Clinical Endocrinology News

CHICAGO – Health insurance should cover treatment for infertility caused by gender-affirming medical interventions, the American Medical Association said June 13 at its House of Delegates meeting.

Speaking on behalf of the Medical Student Section, Justin Magrath, of Louisiana, said, “We as a section feel that these interventions should be considered as additional causes of iatrogenic infertility and be covered by insurance.”

Iatrogenic infertility is infertility caused by surgery, radiotherapy, chemotherapy, or other medically necessary treatment. The AMA voted June 13 to support including the phrase, “impaired fertility as a consequence of gender-affirming hormone therapy and gender-affirming surgery,” in that definition.

The AMA also supports access to fertility preservation services for people who undergo those treatments.

“I’ve had many friends who went through transitions and gender-affirming care and had no idea that these options were available and others who did know they were available but they were so expensive that they couldn’t access them,” said emergency medicine resident Sophia Spadafore, MD, delegate for the Resident and Fellow Section. “So while people might be able to access gender-affirming care, sometimes they have to make the decision between future fertility and having children and accessing this kind of lifesaving care that we support.”

The AMA already had policies that support insurance coverage of treatments for gender dysphoria and the right to seek fertility preservation services for people who undergo gender-affirming hormone therapy or surgery, but until this week, it had not addressed insurance coverage for preserving fertility in those cases.

“The transgender population already faces many barriers to care, such as provider discrimination, legal concerns, financial burden, and emotional cost,” Mr. Magrath said during a reference committee hearing on June 11. “We as a section ask our organization to continue to serve as an ally, providing equitable care for diverse populations and expanding coverage for medically necessary treatments.”

“I am a gender surgeon, so this is pretty important to me,” said Sean Figy, MD, of Nebraska, a delegate for the American Society for Reconstructive Microsurgery.

The original resolution included the words “medically necessary” when referring to gender-affirming treatments, and Dr. Figy expressed hesitancy about those words. An amendment removed them.

“I’ve seen that phrase weaponized against gender-nonconforming patients,” he said.

Ophthalmologist Charles Hickey, MD, of the Ohio delegation, spoke in favor of referral or of waiting to adopt the resolution.

“I think the different amendments being discussed here are evidence that this needs a more thorough and careful treatment than we can do at this point right now,” he said.

A version of this article first appeared on Medscape.com.

CHICAGO – Health insurance should cover treatment for infertility caused by gender-affirming medical interventions, the American Medical Association said June 13 at its House of Delegates meeting.

Speaking on behalf of the Medical Student Section, Justin Magrath, of Louisiana, said, “We as a section feel that these interventions should be considered as additional causes of iatrogenic infertility and be covered by insurance.”

Iatrogenic infertility is infertility caused by surgery, radiotherapy, chemotherapy, or other medically necessary treatment. The AMA voted June 13 to support including the phrase, “impaired fertility as a consequence of gender-affirming hormone therapy and gender-affirming surgery,” in that definition.

The AMA also supports access to fertility preservation services for people who undergo those treatments.

“I’ve had many friends who went through transitions and gender-affirming care and had no idea that these options were available and others who did know they were available but they were so expensive that they couldn’t access them,” said emergency medicine resident Sophia Spadafore, MD, delegate for the Resident and Fellow Section. “So while people might be able to access gender-affirming care, sometimes they have to make the decision between future fertility and having children and accessing this kind of lifesaving care that we support.”

The AMA already had policies that support insurance coverage of treatments for gender dysphoria and the right to seek fertility preservation services for people who undergo gender-affirming hormone therapy or surgery, but until this week, it had not addressed insurance coverage for preserving fertility in those cases.

“The transgender population already faces many barriers to care, such as provider discrimination, legal concerns, financial burden, and emotional cost,” Mr. Magrath said during a reference committee hearing on June 11. “We as a section ask our organization to continue to serve as an ally, providing equitable care for diverse populations and expanding coverage for medically necessary treatments.”

“I am a gender surgeon, so this is pretty important to me,” said Sean Figy, MD, of Nebraska, a delegate for the American Society for Reconstructive Microsurgery.

The original resolution included the words “medically necessary” when referring to gender-affirming treatments, and Dr. Figy expressed hesitancy about those words. An amendment removed them.

“I’ve seen that phrase weaponized against gender-nonconforming patients,” he said.

Ophthalmologist Charles Hickey, MD, of the Ohio delegation, spoke in favor of referral or of waiting to adopt the resolution.

“I think the different amendments being discussed here are evidence that this needs a more thorough and careful treatment than we can do at this point right now,” he said.

A version of this article first appeared on Medscape.com.

CHICAGO – Health insurance should cover treatment for infertility caused by gender-affirming medical interventions, the American Medical Association said June 13 at its House of Delegates meeting.

Speaking on behalf of the Medical Student Section, Justin Magrath, of Louisiana, said, “We as a section feel that these interventions should be considered as additional causes of iatrogenic infertility and be covered by insurance.”

Iatrogenic infertility is infertility caused by surgery, radiotherapy, chemotherapy, or other medically necessary treatment. The AMA voted June 13 to support including the phrase, “impaired fertility as a consequence of gender-affirming hormone therapy and gender-affirming surgery,” in that definition.

The AMA also supports access to fertility preservation services for people who undergo those treatments.

“I’ve had many friends who went through transitions and gender-affirming care and had no idea that these options were available and others who did know they were available but they were so expensive that they couldn’t access them,” said emergency medicine resident Sophia Spadafore, MD, delegate for the Resident and Fellow Section. “So while people might be able to access gender-affirming care, sometimes they have to make the decision between future fertility and having children and accessing this kind of lifesaving care that we support.”

The AMA already had policies that support insurance coverage of treatments for gender dysphoria and the right to seek fertility preservation services for people who undergo gender-affirming hormone therapy or surgery, but until this week, it had not addressed insurance coverage for preserving fertility in those cases.

“The transgender population already faces many barriers to care, such as provider discrimination, legal concerns, financial burden, and emotional cost,” Mr. Magrath said during a reference committee hearing on June 11. “We as a section ask our organization to continue to serve as an ally, providing equitable care for diverse populations and expanding coverage for medically necessary treatments.”

“I am a gender surgeon, so this is pretty important to me,” said Sean Figy, MD, of Nebraska, a delegate for the American Society for Reconstructive Microsurgery.

The original resolution included the words “medically necessary” when referring to gender-affirming treatments, and Dr. Figy expressed hesitancy about those words. An amendment removed them.

“I’ve seen that phrase weaponized against gender-nonconforming patients,” he said.

Ophthalmologist Charles Hickey, MD, of the Ohio delegation, spoke in favor of referral or of waiting to adopt the resolution.

“I think the different amendments being discussed here are evidence that this needs a more thorough and careful treatment than we can do at this point right now,” he said.

A version of this article first appeared on Medscape.com.

A recent series of columns on practice merger options generated a multitude of questions regarding merger, employment, and buyout agreements. The most common question was, “Do I really need to go to the trouble and expense of negotiating them?” If you have more than one physician in your group, you absolutely do need written contracts for a variety of reasons, but mostly to avoid conflicts later on. The proverbial “handshake agreement” is worthless in a major business dispute; everyone loses in such situations except the lawyers and accountants.

Mergers and buy-ins were covered at some length in my two previous columns. If the arrangement is to be one of employer and employees rather than a merger of equal partners, you will need an employment agreement to cover duties, requirements, expectations, and benefits. They define how each practitioner/employee will be paid, along with paid time off, health insurance, expense allowances, and malpractice coverage, among other basics. The more that is spelled out in the employment agreement, the fewer disagreements you are likely to have down the road.

Many employment contracts include a “termination without cause” clause, which benefits both the practice and the practitioners. It allows a practice to terminate a new associate if it feels a mistake has been made, even if he or she has done nothing wrong. On the other hand, the newcomer has the option to terminate if a better offer arises, their spouse hates the area, or for any other reason.

Buyouts should be addressed in advance as well. Several recent correspondents told me they didn’t see the necessity of writing a buyout agreement, because they plan to eventually sell their practice, rendering any buyout conditions moot. But what happens if an associate dies, becomes permanently disabled, or abruptly decides to leave the practice? If you haven’t prepared for such eventualities, you could find yourself receiving a demand from your ex-partner (or surviving spouse) for immediate payment of that partner’s portion of the practice’s value. And your valuation of the practice is likely to be severely at odds with the other party’s. Meanwhile, remaining partners must cover all the practice’s expenses and deal with an increased patient load.

A buyout agreement avoids these problems by planning for such eventualities in advance. You must agree on how a buyout amount will be valued. As I’ve said in previous columns, I strongly advise using a formula, not a fixed amount. If a buyout is based on 15- or 20-year-old reimbursements, the buyout will have no relationship to what the partners are currently being paid. Likewise, any buyout calculated at “appraised value” is a problem, because the buyout amount remains a mystery until an appraisal is performed. If the appraised value ends up being too high, the remaining owners may refuse to pay it. Have an actuary create a formula, so that a buyout figure can be calculated at any time. This area, especially, is where you need experienced, competent legal advice.

To avoid surprises, any buyout should require ample notice (6-12 months is common) to allow time to rearrange finances and recruit a new provider. Vesting schedules, similar to those used in retirement plans, are also popular. If a partner leaves before a prescribed time period has elapsed – say, 20 years – the buyout is proportionally reduced.

Buyouts can also be useful when dealing with noncompete agreements, which are notoriously difficult (and expensive) to enforce. One solution is a buyout penalty; a departing partner can compete with his or her former practice, but at the cost of a substantially reduced buyout. This permits competition, but discourages it, and compensates the targeted practice.

Buyouts are also a potential solution to some buy-in issues. A new associate entering an established practice may not be able to contribute assets equal to existing partners’ stakes and may lack the cash necessary to make up the difference. One alternative is to agree that any inequalities will be compensated at the other end in buyout value. Those partners contributing more assets will receive larger buyouts than those contributing less.

As I’ve said many times, these are not negotiations to undertake on your own. Enlist the aid of a consultant or attorney (or both) with ample medical practice experience.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

A recent series of columns on practice merger options generated a multitude of questions regarding merger, employment, and buyout agreements. The most common question was, “Do I really need to go to the trouble and expense of negotiating them?” If you have more than one physician in your group, you absolutely do need written contracts for a variety of reasons, but mostly to avoid conflicts later on. The proverbial “handshake agreement” is worthless in a major business dispute; everyone loses in such situations except the lawyers and accountants.

Mergers and buy-ins were covered at some length in my two previous columns. If the arrangement is to be one of employer and employees rather than a merger of equal partners, you will need an employment agreement to cover duties, requirements, expectations, and benefits. They define how each practitioner/employee will be paid, along with paid time off, health insurance, expense allowances, and malpractice coverage, among other basics. The more that is spelled out in the employment agreement, the fewer disagreements you are likely to have down the road.

Many employment contracts include a “termination without cause” clause, which benefits both the practice and the practitioners. It allows a practice to terminate a new associate if it feels a mistake has been made, even if he or she has done nothing wrong. On the other hand, the newcomer has the option to terminate if a better offer arises, their spouse hates the area, or for any other reason.

Buyouts should be addressed in advance as well. Several recent correspondents told me they didn’t see the necessity of writing a buyout agreement, because they plan to eventually sell their practice, rendering any buyout conditions moot. But what happens if an associate dies, becomes permanently disabled, or abruptly decides to leave the practice? If you haven’t prepared for such eventualities, you could find yourself receiving a demand from your ex-partner (or surviving spouse) for immediate payment of that partner’s portion of the practice’s value. And your valuation of the practice is likely to be severely at odds with the other party’s. Meanwhile, remaining partners must cover all the practice’s expenses and deal with an increased patient load.

A buyout agreement avoids these problems by planning for such eventualities in advance. You must agree on how a buyout amount will be valued. As I’ve said in previous columns, I strongly advise using a formula, not a fixed amount. If a buyout is based on 15- or 20-year-old reimbursements, the buyout will have no relationship to what the partners are currently being paid. Likewise, any buyout calculated at “appraised value” is a problem, because the buyout amount remains a mystery until an appraisal is performed. If the appraised value ends up being too high, the remaining owners may refuse to pay it. Have an actuary create a formula, so that a buyout figure can be calculated at any time. This area, especially, is where you need experienced, competent legal advice.

To avoid surprises, any buyout should require ample notice (6-12 months is common) to allow time to rearrange finances and recruit a new provider. Vesting schedules, similar to those used in retirement plans, are also popular. If a partner leaves before a prescribed time period has elapsed – say, 20 years – the buyout is proportionally reduced.

Buyouts can also be useful when dealing with noncompete agreements, which are notoriously difficult (and expensive) to enforce. One solution is a buyout penalty; a departing partner can compete with his or her former practice, but at the cost of a substantially reduced buyout. This permits competition, but discourages it, and compensates the targeted practice.

Buyouts are also a potential solution to some buy-in issues. A new associate entering an established practice may not be able to contribute assets equal to existing partners’ stakes and may lack the cash necessary to make up the difference. One alternative is to agree that any inequalities will be compensated at the other end in buyout value. Those partners contributing more assets will receive larger buyouts than those contributing less.

As I’ve said many times, these are not negotiations to undertake on your own. Enlist the aid of a consultant or attorney (or both) with ample medical practice experience.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

A recent series of columns on practice merger options generated a multitude of questions regarding merger, employment, and buyout agreements. The most common question was, “Do I really need to go to the trouble and expense of negotiating them?” If you have more than one physician in your group, you absolutely do need written contracts for a variety of reasons, but mostly to avoid conflicts later on. The proverbial “handshake agreement” is worthless in a major business dispute; everyone loses in such situations except the lawyers and accountants.

Mergers and buy-ins were covered at some length in my two previous columns. If the arrangement is to be one of employer and employees rather than a merger of equal partners, you will need an employment agreement to cover duties, requirements, expectations, and benefits. They define how each practitioner/employee will be paid, along with paid time off, health insurance, expense allowances, and malpractice coverage, among other basics. The more that is spelled out in the employment agreement, the fewer disagreements you are likely to have down the road.

Many employment contracts include a “termination without cause” clause, which benefits both the practice and the practitioners. It allows a practice to terminate a new associate if it feels a mistake has been made, even if he or she has done nothing wrong. On the other hand, the newcomer has the option to terminate if a better offer arises, their spouse hates the area, or for any other reason.

Buyouts should be addressed in advance as well. Several recent correspondents told me they didn’t see the necessity of writing a buyout agreement, because they plan to eventually sell their practice, rendering any buyout conditions moot. But what happens if an associate dies, becomes permanently disabled, or abruptly decides to leave the practice? If you haven’t prepared for such eventualities, you could find yourself receiving a demand from your ex-partner (or surviving spouse) for immediate payment of that partner’s portion of the practice’s value. And your valuation of the practice is likely to be severely at odds with the other party’s. Meanwhile, remaining partners must cover all the practice’s expenses and deal with an increased patient load.

A buyout agreement avoids these problems by planning for such eventualities in advance. You must agree on how a buyout amount will be valued. As I’ve said in previous columns, I strongly advise using a formula, not a fixed amount. If a buyout is based on 15- or 20-year-old reimbursements, the buyout will have no relationship to what the partners are currently being paid. Likewise, any buyout calculated at “appraised value” is a problem, because the buyout amount remains a mystery until an appraisal is performed. If the appraised value ends up being too high, the remaining owners may refuse to pay it. Have an actuary create a formula, so that a buyout figure can be calculated at any time. This area, especially, is where you need experienced, competent legal advice.

To avoid surprises, any buyout should require ample notice (6-12 months is common) to allow time to rearrange finances and recruit a new provider. Vesting schedules, similar to those used in retirement plans, are also popular. If a partner leaves before a prescribed time period has elapsed – say, 20 years – the buyout is proportionally reduced.

Buyouts can also be useful when dealing with noncompete agreements, which are notoriously difficult (and expensive) to enforce. One solution is a buyout penalty; a departing partner can compete with his or her former practice, but at the cost of a substantially reduced buyout. This permits competition, but discourages it, and compensates the targeted practice.

Buyouts are also a potential solution to some buy-in issues. A new associate entering an established practice may not be able to contribute assets equal to existing partners’ stakes and may lack the cash necessary to make up the difference. One alternative is to agree that any inequalities will be compensated at the other end in buyout value. Those partners contributing more assets will receive larger buyouts than those contributing less.

As I’ve said many times, these are not negotiations to undertake on your own. Enlist the aid of a consultant or attorney (or both) with ample medical practice experience.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

Experts engaged in a contentious debate on the usefulness of the NOVA system, which divides foods into different categories based on how much they have been processed, during a session at a virtual conference sponsored by the American Society for Nutrition.

The NOVA system divides foods into “fresh or minimally processed,” such as strawberries or steel-cut oats; “processed culinary ingredients,” such as olive oil; “processed foods,” such as cheeses; and “ultra-processed foods.” UPFs are defined as “industrial formulations made by deconstructing natural food into its chemical constituents, modifying them and recombining them with additives into products liable to displace all other NOVA food groups.”

According to doctors who presented during the meeting, ultra-processed foods are drawing increased attention, because researchers have been examining them in National Institutes of Health–funded studies and journalists have been writing about them.

During the debate session at the meeting, some experts said that, with obesity and poor health skyrocketing, increased awareness and labeling of UPFs can only be a good thing. In contrast others noted at the meeting that the classification system that has come to be used for identifying UPFs – the NOVA Food Classification system – is too mushy, confusing, and, ultimately unhelpful.

Carlos Monteiro, MD, PhD, professor of nutrition and public health at the University of Sao Paolo, was part of the group favoring the NOVA system’s classifying certain foods as UPFs, during the debate. He drew attention to the extent to which the world’s population is getting its calories from UPFs.

Mexico and France get about 30% of calories from these foods. In Canada, it’s 48%. And in the United States, it’s 57%, Dr. Monteiro said.

Studies have found that UPFs, many of which are designed to be exceedingly flavorful and intended to replace consumption of unprocessed whole foods, lead to more overall energy intake, more added sugar in the diet, and less fiber and protein intake, he said.

To further support his arguments, Dr. Monteiro pointed to studies suggesting that it is not just the resulting change in the nutritional intake that is unhealthy, but the UPF manufacturing process itself. When adjusting for fat, sugar, and sodium intake, for example, health outcomes associated with UPFs remain poor, he explained.

“I’m sorry,” he said in the debate. “If you don’t reduce this, you don’t reduce your obesity, your diabetes prevalence.”

A study presented by Jacqueline Vernarelli, PhD, during a different session at the meeting suggested there may be other downsides to consuming UPFs. This research, which was based on the U.S. National Youth Fitness Survey, found that poorer locomotor skills among children aged 3-5 and poorer cardiovascular fitness among those aged 12-15 were associated with getting more calories from UPFs.

Those with lower cardiovascular fitness consumed 1,234 calories a day from UPFs, and those with higher cardiovascular fitness consumed 1,007 calories a day from UPFs (P = .002), according to the new research.

“It’s notable here that, although these differences are significant, both groups are consuming a pretty high proportion of their diet from ultra-processed foods,” said Dr. Vernarelli, associate professor of public health at Sacred Heart University, Fairfield, Conn., during her presentation.

In the debate session, Arne Astrup, MD, PhD, senior project director at the Healthy Weight Center at the Novo Nordisk Foundation, Hellerup, Denmark, presented an opposing view.

He said the definition of UPFs makes it too difficult to categorize many foods, pointing to a study from this year in which about 150 nutrition experts, doctors, and dietitians classified 120 foods. Only three marketed foods and one generic food were classified the same by all the evaluators.

Referring to the study Dr. Astrup cited, Dr. Monteiro said it was a mere “exercise,” and the experts involved in it had conflicts of interest.

Dr. Astrup touted this study’s size and its appearance in the peer-reviewed journal the European Journal of Clinical Nutrition.

Defending his point of view, Dr. Astrup said, “The definition and classification is so ambiguous, and the risk of misclassification is so extremely high, I think we really miss the basic requirement of science, namely that we know what we are talking about,” he said.

If you take an unprocessed food, and insert a “little additive … suddenly it’s an ultra-processed food,” he added.
 

UPF definition doesn’t flag some unhealthy foods

Susan Roberts, PhD, professor of nutrition at Tufts University, Boston, was a discussant at the debate and touched on the merits of both sides. She noted that the UPF definition doesn’t flag some “clearly unhealthy foods,” such as table sugar, but does flag some healthy ones, such as plant-based burgers – to which Dr. Monteiro said that the system was not a system meant to divide foods into healthy and unhealthy groups, during the debate session.

The inclusion of both healthy and unhealthy foods in NOVA’s definition of a UPF is a serious problem, Dr. Roberts said.

“It’s almost like it’s an emotional classification designed to get at the food industry rather than focusing on health – and I think that’s asking for trouble because it’s just going to be such a mess to tell consumers, ‘Well, this ultra-processed food is healthy and this one isn’t,’ ” she said. What’s happening is the term ultra-processed is being used interchangeably with unhealthy.

The discussion that the UPF classification has generated is useful, Dr. Roberts continued. “This definition grew out of that recognition that we’re engaged in an unprecedented experiment of how unhealthy can you make the world without having a major catastrophe.”

She added that the UPF concept deserves a more formalized and rigorous evaluation.

“This is an important topic for the future of public health, and I think it needs big committees to address it seriously,” she said. “I think we should not be dealing with this individually in different labs.”
 

Doctor’s take on usefulness of discussing UPF concept with patients

Mark Corkins, MD, who did not participate in the debate at the meeting, said he talks to parents and children about nutrition at every office visit in which he sees a child with an unhealthy weight.

“Persistence wears down resistance,” said the chair of the American Academy of Pediatrics nutrition committee, in an interview.“A consistent message – you say the same thing and you say it multiple times.”

The idea of “ultra-processed foods” plays a role in those conversations, but largely in the background. It’s a topic that’s important for pediatric health, Dr. Corkins said – but he doesn’t make it the focal point.

“It’s not a direct attack on ultra-processed foods that usually I take as my direction,” said Dr. Corkins, who is also chief of pediatric gastroenterology at Le Bonheur Children’s Hospital in Memphis, Tenn.. “What I try to focus on, and what I think the American Academy of Pediatrics would focus on, is that we need to focus on making the diet better.”

He added, “Parents are aware – they don’t call it ultra-processed food, they call it junk food.”

Dr. Corkins continued that he is reluctant to directly challenge parents on feeding their children unhealthy foods – ultra-processed or not – lest he shame them and harm the relationship.

“Guilt as a motivator isn’t really highly successful,” he said, in an interview.

Dr. Astrup reported advisory committee or board member involvement with Green Leaf Medical and RNPC, France. Dr. Roberts reported advisory committee or board member involvement with Danone, and an ownership interest in Instinct Health Science. Dr. Monteiro and Dr. Corkins reported no relevant disclosures.

Experts engaged in a contentious debate on the usefulness of the NOVA system, which divides foods into different categories based on how much they have been processed, during a session at a virtual conference sponsored by the American Society for Nutrition.

The NOVA system divides foods into “fresh or minimally processed,” such as strawberries or steel-cut oats; “processed culinary ingredients,” such as olive oil; “processed foods,” such as cheeses; and “ultra-processed foods.” UPFs are defined as “industrial formulations made by deconstructing natural food into its chemical constituents, modifying them and recombining them with additives into products liable to displace all other NOVA food groups.”

According to doctors who presented during the meeting, ultra-processed foods are drawing increased attention, because researchers have been examining them in National Institutes of Health–funded studies and journalists have been writing about them.

During the debate session at the meeting, some experts said that, with obesity and poor health skyrocketing, increased awareness and labeling of UPFs can only be a good thing. In contrast others noted at the meeting that the classification system that has come to be used for identifying UPFs – the NOVA Food Classification system – is too mushy, confusing, and, ultimately unhelpful.

Carlos Monteiro, MD, PhD, professor of nutrition and public health at the University of Sao Paolo, was part of the group favoring the NOVA system’s classifying certain foods as UPFs, during the debate. He drew attention to the extent to which the world’s population is getting its calories from UPFs.

Mexico and France get about 30% of calories from these foods. In Canada, it’s 48%. And in the United States, it’s 57%, Dr. Monteiro said.

Studies have found that UPFs, many of which are designed to be exceedingly flavorful and intended to replace consumption of unprocessed whole foods, lead to more overall energy intake, more added sugar in the diet, and less fiber and protein intake, he said.

To further support his arguments, Dr. Monteiro pointed to studies suggesting that it is not just the resulting change in the nutritional intake that is unhealthy, but the UPF manufacturing process itself. When adjusting for fat, sugar, and sodium intake, for example, health outcomes associated with UPFs remain poor, he explained.

“I’m sorry,” he said in the debate. “If you don’t reduce this, you don’t reduce your obesity, your diabetes prevalence.”

A study presented by Jacqueline Vernarelli, PhD, during a different session at the meeting suggested there may be other downsides to consuming UPFs. This research, which was based on the U.S. National Youth Fitness Survey, found that poorer locomotor skills among children aged 3-5 and poorer cardiovascular fitness among those aged 12-15 were associated with getting more calories from UPFs.

Those with lower cardiovascular fitness consumed 1,234 calories a day from UPFs, and those with higher cardiovascular fitness consumed 1,007 calories a day from UPFs (P = .002), according to the new research.

“It’s notable here that, although these differences are significant, both groups are consuming a pretty high proportion of their diet from ultra-processed foods,” said Dr. Vernarelli, associate professor of public health at Sacred Heart University, Fairfield, Conn., during her presentation.

In the debate session, Arne Astrup, MD, PhD, senior project director at the Healthy Weight Center at the Novo Nordisk Foundation, Hellerup, Denmark, presented an opposing view.

He said the definition of UPFs makes it too difficult to categorize many foods, pointing to a study from this year in which about 150 nutrition experts, doctors, and dietitians classified 120 foods. Only three marketed foods and one generic food were classified the same by all the evaluators.

Referring to the study Dr. Astrup cited, Dr. Monteiro said it was a mere “exercise,” and the experts involved in it had conflicts of interest.

Dr. Astrup touted this study’s size and its appearance in the peer-reviewed journal the European Journal of Clinical Nutrition.

Defending his point of view, Dr. Astrup said, “The definition and classification is so ambiguous, and the risk of misclassification is so extremely high, I think we really miss the basic requirement of science, namely that we know what we are talking about,” he said.

If you take an unprocessed food, and insert a “little additive … suddenly it’s an ultra-processed food,” he added.
 

UPF definition doesn’t flag some unhealthy foods

Susan Roberts, PhD, professor of nutrition at Tufts University, Boston, was a discussant at the debate and touched on the merits of both sides. She noted that the UPF definition doesn’t flag some “clearly unhealthy foods,” such as table sugar, but does flag some healthy ones, such as plant-based burgers – to which Dr. Monteiro said that the system was not a system meant to divide foods into healthy and unhealthy groups, during the debate session.

The inclusion of both healthy and unhealthy foods in NOVA’s definition of a UPF is a serious problem, Dr. Roberts said.

“It’s almost like it’s an emotional classification designed to get at the food industry rather than focusing on health – and I think that’s asking for trouble because it’s just going to be such a mess to tell consumers, ‘Well, this ultra-processed food is healthy and this one isn’t,’ ” she said. What’s happening is the term ultra-processed is being used interchangeably with unhealthy.

The discussion that the UPF classification has generated is useful, Dr. Roberts continued. “This definition grew out of that recognition that we’re engaged in an unprecedented experiment of how unhealthy can you make the world without having a major catastrophe.”

She added that the UPF concept deserves a more formalized and rigorous evaluation.

“This is an important topic for the future of public health, and I think it needs big committees to address it seriously,” she said. “I think we should not be dealing with this individually in different labs.”
 

Doctor’s take on usefulness of discussing UPF concept with patients

Mark Corkins, MD, who did not participate in the debate at the meeting, said he talks to parents and children about nutrition at every office visit in which he sees a child with an unhealthy weight.

“Persistence wears down resistance,” said the chair of the American Academy of Pediatrics nutrition committee, in an interview.“A consistent message – you say the same thing and you say it multiple times.”

The idea of “ultra-processed foods” plays a role in those conversations, but largely in the background. It’s a topic that’s important for pediatric health, Dr. Corkins said – but he doesn’t make it the focal point.

“It’s not a direct attack on ultra-processed foods that usually I take as my direction,” said Dr. Corkins, who is also chief of pediatric gastroenterology at Le Bonheur Children’s Hospital in Memphis, Tenn.. “What I try to focus on, and what I think the American Academy of Pediatrics would focus on, is that we need to focus on making the diet better.”

He added, “Parents are aware – they don’t call it ultra-processed food, they call it junk food.”

Dr. Corkins continued that he is reluctant to directly challenge parents on feeding their children unhealthy foods – ultra-processed or not – lest he shame them and harm the relationship.

“Guilt as a motivator isn’t really highly successful,” he said, in an interview.

Dr. Astrup reported advisory committee or board member involvement with Green Leaf Medical and RNPC, France. Dr. Roberts reported advisory committee or board member involvement with Danone, and an ownership interest in Instinct Health Science. Dr. Monteiro and Dr. Corkins reported no relevant disclosures.

Experts engaged in a contentious debate on the usefulness of the NOVA system, which divides foods into different categories based on how much they have been processed, during a session at a virtual conference sponsored by the American Society for Nutrition.

The NOVA system divides foods into “fresh or minimally processed,” such as strawberries or steel-cut oats; “processed culinary ingredients,” such as olive oil; “processed foods,” such as cheeses; and “ultra-processed foods.” UPFs are defined as “industrial formulations made by deconstructing natural food into its chemical constituents, modifying them and recombining them with additives into products liable to displace all other NOVA food groups.”

According to doctors who presented during the meeting, ultra-processed foods are drawing increased attention, because researchers have been examining them in National Institutes of Health–funded studies and journalists have been writing about them.

During the debate session at the meeting, some experts said that, with obesity and poor health skyrocketing, increased awareness and labeling of UPFs can only be a good thing. In contrast others noted at the meeting that the classification system that has come to be used for identifying UPFs – the NOVA Food Classification system – is too mushy, confusing, and, ultimately unhelpful.

Carlos Monteiro, MD, PhD, professor of nutrition and public health at the University of Sao Paolo, was part of the group favoring the NOVA system’s classifying certain foods as UPFs, during the debate. He drew attention to the extent to which the world’s population is getting its calories from UPFs.

Mexico and France get about 30% of calories from these foods. In Canada, it’s 48%. And in the United States, it’s 57%, Dr. Monteiro said.

Studies have found that UPFs, many of which are designed to be exceedingly flavorful and intended to replace consumption of unprocessed whole foods, lead to more overall energy intake, more added sugar in the diet, and less fiber and protein intake, he said.

To further support his arguments, Dr. Monteiro pointed to studies suggesting that it is not just the resulting change in the nutritional intake that is unhealthy, but the UPF manufacturing process itself. When adjusting for fat, sugar, and sodium intake, for example, health outcomes associated with UPFs remain poor, he explained.

“I’m sorry,” he said in the debate. “If you don’t reduce this, you don’t reduce your obesity, your diabetes prevalence.”

A study presented by Jacqueline Vernarelli, PhD, during a different session at the meeting suggested there may be other downsides to consuming UPFs. This research, which was based on the U.S. National Youth Fitness Survey, found that poorer locomotor skills among children aged 3-5 and poorer cardiovascular fitness among those aged 12-15 were associated with getting more calories from UPFs.

Those with lower cardiovascular fitness consumed 1,234 calories a day from UPFs, and those with higher cardiovascular fitness consumed 1,007 calories a day from UPFs (P = .002), according to the new research.

“It’s notable here that, although these differences are significant, both groups are consuming a pretty high proportion of their diet from ultra-processed foods,” said Dr. Vernarelli, associate professor of public health at Sacred Heart University, Fairfield, Conn., during her presentation.

In the debate session, Arne Astrup, MD, PhD, senior project director at the Healthy Weight Center at the Novo Nordisk Foundation, Hellerup, Denmark, presented an opposing view.

He said the definition of UPFs makes it too difficult to categorize many foods, pointing to a study from this year in which about 150 nutrition experts, doctors, and dietitians classified 120 foods. Only three marketed foods and one generic food were classified the same by all the evaluators.

Referring to the study Dr. Astrup cited, Dr. Monteiro said it was a mere “exercise,” and the experts involved in it had conflicts of interest.

Dr. Astrup touted this study’s size and its appearance in the peer-reviewed journal the European Journal of Clinical Nutrition.

Defending his point of view, Dr. Astrup said, “The definition and classification is so ambiguous, and the risk of misclassification is so extremely high, I think we really miss the basic requirement of science, namely that we know what we are talking about,” he said.

If you take an unprocessed food, and insert a “little additive … suddenly it’s an ultra-processed food,” he added.
 

UPF definition doesn’t flag some unhealthy foods

Susan Roberts, PhD, professor of nutrition at Tufts University, Boston, was a discussant at the debate and touched on the merits of both sides. She noted that the UPF definition doesn’t flag some “clearly unhealthy foods,” such as table sugar, but does flag some healthy ones, such as plant-based burgers – to which Dr. Monteiro said that the system was not a system meant to divide foods into healthy and unhealthy groups, during the debate session.

The inclusion of both healthy and unhealthy foods in NOVA’s definition of a UPF is a serious problem, Dr. Roberts said.

“It’s almost like it’s an emotional classification designed to get at the food industry rather than focusing on health – and I think that’s asking for trouble because it’s just going to be such a mess to tell consumers, ‘Well, this ultra-processed food is healthy and this one isn’t,’ ” she said. What’s happening is the term ultra-processed is being used interchangeably with unhealthy.

The discussion that the UPF classification has generated is useful, Dr. Roberts continued. “This definition grew out of that recognition that we’re engaged in an unprecedented experiment of how unhealthy can you make the world without having a major catastrophe.”

She added that the UPF concept deserves a more formalized and rigorous evaluation.

“This is an important topic for the future of public health, and I think it needs big committees to address it seriously,” she said. “I think we should not be dealing with this individually in different labs.”
 

Doctor’s take on usefulness of discussing UPF concept with patients

Mark Corkins, MD, who did not participate in the debate at the meeting, said he talks to parents and children about nutrition at every office visit in which he sees a child with an unhealthy weight.

“Persistence wears down resistance,” said the chair of the American Academy of Pediatrics nutrition committee, in an interview.“A consistent message – you say the same thing and you say it multiple times.”

The idea of “ultra-processed foods” plays a role in those conversations, but largely in the background. It’s a topic that’s important for pediatric health, Dr. Corkins said – but he doesn’t make it the focal point.

“It’s not a direct attack on ultra-processed foods that usually I take as my direction,” said Dr. Corkins, who is also chief of pediatric gastroenterology at Le Bonheur Children’s Hospital in Memphis, Tenn.. “What I try to focus on, and what I think the American Academy of Pediatrics would focus on, is that we need to focus on making the diet better.”

He added, “Parents are aware – they don’t call it ultra-processed food, they call it junk food.”

Dr. Corkins continued that he is reluctant to directly challenge parents on feeding their children unhealthy foods – ultra-processed or not – lest he shame them and harm the relationship.

“Guilt as a motivator isn’t really highly successful,” he said, in an interview.

Dr. Astrup reported advisory committee or board member involvement with Green Leaf Medical and RNPC, France. Dr. Roberts reported advisory committee or board member involvement with Danone, and an ownership interest in Instinct Health Science. Dr. Monteiro and Dr. Corkins reported no relevant disclosures.

ATLANTA – U.S. clinicians caring for people with diabetes should take a more aggressive approach to using combined medical treatments proven to slow the otherwise relentless progression of chronic kidney disease (CKD), according to a new joint statement by the American Diabetes Association and a major international nephrology organization presented during the annual scientific sessions of the American Diabetes Association (ADA).

The statement elevates treatment with an agent from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class to first-line for people with diabetes and laboratory-based evidence of advancing CKD. It also re-emphasizes the key role of concurrent first-line treatment with a renin-angiotensin system inhibitor (an ACE inhibitor or angiotensin-receptor blocker), metformin, and a statin.

The new statement also urges clinicians to rapidly add treatment with the new nonsteroidal mineralocorticoid receptor antagonist finerenone (Kerendia) for further renal protection in the many patients suitable for treatment with this agent, and it recommends the second-line addition of a glucagon-like peptide-1 (GLP-1) receptor agonist as the best add-on for any patient who needs additional glycemic control on top of metformin and an SGLT2 inhibitor.

The consensus joint statement with these updates came from a nine-member writing group assembled by the ADA and the Kidney Disease: Improving Global Outcomes (KDIGO) organization.

“We’re going to try to make this feasible. We have to; I don’t think we have a choice,” commented Amy K. Mottl, MD, a nephrologist at the University of North Carolina, Chapel Hill. Dr. Mottl was not involved with writing the consensus statement but has been active in the Diabetic Kidney Disease Collaborative of the American Society of Nephrology, another group promoting a more aggressive multidrug-class approach to treating CKD in people with diabetes.
 

Wider use of costly drugs

Adoption of this evidence-based approach by U.S. clinicians will both increase the number of agents that many patients receive and drive a significant uptick in the cost and complexity of patient care, a consequence acknowledged by the authors of the joint statement as well as outside experts.

But they view this as unavoidable given what’s now known about the high incidence of worsening CKD in patients with diabetes and the types of interventions proven to blunt this.

Much of the financial implication stems from the price of agents from the new drug classes now emphasized in the consensus recommendations – SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists. All these drugs currently remain on-patent with relatively expensive retail prices in the range of about $600 to $1,000/month.

Commenting on the cost concerns, Dr. Mottl highlighted that she currently has several patients in her practice on agents from two or more of these newer classes, and she has generally found it possible for patients to get much of their expenses covered by insurers and through drug-company assistance programs.

“The major gap is patients on Medicare,” she noted in an interview, because the Federal health insurance program does not allow beneficiaries to receive rebates for their drug costs. “The Diabetic Kidney Disease Collaborative is currently lobbying members of Congress to lift that barrier,” she emphasized.
 

Improved alignment

Details of the KDIGO recommendations feature in a guideline from that organization that appeared as a draft document online in March 2022. The ADA’s version recently appeared as an update to its Standards of Medical Care in Diabetes – 2022, as reported by this news organization. A panel of five KDIGO representatives and four members appointed by the ADA produced the harmonization statement.

Recommendations from both organizations were largely in agreement at the outset, but following the panel’s review, the two groups are now “very well-aligned,” said Peter Rossing, MD, DMSc, a diabetologist and professor at the Steno Diabetes Center, Copenhagen, and a KDIGO representative to the writing committee, who presented the joint statement at the ADA meeting.

“These are very important drugs that are vastly underused,” commented Josef Coresh, MD, PhD, an epidemiologist and professor at Johns Hopkins Bloomberg School of Public Health, Baltimore, who specializes in CKD and was not involved with the new statement.

“Coherence and simplicity are what we need so that there are no excuses about moving forward” with the recommended combination treatment, he stressed.

Moving too slow

“No one is resisting using these new medications, but they are just moving too slowly, and data now show that it’s moving more slowly in the United States than elsewhere. That may be partly because U.S. patients are charged much more for these drugs, and partly because U.S. health care is so much more fragmented,” Dr. Coresh said in an interview.

The new joint consensus statement may help, “but the fragmentation of the United States system and COVID-19 are big enemies” for any short-term increased use of the highlighted agents, he added.

Evidence for low U.S. use of SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists is becoming well known.

Dr. Rossing cited a 2019 report from the CURE-CKD registry of more than 600,000 U.S. patients with CKD showing that less than 1% received an SGLT2 inhibitor and less than 1% a GLP-1 receptor agonist. Not all these patients had diabetes, but a subgroup analysis of those with diabetes, prediabetes, or hypertension showed that usage of each of these two classes remained at less than 1% even in this group.

A separate report at the ADA meeting documented that of more than 1.3 million people with type 2 diabetes in the U.S. Veterans Affairs Healthcare System during 2019 and 2020, just 10% received an SGLT2 inhibitor and 7% a GLP-1 receptor agonist. And this is in a setting where drug cost is not a limiting factor.

In addition to focusing on the updated scheme for drug intervention in the consensus statement, Dr. Rossing highlighted several other important points that the writing committee emphasized.

Lifestyle optimization is a core first-line element of managing patients with diabetes and CKD, including a healthy diet, exercise, smoking cessation, and weight control. Other key steps for management include optimization of blood pressure, glucose, and lipids. The statement also calls out a potentially helpful role for continuous glucose monitoring in patients with type 1 or type 2 diabetes and CKD.

The statement notes that patients who also have atherosclerotic cardiovascular disease usually qualify for and could potentially benefit from more intensified lipid management with ezetimibe or a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, as well as a potential role for treatment with antiplatelet agents.
 

‘If you don’t screen, you won’t find it’

Dr. Rossing also stressed the importance of regular screening for the onset of advanced CKD in patients. Patients whose estimated glomerular filtration rate (eGFR) drops below 60 mL/min/1.73m2, as well as those who develop microalbuminuria with a urinary albumin-to-creatinine ratio of at least 30 mg/g (30 mg/mmol), have a stage of CKD that warrants the drug interventions he outlined.

Guidelines from both the ADA and KDIGO were already in place, recommending annual screening of patients with diabetes for both these parameters starting at diagnosis of type 2 diabetes or 5 years following initial diagnosis of type 1 diabetes.

“If you don’t screen, you won’t find it, and you won’t be able to treat,” Dr. Rossing warned. He also highlighted the panel’s recommendation to treat these patients with an SGLT2 inhibitor as long as their eGFR is at least 20 mL/min/1.73m2. Treatment can then continue even when their eGFR drops lower.

Starting treatment with finerenone requires that patients have a normal level of serum potassium, he emphasized.

One reason for developing the new ADA and KDIGO statement is that “discrepancies in clinical practice guideline recommendations from various professional organizations add to confusion that impedes understanding of best practices,” write Katherine R. Tuttle, MD, and associates in a recent commentary.

The goal of the new statement is to harmonize and promote the shared recommendations of the two organizations, added Dr. Tuttle, who is executive director for research at Providence Healthcare, Spokane, Washington, and a KDIGO representative on the statement writing panel.

Dr. Mottl has reported being a consultant to Bayer. Dr. Rossing has reported being a consultant to or speaker on behalf of Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, MSD, Mundipharma, Novo Nordisk, Sanofi Aventis, and Vifor, as well as receiving research grants from AstraZeneca and Novo Nordisk. Dr. Coresh has reported no relevant financial relationships. Dr. Tuttle has reported being a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Goldfinch Bio, Janssen, Novo Nordisk, and Travere; receiving honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Goldfinch Bio, Novo Nordisk, and Travere; and receiving research funding from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Goldfinch Bio, Novo Nordisk, and Travere.

A version of this article first appeared on Medscape.com.

ATLANTA – U.S. clinicians caring for people with diabetes should take a more aggressive approach to using combined medical treatments proven to slow the otherwise relentless progression of chronic kidney disease (CKD), according to a new joint statement by the American Diabetes Association and a major international nephrology organization presented during the annual scientific sessions of the American Diabetes Association (ADA).

The statement elevates treatment with an agent from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class to first-line for people with diabetes and laboratory-based evidence of advancing CKD. It also re-emphasizes the key role of concurrent first-line treatment with a renin-angiotensin system inhibitor (an ACE inhibitor or angiotensin-receptor blocker), metformin, and a statin.

The new statement also urges clinicians to rapidly add treatment with the new nonsteroidal mineralocorticoid receptor antagonist finerenone (Kerendia) for further renal protection in the many patients suitable for treatment with this agent, and it recommends the second-line addition of a glucagon-like peptide-1 (GLP-1) receptor agonist as the best add-on for any patient who needs additional glycemic control on top of metformin and an SGLT2 inhibitor.

The consensus joint statement with these updates came from a nine-member writing group assembled by the ADA and the Kidney Disease: Improving Global Outcomes (KDIGO) organization.

“We’re going to try to make this feasible. We have to; I don’t think we have a choice,” commented Amy K. Mottl, MD, a nephrologist at the University of North Carolina, Chapel Hill. Dr. Mottl was not involved with writing the consensus statement but has been active in the Diabetic Kidney Disease Collaborative of the American Society of Nephrology, another group promoting a more aggressive multidrug-class approach to treating CKD in people with diabetes.
 

Wider use of costly drugs

Adoption of this evidence-based approach by U.S. clinicians will both increase the number of agents that many patients receive and drive a significant uptick in the cost and complexity of patient care, a consequence acknowledged by the authors of the joint statement as well as outside experts.

But they view this as unavoidable given what’s now known about the high incidence of worsening CKD in patients with diabetes and the types of interventions proven to blunt this.

Much of the financial implication stems from the price of agents from the new drug classes now emphasized in the consensus recommendations – SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists. All these drugs currently remain on-patent with relatively expensive retail prices in the range of about $600 to $1,000/month.

Commenting on the cost concerns, Dr. Mottl highlighted that she currently has several patients in her practice on agents from two or more of these newer classes, and she has generally found it possible for patients to get much of their expenses covered by insurers and through drug-company assistance programs.

“The major gap is patients on Medicare,” she noted in an interview, because the Federal health insurance program does not allow beneficiaries to receive rebates for their drug costs. “The Diabetic Kidney Disease Collaborative is currently lobbying members of Congress to lift that barrier,” she emphasized.
 

Improved alignment

Details of the KDIGO recommendations feature in a guideline from that organization that appeared as a draft document online in March 2022. The ADA’s version recently appeared as an update to its Standards of Medical Care in Diabetes – 2022, as reported by this news organization. A panel of five KDIGO representatives and four members appointed by the ADA produced the harmonization statement.

Recommendations from both organizations were largely in agreement at the outset, but following the panel’s review, the two groups are now “very well-aligned,” said Peter Rossing, MD, DMSc, a diabetologist and professor at the Steno Diabetes Center, Copenhagen, and a KDIGO representative to the writing committee, who presented the joint statement at the ADA meeting.

“These are very important drugs that are vastly underused,” commented Josef Coresh, MD, PhD, an epidemiologist and professor at Johns Hopkins Bloomberg School of Public Health, Baltimore, who specializes in CKD and was not involved with the new statement.

“Coherence and simplicity are what we need so that there are no excuses about moving forward” with the recommended combination treatment, he stressed.

Moving too slow

“No one is resisting using these new medications, but they are just moving too slowly, and data now show that it’s moving more slowly in the United States than elsewhere. That may be partly because U.S. patients are charged much more for these drugs, and partly because U.S. health care is so much more fragmented,” Dr. Coresh said in an interview.

The new joint consensus statement may help, “but the fragmentation of the United States system and COVID-19 are big enemies” for any short-term increased use of the highlighted agents, he added.

Evidence for low U.S. use of SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists is becoming well known.

Dr. Rossing cited a 2019 report from the CURE-CKD registry of more than 600,000 U.S. patients with CKD showing that less than 1% received an SGLT2 inhibitor and less than 1% a GLP-1 receptor agonist. Not all these patients had diabetes, but a subgroup analysis of those with diabetes, prediabetes, or hypertension showed that usage of each of these two classes remained at less than 1% even in this group.

A separate report at the ADA meeting documented that of more than 1.3 million people with type 2 diabetes in the U.S. Veterans Affairs Healthcare System during 2019 and 2020, just 10% received an SGLT2 inhibitor and 7% a GLP-1 receptor agonist. And this is in a setting where drug cost is not a limiting factor.

In addition to focusing on the updated scheme for drug intervention in the consensus statement, Dr. Rossing highlighted several other important points that the writing committee emphasized.

Lifestyle optimization is a core first-line element of managing patients with diabetes and CKD, including a healthy diet, exercise, smoking cessation, and weight control. Other key steps for management include optimization of blood pressure, glucose, and lipids. The statement also calls out a potentially helpful role for continuous glucose monitoring in patients with type 1 or type 2 diabetes and CKD.

The statement notes that patients who also have atherosclerotic cardiovascular disease usually qualify for and could potentially benefit from more intensified lipid management with ezetimibe or a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, as well as a potential role for treatment with antiplatelet agents.
 

‘If you don’t screen, you won’t find it’

Dr. Rossing also stressed the importance of regular screening for the onset of advanced CKD in patients. Patients whose estimated glomerular filtration rate (eGFR) drops below 60 mL/min/1.73m2, as well as those who develop microalbuminuria with a urinary albumin-to-creatinine ratio of at least 30 mg/g (30 mg/mmol), have a stage of CKD that warrants the drug interventions he outlined.

Guidelines from both the ADA and KDIGO were already in place, recommending annual screening of patients with diabetes for both these parameters starting at diagnosis of type 2 diabetes or 5 years following initial diagnosis of type 1 diabetes.

“If you don’t screen, you won’t find it, and you won’t be able to treat,” Dr. Rossing warned. He also highlighted the panel’s recommendation to treat these patients with an SGLT2 inhibitor as long as their eGFR is at least 20 mL/min/1.73m2. Treatment can then continue even when their eGFR drops lower.

Starting treatment with finerenone requires that patients have a normal level of serum potassium, he emphasized.

One reason for developing the new ADA and KDIGO statement is that “discrepancies in clinical practice guideline recommendations from various professional organizations add to confusion that impedes understanding of best practices,” write Katherine R. Tuttle, MD, and associates in a recent commentary.

The goal of the new statement is to harmonize and promote the shared recommendations of the two organizations, added Dr. Tuttle, who is executive director for research at Providence Healthcare, Spokane, Washington, and a KDIGO representative on the statement writing panel.

Dr. Mottl has reported being a consultant to Bayer. Dr. Rossing has reported being a consultant to or speaker on behalf of Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, MSD, Mundipharma, Novo Nordisk, Sanofi Aventis, and Vifor, as well as receiving research grants from AstraZeneca and Novo Nordisk. Dr. Coresh has reported no relevant financial relationships. Dr. Tuttle has reported being a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Goldfinch Bio, Janssen, Novo Nordisk, and Travere; receiving honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Goldfinch Bio, Novo Nordisk, and Travere; and receiving research funding from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Goldfinch Bio, Novo Nordisk, and Travere.

A version of this article first appeared on Medscape.com.

ATLANTA – U.S. clinicians caring for people with diabetes should take a more aggressive approach to using combined medical treatments proven to slow the otherwise relentless progression of chronic kidney disease (CKD), according to a new joint statement by the American Diabetes Association and a major international nephrology organization presented during the annual scientific sessions of the American Diabetes Association (ADA).

The statement elevates treatment with an agent from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class to first-line for people with diabetes and laboratory-based evidence of advancing CKD. It also re-emphasizes the key role of concurrent first-line treatment with a renin-angiotensin system inhibitor (an ACE inhibitor or angiotensin-receptor blocker), metformin, and a statin.

The new statement also urges clinicians to rapidly add treatment with the new nonsteroidal mineralocorticoid receptor antagonist finerenone (Kerendia) for further renal protection in the many patients suitable for treatment with this agent, and it recommends the second-line addition of a glucagon-like peptide-1 (GLP-1) receptor agonist as the best add-on for any patient who needs additional glycemic control on top of metformin and an SGLT2 inhibitor.

The consensus joint statement with these updates came from a nine-member writing group assembled by the ADA and the Kidney Disease: Improving Global Outcomes (KDIGO) organization.

“We’re going to try to make this feasible. We have to; I don’t think we have a choice,” commented Amy K. Mottl, MD, a nephrologist at the University of North Carolina, Chapel Hill. Dr. Mottl was not involved with writing the consensus statement but has been active in the Diabetic Kidney Disease Collaborative of the American Society of Nephrology, another group promoting a more aggressive multidrug-class approach to treating CKD in people with diabetes.
 

Wider use of costly drugs

Adoption of this evidence-based approach by U.S. clinicians will both increase the number of agents that many patients receive and drive a significant uptick in the cost and complexity of patient care, a consequence acknowledged by the authors of the joint statement as well as outside experts.

But they view this as unavoidable given what’s now known about the high incidence of worsening CKD in patients with diabetes and the types of interventions proven to blunt this.

Much of the financial implication stems from the price of agents from the new drug classes now emphasized in the consensus recommendations – SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists. All these drugs currently remain on-patent with relatively expensive retail prices in the range of about $600 to $1,000/month.

Commenting on the cost concerns, Dr. Mottl highlighted that she currently has several patients in her practice on agents from two or more of these newer classes, and she has generally found it possible for patients to get much of their expenses covered by insurers and through drug-company assistance programs.

“The major gap is patients on Medicare,” she noted in an interview, because the Federal health insurance program does not allow beneficiaries to receive rebates for their drug costs. “The Diabetic Kidney Disease Collaborative is currently lobbying members of Congress to lift that barrier,” she emphasized.
 

Improved alignment

Details of the KDIGO recommendations feature in a guideline from that organization that appeared as a draft document online in March 2022. The ADA’s version recently appeared as an update to its Standards of Medical Care in Diabetes – 2022, as reported by this news organization. A panel of five KDIGO representatives and four members appointed by the ADA produced the harmonization statement.

Recommendations from both organizations were largely in agreement at the outset, but following the panel’s review, the two groups are now “very well-aligned,” said Peter Rossing, MD, DMSc, a diabetologist and professor at the Steno Diabetes Center, Copenhagen, and a KDIGO representative to the writing committee, who presented the joint statement at the ADA meeting.

“These are very important drugs that are vastly underused,” commented Josef Coresh, MD, PhD, an epidemiologist and professor at Johns Hopkins Bloomberg School of Public Health, Baltimore, who specializes in CKD and was not involved with the new statement.

“Coherence and simplicity are what we need so that there are no excuses about moving forward” with the recommended combination treatment, he stressed.

Moving too slow

“No one is resisting using these new medications, but they are just moving too slowly, and data now show that it’s moving more slowly in the United States than elsewhere. That may be partly because U.S. patients are charged much more for these drugs, and partly because U.S. health care is so much more fragmented,” Dr. Coresh said in an interview.

The new joint consensus statement may help, “but the fragmentation of the United States system and COVID-19 are big enemies” for any short-term increased use of the highlighted agents, he added.

Evidence for low U.S. use of SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists is becoming well known.

Dr. Rossing cited a 2019 report from the CURE-CKD registry of more than 600,000 U.S. patients with CKD showing that less than 1% received an SGLT2 inhibitor and less than 1% a GLP-1 receptor agonist. Not all these patients had diabetes, but a subgroup analysis of those with diabetes, prediabetes, or hypertension showed that usage of each of these two classes remained at less than 1% even in this group.

A separate report at the ADA meeting documented that of more than 1.3 million people with type 2 diabetes in the U.S. Veterans Affairs Healthcare System during 2019 and 2020, just 10% received an SGLT2 inhibitor and 7% a GLP-1 receptor agonist. And this is in a setting where drug cost is not a limiting factor.

In addition to focusing on the updated scheme for drug intervention in the consensus statement, Dr. Rossing highlighted several other important points that the writing committee emphasized.

Lifestyle optimization is a core first-line element of managing patients with diabetes and CKD, including a healthy diet, exercise, smoking cessation, and weight control. Other key steps for management include optimization of blood pressure, glucose, and lipids. The statement also calls out a potentially helpful role for continuous glucose monitoring in patients with type 1 or type 2 diabetes and CKD.

The statement notes that patients who also have atherosclerotic cardiovascular disease usually qualify for and could potentially benefit from more intensified lipid management with ezetimibe or a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, as well as a potential role for treatment with antiplatelet agents.
 

‘If you don’t screen, you won’t find it’

Dr. Rossing also stressed the importance of regular screening for the onset of advanced CKD in patients. Patients whose estimated glomerular filtration rate (eGFR) drops below 60 mL/min/1.73m2, as well as those who develop microalbuminuria with a urinary albumin-to-creatinine ratio of at least 30 mg/g (30 mg/mmol), have a stage of CKD that warrants the drug interventions he outlined.

Guidelines from both the ADA and KDIGO were already in place, recommending annual screening of patients with diabetes for both these parameters starting at diagnosis of type 2 diabetes or 5 years following initial diagnosis of type 1 diabetes.

“If you don’t screen, you won’t find it, and you won’t be able to treat,” Dr. Rossing warned. He also highlighted the panel’s recommendation to treat these patients with an SGLT2 inhibitor as long as their eGFR is at least 20 mL/min/1.73m2. Treatment can then continue even when their eGFR drops lower.

Starting treatment with finerenone requires that patients have a normal level of serum potassium, he emphasized.

One reason for developing the new ADA and KDIGO statement is that “discrepancies in clinical practice guideline recommendations from various professional organizations add to confusion that impedes understanding of best practices,” write Katherine R. Tuttle, MD, and associates in a recent commentary.

The goal of the new statement is to harmonize and promote the shared recommendations of the two organizations, added Dr. Tuttle, who is executive director for research at Providence Healthcare, Spokane, Washington, and a KDIGO representative on the statement writing panel.

Dr. Mottl has reported being a consultant to Bayer. Dr. Rossing has reported being a consultant to or speaker on behalf of Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, MSD, Mundipharma, Novo Nordisk, Sanofi Aventis, and Vifor, as well as receiving research grants from AstraZeneca and Novo Nordisk. Dr. Coresh has reported no relevant financial relationships. Dr. Tuttle has reported being a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Goldfinch Bio, Janssen, Novo Nordisk, and Travere; receiving honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Goldfinch Bio, Novo Nordisk, and Travere; and receiving research funding from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Goldfinch Bio, Novo Nordisk, and Travere.

A version of this article first appeared on Medscape.com.

Individuals with diabetes who experience COVID-19 are at increased risk for long COVID compared to individuals without diabetes, according to data from a literature review of seven studies.

Diabetes remains a risk factor for severe COVID-19, but whether it is a risk factor for postacute sequelae of COVID-19 (PASC), also known as long COVID, remains unclear, Jessica L. Harding, PhD, of Emory University, said in a late-breaking poster session at the annual scientific sessions of the American Diabetes Association.

Long COVID is generally defined as “sequelae that extend beyond the 4 weeks after initial infection” and may include a range of symptoms that affect multiple organs, Dr. Harding said. A study conducted in January of 2022 suggested that type 2 diabetes was one of several strong risk factors for long COVID, she noted.

Dr. Harding and colleagues reviewed data from seven studies published from Jan. 1, 2020, to Jan. 27, 2022, on the risk of PASC in people with and without diabetes. The studies included patients with a minimum of 4 weeks’ follow-up after COVID-19 diagnosis. All seven studies had a longitudinal cohort design, and included adults from high-income countries, with study populations ranging from 104 to 4,182.

Across the studies, long COVID definitions varied, but included ongoing symptoms of fatigue, cough, and dyspnea, with follow-up periods of 4 weeks to 7 months.

Overall, three of the seven studies indicated that diabetes was a risk factor for long COVID (odds ratio [OR] greater than 4 for all) and four studies indicated that diabetes was not a risk factor for long COVID (OR, 0.5-2.2).

One of the three studies showing increased risk included 2,334 individuals hospitalized with COVID-19; of these about 5% had diabetes. The odds ratio for PASC for individuals with diabetes was 4.18. In another study of 209 persons with COVID-19, of whom 22% had diabetes, diabetes was significantly correlated with respiratory viral disease (meaning at least two respiratory symptoms). The third study showing an increased risk of long COVID in diabetes patients included 104 kidney transplant patients, of whom 20% had diabetes; the odds ratio for PASC was 4.42.

The findings were limited by several factors, including the relatively small number of studies and the heterogeneity of studies regarding definitions of long COVID, specific populations at risk, follow-up times, and risk adjustment, Dr. Harding noted.

More high-quality studies across multiple populations and settings are needed to determine if diabetes is indeed a risk factor for long COVID, she said.

In the meantime, “careful monitoring of people with diabetes for development of PASC may be advised,” Dr. Harding concluded.
 

Findings support need for screening

“Given the devastating impact of COVID on people with diabetes, it’s important to know what data has been accumulated on long COVID for future research and discoveries in this area,” Robert A. Gabbay, MD, chief science and medical officer for the American Diabetes Association, said in an interview. “The more information we have, the better we can understand the implications.”

Courtesy Joslin Diabetes Center

Dr. Gabbay said he was surprised by the current study findings. “We know very little on this subject, so yes, I am surprised to see just how significant the risk of long COVID for people with diabetes seems to be, but clearly, more research needs to be done to understand long COVID,” he emphasized.

The take-home message for clinicians is the importance of screening patients for PASC; also “ask your patients if they had COVID, to better understand any symptoms they might have that could be related to PACS,” he noted. 

“It is crucial that we confirm these results and then look at risk factors in people with diabetes that might explain who is at highest risk and ultimately understand the causes and potential cure,” Dr. Gabbay added.

The study was supported by the National Heart, Lung, and Blood Institute. Dr. Harding and Dr. Gabbay had no financial conflicts to disclose.

Individuals with diabetes who experience COVID-19 are at increased risk for long COVID compared to individuals without diabetes, according to data from a literature review of seven studies.

Diabetes remains a risk factor for severe COVID-19, but whether it is a risk factor for postacute sequelae of COVID-19 (PASC), also known as long COVID, remains unclear, Jessica L. Harding, PhD, of Emory University, said in a late-breaking poster session at the annual scientific sessions of the American Diabetes Association.

Long COVID is generally defined as “sequelae that extend beyond the 4 weeks after initial infection” and may include a range of symptoms that affect multiple organs, Dr. Harding said. A study conducted in January of 2022 suggested that type 2 diabetes was one of several strong risk factors for long COVID, she noted.

Dr. Harding and colleagues reviewed data from seven studies published from Jan. 1, 2020, to Jan. 27, 2022, on the risk of PASC in people with and without diabetes. The studies included patients with a minimum of 4 weeks’ follow-up after COVID-19 diagnosis. All seven studies had a longitudinal cohort design, and included adults from high-income countries, with study populations ranging from 104 to 4,182.

Across the studies, long COVID definitions varied, but included ongoing symptoms of fatigue, cough, and dyspnea, with follow-up periods of 4 weeks to 7 months.

Overall, three of the seven studies indicated that diabetes was a risk factor for long COVID (odds ratio [OR] greater than 4 for all) and four studies indicated that diabetes was not a risk factor for long COVID (OR, 0.5-2.2).

One of the three studies showing increased risk included 2,334 individuals hospitalized with COVID-19; of these about 5% had diabetes. The odds ratio for PASC for individuals with diabetes was 4.18. In another study of 209 persons with COVID-19, of whom 22% had diabetes, diabetes was significantly correlated with respiratory viral disease (meaning at least two respiratory symptoms). The third study showing an increased risk of long COVID in diabetes patients included 104 kidney transplant patients, of whom 20% had diabetes; the odds ratio for PASC was 4.42.

The findings were limited by several factors, including the relatively small number of studies and the heterogeneity of studies regarding definitions of long COVID, specific populations at risk, follow-up times, and risk adjustment, Dr. Harding noted.

More high-quality studies across multiple populations and settings are needed to determine if diabetes is indeed a risk factor for long COVID, she said.

In the meantime, “careful monitoring of people with diabetes for development of PASC may be advised,” Dr. Harding concluded.
 

Findings support need for screening

“Given the devastating impact of COVID on people with diabetes, it’s important to know what data has been accumulated on long COVID for future research and discoveries in this area,” Robert A. Gabbay, MD, chief science and medical officer for the American Diabetes Association, said in an interview. “The more information we have, the better we can understand the implications.”

Courtesy Joslin Diabetes Center

Dr. Gabbay said he was surprised by the current study findings. “We know very little on this subject, so yes, I am surprised to see just how significant the risk of long COVID for people with diabetes seems to be, but clearly, more research needs to be done to understand long COVID,” he emphasized.

The take-home message for clinicians is the importance of screening patients for PASC; also “ask your patients if they had COVID, to better understand any symptoms they might have that could be related to PACS,” he noted. 

“It is crucial that we confirm these results and then look at risk factors in people with diabetes that might explain who is at highest risk and ultimately understand the causes and potential cure,” Dr. Gabbay added.

The study was supported by the National Heart, Lung, and Blood Institute. Dr. Harding and Dr. Gabbay had no financial conflicts to disclose.

Individuals with diabetes who experience COVID-19 are at increased risk for long COVID compared to individuals without diabetes, according to data from a literature review of seven studies.

Diabetes remains a risk factor for severe COVID-19, but whether it is a risk factor for postacute sequelae of COVID-19 (PASC), also known as long COVID, remains unclear, Jessica L. Harding, PhD, of Emory University, said in a late-breaking poster session at the annual scientific sessions of the American Diabetes Association.

Long COVID is generally defined as “sequelae that extend beyond the 4 weeks after initial infection” and may include a range of symptoms that affect multiple organs, Dr. Harding said. A study conducted in January of 2022 suggested that type 2 diabetes was one of several strong risk factors for long COVID, she noted.

Dr. Harding and colleagues reviewed data from seven studies published from Jan. 1, 2020, to Jan. 27, 2022, on the risk of PASC in people with and without diabetes. The studies included patients with a minimum of 4 weeks’ follow-up after COVID-19 diagnosis. All seven studies had a longitudinal cohort design, and included adults from high-income countries, with study populations ranging from 104 to 4,182.

Across the studies, long COVID definitions varied, but included ongoing symptoms of fatigue, cough, and dyspnea, with follow-up periods of 4 weeks to 7 months.

Overall, three of the seven studies indicated that diabetes was a risk factor for long COVID (odds ratio [OR] greater than 4 for all) and four studies indicated that diabetes was not a risk factor for long COVID (OR, 0.5-2.2).

One of the three studies showing increased risk included 2,334 individuals hospitalized with COVID-19; of these about 5% had diabetes. The odds ratio for PASC for individuals with diabetes was 4.18. In another study of 209 persons with COVID-19, of whom 22% had diabetes, diabetes was significantly correlated with respiratory viral disease (meaning at least two respiratory symptoms). The third study showing an increased risk of long COVID in diabetes patients included 104 kidney transplant patients, of whom 20% had diabetes; the odds ratio for PASC was 4.42.

The findings were limited by several factors, including the relatively small number of studies and the heterogeneity of studies regarding definitions of long COVID, specific populations at risk, follow-up times, and risk adjustment, Dr. Harding noted.

More high-quality studies across multiple populations and settings are needed to determine if diabetes is indeed a risk factor for long COVID, she said.

In the meantime, “careful monitoring of people with diabetes for development of PASC may be advised,” Dr. Harding concluded.
 

Findings support need for screening

“Given the devastating impact of COVID on people with diabetes, it’s important to know what data has been accumulated on long COVID for future research and discoveries in this area,” Robert A. Gabbay, MD, chief science and medical officer for the American Diabetes Association, said in an interview. “The more information we have, the better we can understand the implications.”

Courtesy Joslin Diabetes Center

Dr. Gabbay said he was surprised by the current study findings. “We know very little on this subject, so yes, I am surprised to see just how significant the risk of long COVID for people with diabetes seems to be, but clearly, more research needs to be done to understand long COVID,” he emphasized.

The take-home message for clinicians is the importance of screening patients for PASC; also “ask your patients if they had COVID, to better understand any symptoms they might have that could be related to PACS,” he noted. 

“It is crucial that we confirm these results and then look at risk factors in people with diabetes that might explain who is at highest risk and ultimately understand the causes and potential cure,” Dr. Gabbay added.

The study was supported by the National Heart, Lung, and Blood Institute. Dr. Harding and Dr. Gabbay had no financial conflicts to disclose.

Menopause gets a bad rap in medical literature and throughout society, say authors of a new analysis. And they argue that the negativity undermines women’s health outlook in the years that should be a natural life transition.

Menopause has been medicalized over centuries and talked about as if it were a disease, they say, and that may increase women’s anxiety and apprehension about the midlife stage.

It’s time to change the narrative, says Martha Hickey, MD, with the department of obstetrics and gynaecology at the Royal Women’s Hospital in Victoria, Australia, and her coauthors. Their analysis was published online in the BMJ.

“The message that menopause signals decay and decline, which can potentially be delayed or reversed by hormonal treatments, persists and is reinforced by the media, medical literature, and information for women, often driven by marketing interests,” they write.

Such messages may chip away at women’s confidence. Dr. Hickey and colleagues cite surveys in the United States and Ireland that found that most women (65%-77%) feel unprepared for menopause.

“Together with limited public discussion and education and shame attached to ageing in women, this may contribute to embarrassment and negative expectations about menopause,” the authors write.
 

The ‘untold misery of oestrogen-starved women’

These messages have deep roots. Take for instance, gynecologist Robert Wilson’s words in his 1966 book “Feminine Forever.” The authors note he recommended estrogen for all menopausal women “to treat their ‘serious, painful and often crippling disease’ and avoid the ‘untold misery of alcoholism, drug addiction, divorce, and broken

homes caused by these unstable, oestrogen-starved women.’ ”

Women experience menopause in very different ways. Experience with menopause also differs by country, the authors explain. “Women’s experience of menopause is also strongly influenced by social values around reproduction and ageing, with positive or negative ramifications,” they write.

“For example, women tend to have worse experiences of menopause in countries where their value is predicated on youth and reproductive capacity and ageing is associated with decline.”

The authors argue that the medicalization of menopause has condensed the wide range of women’s experiences at a typical age into “a narrowly defined disease requiring treatment.”
 

Promoting exercise, stopping smoking among positive messages

An editorial by Haitham Hamoda, MD, and Sara Moger, with the British Menopause Society, notes that more than 75% of women experiencing menopause report symptoms, and more than 25% describe severe symptoms.

The editorialists point out that the National Institute of Health and Care Excellence and others recommend an individualized approach to addressing menopause that includes a comprehensive approach – advice on exercise, weight management, stopping smoking, and reducing alcohol as well as options such as hormone therapy (HT).

The literature says the main indication for HT is for severe symptoms and not as a preventive measure. “Evidence does not support use of HT to reduce the risk of dementia,” they point out.

While some women may benefit from HT, that should not be explored to the exclusion of other avenues of help, Dr. Hickey and colleagues write. Risks must also be considered.
 

Menopause blamed in a difficult time of life

Jennifer Howell, MD, an obstetrician/gynecologist and certified menopause provider at Duke University in Durham, N.C., told this news organization that menopause is often blamed in a time of life when women naturally are experiencing an array of stressful and emotional changes.

It often coincides with children heading to college, navigating midlife challenges in marriage, helping aging parents, managing demanding careers, and health issues.

People want a reason for changes women experience, and too often the finger gets pointed at menopause, Dr. Howell said.

The message women hear has always been, “It’s got to be your hormones. And people want to hear that there’s a hormonal solution.”

Making menopause the target also has led to nonevidence-based “snake-oil” type remedies sold in unregulated powders, creams, and pellets, Dr. Howell noted.

Dr. Howell has treated thousands of menopausal women in her clinic and she says she spends a good deal of time with them explaining a holistic view of the process, much like what the authors describe, with lifestyle changes and treatment options.

Sometimes HT is the solution, Dr. Howell says, but “it’s become a crutch. Hormones are not a panacea.”

She is frustrated with the amount of disinformation circulating online. Groups like the North American Menopause Society put out reliable evidence-based information, but they compete “with a lot of nonsense,” she says.

The message that women should hear, she says is that “[menopause] is a natural part of aging and there may or may not be symptoms that come along with it. If there are, there are things we can do,” she says.

Menopause gets a bad rap in medical literature and throughout society, say authors of a new analysis. And they argue that the negativity undermines women’s health outlook in the years that should be a natural life transition.

Menopause has been medicalized over centuries and talked about as if it were a disease, they say, and that may increase women’s anxiety and apprehension about the midlife stage.

It’s time to change the narrative, says Martha Hickey, MD, with the department of obstetrics and gynaecology at the Royal Women’s Hospital in Victoria, Australia, and her coauthors. Their analysis was published online in the BMJ.

“The message that menopause signals decay and decline, which can potentially be delayed or reversed by hormonal treatments, persists and is reinforced by the media, medical literature, and information for women, often driven by marketing interests,” they write.

Such messages may chip away at women’s confidence. Dr. Hickey and colleagues cite surveys in the United States and Ireland that found that most women (65%-77%) feel unprepared for menopause.

“Together with limited public discussion and education and shame attached to ageing in women, this may contribute to embarrassment and negative expectations about menopause,” the authors write.
 

The ‘untold misery of oestrogen-starved women’

These messages have deep roots. Take for instance, gynecologist Robert Wilson’s words in his 1966 book “Feminine Forever.” The authors note he recommended estrogen for all menopausal women “to treat their ‘serious, painful and often crippling disease’ and avoid the ‘untold misery of alcoholism, drug addiction, divorce, and broken

homes caused by these unstable, oestrogen-starved women.’ ”

Women experience menopause in very different ways. Experience with menopause also differs by country, the authors explain. “Women’s experience of menopause is also strongly influenced by social values around reproduction and ageing, with positive or negative ramifications,” they write.

“For example, women tend to have worse experiences of menopause in countries where their value is predicated on youth and reproductive capacity and ageing is associated with decline.”

The authors argue that the medicalization of menopause has condensed the wide range of women’s experiences at a typical age into “a narrowly defined disease requiring treatment.”
 

Promoting exercise, stopping smoking among positive messages

An editorial by Haitham Hamoda, MD, and Sara Moger, with the British Menopause Society, notes that more than 75% of women experiencing menopause report symptoms, and more than 25% describe severe symptoms.

The editorialists point out that the National Institute of Health and Care Excellence and others recommend an individualized approach to addressing menopause that includes a comprehensive approach – advice on exercise, weight management, stopping smoking, and reducing alcohol as well as options such as hormone therapy (HT).

The literature says the main indication for HT is for severe symptoms and not as a preventive measure. “Evidence does not support use of HT to reduce the risk of dementia,” they point out.

While some women may benefit from HT, that should not be explored to the exclusion of other avenues of help, Dr. Hickey and colleagues write. Risks must also be considered.
 

Menopause blamed in a difficult time of life

Jennifer Howell, MD, an obstetrician/gynecologist and certified menopause provider at Duke University in Durham, N.C., told this news organization that menopause is often blamed in a time of life when women naturally are experiencing an array of stressful and emotional changes.

It often coincides with children heading to college, navigating midlife challenges in marriage, helping aging parents, managing demanding careers, and health issues.

People want a reason for changes women experience, and too often the finger gets pointed at menopause, Dr. Howell said.

The message women hear has always been, “It’s got to be your hormones. And people want to hear that there’s a hormonal solution.”

Making menopause the target also has led to nonevidence-based “snake-oil” type remedies sold in unregulated powders, creams, and pellets, Dr. Howell noted.

Dr. Howell has treated thousands of menopausal women in her clinic and she says she spends a good deal of time with them explaining a holistic view of the process, much like what the authors describe, with lifestyle changes and treatment options.

Sometimes HT is the solution, Dr. Howell says, but “it’s become a crutch. Hormones are not a panacea.”

She is frustrated with the amount of disinformation circulating online. Groups like the North American Menopause Society put out reliable evidence-based information, but they compete “with a lot of nonsense,” she says.

The message that women should hear, she says is that “[menopause] is a natural part of aging and there may or may not be symptoms that come along with it. If there are, there are things we can do,” she says.

Menopause gets a bad rap in medical literature and throughout society, say authors of a new analysis. And they argue that the negativity undermines women’s health outlook in the years that should be a natural life transition.

Menopause has been medicalized over centuries and talked about as if it were a disease, they say, and that may increase women’s anxiety and apprehension about the midlife stage.

It’s time to change the narrative, says Martha Hickey, MD, with the department of obstetrics and gynaecology at the Royal Women’s Hospital in Victoria, Australia, and her coauthors. Their analysis was published online in the BMJ.

“The message that menopause signals decay and decline, which can potentially be delayed or reversed by hormonal treatments, persists and is reinforced by the media, medical literature, and information for women, often driven by marketing interests,” they write.

Such messages may chip away at women’s confidence. Dr. Hickey and colleagues cite surveys in the United States and Ireland that found that most women (65%-77%) feel unprepared for menopause.

“Together with limited public discussion and education and shame attached to ageing in women, this may contribute to embarrassment and negative expectations about menopause,” the authors write.
 

The ‘untold misery of oestrogen-starved women’

These messages have deep roots. Take for instance, gynecologist Robert Wilson’s words in his 1966 book “Feminine Forever.” The authors note he recommended estrogen for all menopausal women “to treat their ‘serious, painful and often crippling disease’ and avoid the ‘untold misery of alcoholism, drug addiction, divorce, and broken

homes caused by these unstable, oestrogen-starved women.’ ”

Women experience menopause in very different ways. Experience with menopause also differs by country, the authors explain. “Women’s experience of menopause is also strongly influenced by social values around reproduction and ageing, with positive or negative ramifications,” they write.

“For example, women tend to have worse experiences of menopause in countries where their value is predicated on youth and reproductive capacity and ageing is associated with decline.”

The authors argue that the medicalization of menopause has condensed the wide range of women’s experiences at a typical age into “a narrowly defined disease requiring treatment.”
 

Promoting exercise, stopping smoking among positive messages

An editorial by Haitham Hamoda, MD, and Sara Moger, with the British Menopause Society, notes that more than 75% of women experiencing menopause report symptoms, and more than 25% describe severe symptoms.

The editorialists point out that the National Institute of Health and Care Excellence and others recommend an individualized approach to addressing menopause that includes a comprehensive approach – advice on exercise, weight management, stopping smoking, and reducing alcohol as well as options such as hormone therapy (HT).

The literature says the main indication for HT is for severe symptoms and not as a preventive measure. “Evidence does not support use of HT to reduce the risk of dementia,” they point out.

While some women may benefit from HT, that should not be explored to the exclusion of other avenues of help, Dr. Hickey and colleagues write. Risks must also be considered.
 

Menopause blamed in a difficult time of life

Jennifer Howell, MD, an obstetrician/gynecologist and certified menopause provider at Duke University in Durham, N.C., told this news organization that menopause is often blamed in a time of life when women naturally are experiencing an array of stressful and emotional changes.

It often coincides with children heading to college, navigating midlife challenges in marriage, helping aging parents, managing demanding careers, and health issues.

People want a reason for changes women experience, and too often the finger gets pointed at menopause, Dr. Howell said.

The message women hear has always been, “It’s got to be your hormones. And people want to hear that there’s a hormonal solution.”

Making menopause the target also has led to nonevidence-based “snake-oil” type remedies sold in unregulated powders, creams, and pellets, Dr. Howell noted.

Dr. Howell has treated thousands of menopausal women in her clinic and she says she spends a good deal of time with them explaining a holistic view of the process, much like what the authors describe, with lifestyle changes and treatment options.

Sometimes HT is the solution, Dr. Howell says, but “it’s become a crutch. Hormones are not a panacea.”

She is frustrated with the amount of disinformation circulating online. Groups like the North American Menopause Society put out reliable evidence-based information, but they compete “with a lot of nonsense,” she says.

The message that women should hear, she says is that “[menopause] is a natural part of aging and there may or may not be symptoms that come along with it. If there are, there are things we can do,” she says.

President Joe Biden issued an executive order on June 15 banning conversion therapy and offering other LBGTQIA+ protections as part of White House efforts to advance equality during Pride Month.

“My order will use the full force of the federal government to end inhumane practices of conversion therapy,” President Biden said in a speech before signing the order. “This is the first time the federal government is making a coordinated effort against this dangerous and discredited practice.”

Conversion therapy is any emotional or physical therapy used to “cure” or “repair” a person’s attraction to the same sex, or their gender identity and expression. Providers claim these therapies can make someone heterosexual or “straight.” But there’s no evidence to support this.

Medical and mental health experts have rejected conversion therapy practices as dangerous and discriminatory for decades.

The executive order also addresses:

• The LGBTQIA+ youth mental health crisis, in part by expanding suicide prevention resources for that at-risk population.
• Discrimination within the foster care system against LGBTQIA+ children and parents.
• Discrimination, poverty and isolation challenges faced by LGBTQIA+ seniors.
• Efforts to strengthen federal data collection in this population to counter homelessness, housing insecurity and barriers to health care access.

Enforcement of executive order will rely on legal experts, including the Justice Department.

President Biden’s order comes at a time when multiple states are promoting or passing anti-LGBTQIA+ laws.

“I don’t have to tell you about the ultra-MAGA agenda attacking our freedoms. There are more than 300 discriminatory bills introduced in states across this country,” President Biden said. “In Texas, they are knocking on front doors to investigate parents who are raising transgender children, and in Florida they are going after Mickey Mouse for God’s sake.”

First Lady Jill Biden, PhD, said the order will not solve all problems. “Prejudice and discrimination still lurk. We will not let the progress we fought for slip away. Pride is a celebration of the courage it takes to stand up for what’s right.”

The American Psychiatric Association applauded President Biden’s action. This executive order will “protect the mental health of LGBTQ+ people, particularly children. APA has long condemned the practice of so-called ‘conversion therapy’ and we welcome the federal government’s efforts to raise public awareness about its harms, alongside other practices that will help to end it.”

The goal of the order is to “improve the health, wellbeing, and safety of countless families across the country,” senior White House administration officials said in a June 15 media call. “And they will send a powerful signal from the president of the United States to LGBTQIA+ kids across the country – who may be feeling scared and hopeless – that their president has their back.”

Biden also called on Congress to pass the Equality Act “to enshrine the long overdue civil rights to protect all Americans.”

The event was held in the East Room of the White House at a Pride event attended by Vice President Kamala Harris and her husband, the first lady, Transportation Secretary Pete Buttigieg, and hundreds of LGBTQIA+ leaders.
 

Guidance on starting transgender treatment

In other LGBTQIA+-related news, an international group focusing on transgender health lowered the minimum ages they recommend for starting hormone therapy or surgery for transgender youth.

The World Professional Association for Transgender Health said that hormones could be started at 14, 2 years earlier than the group’s previous advice. The association also said some surgeries can be performed at age 15 or 17, a year or so earlier than their previous recommendations.

The group acknowledged potential risks but said it is unethical and harmful to withhold early treatment, according to a report from The Associated Press.

Transgender treatment for teens has been a controversial issue, with experts disagreeing about whether teenagers can fully understand the ramifications of such life-altering decisions.

During the White House background media call, senior administration officials pointed to existing policy regarding transgender care. “We’ve already put out guidance through HHS about civil rights protections and making clear that the denial of medical care based on someone’s gender identity is discriminatory and have invited the members of the public to file complaints with the Office of Civil Rights.”

A version of this article first appeared on WebMD.com.

President Joe Biden issued an executive order on June 15 banning conversion therapy and offering other LBGTQIA+ protections as part of White House efforts to advance equality during Pride Month.

“My order will use the full force of the federal government to end inhumane practices of conversion therapy,” President Biden said in a speech before signing the order. “This is the first time the federal government is making a coordinated effort against this dangerous and discredited practice.”

Conversion therapy is any emotional or physical therapy used to “cure” or “repair” a person’s attraction to the same sex, or their gender identity and expression. Providers claim these therapies can make someone heterosexual or “straight.” But there’s no evidence to support this.

Medical and mental health experts have rejected conversion therapy practices as dangerous and discriminatory for decades.

The executive order also addresses:

• The LGBTQIA+ youth mental health crisis, in part by expanding suicide prevention resources for that at-risk population.
• Discrimination within the foster care system against LGBTQIA+ children and parents.
• Discrimination, poverty and isolation challenges faced by LGBTQIA+ seniors.
• Efforts to strengthen federal data collection in this population to counter homelessness, housing insecurity and barriers to health care access.

Enforcement of executive order will rely on legal experts, including the Justice Department.

President Biden’s order comes at a time when multiple states are promoting or passing anti-LGBTQIA+ laws.

“I don’t have to tell you about the ultra-MAGA agenda attacking our freedoms. There are more than 300 discriminatory bills introduced in states across this country,” President Biden said. “In Texas, they are knocking on front doors to investigate parents who are raising transgender children, and in Florida they are going after Mickey Mouse for God’s sake.”

First Lady Jill Biden, PhD, said the order will not solve all problems. “Prejudice and discrimination still lurk. We will not let the progress we fought for slip away. Pride is a celebration of the courage it takes to stand up for what’s right.”

The American Psychiatric Association applauded President Biden’s action. This executive order will “protect the mental health of LGBTQ+ people, particularly children. APA has long condemned the practice of so-called ‘conversion therapy’ and we welcome the federal government’s efforts to raise public awareness about its harms, alongside other practices that will help to end it.”

The goal of the order is to “improve the health, wellbeing, and safety of countless families across the country,” senior White House administration officials said in a June 15 media call. “And they will send a powerful signal from the president of the United States to LGBTQIA+ kids across the country – who may be feeling scared and hopeless – that their president has their back.”

Biden also called on Congress to pass the Equality Act “to enshrine the long overdue civil rights to protect all Americans.”

The event was held in the East Room of the White House at a Pride event attended by Vice President Kamala Harris and her husband, the first lady, Transportation Secretary Pete Buttigieg, and hundreds of LGBTQIA+ leaders.
 

Guidance on starting transgender treatment

In other LGBTQIA+-related news, an international group focusing on transgender health lowered the minimum ages they recommend for starting hormone therapy or surgery for transgender youth.

The World Professional Association for Transgender Health said that hormones could be started at 14, 2 years earlier than the group’s previous advice. The association also said some surgeries can be performed at age 15 or 17, a year or so earlier than their previous recommendations.

The group acknowledged potential risks but said it is unethical and harmful to withhold early treatment, according to a report from The Associated Press.

Transgender treatment for teens has been a controversial issue, with experts disagreeing about whether teenagers can fully understand the ramifications of such life-altering decisions.

During the White House background media call, senior administration officials pointed to existing policy regarding transgender care. “We’ve already put out guidance through HHS about civil rights protections and making clear that the denial of medical care based on someone’s gender identity is discriminatory and have invited the members of the public to file complaints with the Office of Civil Rights.”

A version of this article first appeared on WebMD.com.

President Joe Biden issued an executive order on June 15 banning conversion therapy and offering other LBGTQIA+ protections as part of White House efforts to advance equality during Pride Month.

“My order will use the full force of the federal government to end inhumane practices of conversion therapy,” President Biden said in a speech before signing the order. “This is the first time the federal government is making a coordinated effort against this dangerous and discredited practice.”

Conversion therapy is any emotional or physical therapy used to “cure” or “repair” a person’s attraction to the same sex, or their gender identity and expression. Providers claim these therapies can make someone heterosexual or “straight.” But there’s no evidence to support this.

Medical and mental health experts have rejected conversion therapy practices as dangerous and discriminatory for decades.

The executive order also addresses:

• The LGBTQIA+ youth mental health crisis, in part by expanding suicide prevention resources for that at-risk population.
• Discrimination within the foster care system against LGBTQIA+ children and parents.
• Discrimination, poverty and isolation challenges faced by LGBTQIA+ seniors.
• Efforts to strengthen federal data collection in this population to counter homelessness, housing insecurity and barriers to health care access.

Enforcement of executive order will rely on legal experts, including the Justice Department.

President Biden’s order comes at a time when multiple states are promoting or passing anti-LGBTQIA+ laws.

“I don’t have to tell you about the ultra-MAGA agenda attacking our freedoms. There are more than 300 discriminatory bills introduced in states across this country,” President Biden said. “In Texas, they are knocking on front doors to investigate parents who are raising transgender children, and in Florida they are going after Mickey Mouse for God’s sake.”

First Lady Jill Biden, PhD, said the order will not solve all problems. “Prejudice and discrimination still lurk. We will not let the progress we fought for slip away. Pride is a celebration of the courage it takes to stand up for what’s right.”

The American Psychiatric Association applauded President Biden’s action. This executive order will “protect the mental health of LGBTQ+ people, particularly children. APA has long condemned the practice of so-called ‘conversion therapy’ and we welcome the federal government’s efforts to raise public awareness about its harms, alongside other practices that will help to end it.”

The goal of the order is to “improve the health, wellbeing, and safety of countless families across the country,” senior White House administration officials said in a June 15 media call. “And they will send a powerful signal from the president of the United States to LGBTQIA+ kids across the country – who may be feeling scared and hopeless – that their president has their back.”

Biden also called on Congress to pass the Equality Act “to enshrine the long overdue civil rights to protect all Americans.”

The event was held in the East Room of the White House at a Pride event attended by Vice President Kamala Harris and her husband, the first lady, Transportation Secretary Pete Buttigieg, and hundreds of LGBTQIA+ leaders.
 

Guidance on starting transgender treatment

In other LGBTQIA+-related news, an international group focusing on transgender health lowered the minimum ages they recommend for starting hormone therapy or surgery for transgender youth.

The World Professional Association for Transgender Health said that hormones could be started at 14, 2 years earlier than the group’s previous advice. The association also said some surgeries can be performed at age 15 or 17, a year or so earlier than their previous recommendations.

The group acknowledged potential risks but said it is unethical and harmful to withhold early treatment, according to a report from The Associated Press.

Transgender treatment for teens has been a controversial issue, with experts disagreeing about whether teenagers can fully understand the ramifications of such life-altering decisions.

During the White House background media call, senior administration officials pointed to existing policy regarding transgender care. “We’ve already put out guidance through HHS about civil rights protections and making clear that the denial of medical care based on someone’s gender identity is discriminatory and have invited the members of the public to file complaints with the Office of Civil Rights.”

A version of this article first appeared on WebMD.com.

ATLANTA -- Liquid formulations of levothyroxine offer the possibility of allowing patients with hypothyroidism to take their medication with meals or coffee and skip the currently recommended 30- to 60-minute waiting period before doing either, new data suggest.

amenic181/Getty Images

Because food, coffee, and certain medications can interfere with intestinal absorption of levothyroxine (also known as LT4), current guidelines recommend that the drug be taken in a fasting state, typically 30-60 minutes before breakfast. However, compliance may be difficult for some patients.

Now, a potential solution may come from new evidence that liquid levothyroxine formulations that bypass the gastric dissolution phase of absorption may mitigate the interference with food and coffee.

Findings from two bioavailability studies showing no difference in comparisons of Thyquidity (levothyroxine sodium oral solution, Vertice Pharma) with or without waiting periods before consuming coffee or a high-fat meal were presented at the annual meeting of the Endocrine Society (ENDO 2022), by Vertice Pharma Medical Director Kris Washington, PharmD.

And just last month, similar data were published in Thyroid for another levothyroxine oral solution, Tirosint-SOL (IBSA). No difference in pharmacokinetic properties were found with this product with a shorter versus a longer waiting period before consuming a high-fat meal.
 

Liquid thyroxine may be less affected by food/drink but is expensive

Both products have been approved by the U.S. Food and Drug Administration, but current labeling for both still calls for a 30- to 60-minute waiting period between taking the medication and eating or drinking. Thyquidity is an oral solution of 100 µg/mL levothyroxine sodium that has been shown to be bioequivalent to one of the most popular branded levothyroxine tablets, Synthroid (AbbVie), under fasting conditions. Tirosint-SOL is also an oral solution that comes in 15 different dosage ampules.

“It is important to note that while these findings are exciting and encouraging, we do want you to continue to follow the current FDA-approved label for Thyquidity, recommending that it be taken on an empty stomach 30-60 minutes prior to breakfast and that patients continue to follow all other label instructions,” Dr. Washington said during a press briefing at ENDO 2022.

When asked whether the new data would be submitted to the FDA for a possible amendment to this message, she replied: “We’re still discussing that. We’re exploring all options. ... This is fairly new data. ... It makes sense and certainly solves a lot of the challenges for people who can’t swallow or don’t choose to swallow, or the challenges of splitting or crushing with tablets.”

Asked to comment, Benjamin J. Gigliotti, MD, a clinical thyroidologist at the University of Rochester, New York, told this news organization: “Liquid levothyroxine has the potential to be a clinically useful formulation,” noting that these recent data corroborate prior findings from Europe and elsewhere that liquid levothyroxine is absorbed more rapidly and thus may be less impacted by food or beverages.

However, Dr. Gigliotti also pointed out, “I don’t think malabsorption is a major contributor to suboptimal treatment because if [patients] malabsorb the hormone, we typically just increase their dose a little bit or ask them to take it separately, and that works just fine for most people.”

And the higher cost of the liquid products is a major issue, he noted. 

A quick search on GoodRx shows that the lowest price of Tirosint-SOL is $115.52 for a 1 month supply and Thyquidity is $181.04/month. “In the few patients where I tried to obtain Tirosint-SOL, it was not covered by insurance, even with a prior authorization,” Dr. Gigliotti commented.

In contrast, generic levothyroxine tablets are about $4/month, while a common brand name of levothyroxine tablets are $47.81/month.

“Until these liquid formulations are more widely covered by insurance for a reasonable copay, or come down in price compared to generic levothyroxine tablets, most of my patients have voiced that they’d rather deal with the inconveniences of a tablet compared to higher medication cost, especially with rising economic insecurity imposed by the COVID-19 pandemic and recent world events,” Dr. Gigliotti said.
 

Bioequivalence with shorter versus longer waits before coffee/breakfast

The Thyquidity coffee study was a single-center open-label, randomized, crossover study of 40 healthy adults randomized after a 10-hour overnight fast to 600 µg Thyquidity with water under fasting conditions or to the same dose given 5 minutes prior to drinking an 8-ounce cup of American coffee without milk or sweeteners. After a 40-day washout period, the same participants received the other treatment.

Mean serum thyroxine (T4) concentrations over 48 hours were nearly identical, demonstrating comparable bioavailability. Pharmacokinetics parameters, including area under the curve (AUC) and Cmax, were also comparable for both groups. The geometric least square mean ratios for baseline-adjusted LT4 were 96.0% for Cmax and 94% for AUC. And the corresponding 90% confidence intervals fell within the 80%-125% FDA acceptance range for absence of a food effect on bioavailability, said Dr. Washington when presenting the findings.

There was one adverse event, a decrease in blood glucose level, which was deemed to be mild and unrelated to study treatment. No deaths, serious adverse events, or discontinuations due to adverse events were reported. There were no significant changes in vital signs or on ECG.

In the second Thyquidity study of 38 healthy adults, after a 10-hour fast, the same doses were given 10 or 30 minutes prior to the consumption of a 950-calorie standardized high-fat breakfast.

Again, over 48 hours, mean serum T4 levels were comparable between the two groups. The geometric least squares mean ratios for both AUC and Cmax for baseline-adjusted LT4 were 88.7% and 85.1%, respectively. Again, the corresponding 90% confidence intervals fell within the FDA’s noninterference definition, again demonstrating lack of a food effect on bioavailability, Dr. Washington noted.

Four adverse events were reported in three participants, with three deemed to be possibly related to the medication. All were isolated lab abnormalities without clinical symptoms and deemed to be mild. Three were normal on repeat testing.

There were no deaths or serious adverse events or study discontinuations for adverse events and no significant findings for vital signs or on ECG.
 

Similar findings for Tirosint-SOL but longer-term studies needed

The recently published Tirosint-SOL study included 36 healthy volunteers randomized to single 600-µg doses of the LT4 oral solution after a 10-hour fast, either 15 or 30 minutes before eating a standardized high-fat, high-calorie meal. Mean serum total thyroxine concentration profiles were similar for both the 15- and 30-minute waits, with similar AUCs.

Geometric mean ratios for AUCs at 48 and 72 hours were 90% and 92%, respectively, and the 90% confidence intervals fell within the 80%-125% FDA boundaries, suggesting similar exposures whether taken 15 or 30 minutes before a meal.

Senior author Francesco S. Celi, MD, chair of the division of endocrinology, diabetes, and metabolism at Virginia Commonwealth University, Richmond, told this news organization: “There is an interest in providing more opportunities for patients and improving adherence to the medication. ... Whatever makes life a bit easier for patients and results in a more predictable response to treatment means down the road there will be fewer visits to the doctor to make adjustments.”

However, he said that in addition to the cost and reimbursement issue, all of these studies have been short term and not conducted in real-life settings.

“Another question is: What happens if the patient goes on low-dose LT4? The studies were conducted on much higher pharmacologic doses. But at least from a safety standpoint, there’s no specific concern.”

Dr. Washington is an employee of Vertice Pharma. Dr. Celi has received unrestricted research grants and worked as a consultant for IBSA. Dr. Gigliotti has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

ATLANTA -- Liquid formulations of levothyroxine offer the possibility of allowing patients with hypothyroidism to take their medication with meals or coffee and skip the currently recommended 30- to 60-minute waiting period before doing either, new data suggest.

amenic181/Getty Images

Because food, coffee, and certain medications can interfere with intestinal absorption of levothyroxine (also known as LT4), current guidelines recommend that the drug be taken in a fasting state, typically 30-60 minutes before breakfast. However, compliance may be difficult for some patients.

Now, a potential solution may come from new evidence that liquid levothyroxine formulations that bypass the gastric dissolution phase of absorption may mitigate the interference with food and coffee.

Findings from two bioavailability studies showing no difference in comparisons of Thyquidity (levothyroxine sodium oral solution, Vertice Pharma) with or without waiting periods before consuming coffee or a high-fat meal were presented at the annual meeting of the Endocrine Society (ENDO 2022), by Vertice Pharma Medical Director Kris Washington, PharmD.

And just last month, similar data were published in Thyroid for another levothyroxine oral solution, Tirosint-SOL (IBSA). No difference in pharmacokinetic properties were found with this product with a shorter versus a longer waiting period before consuming a high-fat meal.
 

Liquid thyroxine may be less affected by food/drink but is expensive

Both products have been approved by the U.S. Food and Drug Administration, but current labeling for both still calls for a 30- to 60-minute waiting period between taking the medication and eating or drinking. Thyquidity is an oral solution of 100 µg/mL levothyroxine sodium that has been shown to be bioequivalent to one of the most popular branded levothyroxine tablets, Synthroid (AbbVie), under fasting conditions. Tirosint-SOL is also an oral solution that comes in 15 different dosage ampules.

“It is important to note that while these findings are exciting and encouraging, we do want you to continue to follow the current FDA-approved label for Thyquidity, recommending that it be taken on an empty stomach 30-60 minutes prior to breakfast and that patients continue to follow all other label instructions,” Dr. Washington said during a press briefing at ENDO 2022.

When asked whether the new data would be submitted to the FDA for a possible amendment to this message, she replied: “We’re still discussing that. We’re exploring all options. ... This is fairly new data. ... It makes sense and certainly solves a lot of the challenges for people who can’t swallow or don’t choose to swallow, or the challenges of splitting or crushing with tablets.”

Asked to comment, Benjamin J. Gigliotti, MD, a clinical thyroidologist at the University of Rochester, New York, told this news organization: “Liquid levothyroxine has the potential to be a clinically useful formulation,” noting that these recent data corroborate prior findings from Europe and elsewhere that liquid levothyroxine is absorbed more rapidly and thus may be less impacted by food or beverages.

However, Dr. Gigliotti also pointed out, “I don’t think malabsorption is a major contributor to suboptimal treatment because if [patients] malabsorb the hormone, we typically just increase their dose a little bit or ask them to take it separately, and that works just fine for most people.”

And the higher cost of the liquid products is a major issue, he noted. 

A quick search on GoodRx shows that the lowest price of Tirosint-SOL is $115.52 for a 1 month supply and Thyquidity is $181.04/month. “In the few patients where I tried to obtain Tirosint-SOL, it was not covered by insurance, even with a prior authorization,” Dr. Gigliotti commented.

In contrast, generic levothyroxine tablets are about $4/month, while a common brand name of levothyroxine tablets are $47.81/month.

“Until these liquid formulations are more widely covered by insurance for a reasonable copay, or come down in price compared to generic levothyroxine tablets, most of my patients have voiced that they’d rather deal with the inconveniences of a tablet compared to higher medication cost, especially with rising economic insecurity imposed by the COVID-19 pandemic and recent world events,” Dr. Gigliotti said.
 

Bioequivalence with shorter versus longer waits before coffee/breakfast

The Thyquidity coffee study was a single-center open-label, randomized, crossover study of 40 healthy adults randomized after a 10-hour overnight fast to 600 µg Thyquidity with water under fasting conditions or to the same dose given 5 minutes prior to drinking an 8-ounce cup of American coffee without milk or sweeteners. After a 40-day washout period, the same participants received the other treatment.

Mean serum thyroxine (T4) concentrations over 48 hours were nearly identical, demonstrating comparable bioavailability. Pharmacokinetics parameters, including area under the curve (AUC) and Cmax, were also comparable for both groups. The geometric least square mean ratios for baseline-adjusted LT4 were 96.0% for Cmax and 94% for AUC. And the corresponding 90% confidence intervals fell within the 80%-125% FDA acceptance range for absence of a food effect on bioavailability, said Dr. Washington when presenting the findings.

There was one adverse event, a decrease in blood glucose level, which was deemed to be mild and unrelated to study treatment. No deaths, serious adverse events, or discontinuations due to adverse events were reported. There were no significant changes in vital signs or on ECG.

In the second Thyquidity study of 38 healthy adults, after a 10-hour fast, the same doses were given 10 or 30 minutes prior to the consumption of a 950-calorie standardized high-fat breakfast.

Again, over 48 hours, mean serum T4 levels were comparable between the two groups. The geometric least squares mean ratios for both AUC and Cmax for baseline-adjusted LT4 were 88.7% and 85.1%, respectively. Again, the corresponding 90% confidence intervals fell within the FDA’s noninterference definition, again demonstrating lack of a food effect on bioavailability, Dr. Washington noted.

Four adverse events were reported in three participants, with three deemed to be possibly related to the medication. All were isolated lab abnormalities without clinical symptoms and deemed to be mild. Three were normal on repeat testing.

There were no deaths or serious adverse events or study discontinuations for adverse events and no significant findings for vital signs or on ECG.
 

Similar findings for Tirosint-SOL but longer-term studies needed

The recently published Tirosint-SOL study included 36 healthy volunteers randomized to single 600-µg doses of the LT4 oral solution after a 10-hour fast, either 15 or 30 minutes before eating a standardized high-fat, high-calorie meal. Mean serum total thyroxine concentration profiles were similar for both the 15- and 30-minute waits, with similar AUCs.

Geometric mean ratios for AUCs at 48 and 72 hours were 90% and 92%, respectively, and the 90% confidence intervals fell within the 80%-125% FDA boundaries, suggesting similar exposures whether taken 15 or 30 minutes before a meal.

Senior author Francesco S. Celi, MD, chair of the division of endocrinology, diabetes, and metabolism at Virginia Commonwealth University, Richmond, told this news organization: “There is an interest in providing more opportunities for patients and improving adherence to the medication. ... Whatever makes life a bit easier for patients and results in a more predictable response to treatment means down the road there will be fewer visits to the doctor to make adjustments.”

However, he said that in addition to the cost and reimbursement issue, all of these studies have been short term and not conducted in real-life settings.

“Another question is: What happens if the patient goes on low-dose LT4? The studies were conducted on much higher pharmacologic doses. But at least from a safety standpoint, there’s no specific concern.”

Dr. Washington is an employee of Vertice Pharma. Dr. Celi has received unrestricted research grants and worked as a consultant for IBSA. Dr. Gigliotti has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

ATLANTA -- Liquid formulations of levothyroxine offer the possibility of allowing patients with hypothyroidism to take their medication with meals or coffee and skip the currently recommended 30- to 60-minute waiting period before doing either, new data suggest.

amenic181/Getty Images

Because food, coffee, and certain medications can interfere with intestinal absorption of levothyroxine (also known as LT4), current guidelines recommend that the drug be taken in a fasting state, typically 30-60 minutes before breakfast. However, compliance may be difficult for some patients.

Now, a potential solution may come from new evidence that liquid levothyroxine formulations that bypass the gastric dissolution phase of absorption may mitigate the interference with food and coffee.

Findings from two bioavailability studies showing no difference in comparisons of Thyquidity (levothyroxine sodium oral solution, Vertice Pharma) with or without waiting periods before consuming coffee or a high-fat meal were presented at the annual meeting of the Endocrine Society (ENDO 2022), by Vertice Pharma Medical Director Kris Washington, PharmD.

And just last month, similar data were published in Thyroid for another levothyroxine oral solution, Tirosint-SOL (IBSA). No difference in pharmacokinetic properties were found with this product with a shorter versus a longer waiting period before consuming a high-fat meal.
 

Liquid thyroxine may be less affected by food/drink but is expensive

Both products have been approved by the U.S. Food and Drug Administration, but current labeling for both still calls for a 30- to 60-minute waiting period between taking the medication and eating or drinking. Thyquidity is an oral solution of 100 µg/mL levothyroxine sodium that has been shown to be bioequivalent to one of the most popular branded levothyroxine tablets, Synthroid (AbbVie), under fasting conditions. Tirosint-SOL is also an oral solution that comes in 15 different dosage ampules.

“It is important to note that while these findings are exciting and encouraging, we do want you to continue to follow the current FDA-approved label for Thyquidity, recommending that it be taken on an empty stomach 30-60 minutes prior to breakfast and that patients continue to follow all other label instructions,” Dr. Washington said during a press briefing at ENDO 2022.

When asked whether the new data would be submitted to the FDA for a possible amendment to this message, she replied: “We’re still discussing that. We’re exploring all options. ... This is fairly new data. ... It makes sense and certainly solves a lot of the challenges for people who can’t swallow or don’t choose to swallow, or the challenges of splitting or crushing with tablets.”

Asked to comment, Benjamin J. Gigliotti, MD, a clinical thyroidologist at the University of Rochester, New York, told this news organization: “Liquid levothyroxine has the potential to be a clinically useful formulation,” noting that these recent data corroborate prior findings from Europe and elsewhere that liquid levothyroxine is absorbed more rapidly and thus may be less impacted by food or beverages.

However, Dr. Gigliotti also pointed out, “I don’t think malabsorption is a major contributor to suboptimal treatment because if [patients] malabsorb the hormone, we typically just increase their dose a little bit or ask them to take it separately, and that works just fine for most people.”

And the higher cost of the liquid products is a major issue, he noted. 

A quick search on GoodRx shows that the lowest price of Tirosint-SOL is $115.52 for a 1 month supply and Thyquidity is $181.04/month. “In the few patients where I tried to obtain Tirosint-SOL, it was not covered by insurance, even with a prior authorization,” Dr. Gigliotti commented.

In contrast, generic levothyroxine tablets are about $4/month, while a common brand name of levothyroxine tablets are $47.81/month.

“Until these liquid formulations are more widely covered by insurance for a reasonable copay, or come down in price compared to generic levothyroxine tablets, most of my patients have voiced that they’d rather deal with the inconveniences of a tablet compared to higher medication cost, especially with rising economic insecurity imposed by the COVID-19 pandemic and recent world events,” Dr. Gigliotti said.
 

Bioequivalence with shorter versus longer waits before coffee/breakfast

The Thyquidity coffee study was a single-center open-label, randomized, crossover study of 40 healthy adults randomized after a 10-hour overnight fast to 600 µg Thyquidity with water under fasting conditions or to the same dose given 5 minutes prior to drinking an 8-ounce cup of American coffee without milk or sweeteners. After a 40-day washout period, the same participants received the other treatment.

Mean serum thyroxine (T4) concentrations over 48 hours were nearly identical, demonstrating comparable bioavailability. Pharmacokinetics parameters, including area under the curve (AUC) and Cmax, were also comparable for both groups. The geometric least square mean ratios for baseline-adjusted LT4 were 96.0% for Cmax and 94% for AUC. And the corresponding 90% confidence intervals fell within the 80%-125% FDA acceptance range for absence of a food effect on bioavailability, said Dr. Washington when presenting the findings.

There was one adverse event, a decrease in blood glucose level, which was deemed to be mild and unrelated to study treatment. No deaths, serious adverse events, or discontinuations due to adverse events were reported. There were no significant changes in vital signs or on ECG.

In the second Thyquidity study of 38 healthy adults, after a 10-hour fast, the same doses were given 10 or 30 minutes prior to the consumption of a 950-calorie standardized high-fat breakfast.

Again, over 48 hours, mean serum T4 levels were comparable between the two groups. The geometric least squares mean ratios for both AUC and Cmax for baseline-adjusted LT4 were 88.7% and 85.1%, respectively. Again, the corresponding 90% confidence intervals fell within the FDA’s noninterference definition, again demonstrating lack of a food effect on bioavailability, Dr. Washington noted.

Four adverse events were reported in three participants, with three deemed to be possibly related to the medication. All were isolated lab abnormalities without clinical symptoms and deemed to be mild. Three were normal on repeat testing.

There were no deaths or serious adverse events or study discontinuations for adverse events and no significant findings for vital signs or on ECG.
 

Similar findings for Tirosint-SOL but longer-term studies needed

The recently published Tirosint-SOL study included 36 healthy volunteers randomized to single 600-µg doses of the LT4 oral solution after a 10-hour fast, either 15 or 30 minutes before eating a standardized high-fat, high-calorie meal. Mean serum total thyroxine concentration profiles were similar for both the 15- and 30-minute waits, with similar AUCs.

Geometric mean ratios for AUCs at 48 and 72 hours were 90% and 92%, respectively, and the 90% confidence intervals fell within the 80%-125% FDA boundaries, suggesting similar exposures whether taken 15 or 30 minutes before a meal.

Senior author Francesco S. Celi, MD, chair of the division of endocrinology, diabetes, and metabolism at Virginia Commonwealth University, Richmond, told this news organization: “There is an interest in providing more opportunities for patients and improving adherence to the medication. ... Whatever makes life a bit easier for patients and results in a more predictable response to treatment means down the road there will be fewer visits to the doctor to make adjustments.”

However, he said that in addition to the cost and reimbursement issue, all of these studies have been short term and not conducted in real-life settings.

“Another question is: What happens if the patient goes on low-dose LT4? The studies were conducted on much higher pharmacologic doses. But at least from a safety standpoint, there’s no specific concern.”

Dr. Washington is an employee of Vertice Pharma. Dr. Celi has received unrestricted research grants and worked as a consultant for IBSA. Dr. Gigliotti has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The U.S. National Lipid Association has issued a new scientific statement on the management of patients with statin intolerance, which recommends different strategies to help patients stay on statin medications, and also suggests alternatives that can be used in patients who really cannot tolerate statin drugs.

The statement was published online in the Journal of Clinical Lipidology.  

It notes that, although statins are generally well tolerated, statin intolerance is reported in 5%-30% of patients and contributes to reduced statin adherence and persistence, as well as higher risk for adverse cardiovascular outcomes.

RogerAshford/Thinkstock

The statement acknowledges the importance of identifying modifiable risk factors for statin intolerance and recognizes the possibility of a “nocebo” effect, basically the patient expectation of harm resulting in perceived side effects.

To identify a tolerable statin regimen, it recommends that clinicians consider using several different strategies (different statin, dose, and/or dosing frequency), and to classify a patient as having statin intolerance, a minimum of two statins should have been attempted, including at least one at the lowest-approved daily dosage.

The statement says that nonstatin therapy may be required for patients who cannot reach therapeutic objectives with lifestyle and maximal tolerated statin therapy, and in these cases, therapies with outcomes data from randomized trials showing reduced cardiovascular events are favored.

In high and very high-risk patients who are statin intolerant, clinicians should consider initiating nonstatin therapy while additional attempts are made to identify a tolerable statin in order to limit the time of exposure to elevated levels of atherogenic lipoproteins, it suggests.

“There is strong evidence that statins reduce risk of cardiovascular events particularly in patients with atherosclerotic cardiovascular disease, but recent research shows that only about half of patients with ASCVD are on a statin,” Kevin C. Maki, PhD, coauthor of the statement and current president of the National Lipid Association, said in an interview.

“There is an urgent problem with underutilization of statins and undertreatment of ASCVD. And we know that perceived side effects associated with statins are a common reason for discontinuation of these drugs and the consequent failure to manage ASCVD adequately,” he said.  

Dr. Maki noted that the NLA’s first message is that, when experiencing symptoms taking statins, a large majority of patients can still tolerate a statin. “They can try a different agent or a different dose. But for those who still can’t tolerate a statin, we then recommend nonstatin therapies and we favor those therapies with evidence from randomized trials.”

He pointed out that many patients who believe they are experiencing side effects from taking statins still experience the same effects on a placebo, a condition known as the nocebo effect.

“Several studies have shown that the nocebo effect is very common and accounts for more than half of perceived statin side effects. It is therefore estimated that many of the complaints of statin intolerance are probably not directly related to the pharmacodynamic actions of the drugs,” Dr. Maki said.

One recent study on the nocebo effect, the SAMSON study, suggested that 90% of symptoms attributed to statins were elicited by placebo tablets too.

But Dr. Maki added that it can be a losing battle for the clinician if patients think their symptoms are related to taking a statin.

“We suggest that clinicians inform patients that most people can tolerate a statin – maybe with a different agent or an alternative dose – and it is really important to lower LDL cholesterol as that will lower the risk of MI and stroke, so we need to find a regimen that works for each individual,” he said. “Most people can find a regimen that works. If this means taking a lower dose of a statin, they can take some additional therapy as well. This is a better situation than stopping taking statins altogether and allowing ASCVD to progress.”

Dr. Maki stressed that statins should still be the first choice as they are effective, taken orally, and inexpensive.

“Other medications do not have all these advantages. For example, PCSK9 inhibitors are very effective but they are expensive and injectable,” he noted. “And while ezetimibe [Zetia] is now generic so inexpensive, it has a more modest effect on LDL-lowering compared to statins, so by itself it is not normally enough for most patients to get to their target LDL, but it is an option for use in combination with a statin.”

He added that the NLA message is to do everything possible to keep patients on a statin, especially patients with preexisting ASCVD.

“We would like these patients to be on high-intensity statins. If they really can’t tolerate this, then they could be on a low-intensity statin plus an additional agent.”

Commenting on the NLA statement, SAMSON study coauthor James Howard, MB BChir, PhD, Imperial College London, said he had reservations about some of the recommendations.

“Whilst I think it is great news that the existence and importance of the nocebo effect is increasingly recognized in international guidelines and statements, I think we need to be very careful about recommending reduced doses and frequencies of statins,” Dr. Howard said.

“Studies such as SAMSON and StatinWISE indicate the vast majority of side effects reported by patients taking statins are not caused by the statin molecule, but instead are caused by either the nocebo effect, or ever-present background symptoms that are wrongly attributed to the statins,” he commented. “Therefore, to recommend that the correct approach in a patient with a history of MI suffering symptoms on 80 mg of atorvastatin is to reduce the dose or try alternate daily dosing. This reinforces the view that these drugs are side-effect prone and need to be carefully titrated.”

Dr. Howard suggested that patients should be educated on the possibility of the nocebo effect or background symptoms and encouraged to retrial statins at the same dose. “If that doesn’t work, then formal recording with a symptom diary might help patients recognize background symptoms,” he added.

Dr. Howard noted that, if symptoms still persist, an “n-of-1” trial could be conducted, in which the patient rotates between multiple periods of taking a statin and a placebo, but he acknowledged that this is expensive and time consuming. 

Also commenting, Steve Nissen, MD, Cleveland Clinic, said he thought the NLA statement was “reasonable and thoughtful.”

“Regardless of whether the symptoms are due to the nocebo effect or not, some patients will just not take a statin no matter how hard you try to convince them to persevere, so we do need alternatives,” Dr. Nissen said.

He noted that current alternatives would include the PCSK9 inhibitors and ezetimibe, but a future candidate could be the oral bempedoic acid (Nexletol), which is currently being evaluated in a large outcomes trial (CLEAR Outcomes).

A version of this article first appeared on Medscape.com.

The U.S. National Lipid Association has issued a new scientific statement on the management of patients with statin intolerance, which recommends different strategies to help patients stay on statin medications, and also suggests alternatives that can be used in patients who really cannot tolerate statin drugs.

The statement was published online in the Journal of Clinical Lipidology.  

It notes that, although statins are generally well tolerated, statin intolerance is reported in 5%-30% of patients and contributes to reduced statin adherence and persistence, as well as higher risk for adverse cardiovascular outcomes.

RogerAshford/Thinkstock

The statement acknowledges the importance of identifying modifiable risk factors for statin intolerance and recognizes the possibility of a “nocebo” effect, basically the patient expectation of harm resulting in perceived side effects.

To identify a tolerable statin regimen, it recommends that clinicians consider using several different strategies (different statin, dose, and/or dosing frequency), and to classify a patient as having statin intolerance, a minimum of two statins should have been attempted, including at least one at the lowest-approved daily dosage.

The statement says that nonstatin therapy may be required for patients who cannot reach therapeutic objectives with lifestyle and maximal tolerated statin therapy, and in these cases, therapies with outcomes data from randomized trials showing reduced cardiovascular events are favored.

In high and very high-risk patients who are statin intolerant, clinicians should consider initiating nonstatin therapy while additional attempts are made to identify a tolerable statin in order to limit the time of exposure to elevated levels of atherogenic lipoproteins, it suggests.

“There is strong evidence that statins reduce risk of cardiovascular events particularly in patients with atherosclerotic cardiovascular disease, but recent research shows that only about half of patients with ASCVD are on a statin,” Kevin C. Maki, PhD, coauthor of the statement and current president of the National Lipid Association, said in an interview.

“There is an urgent problem with underutilization of statins and undertreatment of ASCVD. And we know that perceived side effects associated with statins are a common reason for discontinuation of these drugs and the consequent failure to manage ASCVD adequately,” he said.  

Dr. Maki noted that the NLA’s first message is that, when experiencing symptoms taking statins, a large majority of patients can still tolerate a statin. “They can try a different agent or a different dose. But for those who still can’t tolerate a statin, we then recommend nonstatin therapies and we favor those therapies with evidence from randomized trials.”

He pointed out that many patients who believe they are experiencing side effects from taking statins still experience the same effects on a placebo, a condition known as the nocebo effect.

“Several studies have shown that the nocebo effect is very common and accounts for more than half of perceived statin side effects. It is therefore estimated that many of the complaints of statin intolerance are probably not directly related to the pharmacodynamic actions of the drugs,” Dr. Maki said.

One recent study on the nocebo effect, the SAMSON study, suggested that 90% of symptoms attributed to statins were elicited by placebo tablets too.

But Dr. Maki added that it can be a losing battle for the clinician if patients think their symptoms are related to taking a statin.

“We suggest that clinicians inform patients that most people can tolerate a statin – maybe with a different agent or an alternative dose – and it is really important to lower LDL cholesterol as that will lower the risk of MI and stroke, so we need to find a regimen that works for each individual,” he said. “Most people can find a regimen that works. If this means taking a lower dose of a statin, they can take some additional therapy as well. This is a better situation than stopping taking statins altogether and allowing ASCVD to progress.”

Dr. Maki stressed that statins should still be the first choice as they are effective, taken orally, and inexpensive.

“Other medications do not have all these advantages. For example, PCSK9 inhibitors are very effective but they are expensive and injectable,” he noted. “And while ezetimibe [Zetia] is now generic so inexpensive, it has a more modest effect on LDL-lowering compared to statins, so by itself it is not normally enough for most patients to get to their target LDL, but it is an option for use in combination with a statin.”

He added that the NLA message is to do everything possible to keep patients on a statin, especially patients with preexisting ASCVD.

“We would like these patients to be on high-intensity statins. If they really can’t tolerate this, then they could be on a low-intensity statin plus an additional agent.”

Commenting on the NLA statement, SAMSON study coauthor James Howard, MB BChir, PhD, Imperial College London, said he had reservations about some of the recommendations.

“Whilst I think it is great news that the existence and importance of the nocebo effect is increasingly recognized in international guidelines and statements, I think we need to be very careful about recommending reduced doses and frequencies of statins,” Dr. Howard said.

“Studies such as SAMSON and StatinWISE indicate the vast majority of side effects reported by patients taking statins are not caused by the statin molecule, but instead are caused by either the nocebo effect, or ever-present background symptoms that are wrongly attributed to the statins,” he commented. “Therefore, to recommend that the correct approach in a patient with a history of MI suffering symptoms on 80 mg of atorvastatin is to reduce the dose or try alternate daily dosing. This reinforces the view that these drugs are side-effect prone and need to be carefully titrated.”

Dr. Howard suggested that patients should be educated on the possibility of the nocebo effect or background symptoms and encouraged to retrial statins at the same dose. “If that doesn’t work, then formal recording with a symptom diary might help patients recognize background symptoms,” he added.

Dr. Howard noted that, if symptoms still persist, an “n-of-1” trial could be conducted, in which the patient rotates between multiple periods of taking a statin and a placebo, but he acknowledged that this is expensive and time consuming. 

Also commenting, Steve Nissen, MD, Cleveland Clinic, said he thought the NLA statement was “reasonable and thoughtful.”

“Regardless of whether the symptoms are due to the nocebo effect or not, some patients will just not take a statin no matter how hard you try to convince them to persevere, so we do need alternatives,” Dr. Nissen said.

He noted that current alternatives would include the PCSK9 inhibitors and ezetimibe, but a future candidate could be the oral bempedoic acid (Nexletol), which is currently being evaluated in a large outcomes trial (CLEAR Outcomes).

A version of this article first appeared on Medscape.com.

The U.S. National Lipid Association has issued a new scientific statement on the management of patients with statin intolerance, which recommends different strategies to help patients stay on statin medications, and also suggests alternatives that can be used in patients who really cannot tolerate statin drugs.

The statement was published online in the Journal of Clinical Lipidology.  

It notes that, although statins are generally well tolerated, statin intolerance is reported in 5%-30% of patients and contributes to reduced statin adherence and persistence, as well as higher risk for adverse cardiovascular outcomes.

RogerAshford/Thinkstock

The statement acknowledges the importance of identifying modifiable risk factors for statin intolerance and recognizes the possibility of a “nocebo” effect, basically the patient expectation of harm resulting in perceived side effects.

To identify a tolerable statin regimen, it recommends that clinicians consider using several different strategies (different statin, dose, and/or dosing frequency), and to classify a patient as having statin intolerance, a minimum of two statins should have been attempted, including at least one at the lowest-approved daily dosage.

The statement says that nonstatin therapy may be required for patients who cannot reach therapeutic objectives with lifestyle and maximal tolerated statin therapy, and in these cases, therapies with outcomes data from randomized trials showing reduced cardiovascular events are favored.

In high and very high-risk patients who are statin intolerant, clinicians should consider initiating nonstatin therapy while additional attempts are made to identify a tolerable statin in order to limit the time of exposure to elevated levels of atherogenic lipoproteins, it suggests.

“There is strong evidence that statins reduce risk of cardiovascular events particularly in patients with atherosclerotic cardiovascular disease, but recent research shows that only about half of patients with ASCVD are on a statin,” Kevin C. Maki, PhD, coauthor of the statement and current president of the National Lipid Association, said in an interview.

“There is an urgent problem with underutilization of statins and undertreatment of ASCVD. And we know that perceived side effects associated with statins are a common reason for discontinuation of these drugs and the consequent failure to manage ASCVD adequately,” he said.  

Dr. Maki noted that the NLA’s first message is that, when experiencing symptoms taking statins, a large majority of patients can still tolerate a statin. “They can try a different agent or a different dose. But for those who still can’t tolerate a statin, we then recommend nonstatin therapies and we favor those therapies with evidence from randomized trials.”

He pointed out that many patients who believe they are experiencing side effects from taking statins still experience the same effects on a placebo, a condition known as the nocebo effect.

“Several studies have shown that the nocebo effect is very common and accounts for more than half of perceived statin side effects. It is therefore estimated that many of the complaints of statin intolerance are probably not directly related to the pharmacodynamic actions of the drugs,” Dr. Maki said.

One recent study on the nocebo effect, the SAMSON study, suggested that 90% of symptoms attributed to statins were elicited by placebo tablets too.

But Dr. Maki added that it can be a losing battle for the clinician if patients think their symptoms are related to taking a statin.

“We suggest that clinicians inform patients that most people can tolerate a statin – maybe with a different agent or an alternative dose – and it is really important to lower LDL cholesterol as that will lower the risk of MI and stroke, so we need to find a regimen that works for each individual,” he said. “Most people can find a regimen that works. If this means taking a lower dose of a statin, they can take some additional therapy as well. This is a better situation than stopping taking statins altogether and allowing ASCVD to progress.”

Dr. Maki stressed that statins should still be the first choice as they are effective, taken orally, and inexpensive.

“Other medications do not have all these advantages. For example, PCSK9 inhibitors are very effective but they are expensive and injectable,” he noted. “And while ezetimibe [Zetia] is now generic so inexpensive, it has a more modest effect on LDL-lowering compared to statins, so by itself it is not normally enough for most patients to get to their target LDL, but it is an option for use in combination with a statin.”

He added that the NLA message is to do everything possible to keep patients on a statin, especially patients with preexisting ASCVD.

“We would like these patients to be on high-intensity statins. If they really can’t tolerate this, then they could be on a low-intensity statin plus an additional agent.”

Commenting on the NLA statement, SAMSON study coauthor James Howard, MB BChir, PhD, Imperial College London, said he had reservations about some of the recommendations.

“Whilst I think it is great news that the existence and importance of the nocebo effect is increasingly recognized in international guidelines and statements, I think we need to be very careful about recommending reduced doses and frequencies of statins,” Dr. Howard said.

“Studies such as SAMSON and StatinWISE indicate the vast majority of side effects reported by patients taking statins are not caused by the statin molecule, but instead are caused by either the nocebo effect, or ever-present background symptoms that are wrongly attributed to the statins,” he commented. “Therefore, to recommend that the correct approach in a patient with a history of MI suffering symptoms on 80 mg of atorvastatin is to reduce the dose or try alternate daily dosing. This reinforces the view that these drugs are side-effect prone and need to be carefully titrated.”

Dr. Howard suggested that patients should be educated on the possibility of the nocebo effect or background symptoms and encouraged to retrial statins at the same dose. “If that doesn’t work, then formal recording with a symptom diary might help patients recognize background symptoms,” he added.

Dr. Howard noted that, if symptoms still persist, an “n-of-1” trial could be conducted, in which the patient rotates between multiple periods of taking a statin and a placebo, but he acknowledged that this is expensive and time consuming. 

Also commenting, Steve Nissen, MD, Cleveland Clinic, said he thought the NLA statement was “reasonable and thoughtful.”

“Regardless of whether the symptoms are due to the nocebo effect or not, some patients will just not take a statin no matter how hard you try to convince them to persevere, so we do need alternatives,” Dr. Nissen said.

He noted that current alternatives would include the PCSK9 inhibitors and ezetimibe, but a future candidate could be the oral bempedoic acid (Nexletol), which is currently being evaluated in a large outcomes trial (CLEAR Outcomes).

A version of this article first appeared on Medscape.com.

Your gut microbiome will thank you later

A healthy gut seems like the new catch-all to better overall health these days. Nutrition and diet culture has us drinking kombucha and ginger tea and coffee, but what if we told you that going to happy hour might also help?

In a recent double-blind study published in the Journal of Agricultural and Food Chemistry, 19 men were divided into two groups and asked to drink 11 ounces of alcoholic lager (5.2% by volume) or nonalcoholic lager with dinner for 4 weeks.

Beer? Yes. Beer.

Engin Akyurt/Pixabay

We humans have trillions of microorganisms running rampant through our digestive tracts. When they’re happy, we have a lower chance of developing heart disease and diabetes. You know what else has millions of happy microorganisms from fermentation? Beer. It also has polyphenols that can help the body’s tissues fight cancers, as well as heart disease and inflammation. So beer is looking a little more healthy now, isn’t it?

In the study, the researchers found that both the alcoholic- and nonalcoholic-lager groups had a boost in bacterial diversity in the gut and higher fecal alkaline phosphatase levels, which showed improved intestinal health. They acknowledged, however, that the nonalcoholic route would be safer and healthier for overall health.

So add a lager to the list of gut-healthy foods that you should be consuming. It may give the phrase “beer gut” a whole new meaning.
 

We’ve lost our minds, but at least we know how fast they’re going

The phrase “quantum consciousness” sounds like something out of a particularly cheesy episode of Star Trek: “Oh no, Captain, the quantum consciousness has invaded our computer, and the only way to drive it out is to reverse the polarity of a focused tachyon beam.”

Massimiliano De Deo, LNGS-INFN

When it comes to understanding such basic existential issues as the origin of consciousness, however, quantum mechanics wasn’t off the table. The theory of the quantum origin of consciousness dates back to the 1990s (thanks in part to noted physician Roger Penrose), and goes something like this: There are microtubules within neurons in the brain that are small enough and isolated enough from the warm, wet, and chaotic brain environment where quantum effects can briefly come into play. We’re talking miniscule fractions of a second here, but still, long enough for quantum calculations to take place in the form of system wavefunction collapse, courtesy of gravity.

To plunge even deeper into the rabbit hole of quantum mechanics, the reason Schrödinger’s cat doesn’t occur in real life is wavefunction collapse; the more massive a quantum system is, the more likely it is to collapse into one state or another (alive or dead, in the cat’s case). The quantum origin of consciousness, or Orch OR theory, holds that human consciousness arises from electrical oscillations within the neuronal microtubules caused by the computations stemming from the collapse of small quantum systems.

That is an awful lot of overly simplified explanation, especially considering the study that just came out essentially disproved it. Oops. The research, published in Physics of Life Reviews, is pretty simple. The researchers went to a lab deep underground to avoid interference from cosmic rays, and sat around for months, observing a chunk of germanium for signs of spontaneous radiation, attributable to the same sort of wavefunction collapse that is supposedly occurring in our brains. They found nothing out of the ordinary, pretty definitively disproving most of Orch OR theory.

The researchers were unwilling to completely dismiss the idea (this is quantum mechanics, after all, uncertainty kind of goes with the territory), but it does seem like we’ll have to search elsewhere for sources of human consciousness. Personally, we’re big fans of the cymbal-playing monkey.
 

Missing links: A real fish story

Dear LOTME:

Ear’s a question that’s been keeping me up at night. Is the human middle ear the result of top-secret government experiments involving alien technology, Abraham Lincoln, and the Illuminati?

Restless in Roswell

Dear Restless:

The paleoanthropologic community has been sorting through this mystery for decades, and fossils discovered in China over the past 20 years finally provide a much less conspiratorially satisfying answer.

IVPP

For some time now, experts in the field have believed that the bones of the human middle ear evolved from the spiracular gill of a fish. The spiracle is a small hole behind each eye that opens to the mouth in some fishes and was used to breathe air in the earliest, most primitive species. But how did we get from spiracle to ear?

The missing links come in the form of the cranial anatomy of Shuyu, a 438-million-year-old, fingernail-sized skull of a jawless fish, and the 419-million-year-old fossil of a completely preserved fish with gill filaments in the first branchial chamber.

“These fossils provided the first anatomical and fossil evidence for a vertebrate spiracle originating from fish gills,” senior author Gai Zhikun, PhD, of the Institute of Vertebrate Paleontology and Paleoanthropology, Beijing, said in a written statement.

In many ways, it seems, we are fish: “Many important structures of human beings can be traced back to our fish ancestors, such as our teeth, jaws, middle ears, etc,” added Zhu Min, PhD, also of the institute.

So, Restless, the next time you hear the soothing sounds of an angry mob storming the Capitol or you chew on a slab, slice, or chunk of mutant, laboratory-produced chicken in your favorite fast-food restaurant, be sure to thank Shuyu.
 

Can you lend me an ear?

If you thought locusts were only a nuisance, think again. They have their uses. If you take a locust’s ear and put it inside a robot, the robot will be able to hear and receive signals. Who knew?

850977/Pixabay

Researchers from Tel Aviv University in Israel showed the robot’s hearing abilities by giving clap signals that told the robot what to do: One clap means go forward, two claps mean move back. What do you think the robot would do if it heard the clap break from Cha Cha Slide?

“Our task was to replace the robot’s electronic microphone with a dead insect’s ear, use the ear’s ability to detect the electrical signals from the environment, in this case vibrations in the air, and, using a special chip, convert the insect input to that of the robot,” Ben M. Maoz, PhD, said in a statement from the university.

And how does a dead locust ear work in a robot? Well, Dr. Maoz explained: “My laboratory has developed a special device – Ear-on-a-Chip – that allows the ear to be kept alive throughout the experiment by supplying oxygen and food to the organ while allowing the electrical signals to be taken out of the locust’s ear and amplified and transmitted to the robot.”

The research won’t stop at hearing, he said, as the other four senses also will be taken into consideration. This could help us sense dangers in the future, such as earthquakes or diseases. We said it before and we’ll say it again: We’re rooting for you, science!

Your gut microbiome will thank you later

A healthy gut seems like the new catch-all to better overall health these days. Nutrition and diet culture has us drinking kombucha and ginger tea and coffee, but what if we told you that going to happy hour might also help?

In a recent double-blind study published in the Journal of Agricultural and Food Chemistry, 19 men were divided into two groups and asked to drink 11 ounces of alcoholic lager (5.2% by volume) or nonalcoholic lager with dinner for 4 weeks.

Beer? Yes. Beer.

Engin Akyurt/Pixabay

We humans have trillions of microorganisms running rampant through our digestive tracts. When they’re happy, we have a lower chance of developing heart disease and diabetes. You know what else has millions of happy microorganisms from fermentation? Beer. It also has polyphenols that can help the body’s tissues fight cancers, as well as heart disease and inflammation. So beer is looking a little more healthy now, isn’t it?

In the study, the researchers found that both the alcoholic- and nonalcoholic-lager groups had a boost in bacterial diversity in the gut and higher fecal alkaline phosphatase levels, which showed improved intestinal health. They acknowledged, however, that the nonalcoholic route would be safer and healthier for overall health.

So add a lager to the list of gut-healthy foods that you should be consuming. It may give the phrase “beer gut” a whole new meaning.
 

We’ve lost our minds, but at least we know how fast they’re going

The phrase “quantum consciousness” sounds like something out of a particularly cheesy episode of Star Trek: “Oh no, Captain, the quantum consciousness has invaded our computer, and the only way to drive it out is to reverse the polarity of a focused tachyon beam.”

Massimiliano De Deo, LNGS-INFN

When it comes to understanding such basic existential issues as the origin of consciousness, however, quantum mechanics wasn’t off the table. The theory of the quantum origin of consciousness dates back to the 1990s (thanks in part to noted physician Roger Penrose), and goes something like this: There are microtubules within neurons in the brain that are small enough and isolated enough from the warm, wet, and chaotic brain environment where quantum effects can briefly come into play. We’re talking miniscule fractions of a second here, but still, long enough for quantum calculations to take place in the form of system wavefunction collapse, courtesy of gravity.

To plunge even deeper into the rabbit hole of quantum mechanics, the reason Schrödinger’s cat doesn’t occur in real life is wavefunction collapse; the more massive a quantum system is, the more likely it is to collapse into one state or another (alive or dead, in the cat’s case). The quantum origin of consciousness, or Orch OR theory, holds that human consciousness arises from electrical oscillations within the neuronal microtubules caused by the computations stemming from the collapse of small quantum systems.

That is an awful lot of overly simplified explanation, especially considering the study that just came out essentially disproved it. Oops. The research, published in Physics of Life Reviews, is pretty simple. The researchers went to a lab deep underground to avoid interference from cosmic rays, and sat around for months, observing a chunk of germanium for signs of spontaneous radiation, attributable to the same sort of wavefunction collapse that is supposedly occurring in our brains. They found nothing out of the ordinary, pretty definitively disproving most of Orch OR theory.

The researchers were unwilling to completely dismiss the idea (this is quantum mechanics, after all, uncertainty kind of goes with the territory), but it does seem like we’ll have to search elsewhere for sources of human consciousness. Personally, we’re big fans of the cymbal-playing monkey.
 

Missing links: A real fish story

Dear LOTME:

Ear’s a question that’s been keeping me up at night. Is the human middle ear the result of top-secret government experiments involving alien technology, Abraham Lincoln, and the Illuminati?

Restless in Roswell

Dear Restless:

The paleoanthropologic community has been sorting through this mystery for decades, and fossils discovered in China over the past 20 years finally provide a much less conspiratorially satisfying answer.

IVPP

For some time now, experts in the field have believed that the bones of the human middle ear evolved from the spiracular gill of a fish. The spiracle is a small hole behind each eye that opens to the mouth in some fishes and was used to breathe air in the earliest, most primitive species. But how did we get from spiracle to ear?

The missing links come in the form of the cranial anatomy of Shuyu, a 438-million-year-old, fingernail-sized skull of a jawless fish, and the 419-million-year-old fossil of a completely preserved fish with gill filaments in the first branchial chamber.

“These fossils provided the first anatomical and fossil evidence for a vertebrate spiracle originating from fish gills,” senior author Gai Zhikun, PhD, of the Institute of Vertebrate Paleontology and Paleoanthropology, Beijing, said in a written statement.

In many ways, it seems, we are fish: “Many important structures of human beings can be traced back to our fish ancestors, such as our teeth, jaws, middle ears, etc,” added Zhu Min, PhD, also of the institute.

So, Restless, the next time you hear the soothing sounds of an angry mob storming the Capitol or you chew on a slab, slice, or chunk of mutant, laboratory-produced chicken in your favorite fast-food restaurant, be sure to thank Shuyu.
 

Can you lend me an ear?

If you thought locusts were only a nuisance, think again. They have their uses. If you take a locust’s ear and put it inside a robot, the robot will be able to hear and receive signals. Who knew?

850977/Pixabay

Researchers from Tel Aviv University in Israel showed the robot’s hearing abilities by giving clap signals that told the robot what to do: One clap means go forward, two claps mean move back. What do you think the robot would do if it heard the clap break from Cha Cha Slide?

“Our task was to replace the robot’s electronic microphone with a dead insect’s ear, use the ear’s ability to detect the electrical signals from the environment, in this case vibrations in the air, and, using a special chip, convert the insect input to that of the robot,” Ben M. Maoz, PhD, said in a statement from the university.

And how does a dead locust ear work in a robot? Well, Dr. Maoz explained: “My laboratory has developed a special device – Ear-on-a-Chip – that allows the ear to be kept alive throughout the experiment by supplying oxygen and food to the organ while allowing the electrical signals to be taken out of the locust’s ear and amplified and transmitted to the robot.”

The research won’t stop at hearing, he said, as the other four senses also will be taken into consideration. This could help us sense dangers in the future, such as earthquakes or diseases. We said it before and we’ll say it again: We’re rooting for you, science!

Your gut microbiome will thank you later

A healthy gut seems like the new catch-all to better overall health these days. Nutrition and diet culture has us drinking kombucha and ginger tea and coffee, but what if we told you that going to happy hour might also help?

In a recent double-blind study published in the Journal of Agricultural and Food Chemistry, 19 men were divided into two groups and asked to drink 11 ounces of alcoholic lager (5.2% by volume) or nonalcoholic lager with dinner for 4 weeks.

Beer? Yes. Beer.

Engin Akyurt/Pixabay

We humans have trillions of microorganisms running rampant through our digestive tracts. When they’re happy, we have a lower chance of developing heart disease and diabetes. You know what else has millions of happy microorganisms from fermentation? Beer. It also has polyphenols that can help the body’s tissues fight cancers, as well as heart disease and inflammation. So beer is looking a little more healthy now, isn’t it?

In the study, the researchers found that both the alcoholic- and nonalcoholic-lager groups had a boost in bacterial diversity in the gut and higher fecal alkaline phosphatase levels, which showed improved intestinal health. They acknowledged, however, that the nonalcoholic route would be safer and healthier for overall health.

So add a lager to the list of gut-healthy foods that you should be consuming. It may give the phrase “beer gut” a whole new meaning.
 

We’ve lost our minds, but at least we know how fast they’re going

The phrase “quantum consciousness” sounds like something out of a particularly cheesy episode of Star Trek: “Oh no, Captain, the quantum consciousness has invaded our computer, and the only way to drive it out is to reverse the polarity of a focused tachyon beam.”

Massimiliano De Deo, LNGS-INFN

When it comes to understanding such basic existential issues as the origin of consciousness, however, quantum mechanics wasn’t off the table. The theory of the quantum origin of consciousness dates back to the 1990s (thanks in part to noted physician Roger Penrose), and goes something like this: There are microtubules within neurons in the brain that are small enough and isolated enough from the warm, wet, and chaotic brain environment where quantum effects can briefly come into play. We’re talking miniscule fractions of a second here, but still, long enough for quantum calculations to take place in the form of system wavefunction collapse, courtesy of gravity.

To plunge even deeper into the rabbit hole of quantum mechanics, the reason Schrödinger’s cat doesn’t occur in real life is wavefunction collapse; the more massive a quantum system is, the more likely it is to collapse into one state or another (alive or dead, in the cat’s case). The quantum origin of consciousness, or Orch OR theory, holds that human consciousness arises from electrical oscillations within the neuronal microtubules caused by the computations stemming from the collapse of small quantum systems.

That is an awful lot of overly simplified explanation, especially considering the study that just came out essentially disproved it. Oops. The research, published in Physics of Life Reviews, is pretty simple. The researchers went to a lab deep underground to avoid interference from cosmic rays, and sat around for months, observing a chunk of germanium for signs of spontaneous radiation, attributable to the same sort of wavefunction collapse that is supposedly occurring in our brains. They found nothing out of the ordinary, pretty definitively disproving most of Orch OR theory.

The researchers were unwilling to completely dismiss the idea (this is quantum mechanics, after all, uncertainty kind of goes with the territory), but it does seem like we’ll have to search elsewhere for sources of human consciousness. Personally, we’re big fans of the cymbal-playing monkey.
 

Missing links: A real fish story

Dear LOTME:

Ear’s a question that’s been keeping me up at night. Is the human middle ear the result of top-secret government experiments involving alien technology, Abraham Lincoln, and the Illuminati?

Restless in Roswell

Dear Restless:

The paleoanthropologic community has been sorting through this mystery for decades, and fossils discovered in China over the past 20 years finally provide a much less conspiratorially satisfying answer.

IVPP

For some time now, experts in the field have believed that the bones of the human middle ear evolved from the spiracular gill of a fish. The spiracle is a small hole behind each eye that opens to the mouth in some fishes and was used to breathe air in the earliest, most primitive species. But how did we get from spiracle to ear?

The missing links come in the form of the cranial anatomy of Shuyu, a 438-million-year-old, fingernail-sized skull of a jawless fish, and the 419-million-year-old fossil of a completely preserved fish with gill filaments in the first branchial chamber.

“These fossils provided the first anatomical and fossil evidence for a vertebrate spiracle originating from fish gills,” senior author Gai Zhikun, PhD, of the Institute of Vertebrate Paleontology and Paleoanthropology, Beijing, said in a written statement.

In many ways, it seems, we are fish: “Many important structures of human beings can be traced back to our fish ancestors, such as our teeth, jaws, middle ears, etc,” added Zhu Min, PhD, also of the institute.

So, Restless, the next time you hear the soothing sounds of an angry mob storming the Capitol or you chew on a slab, slice, or chunk of mutant, laboratory-produced chicken in your favorite fast-food restaurant, be sure to thank Shuyu.
 

Can you lend me an ear?

If you thought locusts were only a nuisance, think again. They have their uses. If you take a locust’s ear and put it inside a robot, the robot will be able to hear and receive signals. Who knew?

850977/Pixabay

Researchers from Tel Aviv University in Israel showed the robot’s hearing abilities by giving clap signals that told the robot what to do: One clap means go forward, two claps mean move back. What do you think the robot would do if it heard the clap break from Cha Cha Slide?

“Our task was to replace the robot’s electronic microphone with a dead insect’s ear, use the ear’s ability to detect the electrical signals from the environment, in this case vibrations in the air, and, using a special chip, convert the insect input to that of the robot,” Ben M. Maoz, PhD, said in a statement from the university.

And how does a dead locust ear work in a robot? Well, Dr. Maoz explained: “My laboratory has developed a special device – Ear-on-a-Chip – that allows the ear to be kept alive throughout the experiment by supplying oxygen and food to the organ while allowing the electrical signals to be taken out of the locust’s ear and amplified and transmitted to the robot.”

The research won’t stop at hearing, he said, as the other four senses also will be taken into consideration. This could help us sense dangers in the future, such as earthquakes or diseases. We said it before and we’ll say it again: We’re rooting for you, science!