial function in muscle.” The calorie mimetics he’s studying also activate genes for making more mitochondria and driving them to burn fatty acids. “This generates a lot of energy,” he said. In a January 2024 study in Circulation, Dr. Burris found the drug restores heart function in mice experiencing heart failure. “Very little heart function was lost,” he said. It’s had no serious side effects.
The Future of Exercise and CR Pills
The field has hit some bumps. Some feel inevitable — such as otherwise healthy people misusing the drugs. GW1516, an early experimental exercise mimetic studied by Dr. Evans and abandoned because it triggered tumor growth in lab studies, is used illegally by elite athletes as a performance-enhancing drug despite warnings from the US Anti-Doping Agency. Dr. Burris worries that future CR mimetics could be misused the same way.
But he and others see plenty of benefits in future, FDA-approved drugs. Exercise mimetics like SLU-PP-332 might one day be given to people alongside weight-loss drugs, such as Mounjaro (tirzepatide) or Ozempic (semaglutide) to prevent muscle loss. “SLU-PP-332 doesn’t affect hunger or food intake the way those drugs do,” he said. “It changes muscle.”
Mimetics may one day help older adults and people with muscle disorders rebuild muscle even when they cannot exercise and to delay a range of age-related diseases without onerous dieting. “The chance to intervene and provide a longer healthspan and lifespan — that’s been the moon shot,” Dr. Roth said.
Dr. Guarente noted that CR mimetics may work best for people who aren’t carrying extra pounds but want the health benefits of slashing calories without sacrificing meals and snacks. “Fat is still going to be a problem for joints, cholesterol, inflammation,” he said. “Calorie mimetics are not a panacea for obesity but could help preserve overall health and vitality.”
And what about the billion-dollar question: What happens when these drugs become available to a general public that has issues with actual exercise and healthy diet?
Evans sees only positives. “Our environment is designed to keep people sitting down and consuming high-calorie foods,” he said. “In the absence of people getting motivated to exercise — and there’s no evidence the country is moving in that direction on its own — a pill is an important option to have.”
A version of this article appeared on Medscape.com.
High Cesarean Rates Persist in Obesity Despite Standardized Protocols
NATIONAL HARBOR, MARYLAND — Implementation of a standardized induction of labor protocol had no significant effect on the rates of cesarean delivery in patients with obesity, based on data from more than 5000 individuals.
Previous research has shown that the risk for cesarean delivery increases by 5% with each 1-kg/m2 increase in body mass index (BMI) among nulliparous patients, said Melissa Riegel, MD, of the University of Pennsylvania, Philadelphia, in a presentation at the meeting sponsored by the Society for Maternal-Fetal Medicine. (abstract 82).
Research on the relationship between obesity and higher cesarean delivery rates “has been clouded by the inability to reduce variation in care,” Dr. Riegel said at the meeting sponsored by the Society for Maternal Fetal Medicine. Failed induction of labor (IOL) is a leading indicator for cesarean delivery, and cesarean delivery is 80% more likely in patients with obesity undergoing IOL than in normal-weight patients, Dr. Riegel said.
Possible explanations for these differences include provider factors such as variability in care management, conscious and unconscious biases, or physiologic differences in patients with obesity such as elevated hormones, differences in the labor curve, and higher doses of oxytocin and prostaglandins, Dr. Riegel said.
Dr. Riegel and colleagues hypothesized that differences in cesarean delivery rates would persist despite a standardized labor induction protocol, thereby supporting the effects of factors other than variations in care on increased cesarean delivery risk after IOL in patients with obesity.
The researchers reviewed data from two sites comparing 2-year periods before and after implementation of an IOL protocol from 2018 to 2022. The study population included nulliparous women with singleton pregnancies at term who underwent IOL with intact membranes and unfavorable cervices, and had a BMI of at least 30 kg/m2 at delivery. The preimplementation group (PRE) included 2480 individuals and the postimplementation group (POST) included 2651 individuals. Patients were divided into weight classes based on BMI: 30-34.9; 35-39.9; ≥40.
The standardized protocol consisted of active labor management with cervical exams, with an amniotomy by the time of the first exam with 4 cm or greater cervical dilation, and further intervention with medication such as oxytocin or an intrauterine pressure catheter if no cervical change was noted after 2 hours.
In a multivariate analysis, the overall cesarean delivery rate was 24.9% before the protocol implementation and 26.0% in the postimplementation group. There were no differences in the risk of cesarean delivery in any obesity class from the PRE to POST period.
In addition, no significant differences appeared in the secondary outcomes of duration of labor, maternal morbidity, or neonatal morbidity, Dr. Riegel said. Nonreassuring fetal heart rate tracing was the most common reason for cesarean delivery across all obesity classes and the PRE and POST groups.
Study limitations included the use of data from only two sites, but the results were strengthened by the large sample size, said Dr. Reigel. The results indicate that reducing variation in IOL management had no significant effect on the relationship between obesity and cesarean delivery and support underlying physiologic explanations, she said.
Making the Case for Physiology
“By standardizing induction practices, we were able to minimize differences in care and better answer why the increased cesarean delivery rate exists in this patient population,” Dr. Riegel said in an interview. The findings were in line with the primary hypothesis that standardized induction would not affect cesarean delivery rates in patients with obesity, she said. Instead, the findings support potential physiologic differences as “the driving force behind this relationship,” she added.
Looking ahead, “There is a role for translational work to investigate the specific biological changes in patients with obesity that might contribute to an increased risk of cesarean delivery and there is also a role for investigating the effectiveness of different labor induction interventions specifically in patients with obesity,” Dr. Riegel said.
Different Induction Protocols Needed for Obese Patients?
“Given that severe maternal morbidity and mortality are continuing to increase in the United States, this study is critical, as we know that both cesarean delivery and obesity are driving factors in increasing maternal morbidity,” said Marissa Platner, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, Georgia, in an interview.
However, the novel takeaway message from the current study is that patients with obesity were more likely to require cesarean delivery even with a protocol in which variation in labor induction techniques are minimized, said Dr. Platner, who was not involved in the study. “This leads to the question of [whether] we should have different standards or protocols for our patients with obesity, as well as a need for clear counseling for these patients early on in pregnancy,” she said.
As for further research, “It would be interesting to see if the risk of cesarean delivery changed based on class of obesity, and the primary drivers of cesarean delivery in this study,” Dr. Platner said. “Additionally, it would be helpful to know how much pitocin was needed for patients, based on their BMI category, to achieve successful vaginal delivery,” she noted.
The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Development. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.
NATIONAL HARBOR, MARYLAND — Implementation of a standardized induction of labor protocol had no significant effect on the rates of cesarean delivery in patients with obesity, based on data from more than 5000 individuals.
Previous research has shown that the risk for cesarean delivery increases by 5% with each 1-kg/m2 increase in body mass index (BMI) among nulliparous patients, said Melissa Riegel, MD, of the University of Pennsylvania, Philadelphia, in a presentation at the meeting sponsored by the Society for Maternal-Fetal Medicine. (abstract 82).
Research on the relationship between obesity and higher cesarean delivery rates “has been clouded by the inability to reduce variation in care,” Dr. Riegel said at the meeting sponsored by the Society for Maternal Fetal Medicine. Failed induction of labor (IOL) is a leading indicator for cesarean delivery, and cesarean delivery is 80% more likely in patients with obesity undergoing IOL than in normal-weight patients, Dr. Riegel said.
Possible explanations for these differences include provider factors such as variability in care management, conscious and unconscious biases, or physiologic differences in patients with obesity such as elevated hormones, differences in the labor curve, and higher doses of oxytocin and prostaglandins, Dr. Riegel said.
Dr. Riegel and colleagues hypothesized that differences in cesarean delivery rates would persist despite a standardized labor induction protocol, thereby supporting the effects of factors other than variations in care on increased cesarean delivery risk after IOL in patients with obesity.
The researchers reviewed data from two sites comparing 2-year periods before and after implementation of an IOL protocol from 2018 to 2022. The study population included nulliparous women with singleton pregnancies at term who underwent IOL with intact membranes and unfavorable cervices, and had a BMI of at least 30 kg/m2 at delivery. The preimplementation group (PRE) included 2480 individuals and the postimplementation group (POST) included 2651 individuals. Patients were divided into weight classes based on BMI: 30-34.9; 35-39.9; ≥40.
The standardized protocol consisted of active labor management with cervical exams, with an amniotomy by the time of the first exam with 4 cm or greater cervical dilation, and further intervention with medication such as oxytocin or an intrauterine pressure catheter if no cervical change was noted after 2 hours.
In a multivariate analysis, the overall cesarean delivery rate was 24.9% before the protocol implementation and 26.0% in the postimplementation group. There were no differences in the risk of cesarean delivery in any obesity class from the PRE to POST period.
In addition, no significant differences appeared in the secondary outcomes of duration of labor, maternal morbidity, or neonatal morbidity, Dr. Riegel said. Nonreassuring fetal heart rate tracing was the most common reason for cesarean delivery across all obesity classes and the PRE and POST groups.
Study limitations included the use of data from only two sites, but the results were strengthened by the large sample size, said Dr. Reigel. The results indicate that reducing variation in IOL management had no significant effect on the relationship between obesity and cesarean delivery and support underlying physiologic explanations, she said.
Making the Case for Physiology
“By standardizing induction practices, we were able to minimize differences in care and better answer why the increased cesarean delivery rate exists in this patient population,” Dr. Riegel said in an interview. The findings were in line with the primary hypothesis that standardized induction would not affect cesarean delivery rates in patients with obesity, she said. Instead, the findings support potential physiologic differences as “the driving force behind this relationship,” she added.
Looking ahead, “There is a role for translational work to investigate the specific biological changes in patients with obesity that might contribute to an increased risk of cesarean delivery and there is also a role for investigating the effectiveness of different labor induction interventions specifically in patients with obesity,” Dr. Riegel said.
Different Induction Protocols Needed for Obese Patients?
“Given that severe maternal morbidity and mortality are continuing to increase in the United States, this study is critical, as we know that both cesarean delivery and obesity are driving factors in increasing maternal morbidity,” said Marissa Platner, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, Georgia, in an interview.
However, the novel takeaway message from the current study is that patients with obesity were more likely to require cesarean delivery even with a protocol in which variation in labor induction techniques are minimized, said Dr. Platner, who was not involved in the study. “This leads to the question of [whether] we should have different standards or protocols for our patients with obesity, as well as a need for clear counseling for these patients early on in pregnancy,” she said.
As for further research, “It would be interesting to see if the risk of cesarean delivery changed based on class of obesity, and the primary drivers of cesarean delivery in this study,” Dr. Platner said. “Additionally, it would be helpful to know how much pitocin was needed for patients, based on their BMI category, to achieve successful vaginal delivery,” she noted.
The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Development. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.
NATIONAL HARBOR, MARYLAND — Implementation of a standardized induction of labor protocol had no significant effect on the rates of cesarean delivery in patients with obesity, based on data from more than 5000 individuals.
Previous research has shown that the risk for cesarean delivery increases by 5% with each 1-kg/m2 increase in body mass index (BMI) among nulliparous patients, said Melissa Riegel, MD, of the University of Pennsylvania, Philadelphia, in a presentation at the meeting sponsored by the Society for Maternal-Fetal Medicine. (abstract 82).
Research on the relationship between obesity and higher cesarean delivery rates “has been clouded by the inability to reduce variation in care,” Dr. Riegel said at the meeting sponsored by the Society for Maternal Fetal Medicine. Failed induction of labor (IOL) is a leading indicator for cesarean delivery, and cesarean delivery is 80% more likely in patients with obesity undergoing IOL than in normal-weight patients, Dr. Riegel said.
Possible explanations for these differences include provider factors such as variability in care management, conscious and unconscious biases, or physiologic differences in patients with obesity such as elevated hormones, differences in the labor curve, and higher doses of oxytocin and prostaglandins, Dr. Riegel said.
Dr. Riegel and colleagues hypothesized that differences in cesarean delivery rates would persist despite a standardized labor induction protocol, thereby supporting the effects of factors other than variations in care on increased cesarean delivery risk after IOL in patients with obesity.
The researchers reviewed data from two sites comparing 2-year periods before and after implementation of an IOL protocol from 2018 to 2022. The study population included nulliparous women with singleton pregnancies at term who underwent IOL with intact membranes and unfavorable cervices, and had a BMI of at least 30 kg/m2 at delivery. The preimplementation group (PRE) included 2480 individuals and the postimplementation group (POST) included 2651 individuals. Patients were divided into weight classes based on BMI: 30-34.9; 35-39.9; ≥40.
The standardized protocol consisted of active labor management with cervical exams, with an amniotomy by the time of the first exam with 4 cm or greater cervical dilation, and further intervention with medication such as oxytocin or an intrauterine pressure catheter if no cervical change was noted after 2 hours.
In a multivariate analysis, the overall cesarean delivery rate was 24.9% before the protocol implementation and 26.0% in the postimplementation group. There were no differences in the risk of cesarean delivery in any obesity class from the PRE to POST period.
In addition, no significant differences appeared in the secondary outcomes of duration of labor, maternal morbidity, or neonatal morbidity, Dr. Riegel said. Nonreassuring fetal heart rate tracing was the most common reason for cesarean delivery across all obesity classes and the PRE and POST groups.
Study limitations included the use of data from only two sites, but the results were strengthened by the large sample size, said Dr. Reigel. The results indicate that reducing variation in IOL management had no significant effect on the relationship between obesity and cesarean delivery and support underlying physiologic explanations, she said.
Making the Case for Physiology
“By standardizing induction practices, we were able to minimize differences in care and better answer why the increased cesarean delivery rate exists in this patient population,” Dr. Riegel said in an interview. The findings were in line with the primary hypothesis that standardized induction would not affect cesarean delivery rates in patients with obesity, she said. Instead, the findings support potential physiologic differences as “the driving force behind this relationship,” she added.
Looking ahead, “There is a role for translational work to investigate the specific biological changes in patients with obesity that might contribute to an increased risk of cesarean delivery and there is also a role for investigating the effectiveness of different labor induction interventions specifically in patients with obesity,” Dr. Riegel said.
Different Induction Protocols Needed for Obese Patients?
“Given that severe maternal morbidity and mortality are continuing to increase in the United States, this study is critical, as we know that both cesarean delivery and obesity are driving factors in increasing maternal morbidity,” said Marissa Platner, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, Georgia, in an interview.
However, the novel takeaway message from the current study is that patients with obesity were more likely to require cesarean delivery even with a protocol in which variation in labor induction techniques are minimized, said Dr. Platner, who was not involved in the study. “This leads to the question of [whether] we should have different standards or protocols for our patients with obesity, as well as a need for clear counseling for these patients early on in pregnancy,” she said.
As for further research, “It would be interesting to see if the risk of cesarean delivery changed based on class of obesity, and the primary drivers of cesarean delivery in this study,” Dr. Platner said. “Additionally, it would be helpful to know how much pitocin was needed for patients, based on their BMI category, to achieve successful vaginal delivery,” she noted.
The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Development. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.
AT THE PREGNANCY MEETING
Stem Cell Extension Study Reinforces Signal of Benefit for Progressive MS
WEST PALM BEACH, FLORIDA — , according to data presented as a late-breaker at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
After at least 1 year of follow-up in 23 patients participating in the extension analysis, “there has been favorable effects on cognitive function, neurological functional tests, quality of life, and both of two major biomarkers linked to neurodegeneration,” reported Dimitrios Karussis, MD, PhD, Chairman of the Multiple Sclerosis Center, Hadassah Hospital, Jerusalem.
Based on promising preclinical studies, the initial clinical study with MSCs was published in Brain in 2020. In that study, 48 participants were randomized to receive an intrathecal injection of MSCs, an intravenous injection of MSCs, or a sham injection. The MSCs were collected from the bone marrow of each participant and cultured.
A second injection in the active treatment groups was administered at 6 months. At this time, those initially randomized to a sham injection received either an intrathecal or an IV injection of MSCs harvested from their bone marrow.
No Disease Activity Seen in 60% at 1 Year
When evaluated at the end of 1 year, there was no evidence of disease activity in 58.6% of those receiving the two intrathecal injections of MSCs, 40.6% of those receiving two IV injections of MSCs, and 9.7% of those initially randomized to the sham group. The intrathecal injection of MSCs, which was well tolerated, appeared to offer greater efficacy and was associated with relative benefits on multiple additional measures, including reduced T2 lesion load, lower relapse rates, and sustained cognitive function.
Forty of the patients in the initial study were enrolled in the extension. In the late-breaker presentation, Dr. Karussis provided interim results on 23, of which all had been followed for at least another additional year. These patients had been treated with one to three intrathecal injects of MSCs at intervals of 3 to 6 months.
Of further gains during the extension, Dr. Karussis described gains in cognitive function, represented by a 3-degree improvement in the Symbol Digit Modalities Test (SDMT), a median 17% improvement in the 25-foot walk test, and an improvement in quality of life, captured in domains of both physical and mental function. All of these gains were statistically significant.
The clinical responses were supported by reductions in both serum neurofilament light chain (sNfL) levels and in the glial fibrillary acid protein (GFAP), which Dr. Karussis described as important biomarkers of disease progression. For sNfL, the reduction was 33.2% (P = .001), and there was further decline observed after repeated MSC injections.
The 22% (P < .0004) reduction in GFAP, which Dr. Karussis said has not been shown before, was observed in all 23 patients. Again, there was an additional reduction with repeated MSC treatments.
The safety and tolerability remained encouraging with longer follow-up. As in the original series, there were no serious adverse events. Headache and backache, which were more common among those receiving intrathecal injections of MSC in the original study, continued to be reported in the extension, but these were time-limited.
Although Dr. Karussis emphasized that these interim results await confirmation with longer follow-up and larger studies, he suggested that the consistency of benefit with early report provides “an additional hint of possible neuroprotective and neurotrophic effects.”
Mechanism of MSC Benefit Incompletely Documented
In patients with progressive MS, there is an urgent need for more and better therapies. MSCs, which reside primarily in bone marrow but can be found in other tissues, have been associated with immunomodulatory as well as neuroprotective effects in experimental studies, but whether one or the other or both of these activities are responsible for the clinical benefits observed so far is unresolved.
Others evaluating MSCs in the experimental setting have shown that these “produce a variety of soluble factors with immunomodulatory, neuroprotective, and repair-promoting properties,” said Jeffrey A. Cohen, MD, who was asked to comment on the findings. Dr. Cohen is director of the experimental therapeutics program at the Mellen Center for Multiple Sclerosis, Cleveland Clinic. He said that previous experimental work has encouraged clinical studies, including the work presented by Dr. Karussis.
While the late-breaker presentation provided data suggesting “persistent potent efficacy with good safety and tolerability,” Dr. Cohen pointed out that “the results from this group are substantially better than those reported by several other groups.” He called the difference in results “uncertain,” suggesting that more work is needed to prove that clinical benefit is reliably achieved.
“I think it is too early to tell if MSC transplantation is going to be useful. Other than [the data] reported by the Karussis group, the results have been rather disappointing,” Dr. Cohen said.
Dr. Karussis reports no potential conflicts of interest.
WEST PALM BEACH, FLORIDA — , according to data presented as a late-breaker at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
After at least 1 year of follow-up in 23 patients participating in the extension analysis, “there has been favorable effects on cognitive function, neurological functional tests, quality of life, and both of two major biomarkers linked to neurodegeneration,” reported Dimitrios Karussis, MD, PhD, Chairman of the Multiple Sclerosis Center, Hadassah Hospital, Jerusalem.
Based on promising preclinical studies, the initial clinical study with MSCs was published in Brain in 2020. In that study, 48 participants were randomized to receive an intrathecal injection of MSCs, an intravenous injection of MSCs, or a sham injection. The MSCs were collected from the bone marrow of each participant and cultured.
A second injection in the active treatment groups was administered at 6 months. At this time, those initially randomized to a sham injection received either an intrathecal or an IV injection of MSCs harvested from their bone marrow.
No Disease Activity Seen in 60% at 1 Year
When evaluated at the end of 1 year, there was no evidence of disease activity in 58.6% of those receiving the two intrathecal injections of MSCs, 40.6% of those receiving two IV injections of MSCs, and 9.7% of those initially randomized to the sham group. The intrathecal injection of MSCs, which was well tolerated, appeared to offer greater efficacy and was associated with relative benefits on multiple additional measures, including reduced T2 lesion load, lower relapse rates, and sustained cognitive function.
Forty of the patients in the initial study were enrolled in the extension. In the late-breaker presentation, Dr. Karussis provided interim results on 23, of which all had been followed for at least another additional year. These patients had been treated with one to three intrathecal injects of MSCs at intervals of 3 to 6 months.
Of further gains during the extension, Dr. Karussis described gains in cognitive function, represented by a 3-degree improvement in the Symbol Digit Modalities Test (SDMT), a median 17% improvement in the 25-foot walk test, and an improvement in quality of life, captured in domains of both physical and mental function. All of these gains were statistically significant.
The clinical responses were supported by reductions in both serum neurofilament light chain (sNfL) levels and in the glial fibrillary acid protein (GFAP), which Dr. Karussis described as important biomarkers of disease progression. For sNfL, the reduction was 33.2% (P = .001), and there was further decline observed after repeated MSC injections.
The 22% (P < .0004) reduction in GFAP, which Dr. Karussis said has not been shown before, was observed in all 23 patients. Again, there was an additional reduction with repeated MSC treatments.
The safety and tolerability remained encouraging with longer follow-up. As in the original series, there were no serious adverse events. Headache and backache, which were more common among those receiving intrathecal injections of MSC in the original study, continued to be reported in the extension, but these were time-limited.
Although Dr. Karussis emphasized that these interim results await confirmation with longer follow-up and larger studies, he suggested that the consistency of benefit with early report provides “an additional hint of possible neuroprotective and neurotrophic effects.”
Mechanism of MSC Benefit Incompletely Documented
In patients with progressive MS, there is an urgent need for more and better therapies. MSCs, which reside primarily in bone marrow but can be found in other tissues, have been associated with immunomodulatory as well as neuroprotective effects in experimental studies, but whether one or the other or both of these activities are responsible for the clinical benefits observed so far is unresolved.
Others evaluating MSCs in the experimental setting have shown that these “produce a variety of soluble factors with immunomodulatory, neuroprotective, and repair-promoting properties,” said Jeffrey A. Cohen, MD, who was asked to comment on the findings. Dr. Cohen is director of the experimental therapeutics program at the Mellen Center for Multiple Sclerosis, Cleveland Clinic. He said that previous experimental work has encouraged clinical studies, including the work presented by Dr. Karussis.
While the late-breaker presentation provided data suggesting “persistent potent efficacy with good safety and tolerability,” Dr. Cohen pointed out that “the results from this group are substantially better than those reported by several other groups.” He called the difference in results “uncertain,” suggesting that more work is needed to prove that clinical benefit is reliably achieved.
“I think it is too early to tell if MSC transplantation is going to be useful. Other than [the data] reported by the Karussis group, the results have been rather disappointing,” Dr. Cohen said.
Dr. Karussis reports no potential conflicts of interest.
WEST PALM BEACH, FLORIDA — , according to data presented as a late-breaker at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
After at least 1 year of follow-up in 23 patients participating in the extension analysis, “there has been favorable effects on cognitive function, neurological functional tests, quality of life, and both of two major biomarkers linked to neurodegeneration,” reported Dimitrios Karussis, MD, PhD, Chairman of the Multiple Sclerosis Center, Hadassah Hospital, Jerusalem.
Based on promising preclinical studies, the initial clinical study with MSCs was published in Brain in 2020. In that study, 48 participants were randomized to receive an intrathecal injection of MSCs, an intravenous injection of MSCs, or a sham injection. The MSCs were collected from the bone marrow of each participant and cultured.
A second injection in the active treatment groups was administered at 6 months. At this time, those initially randomized to a sham injection received either an intrathecal or an IV injection of MSCs harvested from their bone marrow.
No Disease Activity Seen in 60% at 1 Year
When evaluated at the end of 1 year, there was no evidence of disease activity in 58.6% of those receiving the two intrathecal injections of MSCs, 40.6% of those receiving two IV injections of MSCs, and 9.7% of those initially randomized to the sham group. The intrathecal injection of MSCs, which was well tolerated, appeared to offer greater efficacy and was associated with relative benefits on multiple additional measures, including reduced T2 lesion load, lower relapse rates, and sustained cognitive function.
Forty of the patients in the initial study were enrolled in the extension. In the late-breaker presentation, Dr. Karussis provided interim results on 23, of which all had been followed for at least another additional year. These patients had been treated with one to three intrathecal injects of MSCs at intervals of 3 to 6 months.
Of further gains during the extension, Dr. Karussis described gains in cognitive function, represented by a 3-degree improvement in the Symbol Digit Modalities Test (SDMT), a median 17% improvement in the 25-foot walk test, and an improvement in quality of life, captured in domains of both physical and mental function. All of these gains were statistically significant.
The clinical responses were supported by reductions in both serum neurofilament light chain (sNfL) levels and in the glial fibrillary acid protein (GFAP), which Dr. Karussis described as important biomarkers of disease progression. For sNfL, the reduction was 33.2% (P = .001), and there was further decline observed after repeated MSC injections.
The 22% (P < .0004) reduction in GFAP, which Dr. Karussis said has not been shown before, was observed in all 23 patients. Again, there was an additional reduction with repeated MSC treatments.
The safety and tolerability remained encouraging with longer follow-up. As in the original series, there were no serious adverse events. Headache and backache, which were more common among those receiving intrathecal injections of MSC in the original study, continued to be reported in the extension, but these were time-limited.
Although Dr. Karussis emphasized that these interim results await confirmation with longer follow-up and larger studies, he suggested that the consistency of benefit with early report provides “an additional hint of possible neuroprotective and neurotrophic effects.”
Mechanism of MSC Benefit Incompletely Documented
In patients with progressive MS, there is an urgent need for more and better therapies. MSCs, which reside primarily in bone marrow but can be found in other tissues, have been associated with immunomodulatory as well as neuroprotective effects in experimental studies, but whether one or the other or both of these activities are responsible for the clinical benefits observed so far is unresolved.
Others evaluating MSCs in the experimental setting have shown that these “produce a variety of soluble factors with immunomodulatory, neuroprotective, and repair-promoting properties,” said Jeffrey A. Cohen, MD, who was asked to comment on the findings. Dr. Cohen is director of the experimental therapeutics program at the Mellen Center for Multiple Sclerosis, Cleveland Clinic. He said that previous experimental work has encouraged clinical studies, including the work presented by Dr. Karussis.
While the late-breaker presentation provided data suggesting “persistent potent efficacy with good safety and tolerability,” Dr. Cohen pointed out that “the results from this group are substantially better than those reported by several other groups.” He called the difference in results “uncertain,” suggesting that more work is needed to prove that clinical benefit is reliably achieved.
“I think it is too early to tell if MSC transplantation is going to be useful. Other than [the data] reported by the Karussis group, the results have been rather disappointing,” Dr. Cohen said.
Dr. Karussis reports no potential conflicts of interest.
FROM ACTRIMS FORUM 2024
Long-term Fremanezumab Effective and Safe in Hard-to-Treat Migraine
Key clinical point: Long-term fremanezumab treatment appears to be highly effective, safe, and well tolerated in patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) who have experienced multiple (more than three) treatment failures and have various comorbidities.
Major finding: At 48 weeks, fremanezumab led to significant reductions in the monthly migraine days in patients with HFEM (mean change −6.4 days) and monthly headache days in patients with CM (mean change −14.5 days; both P < .001). Overall, 7.8% of patients reported mild and transient treatment-emergent adverse events, and none of the patients discontinued the treatment for any reason.
Study details: This prospective, multicenter, cohort study included 130 patients with migraine (49 with HEFM; 81 with CM) and multiple treatment failures who received fremanezumab for at least 48 weeks (≥ 12 doses).
Disclosures: This study was partially supported by the Italian Ministry of Health (Institutional Funding Ricerca Corrente) San Raffaele and Fondazione Italiana Cefalee. Several authors declared receiving travel grants, research support, or honoraria from or having other ties with various sources. Twenty authors declared no conflicts of interest.
Source: Barbanti P, Egeo G, Proietti S, et al for the Italian Migraine Registry study group. Assessing the long-term (48-week) effectiveness, safety, and tolerability of fremanezumab in migraine in real life: Insights from the multicenter, prospective, FRIEND3 study. Neurol Ther. 2024 (Mar 7). doi: 10.1007/s40120-024-00591-z Source
Key clinical point: Long-term fremanezumab treatment appears to be highly effective, safe, and well tolerated in patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) who have experienced multiple (more than three) treatment failures and have various comorbidities.
Major finding: At 48 weeks, fremanezumab led to significant reductions in the monthly migraine days in patients with HFEM (mean change −6.4 days) and monthly headache days in patients with CM (mean change −14.5 days; both P < .001). Overall, 7.8% of patients reported mild and transient treatment-emergent adverse events, and none of the patients discontinued the treatment for any reason.
Study details: This prospective, multicenter, cohort study included 130 patients with migraine (49 with HEFM; 81 with CM) and multiple treatment failures who received fremanezumab for at least 48 weeks (≥ 12 doses).
Disclosures: This study was partially supported by the Italian Ministry of Health (Institutional Funding Ricerca Corrente) San Raffaele and Fondazione Italiana Cefalee. Several authors declared receiving travel grants, research support, or honoraria from or having other ties with various sources. Twenty authors declared no conflicts of interest.
Source: Barbanti P, Egeo G, Proietti S, et al for the Italian Migraine Registry study group. Assessing the long-term (48-week) effectiveness, safety, and tolerability of fremanezumab in migraine in real life: Insights from the multicenter, prospective, FRIEND3 study. Neurol Ther. 2024 (Mar 7). doi: 10.1007/s40120-024-00591-z Source
Key clinical point: Long-term fremanezumab treatment appears to be highly effective, safe, and well tolerated in patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) who have experienced multiple (more than three) treatment failures and have various comorbidities.
Major finding: At 48 weeks, fremanezumab led to significant reductions in the monthly migraine days in patients with HFEM (mean change −6.4 days) and monthly headache days in patients with CM (mean change −14.5 days; both P < .001). Overall, 7.8% of patients reported mild and transient treatment-emergent adverse events, and none of the patients discontinued the treatment for any reason.
Study details: This prospective, multicenter, cohort study included 130 patients with migraine (49 with HEFM; 81 with CM) and multiple treatment failures who received fremanezumab for at least 48 weeks (≥ 12 doses).
Disclosures: This study was partially supported by the Italian Ministry of Health (Institutional Funding Ricerca Corrente) San Raffaele and Fondazione Italiana Cefalee. Several authors declared receiving travel grants, research support, or honoraria from or having other ties with various sources. Twenty authors declared no conflicts of interest.
Source: Barbanti P, Egeo G, Proietti S, et al for the Italian Migraine Registry study group. Assessing the long-term (48-week) effectiveness, safety, and tolerability of fremanezumab in migraine in real life: Insights from the multicenter, prospective, FRIEND3 study. Neurol Ther. 2024 (Mar 7). doi: 10.1007/s40120-024-00591-z Source
Endometriosis and Concomitant Migraine Tied to Severe Pain and Disability
Key clinical point: Untreated women with endometriosis and concomitant migraine (EM-MO) experienced more severe symptoms and frequent painful days than those with endometriosis alone (EM-O) or migraine alone (MG-O).
Major finding: The prevalence of severe adenomyosis (14% vs 4%; P = .027) and posterior (48% vs 30%; P = .031) and anterior (10% vs 2%; P = .029) deep infiltrating endometriosis was higher in women with EM-MO vs EM-O. Women with EM-MO vs MG-O had significantly higher pain intensity (visual analogue scale scores 8.44 vs 7.74; P = .004), monthly migraine days (6.68 vs 5.44 days; P = .042), and Headache Impact Test-6 scores (62.33 vs 57.38; P = .010).
Study details: This prospective case-control study included 50 women with EM-MO and matched control patients with EM-O (n = 100) and MG-O (n = 100) who underwent pelvic and neurologic examination.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Selntigia A, Exacoustos C, Ortoleva C, et al. Correlation between endometriosis and migraine features: Results from a prospective case-control study. Cephalalgia. 2024 (Mar 4). doi: 10.1177/03331024241235 Source
Key clinical point: Untreated women with endometriosis and concomitant migraine (EM-MO) experienced more severe symptoms and frequent painful days than those with endometriosis alone (EM-O) or migraine alone (MG-O).
Major finding: The prevalence of severe adenomyosis (14% vs 4%; P = .027) and posterior (48% vs 30%; P = .031) and anterior (10% vs 2%; P = .029) deep infiltrating endometriosis was higher in women with EM-MO vs EM-O. Women with EM-MO vs MG-O had significantly higher pain intensity (visual analogue scale scores 8.44 vs 7.74; P = .004), monthly migraine days (6.68 vs 5.44 days; P = .042), and Headache Impact Test-6 scores (62.33 vs 57.38; P = .010).
Study details: This prospective case-control study included 50 women with EM-MO and matched control patients with EM-O (n = 100) and MG-O (n = 100) who underwent pelvic and neurologic examination.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Selntigia A, Exacoustos C, Ortoleva C, et al. Correlation between endometriosis and migraine features: Results from a prospective case-control study. Cephalalgia. 2024 (Mar 4). doi: 10.1177/03331024241235 Source
Key clinical point: Untreated women with endometriosis and concomitant migraine (EM-MO) experienced more severe symptoms and frequent painful days than those with endometriosis alone (EM-O) or migraine alone (MG-O).
Major finding: The prevalence of severe adenomyosis (14% vs 4%; P = .027) and posterior (48% vs 30%; P = .031) and anterior (10% vs 2%; P = .029) deep infiltrating endometriosis was higher in women with EM-MO vs EM-O. Women with EM-MO vs MG-O had significantly higher pain intensity (visual analogue scale scores 8.44 vs 7.74; P = .004), monthly migraine days (6.68 vs 5.44 days; P = .042), and Headache Impact Test-6 scores (62.33 vs 57.38; P = .010).
Study details: This prospective case-control study included 50 women with EM-MO and matched control patients with EM-O (n = 100) and MG-O (n = 100) who underwent pelvic and neurologic examination.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Selntigia A, Exacoustos C, Ortoleva C, et al. Correlation between endometriosis and migraine features: Results from a prospective case-control study. Cephalalgia. 2024 (Mar 4). doi: 10.1177/03331024241235 Source
Higher Prevalence of Migraine in Women with Inflammatory Bowel Disease
Key clinical point: Migraine is more prevalent among patients with inflammatory bowel disease (IBD), especially women, suggesting an influence of sex-related factors.
Major finding: The prevalence of migraine was significantly higher in patients with IBD (20.8%; P < .0001) than in the general population (12.6%; P < .0001), and this association was statistically significant in women (29.8%; P < .0001) but not in men (9.6%; P = .30). However, there were no significant differences in migraine prevalence between patients with ulcerative colitis and those with Crohn’s disease (P = .88).
Study details: This cross-sectional study included 283 patients age 18-65 years with IBD, of whom 20.85% had definite (11.66%) or probable (9.18%) migraine based on their response to the ID-Migraine questionnaire.
Disclosures: This study was funded by the Instituto de Salud Carlos III, Spain, and Fondos Europeos de Desarrollo Regional. The authors declared no conflicts of interest.
Source: Pascual-Mato M, Gárate G, de Prado-Tejerina C, et al. Increased prevalence of migraine in women with inflammatory bowel disease: A cross-sectional study. Cephalalgia. 2024 (Mar 1). doi: 10.1177/03331024241233979 Source
Key clinical point: Migraine is more prevalent among patients with inflammatory bowel disease (IBD), especially women, suggesting an influence of sex-related factors.
Major finding: The prevalence of migraine was significantly higher in patients with IBD (20.8%; P < .0001) than in the general population (12.6%; P < .0001), and this association was statistically significant in women (29.8%; P < .0001) but not in men (9.6%; P = .30). However, there were no significant differences in migraine prevalence between patients with ulcerative colitis and those with Crohn’s disease (P = .88).
Study details: This cross-sectional study included 283 patients age 18-65 years with IBD, of whom 20.85% had definite (11.66%) or probable (9.18%) migraine based on their response to the ID-Migraine questionnaire.
Disclosures: This study was funded by the Instituto de Salud Carlos III, Spain, and Fondos Europeos de Desarrollo Regional. The authors declared no conflicts of interest.
Source: Pascual-Mato M, Gárate G, de Prado-Tejerina C, et al. Increased prevalence of migraine in women with inflammatory bowel disease: A cross-sectional study. Cephalalgia. 2024 (Mar 1). doi: 10.1177/03331024241233979 Source
Key clinical point: Migraine is more prevalent among patients with inflammatory bowel disease (IBD), especially women, suggesting an influence of sex-related factors.
Major finding: The prevalence of migraine was significantly higher in patients with IBD (20.8%; P < .0001) than in the general population (12.6%; P < .0001), and this association was statistically significant in women (29.8%; P < .0001) but not in men (9.6%; P = .30). However, there were no significant differences in migraine prevalence between patients with ulcerative colitis and those with Crohn’s disease (P = .88).
Study details: This cross-sectional study included 283 patients age 18-65 years with IBD, of whom 20.85% had definite (11.66%) or probable (9.18%) migraine based on their response to the ID-Migraine questionnaire.
Disclosures: This study was funded by the Instituto de Salud Carlos III, Spain, and Fondos Europeos de Desarrollo Regional. The authors declared no conflicts of interest.
Source: Pascual-Mato M, Gárate G, de Prado-Tejerina C, et al. Increased prevalence of migraine in women with inflammatory bowel disease: A cross-sectional study. Cephalalgia. 2024 (Mar 1). doi: 10.1177/03331024241233979 Source
Increased Headache Burden With Left vs Right-Sided Migraine
Key clinical point: Patients with migraine experiencing typically left-sided headache during attacks had a higher burden of headache frequency and severity than those experiencing typically right-sided headache.
Major finding: Patients with left-sided vs right-sided migraine had 3.5 (95% CI 0.6-6.4) fewer headache-free days and 3.3 (95% CI 1.3-5.4) more severe headache days per 4 weeks. There were no other significant differences in migraine characteristics or psychiatric comorbidities between patients with left- and right-sided migraine.
Study details: This cross-sectional study included 340 patients with migraine, of whom 166 (48.8%) and 174 (51.2%) had left- and right-sided migraines, respectively.
Disclosures: The study did not disclose any funding source. The authors declared no conflicts of interest.
Source: Sprouse Blum AS, DaSilva LA, Greenberg MD, et al. Comparison of migraine with left- versus right-sided headache: A cross-sectional study. Headache. 2024 (Mar 3). doi: 10.1111/head.14689 Source
Key clinical point: Patients with migraine experiencing typically left-sided headache during attacks had a higher burden of headache frequency and severity than those experiencing typically right-sided headache.
Major finding: Patients with left-sided vs right-sided migraine had 3.5 (95% CI 0.6-6.4) fewer headache-free days and 3.3 (95% CI 1.3-5.4) more severe headache days per 4 weeks. There were no other significant differences in migraine characteristics or psychiatric comorbidities between patients with left- and right-sided migraine.
Study details: This cross-sectional study included 340 patients with migraine, of whom 166 (48.8%) and 174 (51.2%) had left- and right-sided migraines, respectively.
Disclosures: The study did not disclose any funding source. The authors declared no conflicts of interest.
Source: Sprouse Blum AS, DaSilva LA, Greenberg MD, et al. Comparison of migraine with left- versus right-sided headache: A cross-sectional study. Headache. 2024 (Mar 3). doi: 10.1111/head.14689 Source
Key clinical point: Patients with migraine experiencing typically left-sided headache during attacks had a higher burden of headache frequency and severity than those experiencing typically right-sided headache.
Major finding: Patients with left-sided vs right-sided migraine had 3.5 (95% CI 0.6-6.4) fewer headache-free days and 3.3 (95% CI 1.3-5.4) more severe headache days per 4 weeks. There were no other significant differences in migraine characteristics or psychiatric comorbidities between patients with left- and right-sided migraine.
Study details: This cross-sectional study included 340 patients with migraine, of whom 166 (48.8%) and 174 (51.2%) had left- and right-sided migraines, respectively.
Disclosures: The study did not disclose any funding source. The authors declared no conflicts of interest.
Source: Sprouse Blum AS, DaSilva LA, Greenberg MD, et al. Comparison of migraine with left- versus right-sided headache: A cross-sectional study. Headache. 2024 (Mar 3). doi: 10.1111/head.14689 Source