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Millions Are Using FDA-Authorized Alternatives to Pharma’s Weight Loss Drugs
Pharmacist Mark Mikhael has lost 50 pounds over the past 12 months. He no longer has diabetes and finds himself “at my ideal body weight,” with his cholesterol below 200 for the first time in 20 years. “I feel fantastic,” he said.
Like millions of others, Mr. Mikhael credits the new class of weight loss drugs. But he isn’t using brand-name Wegovy or Zepbound. Mr. Mikhael, CEO of Orlando, Florida–based Olympia Pharmaceuticals, has been getting by with his own supply: injecting himself with copies of the drugs formulated by his company.
He’s far from alone.
The drug-making behemoths fiercely oppose that compounding business. Novo Nordisk and Lilly lump the compounders together with Internet cowboys and unregulated medical spas peddling bogus semaglutide, and have high-powered legal teams trying to stop them. Novo Nordisk has filed at least 21 lawsuits nationwide against companies making purported copies of its drugs, said Brianna Kelley, a spokesperson for the company, and urges doctors to avoid them. The Food and Drug Administration (FDA), too, has cautioned about the potential danger of the compounds, and leading obesity medicine groups starkly warn patients against their use.
But this isn’t an illegal black market, though it has shades of gray.
The FDA allows and even encourages compounding pharmacies to produce and sell copycats when a drug is in short supply, and the wildly popular glucagon-like peptide 1 (GLP-1) drugs have enduring shortages — first reported in March 2022 for semaglutide and in December 2022 for tirzepatide. The drugs have registered unprecedented success in weight loss. They are also showing promise against heart, kidney, and liver diseases and are being tested against conditions as diverse as Alzheimer’s disease and drug addiction.
In recent years, the US health care system has come to depend on compounding pharmacies, many of which are run as nonprofits, to plug supply holes of crucial drugs like cancer medicines cisplatin, methotrexate, and 5-fluorouracil.
Most compounded drugs are old, cheap generics. Semaglutide and tirzepatide, on the other hand, are under patent and earn Novo Nordisk and Lilly billions of dollars a year. Sales of the diabetes and weight loss drugs in 2024 made Novo Nordisk Europe’s most valuable company and Lilly the world’s biggest pharmaceutical company.
While the companies can’t keep up with demand, they heatedly dispute the right of compounders to make and sell copies. Lilly spokesperson Kristiane Silva Bello said her company was “deeply concerned” about “serious health risks” from compounded drugs that “should not be on the market.”
Yet marketed they are. Even Hims & Hers Health — the telemedicine prescriber that got its start with erectile dysfunction drugs — is now peddling compounded semaglutide. It ran ads for the drugs during NBA playoff games. (According to a Hunterbrook Media report, Hims & Hers’ semaglutide supplier has faced legal scrutiny.)
The compounded forms are significantly cheaper than the branded drugs. Patients pay about $100-$450 a month, compared with list prices of roughly $1,000-$1,400 for Lilly and Novo Nordisk products.
Five compounders and distributors interviewed for this article said they conduct due diligence on every lot of semaglutide or tirzepatide they buy or produce, upholding standards of purity, sterility, and consistency similar to those practiced in the commercial drug industry. Compounders operate under strict federal and state standards, they noted.
However, the raw materials used in the compounded forms may differ from those produced for Novo Nordisk and Lilly, said GLP-1 coinventor Jens Juul Holst, of the University of Copenhagen, adding that care must be taken in drug production lest it cause potentially harmful immune reactions.
To date, according to FDA spokespeople, reports of side effects from taking compounded versions haven’t raised major alarms. But everyone with knowledge of the industry, including the compounders themselves, worry that a single batch of a poorly made drug could kill or maim people and destroy confidence in their business.
“I liken the compounding industry to the airline industry,” Mr. Mikhael said. “When you have an airline crash, it hurts everybody.”
Warnings From the Past
The industry endured just such a catastrophe in 2012, when the New England Compounding Center released a contaminated injectable steroid that killed at least 64 people and harmed hundreds more.
In response, Congress and the FDA had strengthened oversight. Mr. Mikhael’s company is an outsourcing facility, or 503B compounding pharmacy — so-named for a section of the 2013 law that set new requirements for drug compounders. The companies are licensed to make slightly different versions of FDA-approved drugs in response to shortages or a patient’s special needs.
The law created two classes of compounding pharmacies: The FDA regulates the larger 503B compounders with standards like commercial drug companies, while 503A pharmacies make smaller lots of drugs and are largely overseen by state boards of pharmacy.
The 503A facilities also are producing compounded semaglutide and tirzepatide for hundreds of thousands of patients. Like the 503Bs, these operations take the active ingredient, produced as a powder in FDA-registered factories, mostly in China, then reconstitute it with sterile water and an antimicrobial in small glass vials.
Together, the compounding pharmacies may account for up to 30% of the semaglutide sold in the United States, Mr. Mikhael said, although he cautions that is a “wild ballpark figure” since no one, including the FDA, is tracking sales in the industry.
The compounders say the companies should increase production if they’re worried about competition. Like the dozens of other drugs they produce for hospitals and medical practices, the compounders say, the two diet drugs are essential products.
“If you don’t want a 503B facility to make a copy, it’s pretty simple: Don’t go short,” said Lee Rosebush, chair of a trade association for 503B pharmacies. “FDA created this system because these are necessary drugs.”
Novo Nordisk hasn’t specified why it can’t keep up with demand, but the bottleneck apparently lies in the company’s inability to fill and sterilize enough of its special drug auto-injectors, said Evan Seigerman, a managing director at BMO Capital Markets.
The company announced June 24 that it was investing $4.1 billion in new production lines at its Clayton, North Carolina, site. In 2023, the FDA issued a warning over procedural violations at the site and separate cautions at an Indiana facility that Novo Nordisk took over recently.
Compounding for Dummies
At least 28 companies, mostly in China, are registered with the FDA to produce or distribute semaglutide. At least half the companies have entered the market in the past 12 months, driving the raw material’s price down by 35%, according to Scott Welch, who runs a 503A pharmacy in Arlington, Virginia.
Compounders can buy powdered semaglutide from some US distributors for less than $4,000 a gram, said Matthew Johnson, president and CEO of distributor Pharma Source Direct. That comes out to as little as $10 per weekly 2.5-microgram dose – not including overhead and other costs.
While Ozempic or Wegovy patients use a Novo Nordisk device to inject the drug, patients using compounded products draw them from a vial with a small needle, like the device diabetics use for insulin.
Some medical practices provide the compounded drug to patients as part of a weight loss package, with markups. In July 2023, Tabitha Ries, a single mother of six who works as a home health care aide in Garfield, Washington, found an online clinic that charged her $1,000 for 3 months of semaglutide along with counseling. She has lost 35 pounds.
She gets the drug from Mindful Weight Loss, a mostly telehealth-based operation led by physician Vivek Gupta, MD, of Manhattan Beach, California. Dr. Gupta said he’s prescribed the weight loss drugs to 1,500 patients, with about 60% using compounded versions from a 503A pharmacy.
He hasn’t seen any essential difference in patients using the branded and compounded forms, although “some people say the compounding is a little less effective,” Dr. Gupta said.
There’s some risk in using the non–FDA-approved product, he acknowledged, and he requires patients to sign an informed consent waiver.
“Nothing in life is without risk, but I would also argue that the status quo is not safe for people who need the medicine and can’t get it,” he said. “They’re constantly triggered by all this food that’s causing their weight to go up and their sugar to go high, increasing their insulin resistance and affecting their limbs and eyes.”
Compounding semaglutide is a helpful sideline for pharmacists like him, Mr. Welch said, especially given the pinch on drug sale revenue that has led many independents to close in recent years. He figures he earns 95% of his revenue from compounding drugs, rather than traditional prescriptions.
It’s important to distinguish compounded semaglutide from unregulated powders sold as “generic Ozempic” and the like, which may be contaminated or counterfeit, said FDA spokesperson Amanda Hils. But since compounded forms of the drug are not FDA approved, those who make, prescribe, or use them also should have “an increased level of responsibility or awareness,” she said.
Corporate Battles
Novo Nordisk and Lilly, in lawsuits each company has filed against competitors, say their own testing has found bacteria and other impurities in products made by compounding pharmacies. The companies also report patent infringement, but compounders, pointing to the FDA loophole for drugs in shortage, appear to have defeated that argument for now.
When the FDA removes the drugs from the shortage list, 503B compounders must immediately stop selling them. Smaller compounders may be able to produce their products for a reduced number of patients, said Scott Brunner, CEO of the Alliance for Pharmacy Compounding, which represents 503A compounders.
The evaporation of the compounded drug supply could come as a shock to patients.
“I dread it,” said David Wertheimer, an internist in Franklin Lakes, New Jersey, who prescribes compounded semaglutide to some patients. “People are not going to be able to plunk down a grand every month. A lot of people will go off the drug, and that’s a shame.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.
Pharmacist Mark Mikhael has lost 50 pounds over the past 12 months. He no longer has diabetes and finds himself “at my ideal body weight,” with his cholesterol below 200 for the first time in 20 years. “I feel fantastic,” he said.
Like millions of others, Mr. Mikhael credits the new class of weight loss drugs. But he isn’t using brand-name Wegovy or Zepbound. Mr. Mikhael, CEO of Orlando, Florida–based Olympia Pharmaceuticals, has been getting by with his own supply: injecting himself with copies of the drugs formulated by his company.
He’s far from alone.
The drug-making behemoths fiercely oppose that compounding business. Novo Nordisk and Lilly lump the compounders together with Internet cowboys and unregulated medical spas peddling bogus semaglutide, and have high-powered legal teams trying to stop them. Novo Nordisk has filed at least 21 lawsuits nationwide against companies making purported copies of its drugs, said Brianna Kelley, a spokesperson for the company, and urges doctors to avoid them. The Food and Drug Administration (FDA), too, has cautioned about the potential danger of the compounds, and leading obesity medicine groups starkly warn patients against their use.
But this isn’t an illegal black market, though it has shades of gray.
The FDA allows and even encourages compounding pharmacies to produce and sell copycats when a drug is in short supply, and the wildly popular glucagon-like peptide 1 (GLP-1) drugs have enduring shortages — first reported in March 2022 for semaglutide and in December 2022 for tirzepatide. The drugs have registered unprecedented success in weight loss. They are also showing promise against heart, kidney, and liver diseases and are being tested against conditions as diverse as Alzheimer’s disease and drug addiction.
In recent years, the US health care system has come to depend on compounding pharmacies, many of which are run as nonprofits, to plug supply holes of crucial drugs like cancer medicines cisplatin, methotrexate, and 5-fluorouracil.
Most compounded drugs are old, cheap generics. Semaglutide and tirzepatide, on the other hand, are under patent and earn Novo Nordisk and Lilly billions of dollars a year. Sales of the diabetes and weight loss drugs in 2024 made Novo Nordisk Europe’s most valuable company and Lilly the world’s biggest pharmaceutical company.
While the companies can’t keep up with demand, they heatedly dispute the right of compounders to make and sell copies. Lilly spokesperson Kristiane Silva Bello said her company was “deeply concerned” about “serious health risks” from compounded drugs that “should not be on the market.”
Yet marketed they are. Even Hims & Hers Health — the telemedicine prescriber that got its start with erectile dysfunction drugs — is now peddling compounded semaglutide. It ran ads for the drugs during NBA playoff games. (According to a Hunterbrook Media report, Hims & Hers’ semaglutide supplier has faced legal scrutiny.)
The compounded forms are significantly cheaper than the branded drugs. Patients pay about $100-$450 a month, compared with list prices of roughly $1,000-$1,400 for Lilly and Novo Nordisk products.
Five compounders and distributors interviewed for this article said they conduct due diligence on every lot of semaglutide or tirzepatide they buy or produce, upholding standards of purity, sterility, and consistency similar to those practiced in the commercial drug industry. Compounders operate under strict federal and state standards, they noted.
However, the raw materials used in the compounded forms may differ from those produced for Novo Nordisk and Lilly, said GLP-1 coinventor Jens Juul Holst, of the University of Copenhagen, adding that care must be taken in drug production lest it cause potentially harmful immune reactions.
To date, according to FDA spokespeople, reports of side effects from taking compounded versions haven’t raised major alarms. But everyone with knowledge of the industry, including the compounders themselves, worry that a single batch of a poorly made drug could kill or maim people and destroy confidence in their business.
“I liken the compounding industry to the airline industry,” Mr. Mikhael said. “When you have an airline crash, it hurts everybody.”
Warnings From the Past
The industry endured just such a catastrophe in 2012, when the New England Compounding Center released a contaminated injectable steroid that killed at least 64 people and harmed hundreds more.
In response, Congress and the FDA had strengthened oversight. Mr. Mikhael’s company is an outsourcing facility, or 503B compounding pharmacy — so-named for a section of the 2013 law that set new requirements for drug compounders. The companies are licensed to make slightly different versions of FDA-approved drugs in response to shortages or a patient’s special needs.
The law created two classes of compounding pharmacies: The FDA regulates the larger 503B compounders with standards like commercial drug companies, while 503A pharmacies make smaller lots of drugs and are largely overseen by state boards of pharmacy.
The 503A facilities also are producing compounded semaglutide and tirzepatide for hundreds of thousands of patients. Like the 503Bs, these operations take the active ingredient, produced as a powder in FDA-registered factories, mostly in China, then reconstitute it with sterile water and an antimicrobial in small glass vials.
Together, the compounding pharmacies may account for up to 30% of the semaglutide sold in the United States, Mr. Mikhael said, although he cautions that is a “wild ballpark figure” since no one, including the FDA, is tracking sales in the industry.
The compounders say the companies should increase production if they’re worried about competition. Like the dozens of other drugs they produce for hospitals and medical practices, the compounders say, the two diet drugs are essential products.
“If you don’t want a 503B facility to make a copy, it’s pretty simple: Don’t go short,” said Lee Rosebush, chair of a trade association for 503B pharmacies. “FDA created this system because these are necessary drugs.”
Novo Nordisk hasn’t specified why it can’t keep up with demand, but the bottleneck apparently lies in the company’s inability to fill and sterilize enough of its special drug auto-injectors, said Evan Seigerman, a managing director at BMO Capital Markets.
The company announced June 24 that it was investing $4.1 billion in new production lines at its Clayton, North Carolina, site. In 2023, the FDA issued a warning over procedural violations at the site and separate cautions at an Indiana facility that Novo Nordisk took over recently.
Compounding for Dummies
At least 28 companies, mostly in China, are registered with the FDA to produce or distribute semaglutide. At least half the companies have entered the market in the past 12 months, driving the raw material’s price down by 35%, according to Scott Welch, who runs a 503A pharmacy in Arlington, Virginia.
Compounders can buy powdered semaglutide from some US distributors for less than $4,000 a gram, said Matthew Johnson, president and CEO of distributor Pharma Source Direct. That comes out to as little as $10 per weekly 2.5-microgram dose – not including overhead and other costs.
While Ozempic or Wegovy patients use a Novo Nordisk device to inject the drug, patients using compounded products draw them from a vial with a small needle, like the device diabetics use for insulin.
Some medical practices provide the compounded drug to patients as part of a weight loss package, with markups. In July 2023, Tabitha Ries, a single mother of six who works as a home health care aide in Garfield, Washington, found an online clinic that charged her $1,000 for 3 months of semaglutide along with counseling. She has lost 35 pounds.
She gets the drug from Mindful Weight Loss, a mostly telehealth-based operation led by physician Vivek Gupta, MD, of Manhattan Beach, California. Dr. Gupta said he’s prescribed the weight loss drugs to 1,500 patients, with about 60% using compounded versions from a 503A pharmacy.
He hasn’t seen any essential difference in patients using the branded and compounded forms, although “some people say the compounding is a little less effective,” Dr. Gupta said.
There’s some risk in using the non–FDA-approved product, he acknowledged, and he requires patients to sign an informed consent waiver.
“Nothing in life is without risk, but I would also argue that the status quo is not safe for people who need the medicine and can’t get it,” he said. “They’re constantly triggered by all this food that’s causing their weight to go up and their sugar to go high, increasing their insulin resistance and affecting their limbs and eyes.”
Compounding semaglutide is a helpful sideline for pharmacists like him, Mr. Welch said, especially given the pinch on drug sale revenue that has led many independents to close in recent years. He figures he earns 95% of his revenue from compounding drugs, rather than traditional prescriptions.
It’s important to distinguish compounded semaglutide from unregulated powders sold as “generic Ozempic” and the like, which may be contaminated or counterfeit, said FDA spokesperson Amanda Hils. But since compounded forms of the drug are not FDA approved, those who make, prescribe, or use them also should have “an increased level of responsibility or awareness,” she said.
Corporate Battles
Novo Nordisk and Lilly, in lawsuits each company has filed against competitors, say their own testing has found bacteria and other impurities in products made by compounding pharmacies. The companies also report patent infringement, but compounders, pointing to the FDA loophole for drugs in shortage, appear to have defeated that argument for now.
When the FDA removes the drugs from the shortage list, 503B compounders must immediately stop selling them. Smaller compounders may be able to produce their products for a reduced number of patients, said Scott Brunner, CEO of the Alliance for Pharmacy Compounding, which represents 503A compounders.
The evaporation of the compounded drug supply could come as a shock to patients.
“I dread it,” said David Wertheimer, an internist in Franklin Lakes, New Jersey, who prescribes compounded semaglutide to some patients. “People are not going to be able to plunk down a grand every month. A lot of people will go off the drug, and that’s a shame.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.
Pharmacist Mark Mikhael has lost 50 pounds over the past 12 months. He no longer has diabetes and finds himself “at my ideal body weight,” with his cholesterol below 200 for the first time in 20 years. “I feel fantastic,” he said.
Like millions of others, Mr. Mikhael credits the new class of weight loss drugs. But he isn’t using brand-name Wegovy or Zepbound. Mr. Mikhael, CEO of Orlando, Florida–based Olympia Pharmaceuticals, has been getting by with his own supply: injecting himself with copies of the drugs formulated by his company.
He’s far from alone.
The drug-making behemoths fiercely oppose that compounding business. Novo Nordisk and Lilly lump the compounders together with Internet cowboys and unregulated medical spas peddling bogus semaglutide, and have high-powered legal teams trying to stop them. Novo Nordisk has filed at least 21 lawsuits nationwide against companies making purported copies of its drugs, said Brianna Kelley, a spokesperson for the company, and urges doctors to avoid them. The Food and Drug Administration (FDA), too, has cautioned about the potential danger of the compounds, and leading obesity medicine groups starkly warn patients against their use.
But this isn’t an illegal black market, though it has shades of gray.
The FDA allows and even encourages compounding pharmacies to produce and sell copycats when a drug is in short supply, and the wildly popular glucagon-like peptide 1 (GLP-1) drugs have enduring shortages — first reported in March 2022 for semaglutide and in December 2022 for tirzepatide. The drugs have registered unprecedented success in weight loss. They are also showing promise against heart, kidney, and liver diseases and are being tested against conditions as diverse as Alzheimer’s disease and drug addiction.
In recent years, the US health care system has come to depend on compounding pharmacies, many of which are run as nonprofits, to plug supply holes of crucial drugs like cancer medicines cisplatin, methotrexate, and 5-fluorouracil.
Most compounded drugs are old, cheap generics. Semaglutide and tirzepatide, on the other hand, are under patent and earn Novo Nordisk and Lilly billions of dollars a year. Sales of the diabetes and weight loss drugs in 2024 made Novo Nordisk Europe’s most valuable company and Lilly the world’s biggest pharmaceutical company.
While the companies can’t keep up with demand, they heatedly dispute the right of compounders to make and sell copies. Lilly spokesperson Kristiane Silva Bello said her company was “deeply concerned” about “serious health risks” from compounded drugs that “should not be on the market.”
Yet marketed they are. Even Hims & Hers Health — the telemedicine prescriber that got its start with erectile dysfunction drugs — is now peddling compounded semaglutide. It ran ads for the drugs during NBA playoff games. (According to a Hunterbrook Media report, Hims & Hers’ semaglutide supplier has faced legal scrutiny.)
The compounded forms are significantly cheaper than the branded drugs. Patients pay about $100-$450 a month, compared with list prices of roughly $1,000-$1,400 for Lilly and Novo Nordisk products.
Five compounders and distributors interviewed for this article said they conduct due diligence on every lot of semaglutide or tirzepatide they buy or produce, upholding standards of purity, sterility, and consistency similar to those practiced in the commercial drug industry. Compounders operate under strict federal and state standards, they noted.
However, the raw materials used in the compounded forms may differ from those produced for Novo Nordisk and Lilly, said GLP-1 coinventor Jens Juul Holst, of the University of Copenhagen, adding that care must be taken in drug production lest it cause potentially harmful immune reactions.
To date, according to FDA spokespeople, reports of side effects from taking compounded versions haven’t raised major alarms. But everyone with knowledge of the industry, including the compounders themselves, worry that a single batch of a poorly made drug could kill or maim people and destroy confidence in their business.
“I liken the compounding industry to the airline industry,” Mr. Mikhael said. “When you have an airline crash, it hurts everybody.”
Warnings From the Past
The industry endured just such a catastrophe in 2012, when the New England Compounding Center released a contaminated injectable steroid that killed at least 64 people and harmed hundreds more.
In response, Congress and the FDA had strengthened oversight. Mr. Mikhael’s company is an outsourcing facility, or 503B compounding pharmacy — so-named for a section of the 2013 law that set new requirements for drug compounders. The companies are licensed to make slightly different versions of FDA-approved drugs in response to shortages or a patient’s special needs.
The law created two classes of compounding pharmacies: The FDA regulates the larger 503B compounders with standards like commercial drug companies, while 503A pharmacies make smaller lots of drugs and are largely overseen by state boards of pharmacy.
The 503A facilities also are producing compounded semaglutide and tirzepatide for hundreds of thousands of patients. Like the 503Bs, these operations take the active ingredient, produced as a powder in FDA-registered factories, mostly in China, then reconstitute it with sterile water and an antimicrobial in small glass vials.
Together, the compounding pharmacies may account for up to 30% of the semaglutide sold in the United States, Mr. Mikhael said, although he cautions that is a “wild ballpark figure” since no one, including the FDA, is tracking sales in the industry.
The compounders say the companies should increase production if they’re worried about competition. Like the dozens of other drugs they produce for hospitals and medical practices, the compounders say, the two diet drugs are essential products.
“If you don’t want a 503B facility to make a copy, it’s pretty simple: Don’t go short,” said Lee Rosebush, chair of a trade association for 503B pharmacies. “FDA created this system because these are necessary drugs.”
Novo Nordisk hasn’t specified why it can’t keep up with demand, but the bottleneck apparently lies in the company’s inability to fill and sterilize enough of its special drug auto-injectors, said Evan Seigerman, a managing director at BMO Capital Markets.
The company announced June 24 that it was investing $4.1 billion in new production lines at its Clayton, North Carolina, site. In 2023, the FDA issued a warning over procedural violations at the site and separate cautions at an Indiana facility that Novo Nordisk took over recently.
Compounding for Dummies
At least 28 companies, mostly in China, are registered with the FDA to produce or distribute semaglutide. At least half the companies have entered the market in the past 12 months, driving the raw material’s price down by 35%, according to Scott Welch, who runs a 503A pharmacy in Arlington, Virginia.
Compounders can buy powdered semaglutide from some US distributors for less than $4,000 a gram, said Matthew Johnson, president and CEO of distributor Pharma Source Direct. That comes out to as little as $10 per weekly 2.5-microgram dose – not including overhead and other costs.
While Ozempic or Wegovy patients use a Novo Nordisk device to inject the drug, patients using compounded products draw them from a vial with a small needle, like the device diabetics use for insulin.
Some medical practices provide the compounded drug to patients as part of a weight loss package, with markups. In July 2023, Tabitha Ries, a single mother of six who works as a home health care aide in Garfield, Washington, found an online clinic that charged her $1,000 for 3 months of semaglutide along with counseling. She has lost 35 pounds.
She gets the drug from Mindful Weight Loss, a mostly telehealth-based operation led by physician Vivek Gupta, MD, of Manhattan Beach, California. Dr. Gupta said he’s prescribed the weight loss drugs to 1,500 patients, with about 60% using compounded versions from a 503A pharmacy.
He hasn’t seen any essential difference in patients using the branded and compounded forms, although “some people say the compounding is a little less effective,” Dr. Gupta said.
There’s some risk in using the non–FDA-approved product, he acknowledged, and he requires patients to sign an informed consent waiver.
“Nothing in life is without risk, but I would also argue that the status quo is not safe for people who need the medicine and can’t get it,” he said. “They’re constantly triggered by all this food that’s causing their weight to go up and their sugar to go high, increasing their insulin resistance and affecting their limbs and eyes.”
Compounding semaglutide is a helpful sideline for pharmacists like him, Mr. Welch said, especially given the pinch on drug sale revenue that has led many independents to close in recent years. He figures he earns 95% of his revenue from compounding drugs, rather than traditional prescriptions.
It’s important to distinguish compounded semaglutide from unregulated powders sold as “generic Ozempic” and the like, which may be contaminated or counterfeit, said FDA spokesperson Amanda Hils. But since compounded forms of the drug are not FDA approved, those who make, prescribe, or use them also should have “an increased level of responsibility or awareness,” she said.
Corporate Battles
Novo Nordisk and Lilly, in lawsuits each company has filed against competitors, say their own testing has found bacteria and other impurities in products made by compounding pharmacies. The companies also report patent infringement, but compounders, pointing to the FDA loophole for drugs in shortage, appear to have defeated that argument for now.
When the FDA removes the drugs from the shortage list, 503B compounders must immediately stop selling them. Smaller compounders may be able to produce their products for a reduced number of patients, said Scott Brunner, CEO of the Alliance for Pharmacy Compounding, which represents 503A compounders.
The evaporation of the compounded drug supply could come as a shock to patients.
“I dread it,” said David Wertheimer, an internist in Franklin Lakes, New Jersey, who prescribes compounded semaglutide to some patients. “People are not going to be able to plunk down a grand every month. A lot of people will go off the drug, and that’s a shame.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.
Multimorbidity Worsens Quality of Life in Patients With PsA
Key clinical point: Multimorbidity was present in nearly 50% of patients with psoriatic arthritis (PsA) and significantly affected the physical aspects of their quality of life.
Major finding: Multimorbidity was observed in 50.2% patients, with cardiovascular diseases being the most prevalent comorbidity. Patients with vs without multimorbidity had worsened scores for various 36-Item Short Form Health Survey domains, including bodily pain (34.7 vs 47.5; P < .01), physical functioning (52.1 vs 63.1; P < .01), and ability to perform roles due to physical health problems (28.5 vs 42.8; P < .01).
Study details: This cross-sectional observational study included 267 patients with PsA, age > 18 years.
Disclosures: This study was supported by a grant from the National Centre for Research and Development, Warsaw, Poland. The authors declared no conflicts of interest.
Source: Biedroń G, Wilk M, Nowakowski J, et al. Impact of comorbidities on patient-reported outcomes in psoriatic arthritis: A single centre cohort study. Rheumatol Int. Published online 2024;44:1435-1443. Doi: 10.1007/s00296-024-05632-2 Source
Key clinical point: Multimorbidity was present in nearly 50% of patients with psoriatic arthritis (PsA) and significantly affected the physical aspects of their quality of life.
Major finding: Multimorbidity was observed in 50.2% patients, with cardiovascular diseases being the most prevalent comorbidity. Patients with vs without multimorbidity had worsened scores for various 36-Item Short Form Health Survey domains, including bodily pain (34.7 vs 47.5; P < .01), physical functioning (52.1 vs 63.1; P < .01), and ability to perform roles due to physical health problems (28.5 vs 42.8; P < .01).
Study details: This cross-sectional observational study included 267 patients with PsA, age > 18 years.
Disclosures: This study was supported by a grant from the National Centre for Research and Development, Warsaw, Poland. The authors declared no conflicts of interest.
Source: Biedroń G, Wilk M, Nowakowski J, et al. Impact of comorbidities on patient-reported outcomes in psoriatic arthritis: A single centre cohort study. Rheumatol Int. Published online 2024;44:1435-1443. Doi: 10.1007/s00296-024-05632-2 Source
Key clinical point: Multimorbidity was present in nearly 50% of patients with psoriatic arthritis (PsA) and significantly affected the physical aspects of their quality of life.
Major finding: Multimorbidity was observed in 50.2% patients, with cardiovascular diseases being the most prevalent comorbidity. Patients with vs without multimorbidity had worsened scores for various 36-Item Short Form Health Survey domains, including bodily pain (34.7 vs 47.5; P < .01), physical functioning (52.1 vs 63.1; P < .01), and ability to perform roles due to physical health problems (28.5 vs 42.8; P < .01).
Study details: This cross-sectional observational study included 267 patients with PsA, age > 18 years.
Disclosures: This study was supported by a grant from the National Centre for Research and Development, Warsaw, Poland. The authors declared no conflicts of interest.
Source: Biedroń G, Wilk M, Nowakowski J, et al. Impact of comorbidities on patient-reported outcomes in psoriatic arthritis: A single centre cohort study. Rheumatol Int. Published online 2024;44:1435-1443. Doi: 10.1007/s00296-024-05632-2 Source
Biologics Better Than Methotrexate for Preventing PsA in Psoriasis
Key clinical point: The onset rate of psoriatic arthritis (PsA) in patients with psoriasis was lower with biologics than with methotrexate, with topical therapy being associated with the lowest rate.
Major finding: Treatment with biologics vs methotrexate significantly reduced the risk of developing PsA (adjusted hazard ratio [aHR] 0.46; 95% CI 0.35-0.62); however, biologics were associated with an increased risk of developing PsA when compared to topical therapy (aHR 2.16; 95% CI 1.44-3.24). Prior exposure to at least two biologics (odds ratio [OR] 6.09; P < .001) or methotrexate (OR 1.88; P = .026) was tied to increased PsA risk.
Study details: This retrospective cohort study included 58,671 patients with psoriasis treated with biologics, methotrexate, phototherapy, or topical therapy; patients who received phototherapy or topical therapy did not undergo any prior systemic treatment.
Disclosures: This study was supported by an educational grant from Janssen Pharmaceuticals. Alen Zabotti declared being an editorial board member of Rheumatology and Therapy. The other authors declared no conflicts of interest.
Source: Watad A, Zabotti A, Patt YS, et al. From psoriasis to psoriatic arthritis: Decoding the impact of treatment modalities on the prevention of psoriatic arthritis. Rheumatol Ther. 2024;11:963-976 (June 7). Doi: 10.1007/s40744-024-00680-3 Source
Key clinical point: The onset rate of psoriatic arthritis (PsA) in patients with psoriasis was lower with biologics than with methotrexate, with topical therapy being associated with the lowest rate.
Major finding: Treatment with biologics vs methotrexate significantly reduced the risk of developing PsA (adjusted hazard ratio [aHR] 0.46; 95% CI 0.35-0.62); however, biologics were associated with an increased risk of developing PsA when compared to topical therapy (aHR 2.16; 95% CI 1.44-3.24). Prior exposure to at least two biologics (odds ratio [OR] 6.09; P < .001) or methotrexate (OR 1.88; P = .026) was tied to increased PsA risk.
Study details: This retrospective cohort study included 58,671 patients with psoriasis treated with biologics, methotrexate, phototherapy, or topical therapy; patients who received phototherapy or topical therapy did not undergo any prior systemic treatment.
Disclosures: This study was supported by an educational grant from Janssen Pharmaceuticals. Alen Zabotti declared being an editorial board member of Rheumatology and Therapy. The other authors declared no conflicts of interest.
Source: Watad A, Zabotti A, Patt YS, et al. From psoriasis to psoriatic arthritis: Decoding the impact of treatment modalities on the prevention of psoriatic arthritis. Rheumatol Ther. 2024;11:963-976 (June 7). Doi: 10.1007/s40744-024-00680-3 Source
Key clinical point: The onset rate of psoriatic arthritis (PsA) in patients with psoriasis was lower with biologics than with methotrexate, with topical therapy being associated with the lowest rate.
Major finding: Treatment with biologics vs methotrexate significantly reduced the risk of developing PsA (adjusted hazard ratio [aHR] 0.46; 95% CI 0.35-0.62); however, biologics were associated with an increased risk of developing PsA when compared to topical therapy (aHR 2.16; 95% CI 1.44-3.24). Prior exposure to at least two biologics (odds ratio [OR] 6.09; P < .001) or methotrexate (OR 1.88; P = .026) was tied to increased PsA risk.
Study details: This retrospective cohort study included 58,671 patients with psoriasis treated with biologics, methotrexate, phototherapy, or topical therapy; patients who received phototherapy or topical therapy did not undergo any prior systemic treatment.
Disclosures: This study was supported by an educational grant from Janssen Pharmaceuticals. Alen Zabotti declared being an editorial board member of Rheumatology and Therapy. The other authors declared no conflicts of interest.
Source: Watad A, Zabotti A, Patt YS, et al. From psoriasis to psoriatic arthritis: Decoding the impact of treatment modalities on the prevention of psoriatic arthritis. Rheumatol Ther. 2024;11:963-976 (June 7). Doi: 10.1007/s40744-024-00680-3 Source
Achilles Tendon Pain Severely Impairs Function in PsA
Key clinical point: Patients with psoriatic arthritis (PsA) who did vs did not have Achilles tendon (AT) pain reported severe functional impairment and disability.
Major finding: Patients with PsA with vs without AT pain had significantly greater AT-related morning stiffness (90.9% vs 9.1%; P < .001), impaired AT function (median heel raise repetition rate 0.72 vs 1.24; P = .005), worse Psoriatic Arthritis Impact of Disease questionnaire score (mean 5.52 vs 3.38; P = .018), and pain on passive dorsiflexion (36.4% vs 0%; P = .011) and resisted plantarflexion (45.5% vs 0%; P = .003).
Study details: This cross-sectional, observational study included 22 patients with PsA with (n = 11) and without (n = 11) self-reported AT pain and 11 healthy individuals without PsA or AT pain.
Disclosures: This study was funded by a Glasgow (UK) Caledonian University-funded PhD studentship. The authors declared no conflicts of interest.
Source: Patience A, Steultjens M, Siebert S, Hendry G. Significant functional impairment and disability in individuals with psoriatic arthritis and Achilles tendon pain: A cross-sectional observational study. Rheumatol Int. 2024;44:1469-1479 (June 8). Doi: 10.1007/s00296-024-05629-x Source
Key clinical point: Patients with psoriatic arthritis (PsA) who did vs did not have Achilles tendon (AT) pain reported severe functional impairment and disability.
Major finding: Patients with PsA with vs without AT pain had significantly greater AT-related morning stiffness (90.9% vs 9.1%; P < .001), impaired AT function (median heel raise repetition rate 0.72 vs 1.24; P = .005), worse Psoriatic Arthritis Impact of Disease questionnaire score (mean 5.52 vs 3.38; P = .018), and pain on passive dorsiflexion (36.4% vs 0%; P = .011) and resisted plantarflexion (45.5% vs 0%; P = .003).
Study details: This cross-sectional, observational study included 22 patients with PsA with (n = 11) and without (n = 11) self-reported AT pain and 11 healthy individuals without PsA or AT pain.
Disclosures: This study was funded by a Glasgow (UK) Caledonian University-funded PhD studentship. The authors declared no conflicts of interest.
Source: Patience A, Steultjens M, Siebert S, Hendry G. Significant functional impairment and disability in individuals with psoriatic arthritis and Achilles tendon pain: A cross-sectional observational study. Rheumatol Int. 2024;44:1469-1479 (June 8). Doi: 10.1007/s00296-024-05629-x Source
Key clinical point: Patients with psoriatic arthritis (PsA) who did vs did not have Achilles tendon (AT) pain reported severe functional impairment and disability.
Major finding: Patients with PsA with vs without AT pain had significantly greater AT-related morning stiffness (90.9% vs 9.1%; P < .001), impaired AT function (median heel raise repetition rate 0.72 vs 1.24; P = .005), worse Psoriatic Arthritis Impact of Disease questionnaire score (mean 5.52 vs 3.38; P = .018), and pain on passive dorsiflexion (36.4% vs 0%; P = .011) and resisted plantarflexion (45.5% vs 0%; P = .003).
Study details: This cross-sectional, observational study included 22 patients with PsA with (n = 11) and without (n = 11) self-reported AT pain and 11 healthy individuals without PsA or AT pain.
Disclosures: This study was funded by a Glasgow (UK) Caledonian University-funded PhD studentship. The authors declared no conflicts of interest.
Source: Patience A, Steultjens M, Siebert S, Hendry G. Significant functional impairment and disability in individuals with psoriatic arthritis and Achilles tendon pain: A cross-sectional observational study. Rheumatol Int. 2024;44:1469-1479 (June 8). Doi: 10.1007/s00296-024-05629-x Source
Varied Psoriasis Manifestations Pose Differential Risk for Psoriatic Arthritis
Key clinical point: The risk of developing psoriatic arthritis (PsA) varied across different manifestations of psoriasis, with psoriasis vulgaris posing the highest risk.
Major finding: Compared with control individuals without psoriasis, patients with psoriasis vulgaris had the highest risk for incident PsA (hazard ratio [HR] 87.7; P < .0001), followed by those with generalized pustular psoriasis (HR 26.8; P < .0001) and pustulosis palmoplantaris (HR 15.3; P < .0001). The risk for PsA was marginally elevated in female vs male patients with psoriasis vulgaris (HR 1.1; P = .002).
Study details: This population-based retrospective cohort study included patients with psoriasis vulgaris (n = 35,281), pustulosis palmoplantaris (n = 9639), or generalized pustular psoriasis (n = 2281) who were propensity-score matched with an equal number of control individuals without psoriasis.
Disclosures: This study was funded by the Cluster of Excellence "Precision Medicine in Chronic Inflammation" (Deutsche Forschungsgemeinschaft) and other sources. Some authors declared having ties with various sources or serving as editorial board members for Frontiers.
Source: Gershater B, Bieber K, Vorobyev A, et al. Differential risks of psoriatic arthritis development in patients with varied psoriasis manifestations: A sex- and ethnicity-specific analysis. Front Med. 2024;11:1385491 (June 20). Doi: 10.3389/fmed.2024.1385491 Source
Key clinical point: The risk of developing psoriatic arthritis (PsA) varied across different manifestations of psoriasis, with psoriasis vulgaris posing the highest risk.
Major finding: Compared with control individuals without psoriasis, patients with psoriasis vulgaris had the highest risk for incident PsA (hazard ratio [HR] 87.7; P < .0001), followed by those with generalized pustular psoriasis (HR 26.8; P < .0001) and pustulosis palmoplantaris (HR 15.3; P < .0001). The risk for PsA was marginally elevated in female vs male patients with psoriasis vulgaris (HR 1.1; P = .002).
Study details: This population-based retrospective cohort study included patients with psoriasis vulgaris (n = 35,281), pustulosis palmoplantaris (n = 9639), or generalized pustular psoriasis (n = 2281) who were propensity-score matched with an equal number of control individuals without psoriasis.
Disclosures: This study was funded by the Cluster of Excellence "Precision Medicine in Chronic Inflammation" (Deutsche Forschungsgemeinschaft) and other sources. Some authors declared having ties with various sources or serving as editorial board members for Frontiers.
Source: Gershater B, Bieber K, Vorobyev A, et al. Differential risks of psoriatic arthritis development in patients with varied psoriasis manifestations: A sex- and ethnicity-specific analysis. Front Med. 2024;11:1385491 (June 20). Doi: 10.3389/fmed.2024.1385491 Source
Key clinical point: The risk of developing psoriatic arthritis (PsA) varied across different manifestations of psoriasis, with psoriasis vulgaris posing the highest risk.
Major finding: Compared with control individuals without psoriasis, patients with psoriasis vulgaris had the highest risk for incident PsA (hazard ratio [HR] 87.7; P < .0001), followed by those with generalized pustular psoriasis (HR 26.8; P < .0001) and pustulosis palmoplantaris (HR 15.3; P < .0001). The risk for PsA was marginally elevated in female vs male patients with psoriasis vulgaris (HR 1.1; P = .002).
Study details: This population-based retrospective cohort study included patients with psoriasis vulgaris (n = 35,281), pustulosis palmoplantaris (n = 9639), or generalized pustular psoriasis (n = 2281) who were propensity-score matched with an equal number of control individuals without psoriasis.
Disclosures: This study was funded by the Cluster of Excellence "Precision Medicine in Chronic Inflammation" (Deutsche Forschungsgemeinschaft) and other sources. Some authors declared having ties with various sources or serving as editorial board members for Frontiers.
Source: Gershater B, Bieber K, Vorobyev A, et al. Differential risks of psoriatic arthritis development in patients with varied psoriasis manifestations: A sex- and ethnicity-specific analysis. Front Med. 2024;11:1385491 (June 20). Doi: 10.3389/fmed.2024.1385491 Source
Psoriasis Onset at an Older Age Can Hasten PsA Development
Key clinical point: Patients diagnosed with psoriasis at an older vs younger age had a significantly shorter interval between psoriasis and psoriatic arthritis (PsA) diagnoses and also showed a higher likelihood of developing PsA within 6 months of having psoriasis.
Major finding: Patients with psoriasis onset at the age of 42.6 vs 18.9 years had a 62% shorter time interval between psoriasis and PsA diagnoses (exponentiated estimate 0.38; P < .001) and were ~4.6 times more likely to have a concurrent onset of PsA within 6 months of having psoriasis (odds ratio 4.56; P < .001).
Study details: This registry-based study included 384 patients diagnosed with PsA either after or concurrently with their psoriasis diagnosis.
Disclosures: This study was supported in part by a grant from the US National Institutes of Health. One author declared receiving payment or honoraria from and holding leadership or fiduciary roles with various sources.
Source: Cheemalavagu S, Jin Y, Husni ME. What clinical factors affect length of transition to psoriatic arthritis in patients with psoriasis? ACR Open Rheumatol. 2024 (June 28). Doi: 10.1002/acr2.11703 Source
Key clinical point: Patients diagnosed with psoriasis at an older vs younger age had a significantly shorter interval between psoriasis and psoriatic arthritis (PsA) diagnoses and also showed a higher likelihood of developing PsA within 6 months of having psoriasis.
Major finding: Patients with psoriasis onset at the age of 42.6 vs 18.9 years had a 62% shorter time interval between psoriasis and PsA diagnoses (exponentiated estimate 0.38; P < .001) and were ~4.6 times more likely to have a concurrent onset of PsA within 6 months of having psoriasis (odds ratio 4.56; P < .001).
Study details: This registry-based study included 384 patients diagnosed with PsA either after or concurrently with their psoriasis diagnosis.
Disclosures: This study was supported in part by a grant from the US National Institutes of Health. One author declared receiving payment or honoraria from and holding leadership or fiduciary roles with various sources.
Source: Cheemalavagu S, Jin Y, Husni ME. What clinical factors affect length of transition to psoriatic arthritis in patients with psoriasis? ACR Open Rheumatol. 2024 (June 28). Doi: 10.1002/acr2.11703 Source
Key clinical point: Patients diagnosed with psoriasis at an older vs younger age had a significantly shorter interval between psoriasis and psoriatic arthritis (PsA) diagnoses and also showed a higher likelihood of developing PsA within 6 months of having psoriasis.
Major finding: Patients with psoriasis onset at the age of 42.6 vs 18.9 years had a 62% shorter time interval between psoriasis and PsA diagnoses (exponentiated estimate 0.38; P < .001) and were ~4.6 times more likely to have a concurrent onset of PsA within 6 months of having psoriasis (odds ratio 4.56; P < .001).
Study details: This registry-based study included 384 patients diagnosed with PsA either after or concurrently with their psoriasis diagnosis.
Disclosures: This study was supported in part by a grant from the US National Institutes of Health. One author declared receiving payment or honoraria from and holding leadership or fiduciary roles with various sources.
Source: Cheemalavagu S, Jin Y, Husni ME. What clinical factors affect length of transition to psoriatic arthritis in patients with psoriasis? ACR Open Rheumatol. 2024 (June 28). Doi: 10.1002/acr2.11703 Source
Are Beta-Blockers Safe for COPD?
Everyone takes a pharmacology class in medical school that includes a lecture on beta receptors. They’re in the heart (beta-1) and lungs (beta-2), and drug compounds agonize or antagonize one or both. The professor will caution against using antagonists (beta blockade) for patients with chronic obstructive pulmonary disease (COPD) lest they further impair the patient’s irreversibly narrowed airways. Obsequious students mature into obsequious doctors, intent on “doing no harm.” For better or worse, you withhold beta-blockers from your patient with COPD and comorbid cardiac disease.
Perhaps because the pulmonologist isn’t usually the one who decides whether a beta-blocker is prescribed, I’ve been napping on this topic since training. Early in fellowship, I read an ACP Journal Club article about a Cochrane systematic review (yes, I read a review of a review) that concluded that beta-blockers are fine in patients with COPD. The summary appealed to my bias towards evidence-based medicine (EBM) supplanting physiology, medical school, and everything else. I was more apt to believe my stodgy residency attendings than the stodgy pharmacology professor. Even though COPD and cardiovascular disease share multiple risk factors, I had never reinvestigated the relationship between beta-blockers and COPD.
Turns out that while I was sleeping, the debate continued. Go figure. Just last month a prospective, observational study published in JAMA Network Open found that beta-blockers did not increase the risk for cardiovascular or respiratory events among patients with COPD being discharged after hospitalization for acute myocardial infarction. Although this could be viewed as a triumph for EBM over physiology and a validation of my decade-plus of intellectual laziness, the results are actually pretty thin. These studies, in which patients with an indication for a therapy (a beta-blocker in this case) are analyzed by whether or not they received it, are problematic. The fanciest statistics — in this case, they used propensity scores — can’t control for residual confounding. What drove the physicians to prescribe in some cases but not others? We can only guess.
This might be okay if there hadn’t been a randomized controlled trial (RCT) published in 2019 in The New England Journal of Medicine that found that beta-blockers increase the risk for severe COPD exacerbations. In EBM, the RCT trumps all. Ironically, this trial was designed to test whether beta-blockers reduce severe COPD exacerbations. Yes, we’d come full circle. There was enough biologic plausibility to support a positive effect, or so thought the study authors and the Department of Defense (DOD) — for reasons I can’t possibly guess, the DOD funded this RCT. My pharmacology professor must be rolling over in his tenure.
The RCT did leave beta-blockers some wiggle room. The authors purposely excluded anyone with a cardiovascular indication for a beta-blocker. The intent was to ensure beneficial effects were isolated to respiratory and not cardiovascular outcomes. Of course, the reason I’m writing and you’re reading this is that COPD and cardiovascular disease co-occur at a high rate. The RCT notwithstanding, we prescribe beta-blockers to patients with COPD because they have a cardiac indication, not to reduce acute COPD exacerbations. So, it’s possible there’d be a net beta-blocker benefit in patients with COPD and comorbid heart disease.
That’s where the JAMA Network Open study comes in, but as discussed, methodologic weaknesses preclude its being the final word. That said, I think it’s unlikely we’ll see a COPD with comorbid cardiac disease RCT performed to assess whether beta-blockers provide a net benefit, unless maybe the DOD wants to fund another one of these. In the meantime, I’m calling clinical equipoise and punting. Fortunately for me, I don’t have to prescribe beta-blockers.
Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.
A version of this article first appeared on Medscape.com.
Everyone takes a pharmacology class in medical school that includes a lecture on beta receptors. They’re in the heart (beta-1) and lungs (beta-2), and drug compounds agonize or antagonize one or both. The professor will caution against using antagonists (beta blockade) for patients with chronic obstructive pulmonary disease (COPD) lest they further impair the patient’s irreversibly narrowed airways. Obsequious students mature into obsequious doctors, intent on “doing no harm.” For better or worse, you withhold beta-blockers from your patient with COPD and comorbid cardiac disease.
Perhaps because the pulmonologist isn’t usually the one who decides whether a beta-blocker is prescribed, I’ve been napping on this topic since training. Early in fellowship, I read an ACP Journal Club article about a Cochrane systematic review (yes, I read a review of a review) that concluded that beta-blockers are fine in patients with COPD. The summary appealed to my bias towards evidence-based medicine (EBM) supplanting physiology, medical school, and everything else. I was more apt to believe my stodgy residency attendings than the stodgy pharmacology professor. Even though COPD and cardiovascular disease share multiple risk factors, I had never reinvestigated the relationship between beta-blockers and COPD.
Turns out that while I was sleeping, the debate continued. Go figure. Just last month a prospective, observational study published in JAMA Network Open found that beta-blockers did not increase the risk for cardiovascular or respiratory events among patients with COPD being discharged after hospitalization for acute myocardial infarction. Although this could be viewed as a triumph for EBM over physiology and a validation of my decade-plus of intellectual laziness, the results are actually pretty thin. These studies, in which patients with an indication for a therapy (a beta-blocker in this case) are analyzed by whether or not they received it, are problematic. The fanciest statistics — in this case, they used propensity scores — can’t control for residual confounding. What drove the physicians to prescribe in some cases but not others? We can only guess.
This might be okay if there hadn’t been a randomized controlled trial (RCT) published in 2019 in The New England Journal of Medicine that found that beta-blockers increase the risk for severe COPD exacerbations. In EBM, the RCT trumps all. Ironically, this trial was designed to test whether beta-blockers reduce severe COPD exacerbations. Yes, we’d come full circle. There was enough biologic plausibility to support a positive effect, or so thought the study authors and the Department of Defense (DOD) — for reasons I can’t possibly guess, the DOD funded this RCT. My pharmacology professor must be rolling over in his tenure.
The RCT did leave beta-blockers some wiggle room. The authors purposely excluded anyone with a cardiovascular indication for a beta-blocker. The intent was to ensure beneficial effects were isolated to respiratory and not cardiovascular outcomes. Of course, the reason I’m writing and you’re reading this is that COPD and cardiovascular disease co-occur at a high rate. The RCT notwithstanding, we prescribe beta-blockers to patients with COPD because they have a cardiac indication, not to reduce acute COPD exacerbations. So, it’s possible there’d be a net beta-blocker benefit in patients with COPD and comorbid heart disease.
That’s where the JAMA Network Open study comes in, but as discussed, methodologic weaknesses preclude its being the final word. That said, I think it’s unlikely we’ll see a COPD with comorbid cardiac disease RCT performed to assess whether beta-blockers provide a net benefit, unless maybe the DOD wants to fund another one of these. In the meantime, I’m calling clinical equipoise and punting. Fortunately for me, I don’t have to prescribe beta-blockers.
Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.
A version of this article first appeared on Medscape.com.
Everyone takes a pharmacology class in medical school that includes a lecture on beta receptors. They’re in the heart (beta-1) and lungs (beta-2), and drug compounds agonize or antagonize one or both. The professor will caution against using antagonists (beta blockade) for patients with chronic obstructive pulmonary disease (COPD) lest they further impair the patient’s irreversibly narrowed airways. Obsequious students mature into obsequious doctors, intent on “doing no harm.” For better or worse, you withhold beta-blockers from your patient with COPD and comorbid cardiac disease.
Perhaps because the pulmonologist isn’t usually the one who decides whether a beta-blocker is prescribed, I’ve been napping on this topic since training. Early in fellowship, I read an ACP Journal Club article about a Cochrane systematic review (yes, I read a review of a review) that concluded that beta-blockers are fine in patients with COPD. The summary appealed to my bias towards evidence-based medicine (EBM) supplanting physiology, medical school, and everything else. I was more apt to believe my stodgy residency attendings than the stodgy pharmacology professor. Even though COPD and cardiovascular disease share multiple risk factors, I had never reinvestigated the relationship between beta-blockers and COPD.
Turns out that while I was sleeping, the debate continued. Go figure. Just last month a prospective, observational study published in JAMA Network Open found that beta-blockers did not increase the risk for cardiovascular or respiratory events among patients with COPD being discharged after hospitalization for acute myocardial infarction. Although this could be viewed as a triumph for EBM over physiology and a validation of my decade-plus of intellectual laziness, the results are actually pretty thin. These studies, in which patients with an indication for a therapy (a beta-blocker in this case) are analyzed by whether or not they received it, are problematic. The fanciest statistics — in this case, they used propensity scores — can’t control for residual confounding. What drove the physicians to prescribe in some cases but not others? We can only guess.
This might be okay if there hadn’t been a randomized controlled trial (RCT) published in 2019 in The New England Journal of Medicine that found that beta-blockers increase the risk for severe COPD exacerbations. In EBM, the RCT trumps all. Ironically, this trial was designed to test whether beta-blockers reduce severe COPD exacerbations. Yes, we’d come full circle. There was enough biologic plausibility to support a positive effect, or so thought the study authors and the Department of Defense (DOD) — for reasons I can’t possibly guess, the DOD funded this RCT. My pharmacology professor must be rolling over in his tenure.
The RCT did leave beta-blockers some wiggle room. The authors purposely excluded anyone with a cardiovascular indication for a beta-blocker. The intent was to ensure beneficial effects were isolated to respiratory and not cardiovascular outcomes. Of course, the reason I’m writing and you’re reading this is that COPD and cardiovascular disease co-occur at a high rate. The RCT notwithstanding, we prescribe beta-blockers to patients with COPD because they have a cardiac indication, not to reduce acute COPD exacerbations. So, it’s possible there’d be a net beta-blocker benefit in patients with COPD and comorbid heart disease.
That’s where the JAMA Network Open study comes in, but as discussed, methodologic weaknesses preclude its being the final word. That said, I think it’s unlikely we’ll see a COPD with comorbid cardiac disease RCT performed to assess whether beta-blockers provide a net benefit, unless maybe the DOD wants to fund another one of these. In the meantime, I’m calling clinical equipoise and punting. Fortunately for me, I don’t have to prescribe beta-blockers.
Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.
A version of this article first appeared on Medscape.com.
Parental Migraine Ups Major Mental Disorder Risk in Offspring
Key clinical point: Parental migraine was associated with an increased risk for major mental disorders in the offspring, including attention deficit/hyperactivity disorder (ADHD), bipolar disorder, and depressive disorder.
Major finding: Offspring of parents with vs without migraine had a significantly higher risk for ADHD (hazard ratio [HR] 1.37; 95% CI 1.25-1.50), bipolar disorder (HR 1.35; 95% CI 1.06-1.71), and depressive disorder (HR 1.33; 95% CI 1.21-1.47). Sub-analyses revealed that only maternal migraine was a significant risk factor for these disorders.
Study details: This study used data from the Taiwan National Health Insurance Research Database and included 22,747 offspring of parents with migraine and 227,470 matched offspring of parents without migraine.
Disclosures: This study was supported by grants from the Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.
Source: Li D-J, Tsai S-J, Chen T-J, et al. Risk of major mental disorders in the offspring of parents with migraine. Ann Gen Psychiatry. 2024;23:23 (Jun 22). Doi: 10.1186/s12991-024-00508-y Source
Key clinical point: Parental migraine was associated with an increased risk for major mental disorders in the offspring, including attention deficit/hyperactivity disorder (ADHD), bipolar disorder, and depressive disorder.
Major finding: Offspring of parents with vs without migraine had a significantly higher risk for ADHD (hazard ratio [HR] 1.37; 95% CI 1.25-1.50), bipolar disorder (HR 1.35; 95% CI 1.06-1.71), and depressive disorder (HR 1.33; 95% CI 1.21-1.47). Sub-analyses revealed that only maternal migraine was a significant risk factor for these disorders.
Study details: This study used data from the Taiwan National Health Insurance Research Database and included 22,747 offspring of parents with migraine and 227,470 matched offspring of parents without migraine.
Disclosures: This study was supported by grants from the Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.
Source: Li D-J, Tsai S-J, Chen T-J, et al. Risk of major mental disorders in the offspring of parents with migraine. Ann Gen Psychiatry. 2024;23:23 (Jun 22). Doi: 10.1186/s12991-024-00508-y Source
Key clinical point: Parental migraine was associated with an increased risk for major mental disorders in the offspring, including attention deficit/hyperactivity disorder (ADHD), bipolar disorder, and depressive disorder.
Major finding: Offspring of parents with vs without migraine had a significantly higher risk for ADHD (hazard ratio [HR] 1.37; 95% CI 1.25-1.50), bipolar disorder (HR 1.35; 95% CI 1.06-1.71), and depressive disorder (HR 1.33; 95% CI 1.21-1.47). Sub-analyses revealed that only maternal migraine was a significant risk factor for these disorders.
Study details: This study used data from the Taiwan National Health Insurance Research Database and included 22,747 offspring of parents with migraine and 227,470 matched offspring of parents without migraine.
Disclosures: This study was supported by grants from the Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.
Source: Li D-J, Tsai S-J, Chen T-J, et al. Risk of major mental disorders in the offspring of parents with migraine. Ann Gen Psychiatry. 2024;23:23 (Jun 22). Doi: 10.1186/s12991-024-00508-y Source
Increasing Dietary Vitamin C Intake May Prevent Severe Headache or Migraine
Key clinical point: Dietary vitamin C intake was negatively associated with the risk for severe headache or migraine.
Major finding: Each 1 mg/day increase in dietary vitamin C intake was significantly associated with a 6% lower risk for severe headache or migraine (adjusted odd ratio [aOR] 0.94; P = .0007). This inverse association between dietary vitamin C intake and severe headache or migraine risk was significant in women (aOR 0.90; 95% CI 0.87-0.85) but not in men.
Study details: This cross-sectional study included 13,445 participants from the National Health and Nutrition Examination Survey, of whom 2745 (20.42%) had severe headache or migraine.
Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.
Source: Zheng Y, Jin J, Wei C, Huang C. Association of dietary vitamin C consumption with severe headache or migraine among adults: A cross-sectional study of NHANES 1999–2004. Front Nutr. 2024;11:fnut.2024.1412031 (Jun 18). Doi: 10.3389/fnut.2024.1412031 Source
Key clinical point: Dietary vitamin C intake was negatively associated with the risk for severe headache or migraine.
Major finding: Each 1 mg/day increase in dietary vitamin C intake was significantly associated with a 6% lower risk for severe headache or migraine (adjusted odd ratio [aOR] 0.94; P = .0007). This inverse association between dietary vitamin C intake and severe headache or migraine risk was significant in women (aOR 0.90; 95% CI 0.87-0.85) but not in men.
Study details: This cross-sectional study included 13,445 participants from the National Health and Nutrition Examination Survey, of whom 2745 (20.42%) had severe headache or migraine.
Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.
Source: Zheng Y, Jin J, Wei C, Huang C. Association of dietary vitamin C consumption with severe headache or migraine among adults: A cross-sectional study of NHANES 1999–2004. Front Nutr. 2024;11:fnut.2024.1412031 (Jun 18). Doi: 10.3389/fnut.2024.1412031 Source
Key clinical point: Dietary vitamin C intake was negatively associated with the risk for severe headache or migraine.
Major finding: Each 1 mg/day increase in dietary vitamin C intake was significantly associated with a 6% lower risk for severe headache or migraine (adjusted odd ratio [aOR] 0.94; P = .0007). This inverse association between dietary vitamin C intake and severe headache or migraine risk was significant in women (aOR 0.90; 95% CI 0.87-0.85) but not in men.
Study details: This cross-sectional study included 13,445 participants from the National Health and Nutrition Examination Survey, of whom 2745 (20.42%) had severe headache or migraine.
Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.
Source: Zheng Y, Jin J, Wei C, Huang C. Association of dietary vitamin C consumption with severe headache or migraine among adults: A cross-sectional study of NHANES 1999–2004. Front Nutr. 2024;11:fnut.2024.1412031 (Jun 18). Doi: 10.3389/fnut.2024.1412031 Source
Sustained Benefits of CGRP Antibodies in Migraine and Medication Overuse Headache
Key clinical point: Prophylactic migraine therapy with calcitonin gene-related peptide (CGRP) antibodies showed sustained benefits in patients with migraine and medication overuse headache (MOH) or medication overuse (MO) for up to a year.
Major findings: All patients, including those with episodic migraine (EM) with MO, EM without MO, chronic migraine (CM) with MOH, or CM without MOH, had significant reductions in monthly headache days, monthly migraine days, and acute medication days at the last observation timepoint within the first year of CGRP therapy from baseline (all P < .0001). Relapse rates were lower (15.4%) in patients with CM with MOH after successful initiation of CGRP treatment.
Study details: This retrospective real-world analysis included 112 patients with EM (35 with MO and 77 without MO) and 179 patients with CM (109 with MOH and 70 without MOH).
Disclosures: This study was funded by Projekt DEAL. Some authors declared receiving travel fees, honoraria, or scientific support from or serving as consultants or advisors for various sources.
Source: Scheffler A, Basten J, Menzel L, et al. Persistent effectiveness of CGRP antibody therapy in migraine and comorbid medication overuse or medication overuse headache - a retrospective real-world analysis. J Headache Pain. 2024;25:109 (Jul 4). Doi: 10.1186/s10194-024-01813-3 Source
Key clinical point: Prophylactic migraine therapy with calcitonin gene-related peptide (CGRP) antibodies showed sustained benefits in patients with migraine and medication overuse headache (MOH) or medication overuse (MO) for up to a year.
Major findings: All patients, including those with episodic migraine (EM) with MO, EM without MO, chronic migraine (CM) with MOH, or CM without MOH, had significant reductions in monthly headache days, monthly migraine days, and acute medication days at the last observation timepoint within the first year of CGRP therapy from baseline (all P < .0001). Relapse rates were lower (15.4%) in patients with CM with MOH after successful initiation of CGRP treatment.
Study details: This retrospective real-world analysis included 112 patients with EM (35 with MO and 77 without MO) and 179 patients with CM (109 with MOH and 70 without MOH).
Disclosures: This study was funded by Projekt DEAL. Some authors declared receiving travel fees, honoraria, or scientific support from or serving as consultants or advisors for various sources.
Source: Scheffler A, Basten J, Menzel L, et al. Persistent effectiveness of CGRP antibody therapy in migraine and comorbid medication overuse or medication overuse headache - a retrospective real-world analysis. J Headache Pain. 2024;25:109 (Jul 4). Doi: 10.1186/s10194-024-01813-3 Source
Key clinical point: Prophylactic migraine therapy with calcitonin gene-related peptide (CGRP) antibodies showed sustained benefits in patients with migraine and medication overuse headache (MOH) or medication overuse (MO) for up to a year.
Major findings: All patients, including those with episodic migraine (EM) with MO, EM without MO, chronic migraine (CM) with MOH, or CM without MOH, had significant reductions in monthly headache days, monthly migraine days, and acute medication days at the last observation timepoint within the first year of CGRP therapy from baseline (all P < .0001). Relapse rates were lower (15.4%) in patients with CM with MOH after successful initiation of CGRP treatment.
Study details: This retrospective real-world analysis included 112 patients with EM (35 with MO and 77 without MO) and 179 patients with CM (109 with MOH and 70 without MOH).
Disclosures: This study was funded by Projekt DEAL. Some authors declared receiving travel fees, honoraria, or scientific support from or serving as consultants or advisors for various sources.
Source: Scheffler A, Basten J, Menzel L, et al. Persistent effectiveness of CGRP antibody therapy in migraine and comorbid medication overuse or medication overuse headache - a retrospective real-world analysis. J Headache Pain. 2024;25:109 (Jul 4). Doi: 10.1186/s10194-024-01813-3 Source