Seltorexant, an investigational drug being developed by Johnson & Johnson, met all primary and secondary endpoints in a phase 3 trial of patients with major depressive disorder (MDD) with insomnia symptoms, the company has announced.

Seltorexant is an investigational potential first-in-class selective antagonist of the human orexin 2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. Its selective mechanism of action means it has the potential to improve both mood and sleep symptoms associated with depression.

The phase 3 MDD3001 study was a multicenter, randomized, double-blind trial comparing the efficacy and safety of 20-mg oral seltorexant once daily with placebo, added to background selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) therapy, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.

In the study, seltorexant led to “statistically significant and clinically meaningful” improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale total score, as well as improved sleep disturbance outcomes, in patients with moderate to severe depression and severe sleep disturbance who had a prior inadequate response to SSRI/SNRI antidepressants alone, the company announced in a statement.

Consistent with previous trials of seltorexant, the drug was safe and well-tolerated, with similar rates of common adverse events seen in both treatment groups.

“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs, and impact quality of life, and it often goes undertreated despite being one of the most common residual symptoms,” Andrew Krystal, MD, professor of psychiatry, University of California, San Francisco Weill Institute for Neurosciences, said in the statement.

“Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia and, most importantly, to improve outcomes and quality of life for these patients,” Dr. Krystal added.

The topline results are being presented at the American Society of Clinical Psychopharmacology (ASCP) 2024 Annual Meeting in Miami, Florida.

The positive phase 3 data follow earlier promising data reported in 2022, as reported by this news organization.

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

Seltorexant, an investigational drug being developed by Johnson & Johnson, met all primary and secondary endpoints in a phase 3 trial of patients with major depressive disorder (MDD) with insomnia symptoms, the company has announced.

Seltorexant is an investigational potential first-in-class selective antagonist of the human orexin 2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. Its selective mechanism of action means it has the potential to improve both mood and sleep symptoms associated with depression.

The phase 3 MDD3001 study was a multicenter, randomized, double-blind trial comparing the efficacy and safety of 20-mg oral seltorexant once daily with placebo, added to background selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) therapy, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.

In the study, seltorexant led to “statistically significant and clinically meaningful” improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale total score, as well as improved sleep disturbance outcomes, in patients with moderate to severe depression and severe sleep disturbance who had a prior inadequate response to SSRI/SNRI antidepressants alone, the company announced in a statement.

Consistent with previous trials of seltorexant, the drug was safe and well-tolerated, with similar rates of common adverse events seen in both treatment groups.

“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs, and impact quality of life, and it often goes undertreated despite being one of the most common residual symptoms,” Andrew Krystal, MD, professor of psychiatry, University of California, San Francisco Weill Institute for Neurosciences, said in the statement.

“Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia and, most importantly, to improve outcomes and quality of life for these patients,” Dr. Krystal added.

The topline results are being presented at the American Society of Clinical Psychopharmacology (ASCP) 2024 Annual Meeting in Miami, Florida.

The positive phase 3 data follow earlier promising data reported in 2022, as reported by this news organization.

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

Seltorexant, an investigational drug being developed by Johnson & Johnson, met all primary and secondary endpoints in a phase 3 trial of patients with major depressive disorder (MDD) with insomnia symptoms, the company has announced.

Seltorexant is an investigational potential first-in-class selective antagonist of the human orexin 2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. Its selective mechanism of action means it has the potential to improve both mood and sleep symptoms associated with depression.

The phase 3 MDD3001 study was a multicenter, randomized, double-blind trial comparing the efficacy and safety of 20-mg oral seltorexant once daily with placebo, added to background selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) therapy, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.

In the study, seltorexant led to “statistically significant and clinically meaningful” improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale total score, as well as improved sleep disturbance outcomes, in patients with moderate to severe depression and severe sleep disturbance who had a prior inadequate response to SSRI/SNRI antidepressants alone, the company announced in a statement.

Consistent with previous trials of seltorexant, the drug was safe and well-tolerated, with similar rates of common adverse events seen in both treatment groups.

“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs, and impact quality of life, and it often goes undertreated despite being one of the most common residual symptoms,” Andrew Krystal, MD, professor of psychiatry, University of California, San Francisco Weill Institute for Neurosciences, said in the statement.

“Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia and, most importantly, to improve outcomes and quality of life for these patients,” Dr. Krystal added.

The topline results are being presented at the American Society of Clinical Psychopharmacology (ASCP) 2024 Annual Meeting in Miami, Florida.

The positive phase 3 data follow earlier promising data reported in 2022, as reported by this news organization.

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

TOPLINE:

Metformin use lowers the risk for gout by 32% in individuals with prediabetes; however, the treatment doesn’t change serum urate or C-reactive protein levels.

METHODOLOGY:

• Individuals with prediabetes not only are at an elevated risk for diabetes but also face an increased risk for incident gout. Many previous reports have demonstrated the efficacy of antidiabetic medications in reducing the risk for gout in adults with diabetes.
• This study assessed the gout-lowering properties of metformin in 25,064 individuals with prediabetes (age ≥ 18 years; A1c levels, 5.7%-6.4%) who had never reported A1c levels > 6.4%.
• Patients who were initiated on metformin within 18 months after the diagnosis of prediabetes (n = 1154) were propensity score–matched with those who did not initiate metformin or other antidiabetic medications in this period (n = 13,877) and were followed for a median of 3.9 years for the primary outcome of incident gout.

TAKEAWAY:

• Initiation vs no initiation of metformin resulted in 2.4 fewer cases of gout per 1000 person-years and a 32% reduced relative risk for incident gout (hazard ratio, 0.68; 95% CI, 0.48-0.96).
• The results were consistent across different subgroups stratified on the basis of sex, age (≤ 60 vs > 60 years), estimated glomerular filtration rate (≥ 90 vs < 90 mL/min/1.73 m²), and baseline diuretic use.
• Metformin initiation was not associated with significant changes in serum urate or C-reactive protein levels.
• Metformin use was associated with a reduction in A1c levels and body mass index.

IN PRACTICE:

The authors suggested that “metformin may be important in lowering gout risk in individuals with prediabetes.”

SOURCE:

Javier Marrugo, MD, Department of Medicine, Brigham and Women’s Hospital, Boston, led this study, which was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

Although gout is more commonly observed in men, around 60% of the study population consisted of women. Owing to the observational nature of this study, exposure misclassifications might have occurred. Misclassification of the outcome is also possible due to the presence of two or more diagnostic codes for gout and/or the combination of urate-lowering therapies or colchicine with at least one diagnostic code.

DISCLOSURES:

This work was supported by the National Institutes of Health. Some authors declared serving as consultants or receiving salary support or consulting fees from various sources.

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

TOPLINE:

Metformin use lowers the risk for gout by 32% in individuals with prediabetes; however, the treatment doesn’t change serum urate or C-reactive protein levels.

METHODOLOGY:

• Individuals with prediabetes not only are at an elevated risk for diabetes but also face an increased risk for incident gout. Many previous reports have demonstrated the efficacy of antidiabetic medications in reducing the risk for gout in adults with diabetes.
• This study assessed the gout-lowering properties of metformin in 25,064 individuals with prediabetes (age ≥ 18 years; A1c levels, 5.7%-6.4%) who had never reported A1c levels > 6.4%.
• Patients who were initiated on metformin within 18 months after the diagnosis of prediabetes (n = 1154) were propensity score–matched with those who did not initiate metformin or other antidiabetic medications in this period (n = 13,877) and were followed for a median of 3.9 years for the primary outcome of incident gout.

TAKEAWAY:

• Initiation vs no initiation of metformin resulted in 2.4 fewer cases of gout per 1000 person-years and a 32% reduced relative risk for incident gout (hazard ratio, 0.68; 95% CI, 0.48-0.96).
• The results were consistent across different subgroups stratified on the basis of sex, age (≤ 60 vs > 60 years), estimated glomerular filtration rate (≥ 90 vs < 90 mL/min/1.73 m²), and baseline diuretic use.
• Metformin initiation was not associated with significant changes in serum urate or C-reactive protein levels.
• Metformin use was associated with a reduction in A1c levels and body mass index.

IN PRACTICE:

The authors suggested that “metformin may be important in lowering gout risk in individuals with prediabetes.”

SOURCE:

Javier Marrugo, MD, Department of Medicine, Brigham and Women’s Hospital, Boston, led this study, which was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

Although gout is more commonly observed in men, around 60% of the study population consisted of women. Owing to the observational nature of this study, exposure misclassifications might have occurred. Misclassification of the outcome is also possible due to the presence of two or more diagnostic codes for gout and/or the combination of urate-lowering therapies or colchicine with at least one diagnostic code.

DISCLOSURES:

This work was supported by the National Institutes of Health. Some authors declared serving as consultants or receiving salary support or consulting fees from various sources.

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

TOPLINE:

Metformin use lowers the risk for gout by 32% in individuals with prediabetes; however, the treatment doesn’t change serum urate or C-reactive protein levels.

METHODOLOGY:

• Individuals with prediabetes not only are at an elevated risk for diabetes but also face an increased risk for incident gout. Many previous reports have demonstrated the efficacy of antidiabetic medications in reducing the risk for gout in adults with diabetes.
• This study assessed the gout-lowering properties of metformin in 25,064 individuals with prediabetes (age ≥ 18 years; A1c levels, 5.7%-6.4%) who had never reported A1c levels > 6.4%.
• Patients who were initiated on metformin within 18 months after the diagnosis of prediabetes (n = 1154) were propensity score–matched with those who did not initiate metformin or other antidiabetic medications in this period (n = 13,877) and were followed for a median of 3.9 years for the primary outcome of incident gout.

TAKEAWAY:

• Initiation vs no initiation of metformin resulted in 2.4 fewer cases of gout per 1000 person-years and a 32% reduced relative risk for incident gout (hazard ratio, 0.68; 95% CI, 0.48-0.96).
• The results were consistent across different subgroups stratified on the basis of sex, age (≤ 60 vs > 60 years), estimated glomerular filtration rate (≥ 90 vs < 90 mL/min/1.73 m²), and baseline diuretic use.
• Metformin initiation was not associated with significant changes in serum urate or C-reactive protein levels.
• Metformin use was associated with a reduction in A1c levels and body mass index.

IN PRACTICE:

The authors suggested that “metformin may be important in lowering gout risk in individuals with prediabetes.”

SOURCE:

Javier Marrugo, MD, Department of Medicine, Brigham and Women’s Hospital, Boston, led this study, which was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

Although gout is more commonly observed in men, around 60% of the study population consisted of women. Owing to the observational nature of this study, exposure misclassifications might have occurred. Misclassification of the outcome is also possible due to the presence of two or more diagnostic codes for gout and/or the combination of urate-lowering therapies or colchicine with at least one diagnostic code.

DISCLOSURES:

This work was supported by the National Institutes of Health. Some authors declared serving as consultants or receiving salary support or consulting fees from various sources.

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

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.

STOCKHOLM — Improvements in kidney function outcomes observed with glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes extend to patients who are overweight or obese but don›t yet have type 2 diabetes, new research shows.

“These data are important because they are the first data to suggest a kidney benefit of semaglutide in this patient population in the absence of diabetes,” lead author Helen M. Colhoun, MD, of the Institute of Genetics and Cancer, University of Edinburgh, Scotland, United Kingdom, told this news organization.

“This is a population at high risk of chronic kidney disease with an increased need for kidney protection,” she said.

The late-breaking study was presented this week at the 61st European Renal Association (ERA) Congress 2024 and simultaneously published in Nature Medicine.
 

SELECT Trial Patients Without Diabetes

The findings are from a secondary analysis of the randomized SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity) trial, which evaluated cardiovascular outcomes of semaglutide treatment among 17,604 adults with preexisting cardiovascular disease who were overweight or obese — but did not have diabetes.

For its primary endpoint, the trial showed semaglutide was associated with a 20% reduction in major adverse cardiovascular events compared with placebo.

With obesity also associated with a significantly increased risk of chronic kidney disease — and the headline-making FLOW trial, also presented at the congress, showing key benefits of semaglutide in improving kidney function in people with CKD and type 2 diabetes the secondary analysis of SELECT was conducted to investigate whether those kidney benefits extended to people without type 2 diabetes.

Patients were randomized 1:1 to once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. Baseline patient characteristics were well-balanced, including kidney function and albuminuria status.

The primary endpoint for the analysis was a nephropathy composite of time from randomization to the first occurrence of death from kidney causes; initiation of chronic kidney replacement therapy; onset of persistent estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m²; persistent ≥ 50% reduction in eGFR compared with baseline; or onset of persistent macroalbuminuria.

With a median follow-up of 182 weeks, the results showed that the semaglutide group was significantly less likely to develop the primary composite endpoint compared with the placebo group (1.8% vs 2.2%; hazard ratio [HR], 0.78; P = .02).

A significantly reduced decline in eGFR in the semaglutide group was observed at a prespecified 104-week time point, with a treatment effect of 0.75 mL/min/1.73 m² (P < .001), and the effect was more pronounced among participants with baseline eGFR < 60 mL/min/1.73 m² (P < .001). 

Furthermore, those in the semaglutide group had a significantly lower proportionate increase in urinary albumin-to-creatinine ratio (UACR) compared with placebo (–10.7%; P < .001) at the prespecified 104 weeks, with a net treatment benefit of –27.2% and –31.4% among those with randomization to UACR 30 to < 300 mg/g and 2300 mg/g, respectively.

Improvements varied according to baseline UACR status and were more pronounced among those with macroalbuminuria, at –8.1% for those with normoalbuminuria (n = 14,848), –27% for microalbuminuria (n = 1968), and –31% for macroalbuminuria (n = 325).

There were no reports of acute kidney injury associated with semaglutide, regardless of baseline eGFR. 

“We were hopeful that there would be similar benefits as those observed in the diabetes studies, but there are differences in kidney disease among those with and without type 2 diabetes, so we weren’t sure,” Dr. Colhoun told this news organization.
 

Benefits the Result of Weight Loss or Something Else?

Considering the beneficial effects of semaglutide on weight loss, underscored in an analysis also published this month that showed a mean 10.2% reduction in weight sustained for up to 4  years, a key question is whether the kidney benefits are a direct result of weight loss — or the drug mechanism or something else.

But Dr. Colhoun said the role of weight loss in terms of the kidney benefits is still uncertain, particularly considering the various other factors, including cardiometabolic improvements, which could also have an effect.

“It’s a very difficult question to answer,” she said. “We did do a mediation exploratory analysis suggesting a substantial part of the effect might be due to the weight change, but it’s difficult to demonstrate that because you have weight change going on in the placebo arm as well, but for different reasons,” she said.

“So, I would say the data suggest there is some component of this that is attributable to weight, but we certainly can’t attribute all of the [effects] to weight change.”

Small studies involving animals have shown a direct effect of semaglutide on kidney hemodynamics “but they’re small and not definitive,” Dr. Colhoun added.

And although weight loss achieved through other measures such as lifestyle changes show a small benefit on eGFR, “interestingly, those studies showed no effect at all on albuminuria, whereas we see a really substantial effect on albuminuria with semaglutide,” Dr. Colhoun said.

Studies of weight loss through bariatric surgery have shown kidney benefits; however, those were in the context of type 2 diabetes, unlike the current analysis.

In terms of whether the benefits may extend to tirzepatide, the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, increasingly used in weight loss, results from another secondary analysis also show encouraging kidney benefits in people with type 2 diabetes, and there is ongoing research in patients with type 2 diabetes and those with obesity without diabetes, Dr. Colhoun noted.
 

Primary Prevention of CKD?

Limitations of the current analysis include that only about a fifth of participants in SELECT had an eGFR < 60  mL/min/1.73 m² or UACR ≥ 30 mg/g at baseline, suggesting a relatively low proportion of participants with kidney disease. 

Importantly, however, the kidney benefits observed in patients who are at such high risk of kidney disease but do not yet have diabetes or CKD, is encouraging, said Alberto Ortiz, MD, PhD, commenting on the study. Dr. Ortiz is chief of nephrology and the Hypertension Renal Unit, Health Research Institute of the Jiménez Díaz Foundation, Madrid, Spain.

“It is especially significant that protection was observed in participants with an eGFR > 60 mL/min/1.73 m² and across UACR categories, ie, including people without CKD at baseline, in whom it appeared to decrease the incidence of de novo CKD,” Dr. Ortiz told this news organization.

“This suggests a potential role in primary prevention of CKD in this population,” he said.

To further investigate this, he said, “It would have been extremely interesting to assess whether there is a potential role for primary prevention of CKD in people without baseline CKD by assessing subgroup results for the no-CKD, low-risk KDIGO [Kidney Disease: Improving Global Outcomes] category [of patients].”

SELECT was funded by Novo Nordisk. Dr. Colhoun has reported consulting, research, and/or other relationships with Novo Nordisk, Bayer, Sanofi, Roche, and IQVIA. Dr. Ortiz has reported being a member of the European Renal Association council and Madrid Society of Nephrology (SOMANE), which developed a document in 2022 on the treatment of diabetic kidney disease sponsored by Novo Nordisk. He also reported collaborating with companies developing drugs for kidney disease.

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

STOCKHOLM — Improvements in kidney function outcomes observed with glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes extend to patients who are overweight or obese but don›t yet have type 2 diabetes, new research shows.

“These data are important because they are the first data to suggest a kidney benefit of semaglutide in this patient population in the absence of diabetes,” lead author Helen M. Colhoun, MD, of the Institute of Genetics and Cancer, University of Edinburgh, Scotland, United Kingdom, told this news organization.

“This is a population at high risk of chronic kidney disease with an increased need for kidney protection,” she said.

The late-breaking study was presented this week at the 61st European Renal Association (ERA) Congress 2024 and simultaneously published in Nature Medicine.
 

SELECT Trial Patients Without Diabetes

The findings are from a secondary analysis of the randomized SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity) trial, which evaluated cardiovascular outcomes of semaglutide treatment among 17,604 adults with preexisting cardiovascular disease who were overweight or obese — but did not have diabetes.

For its primary endpoint, the trial showed semaglutide was associated with a 20% reduction in major adverse cardiovascular events compared with placebo.

With obesity also associated with a significantly increased risk of chronic kidney disease — and the headline-making FLOW trial, also presented at the congress, showing key benefits of semaglutide in improving kidney function in people with CKD and type 2 diabetes the secondary analysis of SELECT was conducted to investigate whether those kidney benefits extended to people without type 2 diabetes.

Patients were randomized 1:1 to once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. Baseline patient characteristics were well-balanced, including kidney function and albuminuria status.

The primary endpoint for the analysis was a nephropathy composite of time from randomization to the first occurrence of death from kidney causes; initiation of chronic kidney replacement therapy; onset of persistent estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m²; persistent ≥ 50% reduction in eGFR compared with baseline; or onset of persistent macroalbuminuria.

With a median follow-up of 182 weeks, the results showed that the semaglutide group was significantly less likely to develop the primary composite endpoint compared with the placebo group (1.8% vs 2.2%; hazard ratio [HR], 0.78; P = .02).

A significantly reduced decline in eGFR in the semaglutide group was observed at a prespecified 104-week time point, with a treatment effect of 0.75 mL/min/1.73 m² (P < .001), and the effect was more pronounced among participants with baseline eGFR < 60 mL/min/1.73 m² (P < .001). 

Furthermore, those in the semaglutide group had a significantly lower proportionate increase in urinary albumin-to-creatinine ratio (UACR) compared with placebo (–10.7%; P < .001) at the prespecified 104 weeks, with a net treatment benefit of –27.2% and –31.4% among those with randomization to UACR 30 to < 300 mg/g and 2300 mg/g, respectively.

Improvements varied according to baseline UACR status and were more pronounced among those with macroalbuminuria, at –8.1% for those with normoalbuminuria (n = 14,848), –27% for microalbuminuria (n = 1968), and –31% for macroalbuminuria (n = 325).

There were no reports of acute kidney injury associated with semaglutide, regardless of baseline eGFR. 

“We were hopeful that there would be similar benefits as those observed in the diabetes studies, but there are differences in kidney disease among those with and without type 2 diabetes, so we weren’t sure,” Dr. Colhoun told this news organization.
 

Benefits the Result of Weight Loss or Something Else?

Considering the beneficial effects of semaglutide on weight loss, underscored in an analysis also published this month that showed a mean 10.2% reduction in weight sustained for up to 4  years, a key question is whether the kidney benefits are a direct result of weight loss — or the drug mechanism or something else.

But Dr. Colhoun said the role of weight loss in terms of the kidney benefits is still uncertain, particularly considering the various other factors, including cardiometabolic improvements, which could also have an effect.

“It’s a very difficult question to answer,” she said. “We did do a mediation exploratory analysis suggesting a substantial part of the effect might be due to the weight change, but it’s difficult to demonstrate that because you have weight change going on in the placebo arm as well, but for different reasons,” she said.

“So, I would say the data suggest there is some component of this that is attributable to weight, but we certainly can’t attribute all of the [effects] to weight change.”

Small studies involving animals have shown a direct effect of semaglutide on kidney hemodynamics “but they’re small and not definitive,” Dr. Colhoun added.

And although weight loss achieved through other measures such as lifestyle changes show a small benefit on eGFR, “interestingly, those studies showed no effect at all on albuminuria, whereas we see a really substantial effect on albuminuria with semaglutide,” Dr. Colhoun said.

Studies of weight loss through bariatric surgery have shown kidney benefits; however, those were in the context of type 2 diabetes, unlike the current analysis.

In terms of whether the benefits may extend to tirzepatide, the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, increasingly used in weight loss, results from another secondary analysis also show encouraging kidney benefits in people with type 2 diabetes, and there is ongoing research in patients with type 2 diabetes and those with obesity without diabetes, Dr. Colhoun noted.
 

Primary Prevention of CKD?

Limitations of the current analysis include that only about a fifth of participants in SELECT had an eGFR < 60  mL/min/1.73 m² or UACR ≥ 30 mg/g at baseline, suggesting a relatively low proportion of participants with kidney disease. 

Importantly, however, the kidney benefits observed in patients who are at such high risk of kidney disease but do not yet have diabetes or CKD, is encouraging, said Alberto Ortiz, MD, PhD, commenting on the study. Dr. Ortiz is chief of nephrology and the Hypertension Renal Unit, Health Research Institute of the Jiménez Díaz Foundation, Madrid, Spain.

“It is especially significant that protection was observed in participants with an eGFR > 60 mL/min/1.73 m² and across UACR categories, ie, including people without CKD at baseline, in whom it appeared to decrease the incidence of de novo CKD,” Dr. Ortiz told this news organization.

“This suggests a potential role in primary prevention of CKD in this population,” he said.

To further investigate this, he said, “It would have been extremely interesting to assess whether there is a potential role for primary prevention of CKD in people without baseline CKD by assessing subgroup results for the no-CKD, low-risk KDIGO [Kidney Disease: Improving Global Outcomes] category [of patients].”

SELECT was funded by Novo Nordisk. Dr. Colhoun has reported consulting, research, and/or other relationships with Novo Nordisk, Bayer, Sanofi, Roche, and IQVIA. Dr. Ortiz has reported being a member of the European Renal Association council and Madrid Society of Nephrology (SOMANE), which developed a document in 2022 on the treatment of diabetic kidney disease sponsored by Novo Nordisk. He also reported collaborating with companies developing drugs for kidney disease.

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

STOCKHOLM — Improvements in kidney function outcomes observed with glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes extend to patients who are overweight or obese but don›t yet have type 2 diabetes, new research shows.

“These data are important because they are the first data to suggest a kidney benefit of semaglutide in this patient population in the absence of diabetes,” lead author Helen M. Colhoun, MD, of the Institute of Genetics and Cancer, University of Edinburgh, Scotland, United Kingdom, told this news organization.

“This is a population at high risk of chronic kidney disease with an increased need for kidney protection,” she said.

The late-breaking study was presented this week at the 61st European Renal Association (ERA) Congress 2024 and simultaneously published in Nature Medicine.
 

SELECT Trial Patients Without Diabetes

The findings are from a secondary analysis of the randomized SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity) trial, which evaluated cardiovascular outcomes of semaglutide treatment among 17,604 adults with preexisting cardiovascular disease who were overweight or obese — but did not have diabetes.

For its primary endpoint, the trial showed semaglutide was associated with a 20% reduction in major adverse cardiovascular events compared with placebo.

With obesity also associated with a significantly increased risk of chronic kidney disease — and the headline-making FLOW trial, also presented at the congress, showing key benefits of semaglutide in improving kidney function in people with CKD and type 2 diabetes the secondary analysis of SELECT was conducted to investigate whether those kidney benefits extended to people without type 2 diabetes.

Patients were randomized 1:1 to once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. Baseline patient characteristics were well-balanced, including kidney function and albuminuria status.

The primary endpoint for the analysis was a nephropathy composite of time from randomization to the first occurrence of death from kidney causes; initiation of chronic kidney replacement therapy; onset of persistent estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m²; persistent ≥ 50% reduction in eGFR compared with baseline; or onset of persistent macroalbuminuria.

With a median follow-up of 182 weeks, the results showed that the semaglutide group was significantly less likely to develop the primary composite endpoint compared with the placebo group (1.8% vs 2.2%; hazard ratio [HR], 0.78; P = .02).

A significantly reduced decline in eGFR in the semaglutide group was observed at a prespecified 104-week time point, with a treatment effect of 0.75 mL/min/1.73 m² (P < .001), and the effect was more pronounced among participants with baseline eGFR < 60 mL/min/1.73 m² (P < .001). 

Furthermore, those in the semaglutide group had a significantly lower proportionate increase in urinary albumin-to-creatinine ratio (UACR) compared with placebo (–10.7%; P < .001) at the prespecified 104 weeks, with a net treatment benefit of –27.2% and –31.4% among those with randomization to UACR 30 to < 300 mg/g and 2300 mg/g, respectively.

Improvements varied according to baseline UACR status and were more pronounced among those with macroalbuminuria, at –8.1% for those with normoalbuminuria (n = 14,848), –27% for microalbuminuria (n = 1968), and –31% for macroalbuminuria (n = 325).

There were no reports of acute kidney injury associated with semaglutide, regardless of baseline eGFR. 

“We were hopeful that there would be similar benefits as those observed in the diabetes studies, but there are differences in kidney disease among those with and without type 2 diabetes, so we weren’t sure,” Dr. Colhoun told this news organization.
 

Benefits the Result of Weight Loss or Something Else?

Considering the beneficial effects of semaglutide on weight loss, underscored in an analysis also published this month that showed a mean 10.2% reduction in weight sustained for up to 4  years, a key question is whether the kidney benefits are a direct result of weight loss — or the drug mechanism or something else.

But Dr. Colhoun said the role of weight loss in terms of the kidney benefits is still uncertain, particularly considering the various other factors, including cardiometabolic improvements, which could also have an effect.

“It’s a very difficult question to answer,” she said. “We did do a mediation exploratory analysis suggesting a substantial part of the effect might be due to the weight change, but it’s difficult to demonstrate that because you have weight change going on in the placebo arm as well, but for different reasons,” she said.

“So, I would say the data suggest there is some component of this that is attributable to weight, but we certainly can’t attribute all of the [effects] to weight change.”

Small studies involving animals have shown a direct effect of semaglutide on kidney hemodynamics “but they’re small and not definitive,” Dr. Colhoun added.

And although weight loss achieved through other measures such as lifestyle changes show a small benefit on eGFR, “interestingly, those studies showed no effect at all on albuminuria, whereas we see a really substantial effect on albuminuria with semaglutide,” Dr. Colhoun said.

Studies of weight loss through bariatric surgery have shown kidney benefits; however, those were in the context of type 2 diabetes, unlike the current analysis.

In terms of whether the benefits may extend to tirzepatide, the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, increasingly used in weight loss, results from another secondary analysis also show encouraging kidney benefits in people with type 2 diabetes, and there is ongoing research in patients with type 2 diabetes and those with obesity without diabetes, Dr. Colhoun noted.
 

Primary Prevention of CKD?

Limitations of the current analysis include that only about a fifth of participants in SELECT had an eGFR < 60  mL/min/1.73 m² or UACR ≥ 30 mg/g at baseline, suggesting a relatively low proportion of participants with kidney disease. 

Importantly, however, the kidney benefits observed in patients who are at such high risk of kidney disease but do not yet have diabetes or CKD, is encouraging, said Alberto Ortiz, MD, PhD, commenting on the study. Dr. Ortiz is chief of nephrology and the Hypertension Renal Unit, Health Research Institute of the Jiménez Díaz Foundation, Madrid, Spain.

“It is especially significant that protection was observed in participants with an eGFR > 60 mL/min/1.73 m² and across UACR categories, ie, including people without CKD at baseline, in whom it appeared to decrease the incidence of de novo CKD,” Dr. Ortiz told this news organization.

“This suggests a potential role in primary prevention of CKD in this population,” he said.

To further investigate this, he said, “It would have been extremely interesting to assess whether there is a potential role for primary prevention of CKD in people without baseline CKD by assessing subgroup results for the no-CKD, low-risk KDIGO [Kidney Disease: Improving Global Outcomes] category [of patients].”

SELECT was funded by Novo Nordisk. Dr. Colhoun has reported consulting, research, and/or other relationships with Novo Nordisk, Bayer, Sanofi, Roche, and IQVIA. Dr. Ortiz has reported being a member of the European Renal Association council and Madrid Society of Nephrology (SOMANE), which developed a document in 2022 on the treatment of diabetic kidney disease sponsored by Novo Nordisk. He also reported collaborating with companies developing drugs for kidney disease.

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

Fewer than half (42%) of obstetricians/gynecologists in the latest Medscape survey said they were satisfied with their average $352,000/year pay, putting them in the bottom 20% of specialties for pay satisfaction.

The $352,000 listed in the Medscape Ob/Gyn Compensation Report 2024 put the specialty in the middle of physicians overall. Orthopedists made the most at $558,000, followed by plastic surgeons at $536,000. Endocrinologists/diabetes specialists made the least at $256,000.
 

Ob.Gyn. Pay Rose 4%

Ob.gyns.’ pay overall was up 4% this year and the specialty was one of 10 in the survey that saw an increase.

There were contrasts in satisfaction among the specialties: Public health and preventive medicine physicians had the highest rate of satisfaction with pay (65% were satisfied) though they made new the least among physicians ($263,000). Those least satisfied with their pay were infectious disease physicians with only 34% saying they were satisfied.

There was also a contrast between what ob.gyns. thought about all physicians’ pay and what they thought of their own pay. While 68% said they thought physicians were underpaid, only 58% said that about their own specialty.

Elizabeth Woodcock, a healthcare consultant with Woodcock and Associates in Atlanta, Georgia, said this may be a mindset of self-deprecation, where pay is concerned.

“I think their response is a function of their lens — ‘I feel fortunate to have a job, to care for my patients, to be paid for this work,’ ” Ms. Woodcock said in the survey report.
 

Most Billings, Most Pay

“As a rule of thumb, the specialists who generate the most gross billings to commercial payers are more likely to receive the highest compensation,” said Jeff Decker, president of AMN Healthcare’s physician solutions division.

Louise P. King, MD, JD, associate professor of obstetrics and gynecology at Harvard Medical School in Boston, said lower reimbursement for procedures drives her reimbursement as a gynecological surgeon.

“Ob.gyns. — who are primarily surgical and have the highest malpractice risks and costs of almost the entire profession — earn far less than other surgeons,” she said.

The reasons for that are complex, she said, but she explained in a commentary in Obstetrics and Gynecology that “insurers reimburse procedures for women at a lower rate than similar procedures for men, although there is no medically justifiable reason for this disparity.”

She says that doubly affects female gynecological surgeons, who make up a disproportionately high number of surgeons in the field and serve mostly female patients.
 

Implications for Patient Care

Lower reimbursement also has implications for patient care, she says. Lower reimbursement for gynecological surgeries pushes many obstetrics and gynecological surgeons to perform fewer surgeries and more obstetric services, “resulting in a high prevalence of low-volume gynecologic surgeons, a metric that is closely tied to higher complication rates,” said Dr. King.

She added that as a gynecological surgeon, because of the lower reimbursement for services, “I have less access to [operating room] time and supports like midlevel clinicians.”

Fifty-three percent of ob.gyns. reported they have a chance for an incentive bonus and the average was $40,000; this is compared with the highest bonuses — $142,000, which were for dermatologists, followed by orthopedists at $102,000.

Ob.gyns. were also asked about whether they supplemented their income with additional work and 39% this year, about the same percentage as last year, said they did. The percentage is similar to the number of physicians who say they supplement their income. In most cases, for all physicians, the outside work is usually within the medical field.

Ms. Woodcock, Mr. Decker, and Dr. King report no relevant financial disclosures.

Fewer than half (42%) of obstetricians/gynecologists in the latest Medscape survey said they were satisfied with their average $352,000/year pay, putting them in the bottom 20% of specialties for pay satisfaction.

The $352,000 listed in the Medscape Ob/Gyn Compensation Report 2024 put the specialty in the middle of physicians overall. Orthopedists made the most at $558,000, followed by plastic surgeons at $536,000. Endocrinologists/diabetes specialists made the least at $256,000.
 

Ob.Gyn. Pay Rose 4%

Ob.gyns.’ pay overall was up 4% this year and the specialty was one of 10 in the survey that saw an increase.

There were contrasts in satisfaction among the specialties: Public health and preventive medicine physicians had the highest rate of satisfaction with pay (65% were satisfied) though they made new the least among physicians ($263,000). Those least satisfied with their pay were infectious disease physicians with only 34% saying they were satisfied.

There was also a contrast between what ob.gyns. thought about all physicians’ pay and what they thought of their own pay. While 68% said they thought physicians were underpaid, only 58% said that about their own specialty.

Elizabeth Woodcock, a healthcare consultant with Woodcock and Associates in Atlanta, Georgia, said this may be a mindset of self-deprecation, where pay is concerned.

“I think their response is a function of their lens — ‘I feel fortunate to have a job, to care for my patients, to be paid for this work,’ ” Ms. Woodcock said in the survey report.
 

Most Billings, Most Pay

“As a rule of thumb, the specialists who generate the most gross billings to commercial payers are more likely to receive the highest compensation,” said Jeff Decker, president of AMN Healthcare’s physician solutions division.

Louise P. King, MD, JD, associate professor of obstetrics and gynecology at Harvard Medical School in Boston, said lower reimbursement for procedures drives her reimbursement as a gynecological surgeon.

“Ob.gyns. — who are primarily surgical and have the highest malpractice risks and costs of almost the entire profession — earn far less than other surgeons,” she said.

The reasons for that are complex, she said, but she explained in a commentary in Obstetrics and Gynecology that “insurers reimburse procedures for women at a lower rate than similar procedures for men, although there is no medically justifiable reason for this disparity.”

She says that doubly affects female gynecological surgeons, who make up a disproportionately high number of surgeons in the field and serve mostly female patients.
 

Implications for Patient Care

Lower reimbursement also has implications for patient care, she says. Lower reimbursement for gynecological surgeries pushes many obstetrics and gynecological surgeons to perform fewer surgeries and more obstetric services, “resulting in a high prevalence of low-volume gynecologic surgeons, a metric that is closely tied to higher complication rates,” said Dr. King.

She added that as a gynecological surgeon, because of the lower reimbursement for services, “I have less access to [operating room] time and supports like midlevel clinicians.”

Fifty-three percent of ob.gyns. reported they have a chance for an incentive bonus and the average was $40,000; this is compared with the highest bonuses — $142,000, which were for dermatologists, followed by orthopedists at $102,000.

Ob.gyns. were also asked about whether they supplemented their income with additional work and 39% this year, about the same percentage as last year, said they did. The percentage is similar to the number of physicians who say they supplement their income. In most cases, for all physicians, the outside work is usually within the medical field.

Ms. Woodcock, Mr. Decker, and Dr. King report no relevant financial disclosures.

Fewer than half (42%) of obstetricians/gynecologists in the latest Medscape survey said they were satisfied with their average $352,000/year pay, putting them in the bottom 20% of specialties for pay satisfaction.

The $352,000 listed in the Medscape Ob/Gyn Compensation Report 2024 put the specialty in the middle of physicians overall. Orthopedists made the most at $558,000, followed by plastic surgeons at $536,000. Endocrinologists/diabetes specialists made the least at $256,000.
 

Ob.Gyn. Pay Rose 4%

Ob.gyns.’ pay overall was up 4% this year and the specialty was one of 10 in the survey that saw an increase.

There were contrasts in satisfaction among the specialties: Public health and preventive medicine physicians had the highest rate of satisfaction with pay (65% were satisfied) though they made new the least among physicians ($263,000). Those least satisfied with their pay were infectious disease physicians with only 34% saying they were satisfied.

There was also a contrast between what ob.gyns. thought about all physicians’ pay and what they thought of their own pay. While 68% said they thought physicians were underpaid, only 58% said that about their own specialty.

Elizabeth Woodcock, a healthcare consultant with Woodcock and Associates in Atlanta, Georgia, said this may be a mindset of self-deprecation, where pay is concerned.

“I think their response is a function of their lens — ‘I feel fortunate to have a job, to care for my patients, to be paid for this work,’ ” Ms. Woodcock said in the survey report.
 

Most Billings, Most Pay

“As a rule of thumb, the specialists who generate the most gross billings to commercial payers are more likely to receive the highest compensation,” said Jeff Decker, president of AMN Healthcare’s physician solutions division.

Louise P. King, MD, JD, associate professor of obstetrics and gynecology at Harvard Medical School in Boston, said lower reimbursement for procedures drives her reimbursement as a gynecological surgeon.

“Ob.gyns. — who are primarily surgical and have the highest malpractice risks and costs of almost the entire profession — earn far less than other surgeons,” she said.

The reasons for that are complex, she said, but she explained in a commentary in Obstetrics and Gynecology that “insurers reimburse procedures for women at a lower rate than similar procedures for men, although there is no medically justifiable reason for this disparity.”

She says that doubly affects female gynecological surgeons, who make up a disproportionately high number of surgeons in the field and serve mostly female patients.
 

Implications for Patient Care

Lower reimbursement also has implications for patient care, she says. Lower reimbursement for gynecological surgeries pushes many obstetrics and gynecological surgeons to perform fewer surgeries and more obstetric services, “resulting in a high prevalence of low-volume gynecologic surgeons, a metric that is closely tied to higher complication rates,” said Dr. King.

She added that as a gynecological surgeon, because of the lower reimbursement for services, “I have less access to [operating room] time and supports like midlevel clinicians.”

Fifty-three percent of ob.gyns. reported they have a chance for an incentive bonus and the average was $40,000; this is compared with the highest bonuses — $142,000, which were for dermatologists, followed by orthopedists at $102,000.

Ob.gyns. were also asked about whether they supplemented their income with additional work and 39% this year, about the same percentage as last year, said they did. The percentage is similar to the number of physicians who say they supplement their income. In most cases, for all physicians, the outside work is usually within the medical field.

Ms. Woodcock, Mr. Decker, and Dr. King report no relevant financial disclosures.

More than half of family physicians think that physicians in general are underpaid, but 50% said that in their own situations, they felt fairly paid given their work demands, based on data from Medscape’s annual Family Physician Compensation Report.

The report, based on data from 7,000 physicians across the United States, showed similarly that 50% of family physicians were happy with their pay, which put them about midway on a list of 29 specialties ranking happiness with pay, above some of the higher paid specialties including orthopedics and plastic surgery.

The report cited data from the Mercer consulting firm showing an increase of 3% in 2023 over 2022 earnings among physicians in the United States overall. The average annual earnings for family medicine physicians were near the bottom of a list of 29 specialties included in the report, but 90% said that potential pay was not a factor or a minor factor in choosing the specialty.

According to the report, 61% of family physicians reported taking no additional work to boost income, but 20% reported taking on additional medical-related work, and 6% reported non-medical-related work.

For most family physicians compensation for patient care remained approximately the same as previous years, and a majority said that neither competing physician practices nor other medical businesses (such as retail clinics or nonphysician practitioners) had an effect on their incomes (70% and 62%, respectively).

Although 54% of family practice physicians reported opportunities for incentive bonuses, these bonuses are generally based on a combination of clinical, economic, and experience factors, and are lower for primary care physicians than for specialists. The average bonus for a primary care physician in 2023 was $27,000 compared with an average bonus of $51,000 for a specialist, according to the report.

Overall, 32% of the family physicians reported gratitude from and relationships with patients as the most satisfying part of their jobs, followed by being good at their jobs by finding answers to medical questions and making diagnoses (24%), and making the world a better place (19%).
 

Why Money Still Matters

The relatively minor increase in earnings is “the minimum necessary to continue to attract talented individuals into family medicine,” Susan Kuchera, MD, associate director of the Family Medicine Residency Program at Jefferson Health, Abington, Pennsylvania, said in an interview.

The current report referenced a 2023 report of interviews with medical residents, and approximately half of residents overall said that potential earnings were influential in their decisions.

However, the current Medscape report does not reflect the debt burden held by most new physicians, said Dr. Kuchera, who was not involved in the report. “The educational debt and long years of training can be a deterrent for some to choose a lower paying specialty like primary care; if we want to continue to provide our communities with primary care specialists, we need to keep pace with other areas of medicine,” she said.

“It takes a minimum of 7 years to train a primary care physician, we can’t lose sight over time of the factors that impact a person’s choice to pursue primary care,” Dr. Kuchera said.
 

More Support Needed for Community-Based Care

The data from the report were not surprising, given that the work of primary care physicians is hard, but “historically undervalued” compared with procedural medicine, Dr. Kuchera said. With more emphasis on the value of healthy communities, “we will realize that the relationship family physicians have with their communities is paramount to creating a healthy society,” she added.

The fact that patient care accounts for more than 75% of what family doctors feel to be most rewarding in their profession reflects that most do this work because longitudinal care of patients and communities is rewarding, Dr. Kuchera said in an interview.

“Employers need to value the special training of family doctors to take care of communities,” Dr. Kuchera said. This includes finding ways to incentivize value-based care and to provide the necessary resources to care for communities with poor social determinants of health, she added.

Dr. Kuchera had no financial conflicts to disclose.

More than half of family physicians think that physicians in general are underpaid, but 50% said that in their own situations, they felt fairly paid given their work demands, based on data from Medscape’s annual Family Physician Compensation Report.

The report, based on data from 7,000 physicians across the United States, showed similarly that 50% of family physicians were happy with their pay, which put them about midway on a list of 29 specialties ranking happiness with pay, above some of the higher paid specialties including orthopedics and plastic surgery.

The report cited data from the Mercer consulting firm showing an increase of 3% in 2023 over 2022 earnings among physicians in the United States overall. The average annual earnings for family medicine physicians were near the bottom of a list of 29 specialties included in the report, but 90% said that potential pay was not a factor or a minor factor in choosing the specialty.

According to the report, 61% of family physicians reported taking no additional work to boost income, but 20% reported taking on additional medical-related work, and 6% reported non-medical-related work.

For most family physicians compensation for patient care remained approximately the same as previous years, and a majority said that neither competing physician practices nor other medical businesses (such as retail clinics or nonphysician practitioners) had an effect on their incomes (70% and 62%, respectively).

Although 54% of family practice physicians reported opportunities for incentive bonuses, these bonuses are generally based on a combination of clinical, economic, and experience factors, and are lower for primary care physicians than for specialists. The average bonus for a primary care physician in 2023 was $27,000 compared with an average bonus of $51,000 for a specialist, according to the report.

Overall, 32% of the family physicians reported gratitude from and relationships with patients as the most satisfying part of their jobs, followed by being good at their jobs by finding answers to medical questions and making diagnoses (24%), and making the world a better place (19%).
 

Why Money Still Matters

The relatively minor increase in earnings is “the minimum necessary to continue to attract talented individuals into family medicine,” Susan Kuchera, MD, associate director of the Family Medicine Residency Program at Jefferson Health, Abington, Pennsylvania, said in an interview.

The current report referenced a 2023 report of interviews with medical residents, and approximately half of residents overall said that potential earnings were influential in their decisions.

However, the current Medscape report does not reflect the debt burden held by most new physicians, said Dr. Kuchera, who was not involved in the report. “The educational debt and long years of training can be a deterrent for some to choose a lower paying specialty like primary care; if we want to continue to provide our communities with primary care specialists, we need to keep pace with other areas of medicine,” she said.

“It takes a minimum of 7 years to train a primary care physician, we can’t lose sight over time of the factors that impact a person’s choice to pursue primary care,” Dr. Kuchera said.
 

More Support Needed for Community-Based Care

The data from the report were not surprising, given that the work of primary care physicians is hard, but “historically undervalued” compared with procedural medicine, Dr. Kuchera said. With more emphasis on the value of healthy communities, “we will realize that the relationship family physicians have with their communities is paramount to creating a healthy society,” she added.

The fact that patient care accounts for more than 75% of what family doctors feel to be most rewarding in their profession reflects that most do this work because longitudinal care of patients and communities is rewarding, Dr. Kuchera said in an interview.

“Employers need to value the special training of family doctors to take care of communities,” Dr. Kuchera said. This includes finding ways to incentivize value-based care and to provide the necessary resources to care for communities with poor social determinants of health, she added.

Dr. Kuchera had no financial conflicts to disclose.

More than half of family physicians think that physicians in general are underpaid, but 50% said that in their own situations, they felt fairly paid given their work demands, based on data from Medscape’s annual Family Physician Compensation Report.

The report, based on data from 7,000 physicians across the United States, showed similarly that 50% of family physicians were happy with their pay, which put them about midway on a list of 29 specialties ranking happiness with pay, above some of the higher paid specialties including orthopedics and plastic surgery.

The report cited data from the Mercer consulting firm showing an increase of 3% in 2023 over 2022 earnings among physicians in the United States overall. The average annual earnings for family medicine physicians were near the bottom of a list of 29 specialties included in the report, but 90% said that potential pay was not a factor or a minor factor in choosing the specialty.

According to the report, 61% of family physicians reported taking no additional work to boost income, but 20% reported taking on additional medical-related work, and 6% reported non-medical-related work.

For most family physicians compensation for patient care remained approximately the same as previous years, and a majority said that neither competing physician practices nor other medical businesses (such as retail clinics or nonphysician practitioners) had an effect on their incomes (70% and 62%, respectively).

Although 54% of family practice physicians reported opportunities for incentive bonuses, these bonuses are generally based on a combination of clinical, economic, and experience factors, and are lower for primary care physicians than for specialists. The average bonus for a primary care physician in 2023 was $27,000 compared with an average bonus of $51,000 for a specialist, according to the report.

Overall, 32% of the family physicians reported gratitude from and relationships with patients as the most satisfying part of their jobs, followed by being good at their jobs by finding answers to medical questions and making diagnoses (24%), and making the world a better place (19%).
 

Why Money Still Matters

The relatively minor increase in earnings is “the minimum necessary to continue to attract talented individuals into family medicine,” Susan Kuchera, MD, associate director of the Family Medicine Residency Program at Jefferson Health, Abington, Pennsylvania, said in an interview.

The current report referenced a 2023 report of interviews with medical residents, and approximately half of residents overall said that potential earnings were influential in their decisions.

However, the current Medscape report does not reflect the debt burden held by most new physicians, said Dr. Kuchera, who was not involved in the report. “The educational debt and long years of training can be a deterrent for some to choose a lower paying specialty like primary care; if we want to continue to provide our communities with primary care specialists, we need to keep pace with other areas of medicine,” she said.

“It takes a minimum of 7 years to train a primary care physician, we can’t lose sight over time of the factors that impact a person’s choice to pursue primary care,” Dr. Kuchera said.
 

More Support Needed for Community-Based Care

The data from the report were not surprising, given that the work of primary care physicians is hard, but “historically undervalued” compared with procedural medicine, Dr. Kuchera said. With more emphasis on the value of healthy communities, “we will realize that the relationship family physicians have with their communities is paramount to creating a healthy society,” she added.

The fact that patient care accounts for more than 75% of what family doctors feel to be most rewarding in their profession reflects that most do this work because longitudinal care of patients and communities is rewarding, Dr. Kuchera said in an interview.

“Employers need to value the special training of family doctors to take care of communities,” Dr. Kuchera said. This includes finding ways to incentivize value-based care and to provide the necessary resources to care for communities with poor social determinants of health, she added.

Dr. Kuchera had no financial conflicts to disclose.

WASHINGTON ­— Mailing outreach notices for colonoscopies or fecal immunochemical test (FIT) kits may be a great way to increase colorectal cancer (CRC) screening in younger adults, according to a study presented at the annual Digestive Disease Week^® (DDW).

In a comparison of four outreach approaches, sending a FIT kit to people between the ages of 45 and 49 via mail garnered better response rates than opt-in strategies to participate in FIT, inviting them to undergo colonoscopy, or asking them to choose between FIT or colonoscopy. At the same time, when given a choice between colonoscopy and FIT, colonoscopy was preferred across all racial and ethnic groups.

“It is well known that colorectal cancer is the second-leading cause of cancer-related deaths in the United States. The good news is that for the past several decades, we’ve seen a decline in colorectal cancer incidence and mortality in ages 50 and above. However, there has been a recent rise in incidence and mortality in people younger than 50,” said lead author Rebecca Ekeanyanwu, a third-year medical student at Meharry Medical College School of Medicine in Nashville, Tennessee. She was awarded the 2024 AGA Institute Council Healthcare Disparities Research Award for the top oral presentation for research in racial and ethnic health care disparities.

WASHINGTON ­— Mailing outreach notices for colonoscopies or fecal immunochemical test (FIT) kits may be a great way to increase colorectal cancer (CRC) screening in younger adults, according to a study presented at the annual Digestive Disease Week^® (DDW).

In a comparison of four outreach approaches, sending a FIT kit to people between the ages of 45 and 49 via mail garnered better response rates than opt-in strategies to participate in FIT, inviting them to undergo colonoscopy, or asking them to choose between FIT or colonoscopy. At the same time, when given a choice between colonoscopy and FIT, colonoscopy was preferred across all racial and ethnic groups.

“It is well known that colorectal cancer is the second-leading cause of cancer-related deaths in the United States. The good news is that for the past several decades, we’ve seen a decline in colorectal cancer incidence and mortality in ages 50 and above. However, there has been a recent rise in incidence and mortality in people younger than 50,” said lead author Rebecca Ekeanyanwu, a third-year medical student at Meharry Medical College School of Medicine in Nashville, Tennessee. She was awarded the 2024 AGA Institute Council Healthcare Disparities Research Award for the top oral presentation for research in racial and ethnic health care disparities.

WASHINGTON ­— Mailing outreach notices for colonoscopies or fecal immunochemical test (FIT) kits may be a great way to increase colorectal cancer (CRC) screening in younger adults, according to a study presented at the annual Digestive Disease Week^® (DDW).

In a comparison of four outreach approaches, sending a FIT kit to people between the ages of 45 and 49 via mail garnered better response rates than opt-in strategies to participate in FIT, inviting them to undergo colonoscopy, or asking them to choose between FIT or colonoscopy. At the same time, when given a choice between colonoscopy and FIT, colonoscopy was preferred across all racial and ethnic groups.

“It is well known that colorectal cancer is the second-leading cause of cancer-related deaths in the United States. The good news is that for the past several decades, we’ve seen a decline in colorectal cancer incidence and mortality in ages 50 and above. However, there has been a recent rise in incidence and mortality in people younger than 50,” said lead author Rebecca Ekeanyanwu, a third-year medical student at Meharry Medical College School of Medicine in Nashville, Tennessee. She was awarded the 2024 AGA Institute Council Healthcare Disparities Research Award for the top oral presentation for research in racial and ethnic health care disparities.

NASHVILLE, TENNESSEE — Stress in patients with multiple sclerosis (MS) can have serious effects on quality of life, but there is some evidence that it could worsen inflammation through activation of pro-inflammatory cytokines, leading to more relapses.

A new intervention seeks to help patients with MS reduce stress using biofeedback, employing simple, readily available pulse oximeters and focusing on breathing and other simple coping skills.

Observational studies have suggested that stress may lead to relapses, according to Amy Sullivan, PsyD, who spoke during a session at the annual meeting of the Consortium of Multiple Sclerosis Centers.

She cited a study conducted during the 34-day war between Israel and Lebanon in 2006, which found more exacerbations among 156 Israeli patients with relapsing-remitting MS patients during the period of hostilities. There were 18 relapses that occurred during the war, and 44% of those who experienced a relapse reported experience intense subjective stress, versus 20% of those who did not experience a relapse, and 67% of relapsers reported high levels of distress linked to rocket attack exposure, versus 42% of those who did not have a relapse (P = .05).

Another study of 216 Lebanese MS patients found 23 relapses during the 2-month war period, compared with a mean of 8.4 during other 2-month periods.

“So we have two observational studies that are showing us that there’s a pretty strong link or correlation between war, a very stressful life event, and MS relapses,” said Dr. Sullivan.

That relationship has prompted development of interventions to reduce stress in MS patients in hopes of improving clinical outcomes. One that “shaped our practice,” according to Dr. Sullivan, was published in 2012. It was the first high-quality randomized controlled trial of such an intervention, she said.

The program was based on cognitive behavioral therapy (CBT) and lasted 24 weeks and 16 psychotherapy sessions. Compared with controls, participants had fewer MRI brain lesions, but there were no differences after week 24. “[That] tells us that when people stopped the stress management techniques, the intervention did not give them protection,” said Dr. Sullivan.

Her group aimed to build on that work by developing a program that would be easier for busy patients to learn and incorporate into their lives. “Being in a psychotherapist office for 24 weeks to me was not feasible. I didn’t think that this was something that individuals would have interest in,” said Dr. Sullivan.

They focused on skills to manage stress, delivered over four sessions and designed to be employed in their private life. “We want them to go into the world for 4 to 6 weeks to do the skills that we taught them in that particular session, and then they come back and they tell us how that worked. We also recognize that each skill is not going to work. It’s not a one-size-fits-all for each person,” said Dr. Sullivan.

In addition to patient self-reports, the team measured physiological indicators of stress like pulse (beats per minute), breath rate (breaths per minute), and saturated oxygen (%SpO2). The measures were taken before and after stress management exercises.

The first session included psychoeducation and diaphragmatic breathing for relaxation. The second reviewed the nervous system and the stress response. The third introduced visualization and guided imagery that was individualized for each patient. The fourth focused on mindfulness and distress tolerance.

The study included 195 individuals (mean age, 44.4 years; 72.0% female, 71.5% White).

In all four sessions, patients achieved significant in-session improvements in breath rate, pulse, and saturated oxygen, as well as improvements from the first to the final session: Among 124 patients who completed at least 2 sessions, Patient Health Questionnaire-9 (PHQ-9) scores improved by 1.61 (P < .001), Generalized Anxiety Disorder (GAD) scores by 1.08 (P = .004), breaths per minute by 3.38 (P = .001), and SpO2 by 1.67 (P = .016). There was no significant change in pulse.

The high dropout rate could be seen as a weakness, but it was actually designed into the program. “We encouraged people to drop out when they were done. Our program is built on feasibility, and it’s built based on wanting our patients to get what they need out of our treatment, and then go live their lives. We don’t want them to feel tied to our offices, so they voluntarily discontinued after they felt they had sufficiently mastered stress management skills,” said Dr. Sullivan.

The results “suggest that short-term treatment with stress management skills can impact physiological and emotional stress in MS. [The] stress management protocol is likely a great adjunctive treatment to bolster skills traditionally taught during psychotherapy sessions,” said Dr. Sullivan.

During the Q&A period, an audience member asked why the group deviated from traditional cognitive behavioral therapy and moved into more right-brain activities. “In our practice, we’re very eclectic. We don’t believe that just CBT helps, or just behavioral therapy helps, or just [dialectical behavior therapy] helps. We want to teach the skills which we believe are the most important skills to train people on,” said Dr. Sullivan.

Dr. Sullivan did not report any relevant disclosures.

NASHVILLE, TENNESSEE — Stress in patients with multiple sclerosis (MS) can have serious effects on quality of life, but there is some evidence that it could worsen inflammation through activation of pro-inflammatory cytokines, leading to more relapses.

A new intervention seeks to help patients with MS reduce stress using biofeedback, employing simple, readily available pulse oximeters and focusing on breathing and other simple coping skills.

Observational studies have suggested that stress may lead to relapses, according to Amy Sullivan, PsyD, who spoke during a session at the annual meeting of the Consortium of Multiple Sclerosis Centers.

She cited a study conducted during the 34-day war between Israel and Lebanon in 2006, which found more exacerbations among 156 Israeli patients with relapsing-remitting MS patients during the period of hostilities. There were 18 relapses that occurred during the war, and 44% of those who experienced a relapse reported experience intense subjective stress, versus 20% of those who did not experience a relapse, and 67% of relapsers reported high levels of distress linked to rocket attack exposure, versus 42% of those who did not have a relapse (P = .05).

Another study of 216 Lebanese MS patients found 23 relapses during the 2-month war period, compared with a mean of 8.4 during other 2-month periods.

“So we have two observational studies that are showing us that there’s a pretty strong link or correlation between war, a very stressful life event, and MS relapses,” said Dr. Sullivan.

That relationship has prompted development of interventions to reduce stress in MS patients in hopes of improving clinical outcomes. One that “shaped our practice,” according to Dr. Sullivan, was published in 2012. It was the first high-quality randomized controlled trial of such an intervention, she said.

The program was based on cognitive behavioral therapy (CBT) and lasted 24 weeks and 16 psychotherapy sessions. Compared with controls, participants had fewer MRI brain lesions, but there were no differences after week 24. “[That] tells us that when people stopped the stress management techniques, the intervention did not give them protection,” said Dr. Sullivan.

Her group aimed to build on that work by developing a program that would be easier for busy patients to learn and incorporate into their lives. “Being in a psychotherapist office for 24 weeks to me was not feasible. I didn’t think that this was something that individuals would have interest in,” said Dr. Sullivan.

They focused on skills to manage stress, delivered over four sessions and designed to be employed in their private life. “We want them to go into the world for 4 to 6 weeks to do the skills that we taught them in that particular session, and then they come back and they tell us how that worked. We also recognize that each skill is not going to work. It’s not a one-size-fits-all for each person,” said Dr. Sullivan.

In addition to patient self-reports, the team measured physiological indicators of stress like pulse (beats per minute), breath rate (breaths per minute), and saturated oxygen (%SpO2). The measures were taken before and after stress management exercises.

The first session included psychoeducation and diaphragmatic breathing for relaxation. The second reviewed the nervous system and the stress response. The third introduced visualization and guided imagery that was individualized for each patient. The fourth focused on mindfulness and distress tolerance.

The study included 195 individuals (mean age, 44.4 years; 72.0% female, 71.5% White).

In all four sessions, patients achieved significant in-session improvements in breath rate, pulse, and saturated oxygen, as well as improvements from the first to the final session: Among 124 patients who completed at least 2 sessions, Patient Health Questionnaire-9 (PHQ-9) scores improved by 1.61 (P < .001), Generalized Anxiety Disorder (GAD) scores by 1.08 (P = .004), breaths per minute by 3.38 (P = .001), and SpO2 by 1.67 (P = .016). There was no significant change in pulse.

The high dropout rate could be seen as a weakness, but it was actually designed into the program. “We encouraged people to drop out when they were done. Our program is built on feasibility, and it’s built based on wanting our patients to get what they need out of our treatment, and then go live their lives. We don’t want them to feel tied to our offices, so they voluntarily discontinued after they felt they had sufficiently mastered stress management skills,” said Dr. Sullivan.

The results “suggest that short-term treatment with stress management skills can impact physiological and emotional stress in MS. [The] stress management protocol is likely a great adjunctive treatment to bolster skills traditionally taught during psychotherapy sessions,” said Dr. Sullivan.

During the Q&A period, an audience member asked why the group deviated from traditional cognitive behavioral therapy and moved into more right-brain activities. “In our practice, we’re very eclectic. We don’t believe that just CBT helps, or just behavioral therapy helps, or just [dialectical behavior therapy] helps. We want to teach the skills which we believe are the most important skills to train people on,” said Dr. Sullivan.

Dr. Sullivan did not report any relevant disclosures.

NASHVILLE, TENNESSEE — Stress in patients with multiple sclerosis (MS) can have serious effects on quality of life, but there is some evidence that it could worsen inflammation through activation of pro-inflammatory cytokines, leading to more relapses.

A new intervention seeks to help patients with MS reduce stress using biofeedback, employing simple, readily available pulse oximeters and focusing on breathing and other simple coping skills.

Observational studies have suggested that stress may lead to relapses, according to Amy Sullivan, PsyD, who spoke during a session at the annual meeting of the Consortium of Multiple Sclerosis Centers.

She cited a study conducted during the 34-day war between Israel and Lebanon in 2006, which found more exacerbations among 156 Israeli patients with relapsing-remitting MS patients during the period of hostilities. There were 18 relapses that occurred during the war, and 44% of those who experienced a relapse reported experience intense subjective stress, versus 20% of those who did not experience a relapse, and 67% of relapsers reported high levels of distress linked to rocket attack exposure, versus 42% of those who did not have a relapse (P = .05).

Another study of 216 Lebanese MS patients found 23 relapses during the 2-month war period, compared with a mean of 8.4 during other 2-month periods.

“So we have two observational studies that are showing us that there’s a pretty strong link or correlation between war, a very stressful life event, and MS relapses,” said Dr. Sullivan.

That relationship has prompted development of interventions to reduce stress in MS patients in hopes of improving clinical outcomes. One that “shaped our practice,” according to Dr. Sullivan, was published in 2012. It was the first high-quality randomized controlled trial of such an intervention, she said.

The program was based on cognitive behavioral therapy (CBT) and lasted 24 weeks and 16 psychotherapy sessions. Compared with controls, participants had fewer MRI brain lesions, but there were no differences after week 24. “[That] tells us that when people stopped the stress management techniques, the intervention did not give them protection,” said Dr. Sullivan.

Her group aimed to build on that work by developing a program that would be easier for busy patients to learn and incorporate into their lives. “Being in a psychotherapist office for 24 weeks to me was not feasible. I didn’t think that this was something that individuals would have interest in,” said Dr. Sullivan.

They focused on skills to manage stress, delivered over four sessions and designed to be employed in their private life. “We want them to go into the world for 4 to 6 weeks to do the skills that we taught them in that particular session, and then they come back and they tell us how that worked. We also recognize that each skill is not going to work. It’s not a one-size-fits-all for each person,” said Dr. Sullivan.

In addition to patient self-reports, the team measured physiological indicators of stress like pulse (beats per minute), breath rate (breaths per minute), and saturated oxygen (%SpO2). The measures were taken before and after stress management exercises.

The first session included psychoeducation and diaphragmatic breathing for relaxation. The second reviewed the nervous system and the stress response. The third introduced visualization and guided imagery that was individualized for each patient. The fourth focused on mindfulness and distress tolerance.

The study included 195 individuals (mean age, 44.4 years; 72.0% female, 71.5% White).

In all four sessions, patients achieved significant in-session improvements in breath rate, pulse, and saturated oxygen, as well as improvements from the first to the final session: Among 124 patients who completed at least 2 sessions, Patient Health Questionnaire-9 (PHQ-9) scores improved by 1.61 (P < .001), Generalized Anxiety Disorder (GAD) scores by 1.08 (P = .004), breaths per minute by 3.38 (P = .001), and SpO2 by 1.67 (P = .016). There was no significant change in pulse.

The high dropout rate could be seen as a weakness, but it was actually designed into the program. “We encouraged people to drop out when they were done. Our program is built on feasibility, and it’s built based on wanting our patients to get what they need out of our treatment, and then go live their lives. We don’t want them to feel tied to our offices, so they voluntarily discontinued after they felt they had sufficiently mastered stress management skills,” said Dr. Sullivan.

The results “suggest that short-term treatment with stress management skills can impact physiological and emotional stress in MS. [The] stress management protocol is likely a great adjunctive treatment to bolster skills traditionally taught during psychotherapy sessions,” said Dr. Sullivan.

During the Q&A period, an audience member asked why the group deviated from traditional cognitive behavioral therapy and moved into more right-brain activities. “In our practice, we’re very eclectic. We don’t believe that just CBT helps, or just behavioral therapy helps, or just [dialectical behavior therapy] helps. We want to teach the skills which we believe are the most important skills to train people on,” said Dr. Sullivan.

Dr. Sullivan did not report any relevant disclosures.

Florida has become the first state to allow doctors to perform cesarean sections outside of hospitals, siding with a private equity-owned physicians group that says the change will lower costs and give pregnant women the homier birthing atmosphere that many desire.

But the hospital industry and the nation’s leading obstetricians’ association say that even though some Florida hospitals have closed their maternity wards in recent years, performing C-sections in doctor-run clinics will increase the risks for women and babies when complications arise.

“A pregnant patient that is considered low-risk in one moment can suddenly need lifesaving care in the next,” Cole Greves, an Orlando perinatologist who chairs the Florida chapter of the American College of Obstetricians and Gynecologists, said in an email to KFF Health News. The new birth clinics, “even with increased regulation, cannot guarantee the level of safety patients would receive within a hospital.”

This spring, a law was enacted allowing “advanced birth centers,” where physicians can deliver babies vaginally or by C-section to women deemed at low risk of complications. Women would be able to stay overnight at the clinics.

Women’s Care Enterprises, a private equity-owned physicians group with locations mostly in Florida along with California and Kentucky, lobbied the state legislature to make the change. BC Partners, a London-based investment firm, bought Women’s Care in 2020.

“We have patients who don’t want to deliver in a hospital, and that breaks our heart,” said Stephen Snow, who recently retired as an ob.gyn. with Women’s Care and testified before the Florida Legislature advocating for the change in 2018.

Brittany Miller, vice president of strategic initiatives with Women’s Care, said the group would not comment on the issue.

Health experts are leery.

“What this looks like is a poor substitute for quality obstetrical care effectively being billed as something that gives people more choices,” said Alice Abernathy, an assistant professor of obstetrics and gynecology at the University of Pennsylvania Perelman School of Medicine. “This feels like a bad band-aid on a chronic issue that will make outcomes worse rather than better,” Abernathy said.

Nearly one-third of U.S. births occur via C-section, the surgical delivery of a baby through an incision in the mother’s abdomen and uterus. Generally, doctors use the procedure when they believe it is safer than vaginal delivery for the parent, the baby, or both. Such medical decisions can take place months before birth, or in an emergency.

Florida state Sen. Gayle Harrell, the Republican who sponsored the birth center bill, said having a C-section outside of a hospital may seem like a radical change, but so was the opening of outpatient surgery centers in the late 1980s.

Harrell, who managed her husband’s ob.gyn. practice, said birth centers will have to meet the same high standards for staffing, infection control, and other aspects as those at outpatient surgery centers.

“Given where we are with the need, and maternity deserts across the state, this is something that will help us and help moms get the best care,” she said.

Seventeen hospitals in the state have closed their maternity units since 2019, with many citing low insurance reimbursement and high malpractice costs, according to the Florida Hospital Association.

Mary Mayhew, CEO of the Florida Hospital Association, said it is wrong to compare birth centers to ambulatory surgery centers because of the many risks associated with C-sections, such as hemorrhaging.

The Florida law requires advanced birth centers to have a transfer agreement with a hospital, but it does not dictate where the facilities can open nor their proximity to a hospital.

“We have serious concerns about the impact this model has on our collective efforts to improve maternal and infant health,” Mayhew said. “Our hospitals do not see this in the best interest of providing quality and safety in labor and delivery.”

Despite its opposition to the new birth centers, the Florida Hospital Association did not fight passage of the overall bill because it also included a major increase in the amount Medicaid pays hospitals for maternity care.

Mayhew said it is unlikely that the birth centers would help address care shortages. Hospitals are already struggling with a shortage of ob.gyns., she said, and it is unrealistic to expect advanced birth centers to open in rural areas with a large proportion of people on Medicaid, which pays the lowest reimbursement for labor and delivery care.

It is unclear whether insurers will cover the advanced birth centers, though most insurers and Medicaid cover care at midwife-run birth centers. The advanced birth centers will not accept emergency walk-ins and will treat only patients whose insurance contracts with the facilities, making them in-network.

Snow, the retired ob.gyn. with Women’s Care, said the group plans to open an advanced birth center in the Tampa or Orlando area.

The advanced birth center concept is an improvement on midwife care that enables deliveries outside of hospitals, he said, as the centers allow women to stay overnight and, if necessary, offer anesthesia and C-sections.

Snow acknowledged that, with a private equity firm invested in Women’s Care, the birth center idea is also about making money. But he said hospitals have the same profit incentive and, like midwives, likely oppose the idea of centers that can provide C-sections because they could cut into hospital revenue.

“We are trying to reduce the cost of medicine, and this would be more cost-effective and more pleasant for patients,” he said.

Kate Bauer, executive director of the American Association of Birth Centers, said patients could confuse advanced birth centers with the existing, free-standing birth centers for low-risk births that have been run by midwives for decades. There are currently 31 licensed birth centers in Florida and 411 free-standing birth centers in the United States, she said.

“This is a radical departure from the standard of care,” Bauer said. “It’s a bad idea,” she said, because it could increase risks to mom and baby.

No other state allows C-sections outside of hospitals. The only facility that offers similar care is a birth clinic in Wichita, Kansas, which is connected by a short walkway to a hospital, Wesley Medical Center.

The clinic provides “hotel-like” maternity suites where staffers deliver about 100 babies a month, compared with 500 per month in the hospital itself.

Morgan Tracy, a maternity nurse navigator at the center, said the concept works largely because the hospital and birthing suites can share staff and pharmacy access, plus patients can be quickly transferred to the main hospital if complications arise.

“The beauty is there are team members on both sides of the street,” Tracy said.
 

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.

Florida has become the first state to allow doctors to perform cesarean sections outside of hospitals, siding with a private equity-owned physicians group that says the change will lower costs and give pregnant women the homier birthing atmosphere that many desire.

But the hospital industry and the nation’s leading obstetricians’ association say that even though some Florida hospitals have closed their maternity wards in recent years, performing C-sections in doctor-run clinics will increase the risks for women and babies when complications arise.

“A pregnant patient that is considered low-risk in one moment can suddenly need lifesaving care in the next,” Cole Greves, an Orlando perinatologist who chairs the Florida chapter of the American College of Obstetricians and Gynecologists, said in an email to KFF Health News. The new birth clinics, “even with increased regulation, cannot guarantee the level of safety patients would receive within a hospital.”

This spring, a law was enacted allowing “advanced birth centers,” where physicians can deliver babies vaginally or by C-section to women deemed at low risk of complications. Women would be able to stay overnight at the clinics.

Women’s Care Enterprises, a private equity-owned physicians group with locations mostly in Florida along with California and Kentucky, lobbied the state legislature to make the change. BC Partners, a London-based investment firm, bought Women’s Care in 2020.

“We have patients who don’t want to deliver in a hospital, and that breaks our heart,” said Stephen Snow, who recently retired as an ob.gyn. with Women’s Care and testified before the Florida Legislature advocating for the change in 2018.

Brittany Miller, vice president of strategic initiatives with Women’s Care, said the group would not comment on the issue.

Health experts are leery.

“What this looks like is a poor substitute for quality obstetrical care effectively being billed as something that gives people more choices,” said Alice Abernathy, an assistant professor of obstetrics and gynecology at the University of Pennsylvania Perelman School of Medicine. “This feels like a bad band-aid on a chronic issue that will make outcomes worse rather than better,” Abernathy said.

Nearly one-third of U.S. births occur via C-section, the surgical delivery of a baby through an incision in the mother’s abdomen and uterus. Generally, doctors use the procedure when they believe it is safer than vaginal delivery for the parent, the baby, or both. Such medical decisions can take place months before birth, or in an emergency.

Florida state Sen. Gayle Harrell, the Republican who sponsored the birth center bill, said having a C-section outside of a hospital may seem like a radical change, but so was the opening of outpatient surgery centers in the late 1980s.

Harrell, who managed her husband’s ob.gyn. practice, said birth centers will have to meet the same high standards for staffing, infection control, and other aspects as those at outpatient surgery centers.

“Given where we are with the need, and maternity deserts across the state, this is something that will help us and help moms get the best care,” she said.

Seventeen hospitals in the state have closed their maternity units since 2019, with many citing low insurance reimbursement and high malpractice costs, according to the Florida Hospital Association.

Mary Mayhew, CEO of the Florida Hospital Association, said it is wrong to compare birth centers to ambulatory surgery centers because of the many risks associated with C-sections, such as hemorrhaging.

The Florida law requires advanced birth centers to have a transfer agreement with a hospital, but it does not dictate where the facilities can open nor their proximity to a hospital.

“We have serious concerns about the impact this model has on our collective efforts to improve maternal and infant health,” Mayhew said. “Our hospitals do not see this in the best interest of providing quality and safety in labor and delivery.”

Despite its opposition to the new birth centers, the Florida Hospital Association did not fight passage of the overall bill because it also included a major increase in the amount Medicaid pays hospitals for maternity care.

Mayhew said it is unlikely that the birth centers would help address care shortages. Hospitals are already struggling with a shortage of ob.gyns., she said, and it is unrealistic to expect advanced birth centers to open in rural areas with a large proportion of people on Medicaid, which pays the lowest reimbursement for labor and delivery care.

It is unclear whether insurers will cover the advanced birth centers, though most insurers and Medicaid cover care at midwife-run birth centers. The advanced birth centers will not accept emergency walk-ins and will treat only patients whose insurance contracts with the facilities, making them in-network.

Snow, the retired ob.gyn. with Women’s Care, said the group plans to open an advanced birth center in the Tampa or Orlando area.

The advanced birth center concept is an improvement on midwife care that enables deliveries outside of hospitals, he said, as the centers allow women to stay overnight and, if necessary, offer anesthesia and C-sections.

Snow acknowledged that, with a private equity firm invested in Women’s Care, the birth center idea is also about making money. But he said hospitals have the same profit incentive and, like midwives, likely oppose the idea of centers that can provide C-sections because they could cut into hospital revenue.

“We are trying to reduce the cost of medicine, and this would be more cost-effective and more pleasant for patients,” he said.

Kate Bauer, executive director of the American Association of Birth Centers, said patients could confuse advanced birth centers with the existing, free-standing birth centers for low-risk births that have been run by midwives for decades. There are currently 31 licensed birth centers in Florida and 411 free-standing birth centers in the United States, she said.

“This is a radical departure from the standard of care,” Bauer said. “It’s a bad idea,” she said, because it could increase risks to mom and baby.

No other state allows C-sections outside of hospitals. The only facility that offers similar care is a birth clinic in Wichita, Kansas, which is connected by a short walkway to a hospital, Wesley Medical Center.

The clinic provides “hotel-like” maternity suites where staffers deliver about 100 babies a month, compared with 500 per month in the hospital itself.

Morgan Tracy, a maternity nurse navigator at the center, said the concept works largely because the hospital and birthing suites can share staff and pharmacy access, plus patients can be quickly transferred to the main hospital if complications arise.

“The beauty is there are team members on both sides of the street,” Tracy said.
 

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.

Florida has become the first state to allow doctors to perform cesarean sections outside of hospitals, siding with a private equity-owned physicians group that says the change will lower costs and give pregnant women the homier birthing atmosphere that many desire.

But the hospital industry and the nation’s leading obstetricians’ association say that even though some Florida hospitals have closed their maternity wards in recent years, performing C-sections in doctor-run clinics will increase the risks for women and babies when complications arise.

“A pregnant patient that is considered low-risk in one moment can suddenly need lifesaving care in the next,” Cole Greves, an Orlando perinatologist who chairs the Florida chapter of the American College of Obstetricians and Gynecologists, said in an email to KFF Health News. The new birth clinics, “even with increased regulation, cannot guarantee the level of safety patients would receive within a hospital.”

This spring, a law was enacted allowing “advanced birth centers,” where physicians can deliver babies vaginally or by C-section to women deemed at low risk of complications. Women would be able to stay overnight at the clinics.

Women’s Care Enterprises, a private equity-owned physicians group with locations mostly in Florida along with California and Kentucky, lobbied the state legislature to make the change. BC Partners, a London-based investment firm, bought Women’s Care in 2020.

“We have patients who don’t want to deliver in a hospital, and that breaks our heart,” said Stephen Snow, who recently retired as an ob.gyn. with Women’s Care and testified before the Florida Legislature advocating for the change in 2018.

Brittany Miller, vice president of strategic initiatives with Women’s Care, said the group would not comment on the issue.

Health experts are leery.

“What this looks like is a poor substitute for quality obstetrical care effectively being billed as something that gives people more choices,” said Alice Abernathy, an assistant professor of obstetrics and gynecology at the University of Pennsylvania Perelman School of Medicine. “This feels like a bad band-aid on a chronic issue that will make outcomes worse rather than better,” Abernathy said.

Nearly one-third of U.S. births occur via C-section, the surgical delivery of a baby through an incision in the mother’s abdomen and uterus. Generally, doctors use the procedure when they believe it is safer than vaginal delivery for the parent, the baby, or both. Such medical decisions can take place months before birth, or in an emergency.

Florida state Sen. Gayle Harrell, the Republican who sponsored the birth center bill, said having a C-section outside of a hospital may seem like a radical change, but so was the opening of outpatient surgery centers in the late 1980s.

Harrell, who managed her husband’s ob.gyn. practice, said birth centers will have to meet the same high standards for staffing, infection control, and other aspects as those at outpatient surgery centers.

“Given where we are with the need, and maternity deserts across the state, this is something that will help us and help moms get the best care,” she said.

Seventeen hospitals in the state have closed their maternity units since 2019, with many citing low insurance reimbursement and high malpractice costs, according to the Florida Hospital Association.

Mary Mayhew, CEO of the Florida Hospital Association, said it is wrong to compare birth centers to ambulatory surgery centers because of the many risks associated with C-sections, such as hemorrhaging.

The Florida law requires advanced birth centers to have a transfer agreement with a hospital, but it does not dictate where the facilities can open nor their proximity to a hospital.

“We have serious concerns about the impact this model has on our collective efforts to improve maternal and infant health,” Mayhew said. “Our hospitals do not see this in the best interest of providing quality and safety in labor and delivery.”

Despite its opposition to the new birth centers, the Florida Hospital Association did not fight passage of the overall bill because it also included a major increase in the amount Medicaid pays hospitals for maternity care.

Mayhew said it is unlikely that the birth centers would help address care shortages. Hospitals are already struggling with a shortage of ob.gyns., she said, and it is unrealistic to expect advanced birth centers to open in rural areas with a large proportion of people on Medicaid, which pays the lowest reimbursement for labor and delivery care.

It is unclear whether insurers will cover the advanced birth centers, though most insurers and Medicaid cover care at midwife-run birth centers. The advanced birth centers will not accept emergency walk-ins and will treat only patients whose insurance contracts with the facilities, making them in-network.

Snow, the retired ob.gyn. with Women’s Care, said the group plans to open an advanced birth center in the Tampa or Orlando area.

The advanced birth center concept is an improvement on midwife care that enables deliveries outside of hospitals, he said, as the centers allow women to stay overnight and, if necessary, offer anesthesia and C-sections.

Snow acknowledged that, with a private equity firm invested in Women’s Care, the birth center idea is also about making money. But he said hospitals have the same profit incentive and, like midwives, likely oppose the idea of centers that can provide C-sections because they could cut into hospital revenue.

“We are trying to reduce the cost of medicine, and this would be more cost-effective and more pleasant for patients,” he said.

Kate Bauer, executive director of the American Association of Birth Centers, said patients could confuse advanced birth centers with the existing, free-standing birth centers for low-risk births that have been run by midwives for decades. There are currently 31 licensed birth centers in Florida and 411 free-standing birth centers in the United States, she said.

“This is a radical departure from the standard of care,” Bauer said. “It’s a bad idea,” she said, because it could increase risks to mom and baby.

No other state allows C-sections outside of hospitals. The only facility that offers similar care is a birth clinic in Wichita, Kansas, which is connected by a short walkway to a hospital, Wesley Medical Center.

The clinic provides “hotel-like” maternity suites where staffers deliver about 100 babies a month, compared with 500 per month in the hospital itself.

Morgan Tracy, a maternity nurse navigator at the center, said the concept works largely because the hospital and birthing suites can share staff and pharmacy access, plus patients can be quickly transferred to the main hospital if complications arise.

“The beauty is there are team members on both sides of the street,” Tracy said.
 

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.