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FDA approves new type 2 diabetes drug bexagliflozin
The U.S. Food and Drug Administration has approved bexagliflozin (Brenzavvy, TheracosBio) for the treatment of adults with type 2 diabetes.
The once-daily 20-mg oral sodium-glucose cotransporter 2 (SGLT2) inhibitor is indicated as an adjunct to diet and exercise to improve glycemic control for those with type 2 diabetes, but not type 1 diabetes. It can be used in adults with an estimated glomerular filtration rate (eGFR) > 30 mL/min per 1.73 m2.
Approval was based on results from 23 clinical trials with more than 5,000 participants, including more than 300 patients with stage 3 kidney disease (eGFR < 60 and > 30 mL/min per 1.73 m2).
In the phase 3 studies, bexagliflozin significantly reduced hemoglobin A1c and fasting blood glucose at 24 weeks as monotherapy or as add-on to metformin and other glucose-lowering drugs and combinations. It also produced modest reductions in body weight and systolic blood pressure.
In the phase 3 Bexagliflozin Efficacy and Safety Trial (BEST) cardiovascular outcomes trial, the drug met its efficacy and safety objectives in patients at high cardiovascular risk. Noninferiority was demonstrated for the composite outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina.
“As a class of drugs, SGLT2 inhibitors have shown tremendous benefit in treating adults with type 2 diabetes,” said Mason Freeman, MD, director of the Translational Research Center at Massachusetts General Hospital, Boston, in a press release from TheracosBio.
“Being involved in all of the clinical trials for Brenzavvy, I am greatly impressed with the efficacy of the drug in reducing blood glucose levels and I believe it is an important addition to the SGLT2 inhibitor class of drugs.”
As with other SGLT2 inhibitors, adverse events seen in the trials include ketoacidosis, lower limb amputation, volume depletion, urosepsis, pyelonephritis, Fournier’s gangrene, genital mycotic infections, and hypoglycemia when used with insulin or insulin secretagogues.
Bexagliflozin joins an already crowded field of SGLT2 inhibitors, some of which have been approved for additional cardiovascular and kidney indications.
Of interest, bexagliflozin was approved by the FDA for diabetes in cats in December 2022, as the first oral new animal drug to improve glycemic control in otherwise healthy cats with diabetes not previously treated with insulin.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved bexagliflozin (Brenzavvy, TheracosBio) for the treatment of adults with type 2 diabetes.
The once-daily 20-mg oral sodium-glucose cotransporter 2 (SGLT2) inhibitor is indicated as an adjunct to diet and exercise to improve glycemic control for those with type 2 diabetes, but not type 1 diabetes. It can be used in adults with an estimated glomerular filtration rate (eGFR) > 30 mL/min per 1.73 m2.
Approval was based on results from 23 clinical trials with more than 5,000 participants, including more than 300 patients with stage 3 kidney disease (eGFR < 60 and > 30 mL/min per 1.73 m2).
In the phase 3 studies, bexagliflozin significantly reduced hemoglobin A1c and fasting blood glucose at 24 weeks as monotherapy or as add-on to metformin and other glucose-lowering drugs and combinations. It also produced modest reductions in body weight and systolic blood pressure.
In the phase 3 Bexagliflozin Efficacy and Safety Trial (BEST) cardiovascular outcomes trial, the drug met its efficacy and safety objectives in patients at high cardiovascular risk. Noninferiority was demonstrated for the composite outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina.
“As a class of drugs, SGLT2 inhibitors have shown tremendous benefit in treating adults with type 2 diabetes,” said Mason Freeman, MD, director of the Translational Research Center at Massachusetts General Hospital, Boston, in a press release from TheracosBio.
“Being involved in all of the clinical trials for Brenzavvy, I am greatly impressed with the efficacy of the drug in reducing blood glucose levels and I believe it is an important addition to the SGLT2 inhibitor class of drugs.”
As with other SGLT2 inhibitors, adverse events seen in the trials include ketoacidosis, lower limb amputation, volume depletion, urosepsis, pyelonephritis, Fournier’s gangrene, genital mycotic infections, and hypoglycemia when used with insulin or insulin secretagogues.
Bexagliflozin joins an already crowded field of SGLT2 inhibitors, some of which have been approved for additional cardiovascular and kidney indications.
Of interest, bexagliflozin was approved by the FDA for diabetes in cats in December 2022, as the first oral new animal drug to improve glycemic control in otherwise healthy cats with diabetes not previously treated with insulin.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved bexagliflozin (Brenzavvy, TheracosBio) for the treatment of adults with type 2 diabetes.
The once-daily 20-mg oral sodium-glucose cotransporter 2 (SGLT2) inhibitor is indicated as an adjunct to diet and exercise to improve glycemic control for those with type 2 diabetes, but not type 1 diabetes. It can be used in adults with an estimated glomerular filtration rate (eGFR) > 30 mL/min per 1.73 m2.
Approval was based on results from 23 clinical trials with more than 5,000 participants, including more than 300 patients with stage 3 kidney disease (eGFR < 60 and > 30 mL/min per 1.73 m2).
In the phase 3 studies, bexagliflozin significantly reduced hemoglobin A1c and fasting blood glucose at 24 weeks as monotherapy or as add-on to metformin and other glucose-lowering drugs and combinations. It also produced modest reductions in body weight and systolic blood pressure.
In the phase 3 Bexagliflozin Efficacy and Safety Trial (BEST) cardiovascular outcomes trial, the drug met its efficacy and safety objectives in patients at high cardiovascular risk. Noninferiority was demonstrated for the composite outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina.
“As a class of drugs, SGLT2 inhibitors have shown tremendous benefit in treating adults with type 2 diabetes,” said Mason Freeman, MD, director of the Translational Research Center at Massachusetts General Hospital, Boston, in a press release from TheracosBio.
“Being involved in all of the clinical trials for Brenzavvy, I am greatly impressed with the efficacy of the drug in reducing blood glucose levels and I believe it is an important addition to the SGLT2 inhibitor class of drugs.”
As with other SGLT2 inhibitors, adverse events seen in the trials include ketoacidosis, lower limb amputation, volume depletion, urosepsis, pyelonephritis, Fournier’s gangrene, genital mycotic infections, and hypoglycemia when used with insulin or insulin secretagogues.
Bexagliflozin joins an already crowded field of SGLT2 inhibitors, some of which have been approved for additional cardiovascular and kidney indications.
Of interest, bexagliflozin was approved by the FDA for diabetes in cats in December 2022, as the first oral new animal drug to improve glycemic control in otherwise healthy cats with diabetes not previously treated with insulin.
A version of this article first appeared on Medscape.com.
Doctors’ happiness has not rebounded as pandemic drags on
Physicians reported similar levels of unhappiness in 2022 too.
Fewer than half of physicians said they were currently somewhat or very happy at work, compared with 75% of physicians who said they were somewhat or very happy at work in a previous survey conducted before the pandemic, the new Medscape Physician Lifestyle & Happiness Report 2023 shows.*
“I am not surprised that we’re less happy now,” said Amaryllis Sánchez, MD, a board-certified family medicine physician and a certified physician coach.
“I speak to physicians around the country and I hear that their workplaces are understaffed, they’re overworked and they don’t feel safe. Although we’re in a different phase of the pandemic, doctors feel that the ground beneath them is still shaky,” said Dr. Sánchez, the author of “Recapturing Joy in Medicine.”
Most doctors are seeing more patients than they can handle and are expected to do that consistently. “When you no longer have the capacity to give of yourself, that becomes a nearly impossible task,” said Dr. Sánchez.
Also, physicians in understaffed workplaces often must take on additional work such as administrative or nursing duties, said Katie Cole, DO, a board-certified psychiatrist and a physician coach.
While health systems are aware that physicians need time to rest and recharge, staffing shortages prevent doctors from taking time off because they can’t find coverage, said Dr. Cole.
“While we know that it’s important for physicians to take vacations, more than one-third of doctors still take 2 weeks or less of vacation annually,” said Dr. Cole.
Physicians also tend to have less compassion for themselves and sacrifice self-care compared to other health care workers. “When a patient dies, nurses get together, debrief, and hug each other, whereas doctors have another patient to see. The culture of medicine doesn’t support self-compassion for physicians,” said Dr. Cole.
Physicians also felt less safe at work during the pandemic because of to shortages of personal protective equipment, said Dr. Sánchez. They have also witnessed or experienced an increase in abusive behavior, violence and threats of violence.
Physicians’ personal life suffers
Doctors maintain their mental health primarily by spending time with family members and friends, according to 2022’s Medscape Physician Lifestyle & Happiness Report. Yet half of doctors reported in a survey by the Physicians Foundation that they withdrew from family, friends or coworkers in 2022, said Dr. Sánchez.
“When you exceed your mental, emotional, and physical capacity at work, you have no reserve left for your personal life,” said Dr. Cole.
That may explain why only 58% of doctors reported feeling somewhat or very happy outside of work, compared with 84% who felt that way before the pandemic.
More women doctors said they deal with stronger feelings of conflict in trying to balance parenting responsibilities with a highly demanding job. Nearly one in two women physician-parents reported feeling very conflicted at work, compared with about one in four male physician-parents.
When physicians go home, they may be emotionally drained and tired mentally from making a lot of decisions at work, said Dr. Cole.
“As a woman, if you have children and a husband and you’re responsible for dinner, picking up the kids at daycare or helping them with homework, and making all these decisions when you get home, it’s overwhelming,” said Dr. Cole.
Prioritize your well-being
Doctors need to prioritize their own well-being, said Dr. Sánchez. “That’s not being selfish, that’s doing what’s necessary to stay well and be able to take care of patients. If doctors don’t take care of themselves, no one else will.”
Dr. Sánchez recommended that doctors regularly interact with relatives, friends, trusted colleagues, or clergy to help maintain their well-being, rather than waiting until a crisis to reach out.
A good coach, mentor, or counselor can help physicians gain enough self-awareness to handle their emotions and gain more clarity about what changes need to be made, she said.
Dr. Cole suggested that doctors figure out what makes them happy and fulfilled at work and try to spend more time on that activity. “Knowing what makes you happy and your strengths are foundational for creating a life you love.”
She urged doctors to “start thinking now about what you love about medicine and what is going right at home, and what areas you want to change. Then, start advocating for your needs.”
A version of this article originally appeared on Medscape.com.
Correction, 1/26/23: An earlier version of this article misstated the findings of the survey.
Physicians reported similar levels of unhappiness in 2022 too.
Fewer than half of physicians said they were currently somewhat or very happy at work, compared with 75% of physicians who said they were somewhat or very happy at work in a previous survey conducted before the pandemic, the new Medscape Physician Lifestyle & Happiness Report 2023 shows.*
“I am not surprised that we’re less happy now,” said Amaryllis Sánchez, MD, a board-certified family medicine physician and a certified physician coach.
“I speak to physicians around the country and I hear that their workplaces are understaffed, they’re overworked and they don’t feel safe. Although we’re in a different phase of the pandemic, doctors feel that the ground beneath them is still shaky,” said Dr. Sánchez, the author of “Recapturing Joy in Medicine.”
Most doctors are seeing more patients than they can handle and are expected to do that consistently. “When you no longer have the capacity to give of yourself, that becomes a nearly impossible task,” said Dr. Sánchez.
Also, physicians in understaffed workplaces often must take on additional work such as administrative or nursing duties, said Katie Cole, DO, a board-certified psychiatrist and a physician coach.
While health systems are aware that physicians need time to rest and recharge, staffing shortages prevent doctors from taking time off because they can’t find coverage, said Dr. Cole.
“While we know that it’s important for physicians to take vacations, more than one-third of doctors still take 2 weeks or less of vacation annually,” said Dr. Cole.
Physicians also tend to have less compassion for themselves and sacrifice self-care compared to other health care workers. “When a patient dies, nurses get together, debrief, and hug each other, whereas doctors have another patient to see. The culture of medicine doesn’t support self-compassion for physicians,” said Dr. Cole.
Physicians also felt less safe at work during the pandemic because of to shortages of personal protective equipment, said Dr. Sánchez. They have also witnessed or experienced an increase in abusive behavior, violence and threats of violence.
Physicians’ personal life suffers
Doctors maintain their mental health primarily by spending time with family members and friends, according to 2022’s Medscape Physician Lifestyle & Happiness Report. Yet half of doctors reported in a survey by the Physicians Foundation that they withdrew from family, friends or coworkers in 2022, said Dr. Sánchez.
“When you exceed your mental, emotional, and physical capacity at work, you have no reserve left for your personal life,” said Dr. Cole.
That may explain why only 58% of doctors reported feeling somewhat or very happy outside of work, compared with 84% who felt that way before the pandemic.
More women doctors said they deal with stronger feelings of conflict in trying to balance parenting responsibilities with a highly demanding job. Nearly one in two women physician-parents reported feeling very conflicted at work, compared with about one in four male physician-parents.
When physicians go home, they may be emotionally drained and tired mentally from making a lot of decisions at work, said Dr. Cole.
“As a woman, if you have children and a husband and you’re responsible for dinner, picking up the kids at daycare or helping them with homework, and making all these decisions when you get home, it’s overwhelming,” said Dr. Cole.
Prioritize your well-being
Doctors need to prioritize their own well-being, said Dr. Sánchez. “That’s not being selfish, that’s doing what’s necessary to stay well and be able to take care of patients. If doctors don’t take care of themselves, no one else will.”
Dr. Sánchez recommended that doctors regularly interact with relatives, friends, trusted colleagues, or clergy to help maintain their well-being, rather than waiting until a crisis to reach out.
A good coach, mentor, or counselor can help physicians gain enough self-awareness to handle their emotions and gain more clarity about what changes need to be made, she said.
Dr. Cole suggested that doctors figure out what makes them happy and fulfilled at work and try to spend more time on that activity. “Knowing what makes you happy and your strengths are foundational for creating a life you love.”
She urged doctors to “start thinking now about what you love about medicine and what is going right at home, and what areas you want to change. Then, start advocating for your needs.”
A version of this article originally appeared on Medscape.com.
Correction, 1/26/23: An earlier version of this article misstated the findings of the survey.
Physicians reported similar levels of unhappiness in 2022 too.
Fewer than half of physicians said they were currently somewhat or very happy at work, compared with 75% of physicians who said they were somewhat or very happy at work in a previous survey conducted before the pandemic, the new Medscape Physician Lifestyle & Happiness Report 2023 shows.*
“I am not surprised that we’re less happy now,” said Amaryllis Sánchez, MD, a board-certified family medicine physician and a certified physician coach.
“I speak to physicians around the country and I hear that their workplaces are understaffed, they’re overworked and they don’t feel safe. Although we’re in a different phase of the pandemic, doctors feel that the ground beneath them is still shaky,” said Dr. Sánchez, the author of “Recapturing Joy in Medicine.”
Most doctors are seeing more patients than they can handle and are expected to do that consistently. “When you no longer have the capacity to give of yourself, that becomes a nearly impossible task,” said Dr. Sánchez.
Also, physicians in understaffed workplaces often must take on additional work such as administrative or nursing duties, said Katie Cole, DO, a board-certified psychiatrist and a physician coach.
While health systems are aware that physicians need time to rest and recharge, staffing shortages prevent doctors from taking time off because they can’t find coverage, said Dr. Cole.
“While we know that it’s important for physicians to take vacations, more than one-third of doctors still take 2 weeks or less of vacation annually,” said Dr. Cole.
Physicians also tend to have less compassion for themselves and sacrifice self-care compared to other health care workers. “When a patient dies, nurses get together, debrief, and hug each other, whereas doctors have another patient to see. The culture of medicine doesn’t support self-compassion for physicians,” said Dr. Cole.
Physicians also felt less safe at work during the pandemic because of to shortages of personal protective equipment, said Dr. Sánchez. They have also witnessed or experienced an increase in abusive behavior, violence and threats of violence.
Physicians’ personal life suffers
Doctors maintain their mental health primarily by spending time with family members and friends, according to 2022’s Medscape Physician Lifestyle & Happiness Report. Yet half of doctors reported in a survey by the Physicians Foundation that they withdrew from family, friends or coworkers in 2022, said Dr. Sánchez.
“When you exceed your mental, emotional, and physical capacity at work, you have no reserve left for your personal life,” said Dr. Cole.
That may explain why only 58% of doctors reported feeling somewhat or very happy outside of work, compared with 84% who felt that way before the pandemic.
More women doctors said they deal with stronger feelings of conflict in trying to balance parenting responsibilities with a highly demanding job. Nearly one in two women physician-parents reported feeling very conflicted at work, compared with about one in four male physician-parents.
When physicians go home, they may be emotionally drained and tired mentally from making a lot of decisions at work, said Dr. Cole.
“As a woman, if you have children and a husband and you’re responsible for dinner, picking up the kids at daycare or helping them with homework, and making all these decisions when you get home, it’s overwhelming,” said Dr. Cole.
Prioritize your well-being
Doctors need to prioritize their own well-being, said Dr. Sánchez. “That’s not being selfish, that’s doing what’s necessary to stay well and be able to take care of patients. If doctors don’t take care of themselves, no one else will.”
Dr. Sánchez recommended that doctors regularly interact with relatives, friends, trusted colleagues, or clergy to help maintain their well-being, rather than waiting until a crisis to reach out.
A good coach, mentor, or counselor can help physicians gain enough self-awareness to handle their emotions and gain more clarity about what changes need to be made, she said.
Dr. Cole suggested that doctors figure out what makes them happy and fulfilled at work and try to spend more time on that activity. “Knowing what makes you happy and your strengths are foundational for creating a life you love.”
She urged doctors to “start thinking now about what you love about medicine and what is going right at home, and what areas you want to change. Then, start advocating for your needs.”
A version of this article originally appeared on Medscape.com.
Correction, 1/26/23: An earlier version of this article misstated the findings of the survey.
Is it time for yet another COVID booster? It’s complicated
For some people who have received a two-dose primary series and all the recommended boosters, that could mean a sixth shot since COVID-19 vaccines became available. But is even that enough (or too much)?
At this point, no one knows for sure, but new guidance may be on the docket.
On Jan. 26, the FDA’s Vaccines and Related Biological Products Advisory Committee is meeting. On the agenda is discussion about plans for future vaccinations for COVID-19.The committee, made up of external advisers, evaluates data on vaccines and other products for the agency.
According to the FDA announcement, after the meeting, “the FDA will consider whether to recommend adjustments to the current authorizations and approvals, and the FDA will consider the most efficient and transparent process to use for selection of strains for inclusion in the primary and booster vaccines.”
From there, the CDC will take up the issue and decide on recommendations.
The issue is important, as more than 550 Americans a day are still dying from COVID-19, as of the week ending Jan. 13, the CDC reported. That’s up from 346 a day for the week ending Dec. 28.
Yet, uptake of the newest vaccine, the bivalent booster, has been slow. As of Jan. 11, just 15.9% of the population 5 years and up has gotten it; for those most vulnerable to COVID19 – those 65 and up – the number is just 39%.
COVID vaccines, 2023 and beyond
Meanwhile, infectious disease experts have widely differing views on what the vaccination landscape of 2023 and beyond should look like. Among the areas of disagreement are how effective the bivalent vaccine is, which people most need another shot, and what type of vaccine is best.
“I think we probably will need another booster,” says Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine at Baylor College of Medicine, and codirector of the Center for Vaccine Development at Texas Children’s Hospital in Houston. “The question is, what is it going to be? Is it going to be the same bivalent that we just got, or will it be a new bivalent or even a trivalent?”
The trivalent booster, he suggested, might include something more protective against XBB.1.5.
The bivalent booster gives “broadened immunity” that is improved from the original booster shots, says Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape, WebMD’s sister site for health professionals.
In his publication Ground Truths, Dr. Topol on Jan. 11 explained how new data caused him to reverse his previously skeptical view of how the FDA authorized the bivalent vaccine in September without data on how it affected humans at the time.
Paul Offit, MD, director of the Vaccine Education Center and a professor of pediatrics at the Children’s Hospital of Philadelphia, is a member of the FDA advisory committee for vaccines. He still takes a dimmer view of more bivalent booster vaccines, at least as a blanket recommendation.
While he acknowledges that boosters can help some groups – such as older adults, people with multiple health conditions, and those with compromised immune systems – he opposes a recommendation that’s population-wide.
“People who fall into those three groups do benefit,” he says, “but the recommendation is everyone over 6 months get the bivalent, and what I’m asking is, ‘Where is the data that a healthy 12-year-old boy needs a booster to stay out of the hospital?’ ”
Evolving research
“We are trying to understand how to stay one step ahead rather than several steps behind [the virus],“ says Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.
Among the key questions: How well can a vaccine work against a single subvariant, when no one can say for sure what the next predominant subvariant will be?
Much more research has become available recently about the bivalent vaccine and its effectiveness, Dr. Osterholm says. “The bivalent vaccine is working as well as we could have expected,” he says, especially in high-risk people and in those over age 65. “The challenge we have is, what does that mean going forward?”
In his review, Dr. Topol concludes: “There is now more than ample, highly consistent evidence via lab studies and clinical outcomes to support the bivalent’s benefit over the original booster.”
Among other evidence, he looked at eight studies, including four that used a live virus as part of the research. Six of the eight studies showed the bivalent booster is more effective against the BA.5 variant, compared with the original booster shots. Two others showed no real difference.
“The four live virus studies offer consistent evidence of broadened immunity for the BA.5 vaccine that is improved over the original booster shots,” Dr. Topol wrote. The evidence also found the bivalent antibody response superior against XBB, he wrote.
Dr. Topol also cited CDC data that supports the benefits of the bivalent shot on hospitalization in older adults. During November, hospitalization of adults 65 and above was 2.5 times higher for those vaccinated who did not get the booster, compared to those who got the updated bivalent booster.
Boosters do matter, Dr. Offit says. “But not for all.” In a perspective published Jan. 11 in the New England Journal of Medicine – the same issue that published the two studies finding few differences between the original and bivalent – Dr. Offit wrote that boosting is best reserved for vulnerable groups.
Chasing the variants with a bivalent vaccine, he says, “has not panned out. There remains no evidence that a bivalent vaccine is any better than what we had. Please, show me the data that one is better than the other.”
Dr. Offit believes the goal should not be to prevent all symptomatic infections in healthy, young people by boosting them “with vaccines containing mRNA from strains that might disappear a few months later.”
The CDC needs to parse the data by subgroups, Dr. Offit says. “The critical question is, ‘Who gets hospitalized and who is dying? Who are they?’ ”
That data should take into account age, ethnicity, vaccine history, and other factors, Dr. Offit says, because right now, there is no great data to say, “OK, everyone gets a boost.”
Future vaccine costs
Another debate – for not only current boosters but future ones, too – centers on cost. Without congressional action to fund more vaccines, vaccine makers have suggested their prices may reach $130 a dose, compared with the average $20-per-dose cost the federal government pays now, according to a Kaiser Family Foundation report.
The government has spent more than $30 billion on COVID-19 vaccines, including the bivalent, to provide them free of charge.
The suggested price increase infuriated many. On Jan. 10, Sen. Bernie Sanders (I-Vt.), incoming chair of the Senate Committee on Health, Education, Labor and Pensions, sent a letter to Moderna CEO Stéphane Bancel, urging him to reconsider and refrain from any price increase.
“The huge increase in price that you have proposed will have a significantly negative impact on the budgets of Medicaid, Medicare and other government programs that will continue covering the vaccine without cost-sharing for patients.”
He pointed out, too, the $19 billion in profits Moderna has made over the past 2 years.
While most people with health insurance would likely still get the vaccines and booster for free, according to the Kaiser analysis, will a higher price discourage people from keeping up with recommended vaccinations, including a possible new booster?
“I think so, yes,” Dr. Hotez says, noting that vaccine reluctance is high as it is, even with free vaccinations and easy access.
“The government is balking at paying for the boosters,” he says. “I think it’s very tone deaf from the pharmaceutical companies [to increase the price]. Given all the help they’ve gotten from the American people, I think they should not be gouging at this point.”
He noted that the federal government provided not just money to the companies for the vaccines, but a “glide path” through the FDA for the vaccine approvals.
Are new, variant-specific boosters coming?
Are Moderna, Pfizer-BioNTech, and others developing more variant-specific vaccines, boosters, or other advances?
Novavax, approved in July 2022 as a primary series and in some cases as a booster, is “also developing an Omicron-containing bivalent vaccine at the direction of public health agencies,” says spokesperson Alison Chartan.
Pfizer responded: “When and if we have something to share we will let you know.”
Moderna did not respond.
A version of this article first appeared on WebMD.com.
For some people who have received a two-dose primary series and all the recommended boosters, that could mean a sixth shot since COVID-19 vaccines became available. But is even that enough (or too much)?
At this point, no one knows for sure, but new guidance may be on the docket.
On Jan. 26, the FDA’s Vaccines and Related Biological Products Advisory Committee is meeting. On the agenda is discussion about plans for future vaccinations for COVID-19.The committee, made up of external advisers, evaluates data on vaccines and other products for the agency.
According to the FDA announcement, after the meeting, “the FDA will consider whether to recommend adjustments to the current authorizations and approvals, and the FDA will consider the most efficient and transparent process to use for selection of strains for inclusion in the primary and booster vaccines.”
From there, the CDC will take up the issue and decide on recommendations.
The issue is important, as more than 550 Americans a day are still dying from COVID-19, as of the week ending Jan. 13, the CDC reported. That’s up from 346 a day for the week ending Dec. 28.
Yet, uptake of the newest vaccine, the bivalent booster, has been slow. As of Jan. 11, just 15.9% of the population 5 years and up has gotten it; for those most vulnerable to COVID19 – those 65 and up – the number is just 39%.
COVID vaccines, 2023 and beyond
Meanwhile, infectious disease experts have widely differing views on what the vaccination landscape of 2023 and beyond should look like. Among the areas of disagreement are how effective the bivalent vaccine is, which people most need another shot, and what type of vaccine is best.
“I think we probably will need another booster,” says Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine at Baylor College of Medicine, and codirector of the Center for Vaccine Development at Texas Children’s Hospital in Houston. “The question is, what is it going to be? Is it going to be the same bivalent that we just got, or will it be a new bivalent or even a trivalent?”
The trivalent booster, he suggested, might include something more protective against XBB.1.5.
The bivalent booster gives “broadened immunity” that is improved from the original booster shots, says Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape, WebMD’s sister site for health professionals.
In his publication Ground Truths, Dr. Topol on Jan. 11 explained how new data caused him to reverse his previously skeptical view of how the FDA authorized the bivalent vaccine in September without data on how it affected humans at the time.
Paul Offit, MD, director of the Vaccine Education Center and a professor of pediatrics at the Children’s Hospital of Philadelphia, is a member of the FDA advisory committee for vaccines. He still takes a dimmer view of more bivalent booster vaccines, at least as a blanket recommendation.
While he acknowledges that boosters can help some groups – such as older adults, people with multiple health conditions, and those with compromised immune systems – he opposes a recommendation that’s population-wide.
“People who fall into those three groups do benefit,” he says, “but the recommendation is everyone over 6 months get the bivalent, and what I’m asking is, ‘Where is the data that a healthy 12-year-old boy needs a booster to stay out of the hospital?’ ”
Evolving research
“We are trying to understand how to stay one step ahead rather than several steps behind [the virus],“ says Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.
Among the key questions: How well can a vaccine work against a single subvariant, when no one can say for sure what the next predominant subvariant will be?
Much more research has become available recently about the bivalent vaccine and its effectiveness, Dr. Osterholm says. “The bivalent vaccine is working as well as we could have expected,” he says, especially in high-risk people and in those over age 65. “The challenge we have is, what does that mean going forward?”
In his review, Dr. Topol concludes: “There is now more than ample, highly consistent evidence via lab studies and clinical outcomes to support the bivalent’s benefit over the original booster.”
Among other evidence, he looked at eight studies, including four that used a live virus as part of the research. Six of the eight studies showed the bivalent booster is more effective against the BA.5 variant, compared with the original booster shots. Two others showed no real difference.
“The four live virus studies offer consistent evidence of broadened immunity for the BA.5 vaccine that is improved over the original booster shots,” Dr. Topol wrote. The evidence also found the bivalent antibody response superior against XBB, he wrote.
Dr. Topol also cited CDC data that supports the benefits of the bivalent shot on hospitalization in older adults. During November, hospitalization of adults 65 and above was 2.5 times higher for those vaccinated who did not get the booster, compared to those who got the updated bivalent booster.
Boosters do matter, Dr. Offit says. “But not for all.” In a perspective published Jan. 11 in the New England Journal of Medicine – the same issue that published the two studies finding few differences between the original and bivalent – Dr. Offit wrote that boosting is best reserved for vulnerable groups.
Chasing the variants with a bivalent vaccine, he says, “has not panned out. There remains no evidence that a bivalent vaccine is any better than what we had. Please, show me the data that one is better than the other.”
Dr. Offit believes the goal should not be to prevent all symptomatic infections in healthy, young people by boosting them “with vaccines containing mRNA from strains that might disappear a few months later.”
The CDC needs to parse the data by subgroups, Dr. Offit says. “The critical question is, ‘Who gets hospitalized and who is dying? Who are they?’ ”
That data should take into account age, ethnicity, vaccine history, and other factors, Dr. Offit says, because right now, there is no great data to say, “OK, everyone gets a boost.”
Future vaccine costs
Another debate – for not only current boosters but future ones, too – centers on cost. Without congressional action to fund more vaccines, vaccine makers have suggested their prices may reach $130 a dose, compared with the average $20-per-dose cost the federal government pays now, according to a Kaiser Family Foundation report.
The government has spent more than $30 billion on COVID-19 vaccines, including the bivalent, to provide them free of charge.
The suggested price increase infuriated many. On Jan. 10, Sen. Bernie Sanders (I-Vt.), incoming chair of the Senate Committee on Health, Education, Labor and Pensions, sent a letter to Moderna CEO Stéphane Bancel, urging him to reconsider and refrain from any price increase.
“The huge increase in price that you have proposed will have a significantly negative impact on the budgets of Medicaid, Medicare and other government programs that will continue covering the vaccine without cost-sharing for patients.”
He pointed out, too, the $19 billion in profits Moderna has made over the past 2 years.
While most people with health insurance would likely still get the vaccines and booster for free, according to the Kaiser analysis, will a higher price discourage people from keeping up with recommended vaccinations, including a possible new booster?
“I think so, yes,” Dr. Hotez says, noting that vaccine reluctance is high as it is, even with free vaccinations and easy access.
“The government is balking at paying for the boosters,” he says. “I think it’s very tone deaf from the pharmaceutical companies [to increase the price]. Given all the help they’ve gotten from the American people, I think they should not be gouging at this point.”
He noted that the federal government provided not just money to the companies for the vaccines, but a “glide path” through the FDA for the vaccine approvals.
Are new, variant-specific boosters coming?
Are Moderna, Pfizer-BioNTech, and others developing more variant-specific vaccines, boosters, or other advances?
Novavax, approved in July 2022 as a primary series and in some cases as a booster, is “also developing an Omicron-containing bivalent vaccine at the direction of public health agencies,” says spokesperson Alison Chartan.
Pfizer responded: “When and if we have something to share we will let you know.”
Moderna did not respond.
A version of this article first appeared on WebMD.com.
For some people who have received a two-dose primary series and all the recommended boosters, that could mean a sixth shot since COVID-19 vaccines became available. But is even that enough (or too much)?
At this point, no one knows for sure, but new guidance may be on the docket.
On Jan. 26, the FDA’s Vaccines and Related Biological Products Advisory Committee is meeting. On the agenda is discussion about plans for future vaccinations for COVID-19.The committee, made up of external advisers, evaluates data on vaccines and other products for the agency.
According to the FDA announcement, after the meeting, “the FDA will consider whether to recommend adjustments to the current authorizations and approvals, and the FDA will consider the most efficient and transparent process to use for selection of strains for inclusion in the primary and booster vaccines.”
From there, the CDC will take up the issue and decide on recommendations.
The issue is important, as more than 550 Americans a day are still dying from COVID-19, as of the week ending Jan. 13, the CDC reported. That’s up from 346 a day for the week ending Dec. 28.
Yet, uptake of the newest vaccine, the bivalent booster, has been slow. As of Jan. 11, just 15.9% of the population 5 years and up has gotten it; for those most vulnerable to COVID19 – those 65 and up – the number is just 39%.
COVID vaccines, 2023 and beyond
Meanwhile, infectious disease experts have widely differing views on what the vaccination landscape of 2023 and beyond should look like. Among the areas of disagreement are how effective the bivalent vaccine is, which people most need another shot, and what type of vaccine is best.
“I think we probably will need another booster,” says Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine at Baylor College of Medicine, and codirector of the Center for Vaccine Development at Texas Children’s Hospital in Houston. “The question is, what is it going to be? Is it going to be the same bivalent that we just got, or will it be a new bivalent or even a trivalent?”
The trivalent booster, he suggested, might include something more protective against XBB.1.5.
The bivalent booster gives “broadened immunity” that is improved from the original booster shots, says Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape, WebMD’s sister site for health professionals.
In his publication Ground Truths, Dr. Topol on Jan. 11 explained how new data caused him to reverse his previously skeptical view of how the FDA authorized the bivalent vaccine in September without data on how it affected humans at the time.
Paul Offit, MD, director of the Vaccine Education Center and a professor of pediatrics at the Children’s Hospital of Philadelphia, is a member of the FDA advisory committee for vaccines. He still takes a dimmer view of more bivalent booster vaccines, at least as a blanket recommendation.
While he acknowledges that boosters can help some groups – such as older adults, people with multiple health conditions, and those with compromised immune systems – he opposes a recommendation that’s population-wide.
“People who fall into those three groups do benefit,” he says, “but the recommendation is everyone over 6 months get the bivalent, and what I’m asking is, ‘Where is the data that a healthy 12-year-old boy needs a booster to stay out of the hospital?’ ”
Evolving research
“We are trying to understand how to stay one step ahead rather than several steps behind [the virus],“ says Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.
Among the key questions: How well can a vaccine work against a single subvariant, when no one can say for sure what the next predominant subvariant will be?
Much more research has become available recently about the bivalent vaccine and its effectiveness, Dr. Osterholm says. “The bivalent vaccine is working as well as we could have expected,” he says, especially in high-risk people and in those over age 65. “The challenge we have is, what does that mean going forward?”
In his review, Dr. Topol concludes: “There is now more than ample, highly consistent evidence via lab studies and clinical outcomes to support the bivalent’s benefit over the original booster.”
Among other evidence, he looked at eight studies, including four that used a live virus as part of the research. Six of the eight studies showed the bivalent booster is more effective against the BA.5 variant, compared with the original booster shots. Two others showed no real difference.
“The four live virus studies offer consistent evidence of broadened immunity for the BA.5 vaccine that is improved over the original booster shots,” Dr. Topol wrote. The evidence also found the bivalent antibody response superior against XBB, he wrote.
Dr. Topol also cited CDC data that supports the benefits of the bivalent shot on hospitalization in older adults. During November, hospitalization of adults 65 and above was 2.5 times higher for those vaccinated who did not get the booster, compared to those who got the updated bivalent booster.
Boosters do matter, Dr. Offit says. “But not for all.” In a perspective published Jan. 11 in the New England Journal of Medicine – the same issue that published the two studies finding few differences between the original and bivalent – Dr. Offit wrote that boosting is best reserved for vulnerable groups.
Chasing the variants with a bivalent vaccine, he says, “has not panned out. There remains no evidence that a bivalent vaccine is any better than what we had. Please, show me the data that one is better than the other.”
Dr. Offit believes the goal should not be to prevent all symptomatic infections in healthy, young people by boosting them “with vaccines containing mRNA from strains that might disappear a few months later.”
The CDC needs to parse the data by subgroups, Dr. Offit says. “The critical question is, ‘Who gets hospitalized and who is dying? Who are they?’ ”
That data should take into account age, ethnicity, vaccine history, and other factors, Dr. Offit says, because right now, there is no great data to say, “OK, everyone gets a boost.”
Future vaccine costs
Another debate – for not only current boosters but future ones, too – centers on cost. Without congressional action to fund more vaccines, vaccine makers have suggested their prices may reach $130 a dose, compared with the average $20-per-dose cost the federal government pays now, according to a Kaiser Family Foundation report.
The government has spent more than $30 billion on COVID-19 vaccines, including the bivalent, to provide them free of charge.
The suggested price increase infuriated many. On Jan. 10, Sen. Bernie Sanders (I-Vt.), incoming chair of the Senate Committee on Health, Education, Labor and Pensions, sent a letter to Moderna CEO Stéphane Bancel, urging him to reconsider and refrain from any price increase.
“The huge increase in price that you have proposed will have a significantly negative impact on the budgets of Medicaid, Medicare and other government programs that will continue covering the vaccine without cost-sharing for patients.”
He pointed out, too, the $19 billion in profits Moderna has made over the past 2 years.
While most people with health insurance would likely still get the vaccines and booster for free, according to the Kaiser analysis, will a higher price discourage people from keeping up with recommended vaccinations, including a possible new booster?
“I think so, yes,” Dr. Hotez says, noting that vaccine reluctance is high as it is, even with free vaccinations and easy access.
“The government is balking at paying for the boosters,” he says. “I think it’s very tone deaf from the pharmaceutical companies [to increase the price]. Given all the help they’ve gotten from the American people, I think they should not be gouging at this point.”
He noted that the federal government provided not just money to the companies for the vaccines, but a “glide path” through the FDA for the vaccine approvals.
Are new, variant-specific boosters coming?
Are Moderna, Pfizer-BioNTech, and others developing more variant-specific vaccines, boosters, or other advances?
Novavax, approved in July 2022 as a primary series and in some cases as a booster, is “also developing an Omicron-containing bivalent vaccine at the direction of public health agencies,” says spokesperson Alison Chartan.
Pfizer responded: “When and if we have something to share we will let you know.”
Moderna did not respond.
A version of this article first appeared on WebMD.com.
Nitrite food additives may increase risk of type 2 diabetes
Consuming a large amount of nitrites from food additives versus none was associated with a greater risk of developing type 2 diabetes in the NutriNet-Santé study in France, researchers report.
However, a few experts who were not involved with this research question the strength of the findings because of study limitations.
The study involved more than 100,000 adults with a mean age of 43, and 79% were women.
Individuals with the highest intakes of nitrites from food additives (top third) had a 53% higher risk of developing type 2 diabetes during a median follow-up of 7 years compared with those with the lowest intake of this food additive after controlling for intake of sugars, red and processed meats, heme iron, salt, and saturated fatty acids. Consumption of nitrates from food additives was not associated with risk of type 2 diabetes.
“Our findings suggest a direct association between additives-originated nitrites and [type 2 diabetes] risk and corroborate previously suggested associations between total dietary nitrites and [type 2 diabetes],” the researchers report in an article published online in PLoS Medicine.
However, “as this is the first large-scale study finding these associations, these results need to be replicated in other large-scale cohorts,” senior author Mathilde Touvier, PhD, head of the Nutritional Epidemiology Research Team (EREN-CRESS), INSERM, INRAE, Sorbonne Paris Nord University, and lead author Bernard Srour, PhD, PharmD, a scientist at the same institution, said in a joint email to this news organization.
Short-term intervention studies to determine insulin resistance could also be tested, they add.
In the meantime, “this study adds further evidence to the existing strong link between nitrites and colorectal cancer risk, and supports the importance of further regulation of nitrites as food additives and nitrogen fertilizers,” they say.
According to Dr. Touvier and Dr. Srour, the takeaway message for clinicians is the finding that nitrites from food additives are associated with type 2 diabetes, “support existing guidelines recommending [limiting] the consumption of processed meats to prevent chronic diseases. However, the consumption of vegetables should be encouraged as they contain several beneficial compounds and contribute to chronic disease prevention.”
Some experts are skeptical
But three experts who were not involved with the research were skeptical about the conclusions, in comments made to the U.K. Science Media Centre.
“The fundamental weakness of this study is how the food additive intake was assessed,” said Tom Sanders, DSc, PhD, professor emeritus of nutrition and dietetics, King’s College London. “Estimates of intake were based on recalls of dietary intake on two separate occasions at the beginning of the study with no further estimates in the follow-up period of over 7 years,” he noted.
Other limitations include the relatively young age of the cohort and relatively low incidence of new cases of type 2 diabetes (about 1% of the study population over 7 years).
Moreover, the level of nitrite food additive ingestion is much lower than the acceptable daily intake. The findings would need to be replicated with appropriate adjustment for differences in body weight.
Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading, England, said that “the study does not support the claim in the press release and paper that food additives are responsible for the increased risk.”
He pointed out that “nitrite from additives contributes only about 4%-6% of total nitrite intake in the population, and it is not clear why this should have a stronger impact on risk than nitrite from other sources,” such as nitrate found in food and water.
Duane Mellor, PhD, registered dietitian and senior lecturer, Aston University, Birmingham, England, said: “It could be questioned how accurate estimating intakes of individual additives like sodium nitrite, which was less than 1 mg per day from a record of just 2 days food intake per year, as it assumes people ate the same the other 363 days of the year.”
Moreover, “it is perhaps worth noting that the use of nitrites as an additive is often as sodium nitrite, which is used to cure meats like bacon, which if someone is seeking to reduce their risk of type 2 diabetes would be something people would be encouraged to eat less of [anyway].”
“The best way to reduce your risk of developing type 2 diabetes,” he said, “is to be physically active, maintain a healthy weight for you, and eat a varied diet based on vegetables, pulses, nuts, seeds, and fruit along with wholegrain and moderate intakes of dairy foods and meat (especially processed meats).”
Study details
Nitrites and nitrates are used as food additives to prevent bacterial growth, mainly in processed meats, and they are also found in foods (mainly green leafy vegetables) and water (nitrates from the use of nitrogen fertilizer can enter the water supply).
The researchers analyzed data from 104,168 participants in NutriNet-Santé who had no diabetes at baseline and who completed 24-hour dietary intake records. They investigated the association between exposure to nitrites and nitrates (in food and water or in additives) and incident type 2 diabetes.
Most nitrites came from food (95.3%), and less often from food additives (4.7%) and water (< 0.01%). The nitrites in foods were mainly from vegetables (60%) and seasonings (23%).
Most nitrates also came from food (93%), followed by water (6.9%) and food additives (0.1%). The nitrates in foods were mainly from vegetables (41%), processed meat (19%), and meat (17%).
During a median follow-up of 7.3 years, there were 969 incident cases of type 2 diabetes.
Compared with individuals in the lowest third of nitrites from food and water, those in the highest tertile had a 27% higher risk of incident type 2 diabetes, after adjusting for multiple variables (hazard ratio, 1.27; P = .009).
The risk of type 2 diabetes associated with the highest intake of nitrites from additives was as previously described, 53% higher, than that for those with the lowest intake.
There was no evidence of an association between nitrates and risk of type 2 diabetes.
The researchers acknowledge that study limitations include potential errors in assessment of nitrate and nitrate exposure, potential selection bias (participants in the web-based study may have had healthier behaviors than the general population), and potential unaccounted confounders (because it was an observational study).
A version of this article first appeared on Medscape.com.
Consuming a large amount of nitrites from food additives versus none was associated with a greater risk of developing type 2 diabetes in the NutriNet-Santé study in France, researchers report.
However, a few experts who were not involved with this research question the strength of the findings because of study limitations.
The study involved more than 100,000 adults with a mean age of 43, and 79% were women.
Individuals with the highest intakes of nitrites from food additives (top third) had a 53% higher risk of developing type 2 diabetes during a median follow-up of 7 years compared with those with the lowest intake of this food additive after controlling for intake of sugars, red and processed meats, heme iron, salt, and saturated fatty acids. Consumption of nitrates from food additives was not associated with risk of type 2 diabetes.
“Our findings suggest a direct association between additives-originated nitrites and [type 2 diabetes] risk and corroborate previously suggested associations between total dietary nitrites and [type 2 diabetes],” the researchers report in an article published online in PLoS Medicine.
However, “as this is the first large-scale study finding these associations, these results need to be replicated in other large-scale cohorts,” senior author Mathilde Touvier, PhD, head of the Nutritional Epidemiology Research Team (EREN-CRESS), INSERM, INRAE, Sorbonne Paris Nord University, and lead author Bernard Srour, PhD, PharmD, a scientist at the same institution, said in a joint email to this news organization.
Short-term intervention studies to determine insulin resistance could also be tested, they add.
In the meantime, “this study adds further evidence to the existing strong link between nitrites and colorectal cancer risk, and supports the importance of further regulation of nitrites as food additives and nitrogen fertilizers,” they say.
According to Dr. Touvier and Dr. Srour, the takeaway message for clinicians is the finding that nitrites from food additives are associated with type 2 diabetes, “support existing guidelines recommending [limiting] the consumption of processed meats to prevent chronic diseases. However, the consumption of vegetables should be encouraged as they contain several beneficial compounds and contribute to chronic disease prevention.”
Some experts are skeptical
But three experts who were not involved with the research were skeptical about the conclusions, in comments made to the U.K. Science Media Centre.
“The fundamental weakness of this study is how the food additive intake was assessed,” said Tom Sanders, DSc, PhD, professor emeritus of nutrition and dietetics, King’s College London. “Estimates of intake were based on recalls of dietary intake on two separate occasions at the beginning of the study with no further estimates in the follow-up period of over 7 years,” he noted.
Other limitations include the relatively young age of the cohort and relatively low incidence of new cases of type 2 diabetes (about 1% of the study population over 7 years).
Moreover, the level of nitrite food additive ingestion is much lower than the acceptable daily intake. The findings would need to be replicated with appropriate adjustment for differences in body weight.
Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading, England, said that “the study does not support the claim in the press release and paper that food additives are responsible for the increased risk.”
He pointed out that “nitrite from additives contributes only about 4%-6% of total nitrite intake in the population, and it is not clear why this should have a stronger impact on risk than nitrite from other sources,” such as nitrate found in food and water.
Duane Mellor, PhD, registered dietitian and senior lecturer, Aston University, Birmingham, England, said: “It could be questioned how accurate estimating intakes of individual additives like sodium nitrite, which was less than 1 mg per day from a record of just 2 days food intake per year, as it assumes people ate the same the other 363 days of the year.”
Moreover, “it is perhaps worth noting that the use of nitrites as an additive is often as sodium nitrite, which is used to cure meats like bacon, which if someone is seeking to reduce their risk of type 2 diabetes would be something people would be encouraged to eat less of [anyway].”
“The best way to reduce your risk of developing type 2 diabetes,” he said, “is to be physically active, maintain a healthy weight for you, and eat a varied diet based on vegetables, pulses, nuts, seeds, and fruit along with wholegrain and moderate intakes of dairy foods and meat (especially processed meats).”
Study details
Nitrites and nitrates are used as food additives to prevent bacterial growth, mainly in processed meats, and they are also found in foods (mainly green leafy vegetables) and water (nitrates from the use of nitrogen fertilizer can enter the water supply).
The researchers analyzed data from 104,168 participants in NutriNet-Santé who had no diabetes at baseline and who completed 24-hour dietary intake records. They investigated the association between exposure to nitrites and nitrates (in food and water or in additives) and incident type 2 diabetes.
Most nitrites came from food (95.3%), and less often from food additives (4.7%) and water (< 0.01%). The nitrites in foods were mainly from vegetables (60%) and seasonings (23%).
Most nitrates also came from food (93%), followed by water (6.9%) and food additives (0.1%). The nitrates in foods were mainly from vegetables (41%), processed meat (19%), and meat (17%).
During a median follow-up of 7.3 years, there were 969 incident cases of type 2 diabetes.
Compared with individuals in the lowest third of nitrites from food and water, those in the highest tertile had a 27% higher risk of incident type 2 diabetes, after adjusting for multiple variables (hazard ratio, 1.27; P = .009).
The risk of type 2 diabetes associated with the highest intake of nitrites from additives was as previously described, 53% higher, than that for those with the lowest intake.
There was no evidence of an association between nitrates and risk of type 2 diabetes.
The researchers acknowledge that study limitations include potential errors in assessment of nitrate and nitrate exposure, potential selection bias (participants in the web-based study may have had healthier behaviors than the general population), and potential unaccounted confounders (because it was an observational study).
A version of this article first appeared on Medscape.com.
Consuming a large amount of nitrites from food additives versus none was associated with a greater risk of developing type 2 diabetes in the NutriNet-Santé study in France, researchers report.
However, a few experts who were not involved with this research question the strength of the findings because of study limitations.
The study involved more than 100,000 adults with a mean age of 43, and 79% were women.
Individuals with the highest intakes of nitrites from food additives (top third) had a 53% higher risk of developing type 2 diabetes during a median follow-up of 7 years compared with those with the lowest intake of this food additive after controlling for intake of sugars, red and processed meats, heme iron, salt, and saturated fatty acids. Consumption of nitrates from food additives was not associated with risk of type 2 diabetes.
“Our findings suggest a direct association between additives-originated nitrites and [type 2 diabetes] risk and corroborate previously suggested associations between total dietary nitrites and [type 2 diabetes],” the researchers report in an article published online in PLoS Medicine.
However, “as this is the first large-scale study finding these associations, these results need to be replicated in other large-scale cohorts,” senior author Mathilde Touvier, PhD, head of the Nutritional Epidemiology Research Team (EREN-CRESS), INSERM, INRAE, Sorbonne Paris Nord University, and lead author Bernard Srour, PhD, PharmD, a scientist at the same institution, said in a joint email to this news organization.
Short-term intervention studies to determine insulin resistance could also be tested, they add.
In the meantime, “this study adds further evidence to the existing strong link between nitrites and colorectal cancer risk, and supports the importance of further regulation of nitrites as food additives and nitrogen fertilizers,” they say.
According to Dr. Touvier and Dr. Srour, the takeaway message for clinicians is the finding that nitrites from food additives are associated with type 2 diabetes, “support existing guidelines recommending [limiting] the consumption of processed meats to prevent chronic diseases. However, the consumption of vegetables should be encouraged as they contain several beneficial compounds and contribute to chronic disease prevention.”
Some experts are skeptical
But three experts who were not involved with the research were skeptical about the conclusions, in comments made to the U.K. Science Media Centre.
“The fundamental weakness of this study is how the food additive intake was assessed,” said Tom Sanders, DSc, PhD, professor emeritus of nutrition and dietetics, King’s College London. “Estimates of intake were based on recalls of dietary intake on two separate occasions at the beginning of the study with no further estimates in the follow-up period of over 7 years,” he noted.
Other limitations include the relatively young age of the cohort and relatively low incidence of new cases of type 2 diabetes (about 1% of the study population over 7 years).
Moreover, the level of nitrite food additive ingestion is much lower than the acceptable daily intake. The findings would need to be replicated with appropriate adjustment for differences in body weight.
Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading, England, said that “the study does not support the claim in the press release and paper that food additives are responsible for the increased risk.”
He pointed out that “nitrite from additives contributes only about 4%-6% of total nitrite intake in the population, and it is not clear why this should have a stronger impact on risk than nitrite from other sources,” such as nitrate found in food and water.
Duane Mellor, PhD, registered dietitian and senior lecturer, Aston University, Birmingham, England, said: “It could be questioned how accurate estimating intakes of individual additives like sodium nitrite, which was less than 1 mg per day from a record of just 2 days food intake per year, as it assumes people ate the same the other 363 days of the year.”
Moreover, “it is perhaps worth noting that the use of nitrites as an additive is often as sodium nitrite, which is used to cure meats like bacon, which if someone is seeking to reduce their risk of type 2 diabetes would be something people would be encouraged to eat less of [anyway].”
“The best way to reduce your risk of developing type 2 diabetes,” he said, “is to be physically active, maintain a healthy weight for you, and eat a varied diet based on vegetables, pulses, nuts, seeds, and fruit along with wholegrain and moderate intakes of dairy foods and meat (especially processed meats).”
Study details
Nitrites and nitrates are used as food additives to prevent bacterial growth, mainly in processed meats, and they are also found in foods (mainly green leafy vegetables) and water (nitrates from the use of nitrogen fertilizer can enter the water supply).
The researchers analyzed data from 104,168 participants in NutriNet-Santé who had no diabetes at baseline and who completed 24-hour dietary intake records. They investigated the association between exposure to nitrites and nitrates (in food and water or in additives) and incident type 2 diabetes.
Most nitrites came from food (95.3%), and less often from food additives (4.7%) and water (< 0.01%). The nitrites in foods were mainly from vegetables (60%) and seasonings (23%).
Most nitrates also came from food (93%), followed by water (6.9%) and food additives (0.1%). The nitrates in foods were mainly from vegetables (41%), processed meat (19%), and meat (17%).
During a median follow-up of 7.3 years, there were 969 incident cases of type 2 diabetes.
Compared with individuals in the lowest third of nitrites from food and water, those in the highest tertile had a 27% higher risk of incident type 2 diabetes, after adjusting for multiple variables (hazard ratio, 1.27; P = .009).
The risk of type 2 diabetes associated with the highest intake of nitrites from additives was as previously described, 53% higher, than that for those with the lowest intake.
There was no evidence of an association between nitrates and risk of type 2 diabetes.
The researchers acknowledge that study limitations include potential errors in assessment of nitrate and nitrate exposure, potential selection bias (participants in the web-based study may have had healthier behaviors than the general population), and potential unaccounted confounders (because it was an observational study).
A version of this article first appeared on Medscape.com.
FROM PLOS MEDICINE
Diet packed with fast food found hard on the liver
The study finds that getting one-fifth or more of total daily calories from fast food can increase the risk of nonalcoholic fatty liver disease, which can lead to cirrhosis and its complications, including liver failure and liver cancer.
Although the magnitude of association was modest among the general population, “striking” elevations in steatosis were evident among persons with obesity and diabetes who consumed fast food, in comparison with their counterparts who did not have obesity and diabetes, the researchers reported.
“My hope is that this study encourages people to seek out more nutritious, healthy food options and provides information that clinicians can use to counsel their patients, particularly those with underlying metabolic risk factors, of the importance of avoiding foods that are high in fat, carbohydrates, and processed sugars,” lead investigator Ani Kardashian, MD, hepatologist with the University of Southern California, Los Angeles, said in an interview.
“At a policy level, public health efforts are needed to improve access to affordable, healthy, and nutritious food options across the U.S. This is especially important as more people have turned to fast foods during the pandemic and as the price of food as risen dramatically over the past year due to food inflation,” Dr. Kardashian added.
The study was published online in Clinical Gastroenterology and Hepatology.
More fast food, greater steatosis
The findings are based on data from 3,954 adults who participated in the National Health and Nutrition Examination Survey (NHANES) of 2017-2018 and who underwent vibration-controlled transient elastography. Of these participants, data regarding 1- or 2-day dietary recall were available.
Steatosis, the primary outcome, was measured via controlled attenuation parameter (CAP). Two validated cutoffs were utilized (CAP ≥ 263 dB/m and CAP ≥ 285 dB/m).
Of those surveyed, 52% consumed any fast food, and 29% derived 20% or more of their daily calories from fast food.
Fast-food intake of 20% or more of daily calories was significantly associated with greater steatosis after multivariable adjustment, both as a continuous measure (4.6 dB/m higher CAP score) and with respect to the CAP ≥ 263 dB/m cutoff (odds ratio [OR], 1.45).
“The negative effects are particularly severe in people who already have diabetes and obesity,” Dr. Kardashian told this news organization.
For example, with diabetes and fast-food intake of 20% or more of daily calories, the ORs of meeting the CAP ≥ 263 dB/m cutoff and the CAP ≥ 285 dB/m cutoff were 2.3 and 2.48, respectively.
The researchers said their findings are particularly “alarming,” given the overall increase in fast-food consumption over the past 50 years in the United States, regardless of socioeconomic status.
Diet coaching
The finding that fast food has more deleterious impact on those with obesity and diabetes “emphasizes that it is not just one insult but multiple factors that contribute to overall health,” said Nancy Reau, MD, section chief of hepatology at Rush University Medical Center in Chicago.
“This is actually great news, because diet is modifiable, vs. your genetics, which you currently can’t change. This doesn’t mean if you’re lean you can eat whatever you want, but if you are overweight, being careful with your diet does have impact, even if it doesn’t lead to substantial weight changes,” said Dr. Reau, who is not affiliated with the study.
For people who have limited options and need to eat fast food, “there are healthy choices at most restaurants; you just need to be smart about reading labels, watching calories, and ordering the healthier options,” Dr. Reau said in an interview.
Fast food and fatty liver go “hand in hand,” Lisa Ganjhu, DO, gastroenterologist and hepatologist at NYU Langone Health in New York, told this news organization.
“I counsel and coach my patients on healthy diet and exercise, and I’ve been pretty successful,” said Dr. Ganjhu, who was not involved with the study.
“If my patient is eating at McDonald’s a lot, I basically walk through the menu with them and help them find something healthy. When patients see the benefits of cutting out fat and reducing carbohydrates, they are more apt to continue,” Dr. Ganjhu said.
The study was funded by the University of Southern California. Dr. Kardashian, Dr. Reau, and Dr. Ganjhu have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The study finds that getting one-fifth or more of total daily calories from fast food can increase the risk of nonalcoholic fatty liver disease, which can lead to cirrhosis and its complications, including liver failure and liver cancer.
Although the magnitude of association was modest among the general population, “striking” elevations in steatosis were evident among persons with obesity and diabetes who consumed fast food, in comparison with their counterparts who did not have obesity and diabetes, the researchers reported.
“My hope is that this study encourages people to seek out more nutritious, healthy food options and provides information that clinicians can use to counsel their patients, particularly those with underlying metabolic risk factors, of the importance of avoiding foods that are high in fat, carbohydrates, and processed sugars,” lead investigator Ani Kardashian, MD, hepatologist with the University of Southern California, Los Angeles, said in an interview.
“At a policy level, public health efforts are needed to improve access to affordable, healthy, and nutritious food options across the U.S. This is especially important as more people have turned to fast foods during the pandemic and as the price of food as risen dramatically over the past year due to food inflation,” Dr. Kardashian added.
The study was published online in Clinical Gastroenterology and Hepatology.
More fast food, greater steatosis
The findings are based on data from 3,954 adults who participated in the National Health and Nutrition Examination Survey (NHANES) of 2017-2018 and who underwent vibration-controlled transient elastography. Of these participants, data regarding 1- or 2-day dietary recall were available.
Steatosis, the primary outcome, was measured via controlled attenuation parameter (CAP). Two validated cutoffs were utilized (CAP ≥ 263 dB/m and CAP ≥ 285 dB/m).
Of those surveyed, 52% consumed any fast food, and 29% derived 20% or more of their daily calories from fast food.
Fast-food intake of 20% or more of daily calories was significantly associated with greater steatosis after multivariable adjustment, both as a continuous measure (4.6 dB/m higher CAP score) and with respect to the CAP ≥ 263 dB/m cutoff (odds ratio [OR], 1.45).
“The negative effects are particularly severe in people who already have diabetes and obesity,” Dr. Kardashian told this news organization.
For example, with diabetes and fast-food intake of 20% or more of daily calories, the ORs of meeting the CAP ≥ 263 dB/m cutoff and the CAP ≥ 285 dB/m cutoff were 2.3 and 2.48, respectively.
The researchers said their findings are particularly “alarming,” given the overall increase in fast-food consumption over the past 50 years in the United States, regardless of socioeconomic status.
Diet coaching
The finding that fast food has more deleterious impact on those with obesity and diabetes “emphasizes that it is not just one insult but multiple factors that contribute to overall health,” said Nancy Reau, MD, section chief of hepatology at Rush University Medical Center in Chicago.
“This is actually great news, because diet is modifiable, vs. your genetics, which you currently can’t change. This doesn’t mean if you’re lean you can eat whatever you want, but if you are overweight, being careful with your diet does have impact, even if it doesn’t lead to substantial weight changes,” said Dr. Reau, who is not affiliated with the study.
For people who have limited options and need to eat fast food, “there are healthy choices at most restaurants; you just need to be smart about reading labels, watching calories, and ordering the healthier options,” Dr. Reau said in an interview.
Fast food and fatty liver go “hand in hand,” Lisa Ganjhu, DO, gastroenterologist and hepatologist at NYU Langone Health in New York, told this news organization.
“I counsel and coach my patients on healthy diet and exercise, and I’ve been pretty successful,” said Dr. Ganjhu, who was not involved with the study.
“If my patient is eating at McDonald’s a lot, I basically walk through the menu with them and help them find something healthy. When patients see the benefits of cutting out fat and reducing carbohydrates, they are more apt to continue,” Dr. Ganjhu said.
The study was funded by the University of Southern California. Dr. Kardashian, Dr. Reau, and Dr. Ganjhu have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The study finds that getting one-fifth or more of total daily calories from fast food can increase the risk of nonalcoholic fatty liver disease, which can lead to cirrhosis and its complications, including liver failure and liver cancer.
Although the magnitude of association was modest among the general population, “striking” elevations in steatosis were evident among persons with obesity and diabetes who consumed fast food, in comparison with their counterparts who did not have obesity and diabetes, the researchers reported.
“My hope is that this study encourages people to seek out more nutritious, healthy food options and provides information that clinicians can use to counsel their patients, particularly those with underlying metabolic risk factors, of the importance of avoiding foods that are high in fat, carbohydrates, and processed sugars,” lead investigator Ani Kardashian, MD, hepatologist with the University of Southern California, Los Angeles, said in an interview.
“At a policy level, public health efforts are needed to improve access to affordable, healthy, and nutritious food options across the U.S. This is especially important as more people have turned to fast foods during the pandemic and as the price of food as risen dramatically over the past year due to food inflation,” Dr. Kardashian added.
The study was published online in Clinical Gastroenterology and Hepatology.
More fast food, greater steatosis
The findings are based on data from 3,954 adults who participated in the National Health and Nutrition Examination Survey (NHANES) of 2017-2018 and who underwent vibration-controlled transient elastography. Of these participants, data regarding 1- or 2-day dietary recall were available.
Steatosis, the primary outcome, was measured via controlled attenuation parameter (CAP). Two validated cutoffs were utilized (CAP ≥ 263 dB/m and CAP ≥ 285 dB/m).
Of those surveyed, 52% consumed any fast food, and 29% derived 20% or more of their daily calories from fast food.
Fast-food intake of 20% or more of daily calories was significantly associated with greater steatosis after multivariable adjustment, both as a continuous measure (4.6 dB/m higher CAP score) and with respect to the CAP ≥ 263 dB/m cutoff (odds ratio [OR], 1.45).
“The negative effects are particularly severe in people who already have diabetes and obesity,” Dr. Kardashian told this news organization.
For example, with diabetes and fast-food intake of 20% or more of daily calories, the ORs of meeting the CAP ≥ 263 dB/m cutoff and the CAP ≥ 285 dB/m cutoff were 2.3 and 2.48, respectively.
The researchers said their findings are particularly “alarming,” given the overall increase in fast-food consumption over the past 50 years in the United States, regardless of socioeconomic status.
Diet coaching
The finding that fast food has more deleterious impact on those with obesity and diabetes “emphasizes that it is not just one insult but multiple factors that contribute to overall health,” said Nancy Reau, MD, section chief of hepatology at Rush University Medical Center in Chicago.
“This is actually great news, because diet is modifiable, vs. your genetics, which you currently can’t change. This doesn’t mean if you’re lean you can eat whatever you want, but if you are overweight, being careful with your diet does have impact, even if it doesn’t lead to substantial weight changes,” said Dr. Reau, who is not affiliated with the study.
For people who have limited options and need to eat fast food, “there are healthy choices at most restaurants; you just need to be smart about reading labels, watching calories, and ordering the healthier options,” Dr. Reau said in an interview.
Fast food and fatty liver go “hand in hand,” Lisa Ganjhu, DO, gastroenterologist and hepatologist at NYU Langone Health in New York, told this news organization.
“I counsel and coach my patients on healthy diet and exercise, and I’ve been pretty successful,” said Dr. Ganjhu, who was not involved with the study.
“If my patient is eating at McDonald’s a lot, I basically walk through the menu with them and help them find something healthy. When patients see the benefits of cutting out fat and reducing carbohydrates, they are more apt to continue,” Dr. Ganjhu said.
The study was funded by the University of Southern California. Dr. Kardashian, Dr. Reau, and Dr. Ganjhu have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Possible bivalent vaccine link to strokes in people over 65
who got the shot, the Centers for Disease Control and Prevention and the Food and Drug Administration said in a joint news release.
The release did not recommend people change their vaccine practices, saying the database finding probably did not represent a “true clinical risk.” The CDC said everybody, including people over 65, should stay up to date on their COVID vaccines, including the bivalent booster.
The news release said the Vaccine Safety Datalink (VSD), “a near real-time surveillance system,” raised a safety concern about the Pfizer/BioNTech booster.
“Rapid-response investigation of the signal in the VSD raised a question of whether people 65 and older who have received the Pfizer-BioNTech COVID-19 Vaccine, Bivalent were more likely to have an ischemic stroke in the 21 days following vaccination compared with days 22-44 following vaccination,” the news release said.
Ischemic strokes are blockages of blood to the brain, often caused by blood clots.
“Although the totality of the data currently suggests that it is very unlikely that the signal in VSD (Vaccine Safety Datalink) represents a true clinical risk, we believe it is important to share this information with the public, as we have in the past, when one of our safety monitoring systems detects a signal,” the release said.
No higher likelihood of strokes linked to the Pfizer bivalent vaccine had been found by Pfizer/BioNTech, the Department of Veterans Affairs, the Vaccine Adverse Event Reporting System maintained by the CDC and the FDA, or other agencies that monitor reactions of vaccines, the news release said. No safety issues about strokes have been identified with the Moderna bivalent vaccine.
CNN, citing a CDC official, reported that about 550,000 seniors who got Pfizer bivalent boosters were tracked by the VSD, and 130 of them had strokes within 3 weeks of getting the shot. None of those 130 people died, CNN said. The official spoke on the condition of anonymity because they weren’t authorized to share the data.
The issue will be discussed at the January meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.
In a joint statement, Pfizer and BioNTech said: “Neither Pfizer and BioNTech nor the CDC or FDA have observed similar findings across numerous other monitoring systems in the U.S. and globally and there is no evidence to conclude that ischemic stroke is associated with the use of the companies’ COVID-19 vaccines.”
Bivalent boosters contain two strains of vaccine – one to protect against the original COVID-19 virus and another targeting Omicron subvariants.
A version of this article first appeared on WebMD.com.
who got the shot, the Centers for Disease Control and Prevention and the Food and Drug Administration said in a joint news release.
The release did not recommend people change their vaccine practices, saying the database finding probably did not represent a “true clinical risk.” The CDC said everybody, including people over 65, should stay up to date on their COVID vaccines, including the bivalent booster.
The news release said the Vaccine Safety Datalink (VSD), “a near real-time surveillance system,” raised a safety concern about the Pfizer/BioNTech booster.
“Rapid-response investigation of the signal in the VSD raised a question of whether people 65 and older who have received the Pfizer-BioNTech COVID-19 Vaccine, Bivalent were more likely to have an ischemic stroke in the 21 days following vaccination compared with days 22-44 following vaccination,” the news release said.
Ischemic strokes are blockages of blood to the brain, often caused by blood clots.
“Although the totality of the data currently suggests that it is very unlikely that the signal in VSD (Vaccine Safety Datalink) represents a true clinical risk, we believe it is important to share this information with the public, as we have in the past, when one of our safety monitoring systems detects a signal,” the release said.
No higher likelihood of strokes linked to the Pfizer bivalent vaccine had been found by Pfizer/BioNTech, the Department of Veterans Affairs, the Vaccine Adverse Event Reporting System maintained by the CDC and the FDA, or other agencies that monitor reactions of vaccines, the news release said. No safety issues about strokes have been identified with the Moderna bivalent vaccine.
CNN, citing a CDC official, reported that about 550,000 seniors who got Pfizer bivalent boosters were tracked by the VSD, and 130 of them had strokes within 3 weeks of getting the shot. None of those 130 people died, CNN said. The official spoke on the condition of anonymity because they weren’t authorized to share the data.
The issue will be discussed at the January meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.
In a joint statement, Pfizer and BioNTech said: “Neither Pfizer and BioNTech nor the CDC or FDA have observed similar findings across numerous other monitoring systems in the U.S. and globally and there is no evidence to conclude that ischemic stroke is associated with the use of the companies’ COVID-19 vaccines.”
Bivalent boosters contain two strains of vaccine – one to protect against the original COVID-19 virus and another targeting Omicron subvariants.
A version of this article first appeared on WebMD.com.
who got the shot, the Centers for Disease Control and Prevention and the Food and Drug Administration said in a joint news release.
The release did not recommend people change their vaccine practices, saying the database finding probably did not represent a “true clinical risk.” The CDC said everybody, including people over 65, should stay up to date on their COVID vaccines, including the bivalent booster.
The news release said the Vaccine Safety Datalink (VSD), “a near real-time surveillance system,” raised a safety concern about the Pfizer/BioNTech booster.
“Rapid-response investigation of the signal in the VSD raised a question of whether people 65 and older who have received the Pfizer-BioNTech COVID-19 Vaccine, Bivalent were more likely to have an ischemic stroke in the 21 days following vaccination compared with days 22-44 following vaccination,” the news release said.
Ischemic strokes are blockages of blood to the brain, often caused by blood clots.
“Although the totality of the data currently suggests that it is very unlikely that the signal in VSD (Vaccine Safety Datalink) represents a true clinical risk, we believe it is important to share this information with the public, as we have in the past, when one of our safety monitoring systems detects a signal,” the release said.
No higher likelihood of strokes linked to the Pfizer bivalent vaccine had been found by Pfizer/BioNTech, the Department of Veterans Affairs, the Vaccine Adverse Event Reporting System maintained by the CDC and the FDA, or other agencies that monitor reactions of vaccines, the news release said. No safety issues about strokes have been identified with the Moderna bivalent vaccine.
CNN, citing a CDC official, reported that about 550,000 seniors who got Pfizer bivalent boosters were tracked by the VSD, and 130 of them had strokes within 3 weeks of getting the shot. None of those 130 people died, CNN said. The official spoke on the condition of anonymity because they weren’t authorized to share the data.
The issue will be discussed at the January meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.
In a joint statement, Pfizer and BioNTech said: “Neither Pfizer and BioNTech nor the CDC or FDA have observed similar findings across numerous other monitoring systems in the U.S. and globally and there is no evidence to conclude that ischemic stroke is associated with the use of the companies’ COVID-19 vaccines.”
Bivalent boosters contain two strains of vaccine – one to protect against the original COVID-19 virus and another targeting Omicron subvariants.
A version of this article first appeared on WebMD.com.
Add this to the list of long COVID symptoms: Stigma
Most people with long COVID find they’re facing stigma due to their condition, according to a new report from researchers in the United Kingdom. In short: Relatives and friends may not believe they’re truly sick.
The U.K. team found that more than three-quarters of people studied had experienced stigma often or always.
In fact, 95% of people with long COVID faced at least one type of stigma at least sometimes, according to the study, published in November in the journal PLOS One.
Those conclusions had surprised the study’s lead researcher, Marija Pantelic, PhD, a public health lecturer at Brighton and Sussex Medical School, England.
“After years of working on HIV-related stigma, I was shocked to see how many people were turning a blind eye to and dismissing the difficulties experienced by people with long COVID,” Dr. Pantelic says. “It has also been clear to me from the start that this stigma is detrimental not just for people’s dignity, but also public health.”
Even some doctors argue that the growing attention paid to long COVID is excessive.
“It’s often normal to experience mild fatigue or weaknesses for weeks after being sick and inactive and not eating well. Calling these cases long COVID is the medicalization of modern life,” Marty Makary, MD, a surgeon and public policy researcher at Johns Hopkins University, Baltimore, wrote in a commentary in the Wall Street Journal.
Other doctors strongly disagree, including Alba Azola, MD, codirector of the Johns Hopkins Post-Acute COVID-19 Team and an expert in the stigma surrounding long COVID.
“Putting that spin on things, it’s just hurting people,” she says.
One example is people who cannot return to work.
“A lot of their family members tell me that they’re being lazy,” Dr. Azola says. “That’s part of the public stigma, that these are people just trying to get out of work.”
Some experts say the U.K. study represents a landmark.
“When you have data like this on long COVID stigma, it becomes more difficult to deny its existence or address it,” says Naomi Torres-Mackie, PhD, a clinical psychologist at Lenox Hill Hospital in New York. She also is head of research at the New York–based Mental Health Coalition, a group of experts working to end the stigma surrounding mental health.
She recalls her first patient with long COVID.
“She experienced the discomfort and pain itself, and then she had this crushing feeling that it wasn’t valid, or real. She felt very alone in it,” Dr. Torres-Mackie says.
Another one of her patients is working at her job from home but facing doubt about her condition from her employers.
“Every month, her medical doctor has to produce a letter confirming her medical condition,” Dr. Torres-Mackie says.
Taking part in the British stigma survey were 1,166 people, including 966 residents of the United Kingdom, with the average age of 48. Nearly 85% were female, and more than three-quarters were educated at the university level or higher.
Half of them said they had a clinical diagnosis of long COVID.
More than 60% of them said that at least some of the time, they were cautious about who they talked to about their condition. And fully 34% of those who did disclose their diagnosis said that they regretted having done so.
That’s a difficult experience for those with long COVID, says Leonard Jason, PhD, a professor of psychology at DePaul University in Chicago.
“It’s like they’re traumatized by the initial experience of being sick, and retraumatized by the response of others to them,” he says.
Unexplained illnesses are not well-regarded by the general public, Dr. Jason says.
He gave the example of multiple sclerosis. Before the 1980s, those with MS were considered to have a psychological illness, he says. “Then, in the 1980s, there were biomarkers that said, ‘Here’s the evidence.’ ”
The British study described three types of stigma stemming from the long COVID diagnosis of those questioned:
- Enacted stigma: People were directly treated unfairly because of their condition.
- Internalized stigma: People felt embarrassed by that condition.
- Anticipated stigma: People expected they would be treated poorly because of their diagnosis.
Dr. Azola calls the medical community a major problem when it comes to dealing with long COVID.
“What I see with my patients is medical trauma,” she says. They may have symptoms that send them to the emergency room, and then the tests come back negative. “Instead of tracking the patients’ symptoms, patients get told, ‘Everything looks good, you can go home, this is a panic attack,’ ” she says.
Some people go online to search for treatments, sometimes launching GoFundMe campaigns to raise money for unreliable treatments.
Long COVID patients may have gone through 5 to 10 doctors before they arrive for treatment with the Johns Hopkins Post-Acute COVID-19 Team. The clinic began in April 2020 remotely and in August of that year in person.
Today, the clinic staff spends an hour with a first-time long COVID patient, hearing their stories and helping relieve anxiety, Dr. Azola says.
The phenomenon of long COVID is similar to what patients have had with chronic fatigue syndrome, lupus, or fibromyalgia, where people have symptoms that are hard to explain, says Jennifer Chevinsky, MD, deputy public health officer for Riverside County, Calif.
“Stigma within medicine or health care is nothing new,” she says.
In Chicago, Dr. Jason notes that the federal government’s decision to invest hundreds of millions of dollars in long COVID research “shows the government is helping destigmatize it.”
Dr. Pantelic says she and her colleagues are continuing their research.
“We are interested in understanding the impacts of this stigma, and how to mitigate any adverse outcomes for patients and services,” she says.
A version of this article first appeared on WebMD.com.
Most people with long COVID find they’re facing stigma due to their condition, according to a new report from researchers in the United Kingdom. In short: Relatives and friends may not believe they’re truly sick.
The U.K. team found that more than three-quarters of people studied had experienced stigma often or always.
In fact, 95% of people with long COVID faced at least one type of stigma at least sometimes, according to the study, published in November in the journal PLOS One.
Those conclusions had surprised the study’s lead researcher, Marija Pantelic, PhD, a public health lecturer at Brighton and Sussex Medical School, England.
“After years of working on HIV-related stigma, I was shocked to see how many people were turning a blind eye to and dismissing the difficulties experienced by people with long COVID,” Dr. Pantelic says. “It has also been clear to me from the start that this stigma is detrimental not just for people’s dignity, but also public health.”
Even some doctors argue that the growing attention paid to long COVID is excessive.
“It’s often normal to experience mild fatigue or weaknesses for weeks after being sick and inactive and not eating well. Calling these cases long COVID is the medicalization of modern life,” Marty Makary, MD, a surgeon and public policy researcher at Johns Hopkins University, Baltimore, wrote in a commentary in the Wall Street Journal.
Other doctors strongly disagree, including Alba Azola, MD, codirector of the Johns Hopkins Post-Acute COVID-19 Team and an expert in the stigma surrounding long COVID.
“Putting that spin on things, it’s just hurting people,” she says.
One example is people who cannot return to work.
“A lot of their family members tell me that they’re being lazy,” Dr. Azola says. “That’s part of the public stigma, that these are people just trying to get out of work.”
Some experts say the U.K. study represents a landmark.
“When you have data like this on long COVID stigma, it becomes more difficult to deny its existence or address it,” says Naomi Torres-Mackie, PhD, a clinical psychologist at Lenox Hill Hospital in New York. She also is head of research at the New York–based Mental Health Coalition, a group of experts working to end the stigma surrounding mental health.
She recalls her first patient with long COVID.
“She experienced the discomfort and pain itself, and then she had this crushing feeling that it wasn’t valid, or real. She felt very alone in it,” Dr. Torres-Mackie says.
Another one of her patients is working at her job from home but facing doubt about her condition from her employers.
“Every month, her medical doctor has to produce a letter confirming her medical condition,” Dr. Torres-Mackie says.
Taking part in the British stigma survey were 1,166 people, including 966 residents of the United Kingdom, with the average age of 48. Nearly 85% were female, and more than three-quarters were educated at the university level or higher.
Half of them said they had a clinical diagnosis of long COVID.
More than 60% of them said that at least some of the time, they were cautious about who they talked to about their condition. And fully 34% of those who did disclose their diagnosis said that they regretted having done so.
That’s a difficult experience for those with long COVID, says Leonard Jason, PhD, a professor of psychology at DePaul University in Chicago.
“It’s like they’re traumatized by the initial experience of being sick, and retraumatized by the response of others to them,” he says.
Unexplained illnesses are not well-regarded by the general public, Dr. Jason says.
He gave the example of multiple sclerosis. Before the 1980s, those with MS were considered to have a psychological illness, he says. “Then, in the 1980s, there were biomarkers that said, ‘Here’s the evidence.’ ”
The British study described three types of stigma stemming from the long COVID diagnosis of those questioned:
- Enacted stigma: People were directly treated unfairly because of their condition.
- Internalized stigma: People felt embarrassed by that condition.
- Anticipated stigma: People expected they would be treated poorly because of their diagnosis.
Dr. Azola calls the medical community a major problem when it comes to dealing with long COVID.
“What I see with my patients is medical trauma,” she says. They may have symptoms that send them to the emergency room, and then the tests come back negative. “Instead of tracking the patients’ symptoms, patients get told, ‘Everything looks good, you can go home, this is a panic attack,’ ” she says.
Some people go online to search for treatments, sometimes launching GoFundMe campaigns to raise money for unreliable treatments.
Long COVID patients may have gone through 5 to 10 doctors before they arrive for treatment with the Johns Hopkins Post-Acute COVID-19 Team. The clinic began in April 2020 remotely and in August of that year in person.
Today, the clinic staff spends an hour with a first-time long COVID patient, hearing their stories and helping relieve anxiety, Dr. Azola says.
The phenomenon of long COVID is similar to what patients have had with chronic fatigue syndrome, lupus, or fibromyalgia, where people have symptoms that are hard to explain, says Jennifer Chevinsky, MD, deputy public health officer for Riverside County, Calif.
“Stigma within medicine or health care is nothing new,” she says.
In Chicago, Dr. Jason notes that the federal government’s decision to invest hundreds of millions of dollars in long COVID research “shows the government is helping destigmatize it.”
Dr. Pantelic says she and her colleagues are continuing their research.
“We are interested in understanding the impacts of this stigma, and how to mitigate any adverse outcomes for patients and services,” she says.
A version of this article first appeared on WebMD.com.
Most people with long COVID find they’re facing stigma due to their condition, according to a new report from researchers in the United Kingdom. In short: Relatives and friends may not believe they’re truly sick.
The U.K. team found that more than three-quarters of people studied had experienced stigma often or always.
In fact, 95% of people with long COVID faced at least one type of stigma at least sometimes, according to the study, published in November in the journal PLOS One.
Those conclusions had surprised the study’s lead researcher, Marija Pantelic, PhD, a public health lecturer at Brighton and Sussex Medical School, England.
“After years of working on HIV-related stigma, I was shocked to see how many people were turning a blind eye to and dismissing the difficulties experienced by people with long COVID,” Dr. Pantelic says. “It has also been clear to me from the start that this stigma is detrimental not just for people’s dignity, but also public health.”
Even some doctors argue that the growing attention paid to long COVID is excessive.
“It’s often normal to experience mild fatigue or weaknesses for weeks after being sick and inactive and not eating well. Calling these cases long COVID is the medicalization of modern life,” Marty Makary, MD, a surgeon and public policy researcher at Johns Hopkins University, Baltimore, wrote in a commentary in the Wall Street Journal.
Other doctors strongly disagree, including Alba Azola, MD, codirector of the Johns Hopkins Post-Acute COVID-19 Team and an expert in the stigma surrounding long COVID.
“Putting that spin on things, it’s just hurting people,” she says.
One example is people who cannot return to work.
“A lot of their family members tell me that they’re being lazy,” Dr. Azola says. “That’s part of the public stigma, that these are people just trying to get out of work.”
Some experts say the U.K. study represents a landmark.
“When you have data like this on long COVID stigma, it becomes more difficult to deny its existence or address it,” says Naomi Torres-Mackie, PhD, a clinical psychologist at Lenox Hill Hospital in New York. She also is head of research at the New York–based Mental Health Coalition, a group of experts working to end the stigma surrounding mental health.
She recalls her first patient with long COVID.
“She experienced the discomfort and pain itself, and then she had this crushing feeling that it wasn’t valid, or real. She felt very alone in it,” Dr. Torres-Mackie says.
Another one of her patients is working at her job from home but facing doubt about her condition from her employers.
“Every month, her medical doctor has to produce a letter confirming her medical condition,” Dr. Torres-Mackie says.
Taking part in the British stigma survey were 1,166 people, including 966 residents of the United Kingdom, with the average age of 48. Nearly 85% were female, and more than three-quarters were educated at the university level or higher.
Half of them said they had a clinical diagnosis of long COVID.
More than 60% of them said that at least some of the time, they were cautious about who they talked to about their condition. And fully 34% of those who did disclose their diagnosis said that they regretted having done so.
That’s a difficult experience for those with long COVID, says Leonard Jason, PhD, a professor of psychology at DePaul University in Chicago.
“It’s like they’re traumatized by the initial experience of being sick, and retraumatized by the response of others to them,” he says.
Unexplained illnesses are not well-regarded by the general public, Dr. Jason says.
He gave the example of multiple sclerosis. Before the 1980s, those with MS were considered to have a psychological illness, he says. “Then, in the 1980s, there were biomarkers that said, ‘Here’s the evidence.’ ”
The British study described three types of stigma stemming from the long COVID diagnosis of those questioned:
- Enacted stigma: People were directly treated unfairly because of their condition.
- Internalized stigma: People felt embarrassed by that condition.
- Anticipated stigma: People expected they would be treated poorly because of their diagnosis.
Dr. Azola calls the medical community a major problem when it comes to dealing with long COVID.
“What I see with my patients is medical trauma,” she says. They may have symptoms that send them to the emergency room, and then the tests come back negative. “Instead of tracking the patients’ symptoms, patients get told, ‘Everything looks good, you can go home, this is a panic attack,’ ” she says.
Some people go online to search for treatments, sometimes launching GoFundMe campaigns to raise money for unreliable treatments.
Long COVID patients may have gone through 5 to 10 doctors before they arrive for treatment with the Johns Hopkins Post-Acute COVID-19 Team. The clinic began in April 2020 remotely and in August of that year in person.
Today, the clinic staff spends an hour with a first-time long COVID patient, hearing their stories and helping relieve anxiety, Dr. Azola says.
The phenomenon of long COVID is similar to what patients have had with chronic fatigue syndrome, lupus, or fibromyalgia, where people have symptoms that are hard to explain, says Jennifer Chevinsky, MD, deputy public health officer for Riverside County, Calif.
“Stigma within medicine or health care is nothing new,” she says.
In Chicago, Dr. Jason notes that the federal government’s decision to invest hundreds of millions of dollars in long COVID research “shows the government is helping destigmatize it.”
Dr. Pantelic says she and her colleagues are continuing their research.
“We are interested in understanding the impacts of this stigma, and how to mitigate any adverse outcomes for patients and services,” she says.
A version of this article first appeared on WebMD.com.
PLOS ONE
Metformin monotherapy not always best start in type 2 diabetes
Metformin failure in people with type 2 diabetes is very common, particularly among those with high hemoglobin A1c levels at the time of diagnosis, new findings suggest.
An analysis of electronic health record data for more than 22,000 patients starting metformin at three U.S. clinical sites found that over 40% experienced metformin failure.
This was defined as either failure to achieve or maintain A1c less than 7% within 18 months or the use of additional glucose-lowering medications.
Other predictors that metformin use wouldn’t be successful included increasing age, male sex, and race/ethnicity. However, the latter ceased to be linked after adjustment for other clinical risk factors.
“Our study results suggest increased monitoring with potentially earlier treatment intensification to achieve glycemic control may be appropriate in patients with clinical parameters described in this paper,” Suzette J. Bielinski, PhD, and colleagues wrote.
“Further, these results call into question the ubiquitous use of metformin as the first-line therapy and suggest a more individualized approach may be needed to optimize therapy,” they added in their article, published online in the Journal of Clinical Endocrinology and Metabolism.
The study is also noteworthy in that it demonstrated the feasibility of using EHR data with a machine-learning approach to discover risk biomarkers, Dr. Bielinski, professor of epidemiology at the Mayo Clinic, Rochester, Minn., said in an interview.
“We wanted to repurpose clinical data to answer questions ... I think more studies using these types of techniques repurposing data meant for one thing could potentially impact care in other domains. ... If we can get the bang for the buck from all these data that we generate on people I just think it will improve health care and maybe save health care dollars.”
Baseline A1c strongest predictor of metformin failure
The investigators identified a total of 22,047 metformin initiators from three clinical primary care sites: the University of Mississippi’s Jackson centers, which serves a mostly African American population, the Mountain Park Health Center in Arizona, a seven-clinic federally qualified community health center in Phoenix that serves a mostly Latino population, and the Rochester Epidemiology Project, which includes the Mayo Clinic and serves a primarily White population.
Overall, a total of 43% (9,407) of patients met one of two criteria for metformin failure by 18 months. Among those, median time to failure on metformin was 3.9 months.
Unadjusted failure rates were higher among African Americans, Hispanics, and other racial groups, compared with non-Hispanic White patients.
However, the racial groups also differed by baseline characteristics. Mean A1c was 7.7% overall, 8.1% for the African American group, 7.9% for Asians, and 8.2% for Hispanics, compared with 7.6% for non-Hispanic Whites.
Of 150 clinical factors examined, higher A1c was the strongest predictor of metformin failure, with a rapid increase in risk appearing between 7.5% and 8.0%.
“The slope is steep. It gives us some clinical guidance,” Dr. Bielinski said.
Other variables positively correlated with metformin failure included “diabetes with complications,” increased age, and higher levels of potassium, triglycerides, heart rate, and mean cell hemoglobin.
Factors inversely correlated with metformin failure were having received screening for other suspected conditions and medical examination/evaluation, and lower levels of sodium, albumin, and HDL cholesterol.
Three variables – body mass index, LDL cholesterol, and creatinine – had a U-shaped relationship with metformin failure, so that both high and low values were associated with increased risk.
“The racial/ethnic differences disappeared once other clinical factors were considered suggesting that the biological response to metformin is similar regardless of race/ethnicity,” Dr. Bielinski and colleagues wrote.
They also noted that the abnormal lab results which correlated with metformin failure “likely represent biomarkers for chronic illnesses. However, the effect size for lab abnormalities was small compared with that of baseline A1c.”
Dr. Bielinski urged caution in interpreting the findings. “Electronic health records data have limitations. We have evidence that these people were prescribed metformin. We have no idea if they took it. ... I would really be hesitant to be too strong in making clinical recommendations.”
However, she said that the data are “suggestive to say maybe we need to have some kind of threshold where if someone comes in with an A1c of X that they go on dual therapy right away. I think this is opening the door to that.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Metformin failure in people with type 2 diabetes is very common, particularly among those with high hemoglobin A1c levels at the time of diagnosis, new findings suggest.
An analysis of electronic health record data for more than 22,000 patients starting metformin at three U.S. clinical sites found that over 40% experienced metformin failure.
This was defined as either failure to achieve or maintain A1c less than 7% within 18 months or the use of additional glucose-lowering medications.
Other predictors that metformin use wouldn’t be successful included increasing age, male sex, and race/ethnicity. However, the latter ceased to be linked after adjustment for other clinical risk factors.
“Our study results suggest increased monitoring with potentially earlier treatment intensification to achieve glycemic control may be appropriate in patients with clinical parameters described in this paper,” Suzette J. Bielinski, PhD, and colleagues wrote.
“Further, these results call into question the ubiquitous use of metformin as the first-line therapy and suggest a more individualized approach may be needed to optimize therapy,” they added in their article, published online in the Journal of Clinical Endocrinology and Metabolism.
The study is also noteworthy in that it demonstrated the feasibility of using EHR data with a machine-learning approach to discover risk biomarkers, Dr. Bielinski, professor of epidemiology at the Mayo Clinic, Rochester, Minn., said in an interview.
“We wanted to repurpose clinical data to answer questions ... I think more studies using these types of techniques repurposing data meant for one thing could potentially impact care in other domains. ... If we can get the bang for the buck from all these data that we generate on people I just think it will improve health care and maybe save health care dollars.”
Baseline A1c strongest predictor of metformin failure
The investigators identified a total of 22,047 metformin initiators from three clinical primary care sites: the University of Mississippi’s Jackson centers, which serves a mostly African American population, the Mountain Park Health Center in Arizona, a seven-clinic federally qualified community health center in Phoenix that serves a mostly Latino population, and the Rochester Epidemiology Project, which includes the Mayo Clinic and serves a primarily White population.
Overall, a total of 43% (9,407) of patients met one of two criteria for metformin failure by 18 months. Among those, median time to failure on metformin was 3.9 months.
Unadjusted failure rates were higher among African Americans, Hispanics, and other racial groups, compared with non-Hispanic White patients.
However, the racial groups also differed by baseline characteristics. Mean A1c was 7.7% overall, 8.1% for the African American group, 7.9% for Asians, and 8.2% for Hispanics, compared with 7.6% for non-Hispanic Whites.
Of 150 clinical factors examined, higher A1c was the strongest predictor of metformin failure, with a rapid increase in risk appearing between 7.5% and 8.0%.
“The slope is steep. It gives us some clinical guidance,” Dr. Bielinski said.
Other variables positively correlated with metformin failure included “diabetes with complications,” increased age, and higher levels of potassium, triglycerides, heart rate, and mean cell hemoglobin.
Factors inversely correlated with metformin failure were having received screening for other suspected conditions and medical examination/evaluation, and lower levels of sodium, albumin, and HDL cholesterol.
Three variables – body mass index, LDL cholesterol, and creatinine – had a U-shaped relationship with metformin failure, so that both high and low values were associated with increased risk.
“The racial/ethnic differences disappeared once other clinical factors were considered suggesting that the biological response to metformin is similar regardless of race/ethnicity,” Dr. Bielinski and colleagues wrote.
They also noted that the abnormal lab results which correlated with metformin failure “likely represent biomarkers for chronic illnesses. However, the effect size for lab abnormalities was small compared with that of baseline A1c.”
Dr. Bielinski urged caution in interpreting the findings. “Electronic health records data have limitations. We have evidence that these people were prescribed metformin. We have no idea if they took it. ... I would really be hesitant to be too strong in making clinical recommendations.”
However, she said that the data are “suggestive to say maybe we need to have some kind of threshold where if someone comes in with an A1c of X that they go on dual therapy right away. I think this is opening the door to that.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Metformin failure in people with type 2 diabetes is very common, particularly among those with high hemoglobin A1c levels at the time of diagnosis, new findings suggest.
An analysis of electronic health record data for more than 22,000 patients starting metformin at three U.S. clinical sites found that over 40% experienced metformin failure.
This was defined as either failure to achieve or maintain A1c less than 7% within 18 months or the use of additional glucose-lowering medications.
Other predictors that metformin use wouldn’t be successful included increasing age, male sex, and race/ethnicity. However, the latter ceased to be linked after adjustment for other clinical risk factors.
“Our study results suggest increased monitoring with potentially earlier treatment intensification to achieve glycemic control may be appropriate in patients with clinical parameters described in this paper,” Suzette J. Bielinski, PhD, and colleagues wrote.
“Further, these results call into question the ubiquitous use of metformin as the first-line therapy and suggest a more individualized approach may be needed to optimize therapy,” they added in their article, published online in the Journal of Clinical Endocrinology and Metabolism.
The study is also noteworthy in that it demonstrated the feasibility of using EHR data with a machine-learning approach to discover risk biomarkers, Dr. Bielinski, professor of epidemiology at the Mayo Clinic, Rochester, Minn., said in an interview.
“We wanted to repurpose clinical data to answer questions ... I think more studies using these types of techniques repurposing data meant for one thing could potentially impact care in other domains. ... If we can get the bang for the buck from all these data that we generate on people I just think it will improve health care and maybe save health care dollars.”
Baseline A1c strongest predictor of metformin failure
The investigators identified a total of 22,047 metformin initiators from three clinical primary care sites: the University of Mississippi’s Jackson centers, which serves a mostly African American population, the Mountain Park Health Center in Arizona, a seven-clinic federally qualified community health center in Phoenix that serves a mostly Latino population, and the Rochester Epidemiology Project, which includes the Mayo Clinic and serves a primarily White population.
Overall, a total of 43% (9,407) of patients met one of two criteria for metformin failure by 18 months. Among those, median time to failure on metformin was 3.9 months.
Unadjusted failure rates were higher among African Americans, Hispanics, and other racial groups, compared with non-Hispanic White patients.
However, the racial groups also differed by baseline characteristics. Mean A1c was 7.7% overall, 8.1% for the African American group, 7.9% for Asians, and 8.2% for Hispanics, compared with 7.6% for non-Hispanic Whites.
Of 150 clinical factors examined, higher A1c was the strongest predictor of metformin failure, with a rapid increase in risk appearing between 7.5% and 8.0%.
“The slope is steep. It gives us some clinical guidance,” Dr. Bielinski said.
Other variables positively correlated with metformin failure included “diabetes with complications,” increased age, and higher levels of potassium, triglycerides, heart rate, and mean cell hemoglobin.
Factors inversely correlated with metformin failure were having received screening for other suspected conditions and medical examination/evaluation, and lower levels of sodium, albumin, and HDL cholesterol.
Three variables – body mass index, LDL cholesterol, and creatinine – had a U-shaped relationship with metformin failure, so that both high and low values were associated with increased risk.
“The racial/ethnic differences disappeared once other clinical factors were considered suggesting that the biological response to metformin is similar regardless of race/ethnicity,” Dr. Bielinski and colleagues wrote.
They also noted that the abnormal lab results which correlated with metformin failure “likely represent biomarkers for chronic illnesses. However, the effect size for lab abnormalities was small compared with that of baseline A1c.”
Dr. Bielinski urged caution in interpreting the findings. “Electronic health records data have limitations. We have evidence that these people were prescribed metformin. We have no idea if they took it. ... I would really be hesitant to be too strong in making clinical recommendations.”
However, she said that the data are “suggestive to say maybe we need to have some kind of threshold where if someone comes in with an A1c of X that they go on dual therapy right away. I think this is opening the door to that.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Oramed oral insulin fails to meet goal in type 2 diabetes
Oramed Pharmaceuticals’ investigational oral insulin failed to achieve its primary endpoint in a phase 3 trial, according to top-line results announced by the company.
“Therefore, Oramed expects to discontinue its oral insulin clinical activities for [type 2 diabetes],” according to a company statement.
, ORA-D-013-1, comparing the efficacy of the insulin product ORMD-0801 to placebo in 710 people with type 2 diabetes with inadequate glycemic control on two or three oral glucose-lowering agents.
The participants were randomized 2:2:1:1 into ORMD-0801 dosed at 8 mg once or twice daily, or placebo dosed once or twice daily. They completed a 21-day screening period, followed by a 26-week double-blind treatment period.
The product didn’t achieve the primary endpoint comparing reduction in hemoglobin A1c from baseline to 26 weeks, or the secondary endpoint of mean change in fasting plasma glucose at 26 weeks. There were no serious adverse events.
Oramed Pharmaceuticals specializes in developing oral delivery formulations of drugs currently delivered via injection. The company has offices in the United States and Israel.
Oramed CEO Nadav Kidron commented in the statement, “Today’s outcome is very disappointing, given the positive results from prior trials. Once full data from the studies are available, we expect to share relevant learnings and future plans. We thank all the patients, families, and health care professionals who participated in the trial.”
Insulin manufacturer Novo Nordisk had also been developing an oral insulin product. Successful phase 2a results were presented at the American Diabetes Association’s 2017 Scientific Sessions and full phase 2 feasibility results were published in Lancet Diabetes & Endocrinology in 2019.
However, Novo Nordisk, which manufactures the oral glucagon-like peptide-1 receptor agonist semaglutide (Rybelsus), subsequently discontinued development of their oral insulin product. According to a statement, “Initial results raised questions about truly addressing patients’ unmet needs with insulin therapy. Therefore, we discontinued this work to focus on projects that could in fact improve cardiometabolic outcomes for people living with diabetes.”
A version of this article first appeared on Medscape.com.
Oramed Pharmaceuticals’ investigational oral insulin failed to achieve its primary endpoint in a phase 3 trial, according to top-line results announced by the company.
“Therefore, Oramed expects to discontinue its oral insulin clinical activities for [type 2 diabetes],” according to a company statement.
, ORA-D-013-1, comparing the efficacy of the insulin product ORMD-0801 to placebo in 710 people with type 2 diabetes with inadequate glycemic control on two or three oral glucose-lowering agents.
The participants were randomized 2:2:1:1 into ORMD-0801 dosed at 8 mg once or twice daily, or placebo dosed once or twice daily. They completed a 21-day screening period, followed by a 26-week double-blind treatment period.
The product didn’t achieve the primary endpoint comparing reduction in hemoglobin A1c from baseline to 26 weeks, or the secondary endpoint of mean change in fasting plasma glucose at 26 weeks. There were no serious adverse events.
Oramed Pharmaceuticals specializes in developing oral delivery formulations of drugs currently delivered via injection. The company has offices in the United States and Israel.
Oramed CEO Nadav Kidron commented in the statement, “Today’s outcome is very disappointing, given the positive results from prior trials. Once full data from the studies are available, we expect to share relevant learnings and future plans. We thank all the patients, families, and health care professionals who participated in the trial.”
Insulin manufacturer Novo Nordisk had also been developing an oral insulin product. Successful phase 2a results were presented at the American Diabetes Association’s 2017 Scientific Sessions and full phase 2 feasibility results were published in Lancet Diabetes & Endocrinology in 2019.
However, Novo Nordisk, which manufactures the oral glucagon-like peptide-1 receptor agonist semaglutide (Rybelsus), subsequently discontinued development of their oral insulin product. According to a statement, “Initial results raised questions about truly addressing patients’ unmet needs with insulin therapy. Therefore, we discontinued this work to focus on projects that could in fact improve cardiometabolic outcomes for people living with diabetes.”
A version of this article first appeared on Medscape.com.
Oramed Pharmaceuticals’ investigational oral insulin failed to achieve its primary endpoint in a phase 3 trial, according to top-line results announced by the company.
“Therefore, Oramed expects to discontinue its oral insulin clinical activities for [type 2 diabetes],” according to a company statement.
, ORA-D-013-1, comparing the efficacy of the insulin product ORMD-0801 to placebo in 710 people with type 2 diabetes with inadequate glycemic control on two or three oral glucose-lowering agents.
The participants were randomized 2:2:1:1 into ORMD-0801 dosed at 8 mg once or twice daily, or placebo dosed once or twice daily. They completed a 21-day screening period, followed by a 26-week double-blind treatment period.
The product didn’t achieve the primary endpoint comparing reduction in hemoglobin A1c from baseline to 26 weeks, or the secondary endpoint of mean change in fasting plasma glucose at 26 weeks. There were no serious adverse events.
Oramed Pharmaceuticals specializes in developing oral delivery formulations of drugs currently delivered via injection. The company has offices in the United States and Israel.
Oramed CEO Nadav Kidron commented in the statement, “Today’s outcome is very disappointing, given the positive results from prior trials. Once full data from the studies are available, we expect to share relevant learnings and future plans. We thank all the patients, families, and health care professionals who participated in the trial.”
Insulin manufacturer Novo Nordisk had also been developing an oral insulin product. Successful phase 2a results were presented at the American Diabetes Association’s 2017 Scientific Sessions and full phase 2 feasibility results were published in Lancet Diabetes & Endocrinology in 2019.
However, Novo Nordisk, which manufactures the oral glucagon-like peptide-1 receptor agonist semaglutide (Rybelsus), subsequently discontinued development of their oral insulin product. According to a statement, “Initial results raised questions about truly addressing patients’ unmet needs with insulin therapy. Therefore, we discontinued this work to focus on projects that could in fact improve cardiometabolic outcomes for people living with diabetes.”
A version of this article first appeared on Medscape.com.
Which treatments improve long-term outcomes of critical COVID illness?
, according to new data.
However, survival wasn’t improved with therapeutic anticoagulation, convalescent plasma, or lopinavir-ritonavir, and survival was worsened with hydroxychloroquine.
“After critically ill patients leave the hospital, there’s a high risk of readmission, death after discharge, or exacerbations of chronic illness,” study author Patrick Lawler, MD, a clinician-scientist at the Peter Munk Cardiac Centre at University Health Network and an assistant professor of medicine at the University of Toronto, said in an interview.
“When looking at the impact of treatment, we don’t want to improve short-term outcomes yet worsen long-term disability,” he said. “That long-term, 6-month horizon is what matters most to patients.”
The study was published online in JAMA.
Investigating treatments
The investigators analyzed data from an ongoing platform trial called Randomized Embedded Multifactorial Adaptive Platform for Community Acquired Pneumonia (REMAP-CAP). The trial is evaluating treatments for patients with severe pneumonia in pandemic and nonpandemic settings.
In the trial, patients are randomly assigned to receive one or more interventions within the following six treatment domains: immune modulators, convalescent plasma, antiplatelet therapy, anticoagulation, antivirals, and corticosteroids. The trial’s primary outcome for patients with COVID-19 is hospital survival and organ support–free days up to 21 days. Researchers previously observed improvement after treatment with IL-6 receptor antagonists (which are immune modulators).
For this study, the research team analyzed data for 4,869 critically ill adult patients with COVID-19 who were enrolled between March 2020 and June 2021 at 197 sites in 14 countries. A 180-day follow-up was completed in March 2022. The critically ill patients had been admitted to an intensive care unit and had received respiratory or cardiovascular organ support.
The researchers examined survival through day 180. A hazard ratio of less than 1 represented improved survival, and an HR greater than 1 represented harm. Futility was represented by a relative improvement in outcome of less than 20%, which was shown by an HR greater than 0.83.
Among the 4,869 patients, 4,107 patients had a known mortality status, and 2,590 were alive at day 180. Among the 1,517 patients who died by day 180, 91 deaths (6%) occurred between hospital discharge and day 180.
Overall, use of IL-6 receptor antagonists (either tocilizumab or sarilumab) had a greater than 99.9% probability of improving 6-month survival, and use of antiplatelet agents (aspirin or a P2Y12 inhibitor such as clopidogrel, prasugrel, or ticagrelor) had a 95% probability of improving 6-month survival, compared with control therapies.
In contrast, long-term survival wasn’t improved with therapeutic anticoagulation (11.5%), convalescent plasma (54.7%), or lopinavir-ritonavir (31.9%). The probability of trial-defined statistical futility was high for anticoagulation (99.9%), convalescent plasma (99.2%), and lopinavir-ritonavir (96.6%).
Long-term survival was worsened with hydroxychloroquine, with a posterior probability of harm of 96.9%. In addition, the combination of lopinavir-ritonavir and hydroxychloroquine had a 96.8% probability of harm.
Corticosteroids didn’t improve long-term outcomes, although enrollment in the treatment domain was terminated early in response to external evidence. The probability of improving 6-month survival ranged from 57.1% to 61.6% for various hydrocortisone dosing strategies.
Consistent treatment effects
When considered along with previously reported short-term results from the REMAP-CAP trial, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.
“We were very relieved to see that treatments with a favorable benefit for patients in the short term also appeared to be beneficial through 180 days,” said Dr. Lawler. “This supports the current clinical practice strategy in providing treatment to critically ill patients with COVID-19.”
In a subgroup analysis of 989 patients, health-related quality of life at day 180 was higher among those treated with IL-6 receptor antagonists and antiplatelet agents. The average quality-of-life score for the lopinavir-ritonavir group was lower than for control patients.
Among 720 survivors, 273 patients (37.9%) had moderate, severe, or complete disability at day 180. IL-6 receptor antagonists had a 92.6% probability of reducing disability, and anakinra (an IL-1 receptor antagonist) had a 90.8% probability of reducing disability. However, lopinavir-ritonavir had a 91.7% probability of worsening disability.
The REMAP-CAP trial investigators will continue to assess treatment domains and long-term outcomes among COVID-19 patients. They will evaluate additional data regarding disability, quality of life, and long-COVID outcomes.
“Reassuring” results
Commenting on the study, Angela Cheung, MD, PhD, a professor of medicine at the University of Toronto and senior scientist at the Toronto General Research Institute, said, “It is important to look at the longer-term effects of these therapies, as sometimes we may improve things in the short term, but that may not translate to longer-term gains. Historically, most trials conducted in this patient population assess only short outcomes, such as organ failure or 28-day mortality.”
Dr. Cheung, who wasn’t involved with this study, serves as the co-lead for the Canadian COVID-19 Prospective Cohort Study (CANCOV) and the Recovering From COVID-19 Lingering Symptoms Adaptive Integrative Medicine Trial (RECLAIM). These studies are also analyzing long-term outcomes among COVID-19 patients.
“It is reassuring to see that the 6-month outcomes are consistent with the short-term outcomes,” she said. “This study will help guide critical care medicine physicians in their treatment of critically ill patients with COVID-19.”
The study was supported by numerous grants and funds, including the Canadian Institute of Health Research COVID-19 Rapid Research Funding. Amgen and Eisai also provided funding. Dr. Lawler received grants from Canadian Institutes for Health Research and the Heart and Stroke Foundation of Canada during the conduct of the study and personal fees from Novartis, CorEvitas, Partners Healthcare, and the American College of Cardiology outside the submitted work. Dr. Cheung has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, according to new data.
However, survival wasn’t improved with therapeutic anticoagulation, convalescent plasma, or lopinavir-ritonavir, and survival was worsened with hydroxychloroquine.
“After critically ill patients leave the hospital, there’s a high risk of readmission, death after discharge, or exacerbations of chronic illness,” study author Patrick Lawler, MD, a clinician-scientist at the Peter Munk Cardiac Centre at University Health Network and an assistant professor of medicine at the University of Toronto, said in an interview.
“When looking at the impact of treatment, we don’t want to improve short-term outcomes yet worsen long-term disability,” he said. “That long-term, 6-month horizon is what matters most to patients.”
The study was published online in JAMA.
Investigating treatments
The investigators analyzed data from an ongoing platform trial called Randomized Embedded Multifactorial Adaptive Platform for Community Acquired Pneumonia (REMAP-CAP). The trial is evaluating treatments for patients with severe pneumonia in pandemic and nonpandemic settings.
In the trial, patients are randomly assigned to receive one or more interventions within the following six treatment domains: immune modulators, convalescent plasma, antiplatelet therapy, anticoagulation, antivirals, and corticosteroids. The trial’s primary outcome for patients with COVID-19 is hospital survival and organ support–free days up to 21 days. Researchers previously observed improvement after treatment with IL-6 receptor antagonists (which are immune modulators).
For this study, the research team analyzed data for 4,869 critically ill adult patients with COVID-19 who were enrolled between March 2020 and June 2021 at 197 sites in 14 countries. A 180-day follow-up was completed in March 2022. The critically ill patients had been admitted to an intensive care unit and had received respiratory or cardiovascular organ support.
The researchers examined survival through day 180. A hazard ratio of less than 1 represented improved survival, and an HR greater than 1 represented harm. Futility was represented by a relative improvement in outcome of less than 20%, which was shown by an HR greater than 0.83.
Among the 4,869 patients, 4,107 patients had a known mortality status, and 2,590 were alive at day 180. Among the 1,517 patients who died by day 180, 91 deaths (6%) occurred between hospital discharge and day 180.
Overall, use of IL-6 receptor antagonists (either tocilizumab or sarilumab) had a greater than 99.9% probability of improving 6-month survival, and use of antiplatelet agents (aspirin or a P2Y12 inhibitor such as clopidogrel, prasugrel, or ticagrelor) had a 95% probability of improving 6-month survival, compared with control therapies.
In contrast, long-term survival wasn’t improved with therapeutic anticoagulation (11.5%), convalescent plasma (54.7%), or lopinavir-ritonavir (31.9%). The probability of trial-defined statistical futility was high for anticoagulation (99.9%), convalescent plasma (99.2%), and lopinavir-ritonavir (96.6%).
Long-term survival was worsened with hydroxychloroquine, with a posterior probability of harm of 96.9%. In addition, the combination of lopinavir-ritonavir and hydroxychloroquine had a 96.8% probability of harm.
Corticosteroids didn’t improve long-term outcomes, although enrollment in the treatment domain was terminated early in response to external evidence. The probability of improving 6-month survival ranged from 57.1% to 61.6% for various hydrocortisone dosing strategies.
Consistent treatment effects
When considered along with previously reported short-term results from the REMAP-CAP trial, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.
“We were very relieved to see that treatments with a favorable benefit for patients in the short term also appeared to be beneficial through 180 days,” said Dr. Lawler. “This supports the current clinical practice strategy in providing treatment to critically ill patients with COVID-19.”
In a subgroup analysis of 989 patients, health-related quality of life at day 180 was higher among those treated with IL-6 receptor antagonists and antiplatelet agents. The average quality-of-life score for the lopinavir-ritonavir group was lower than for control patients.
Among 720 survivors, 273 patients (37.9%) had moderate, severe, or complete disability at day 180. IL-6 receptor antagonists had a 92.6% probability of reducing disability, and anakinra (an IL-1 receptor antagonist) had a 90.8% probability of reducing disability. However, lopinavir-ritonavir had a 91.7% probability of worsening disability.
The REMAP-CAP trial investigators will continue to assess treatment domains and long-term outcomes among COVID-19 patients. They will evaluate additional data regarding disability, quality of life, and long-COVID outcomes.
“Reassuring” results
Commenting on the study, Angela Cheung, MD, PhD, a professor of medicine at the University of Toronto and senior scientist at the Toronto General Research Institute, said, “It is important to look at the longer-term effects of these therapies, as sometimes we may improve things in the short term, but that may not translate to longer-term gains. Historically, most trials conducted in this patient population assess only short outcomes, such as organ failure or 28-day mortality.”
Dr. Cheung, who wasn’t involved with this study, serves as the co-lead for the Canadian COVID-19 Prospective Cohort Study (CANCOV) and the Recovering From COVID-19 Lingering Symptoms Adaptive Integrative Medicine Trial (RECLAIM). These studies are also analyzing long-term outcomes among COVID-19 patients.
“It is reassuring to see that the 6-month outcomes are consistent with the short-term outcomes,” she said. “This study will help guide critical care medicine physicians in their treatment of critically ill patients with COVID-19.”
The study was supported by numerous grants and funds, including the Canadian Institute of Health Research COVID-19 Rapid Research Funding. Amgen and Eisai also provided funding. Dr. Lawler received grants from Canadian Institutes for Health Research and the Heart and Stroke Foundation of Canada during the conduct of the study and personal fees from Novartis, CorEvitas, Partners Healthcare, and the American College of Cardiology outside the submitted work. Dr. Cheung has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, according to new data.
However, survival wasn’t improved with therapeutic anticoagulation, convalescent plasma, or lopinavir-ritonavir, and survival was worsened with hydroxychloroquine.
“After critically ill patients leave the hospital, there’s a high risk of readmission, death after discharge, or exacerbations of chronic illness,” study author Patrick Lawler, MD, a clinician-scientist at the Peter Munk Cardiac Centre at University Health Network and an assistant professor of medicine at the University of Toronto, said in an interview.
“When looking at the impact of treatment, we don’t want to improve short-term outcomes yet worsen long-term disability,” he said. “That long-term, 6-month horizon is what matters most to patients.”
The study was published online in JAMA.
Investigating treatments
The investigators analyzed data from an ongoing platform trial called Randomized Embedded Multifactorial Adaptive Platform for Community Acquired Pneumonia (REMAP-CAP). The trial is evaluating treatments for patients with severe pneumonia in pandemic and nonpandemic settings.
In the trial, patients are randomly assigned to receive one or more interventions within the following six treatment domains: immune modulators, convalescent plasma, antiplatelet therapy, anticoagulation, antivirals, and corticosteroids. The trial’s primary outcome for patients with COVID-19 is hospital survival and organ support–free days up to 21 days. Researchers previously observed improvement after treatment with IL-6 receptor antagonists (which are immune modulators).
For this study, the research team analyzed data for 4,869 critically ill adult patients with COVID-19 who were enrolled between March 2020 and June 2021 at 197 sites in 14 countries. A 180-day follow-up was completed in March 2022. The critically ill patients had been admitted to an intensive care unit and had received respiratory or cardiovascular organ support.
The researchers examined survival through day 180. A hazard ratio of less than 1 represented improved survival, and an HR greater than 1 represented harm. Futility was represented by a relative improvement in outcome of less than 20%, which was shown by an HR greater than 0.83.
Among the 4,869 patients, 4,107 patients had a known mortality status, and 2,590 were alive at day 180. Among the 1,517 patients who died by day 180, 91 deaths (6%) occurred between hospital discharge and day 180.
Overall, use of IL-6 receptor antagonists (either tocilizumab or sarilumab) had a greater than 99.9% probability of improving 6-month survival, and use of antiplatelet agents (aspirin or a P2Y12 inhibitor such as clopidogrel, prasugrel, or ticagrelor) had a 95% probability of improving 6-month survival, compared with control therapies.
In contrast, long-term survival wasn’t improved with therapeutic anticoagulation (11.5%), convalescent plasma (54.7%), or lopinavir-ritonavir (31.9%). The probability of trial-defined statistical futility was high for anticoagulation (99.9%), convalescent plasma (99.2%), and lopinavir-ritonavir (96.6%).
Long-term survival was worsened with hydroxychloroquine, with a posterior probability of harm of 96.9%. In addition, the combination of lopinavir-ritonavir and hydroxychloroquine had a 96.8% probability of harm.
Corticosteroids didn’t improve long-term outcomes, although enrollment in the treatment domain was terminated early in response to external evidence. The probability of improving 6-month survival ranged from 57.1% to 61.6% for various hydrocortisone dosing strategies.
Consistent treatment effects
When considered along with previously reported short-term results from the REMAP-CAP trial, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.
“We were very relieved to see that treatments with a favorable benefit for patients in the short term also appeared to be beneficial through 180 days,” said Dr. Lawler. “This supports the current clinical practice strategy in providing treatment to critically ill patients with COVID-19.”
In a subgroup analysis of 989 patients, health-related quality of life at day 180 was higher among those treated with IL-6 receptor antagonists and antiplatelet agents. The average quality-of-life score for the lopinavir-ritonavir group was lower than for control patients.
Among 720 survivors, 273 patients (37.9%) had moderate, severe, or complete disability at day 180. IL-6 receptor antagonists had a 92.6% probability of reducing disability, and anakinra (an IL-1 receptor antagonist) had a 90.8% probability of reducing disability. However, lopinavir-ritonavir had a 91.7% probability of worsening disability.
The REMAP-CAP trial investigators will continue to assess treatment domains and long-term outcomes among COVID-19 patients. They will evaluate additional data regarding disability, quality of life, and long-COVID outcomes.
“Reassuring” results
Commenting on the study, Angela Cheung, MD, PhD, a professor of medicine at the University of Toronto and senior scientist at the Toronto General Research Institute, said, “It is important to look at the longer-term effects of these therapies, as sometimes we may improve things in the short term, but that may not translate to longer-term gains. Historically, most trials conducted in this patient population assess only short outcomes, such as organ failure or 28-day mortality.”
Dr. Cheung, who wasn’t involved with this study, serves as the co-lead for the Canadian COVID-19 Prospective Cohort Study (CANCOV) and the Recovering From COVID-19 Lingering Symptoms Adaptive Integrative Medicine Trial (RECLAIM). These studies are also analyzing long-term outcomes among COVID-19 patients.
“It is reassuring to see that the 6-month outcomes are consistent with the short-term outcomes,” she said. “This study will help guide critical care medicine physicians in their treatment of critically ill patients with COVID-19.”
The study was supported by numerous grants and funds, including the Canadian Institute of Health Research COVID-19 Rapid Research Funding. Amgen and Eisai also provided funding. Dr. Lawler received grants from Canadian Institutes for Health Research and the Heart and Stroke Foundation of Canada during the conduct of the study and personal fees from Novartis, CorEvitas, Partners Healthcare, and the American College of Cardiology outside the submitted work. Dr. Cheung has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA