Fifth pregnancy, first baby.

After four pregnancies resulted in losses – and doing things as natural as possible and leaving it up to the birds, bees, and fate – my husband and I decided to explore in vitro fertilization (IVF).

Drugs to direct my follicles to produce more eggs, an egg retrieval procedure, genetic testing of our embryos, a quick procedure to remove a residual uterine septum from my uterus, drugs to thicken my endometrial lining to prepare my body to receive an embryo, an embryo transfer, steroids to suppress my immune system so my body would accept the pregnancy, blood thinner shots to promote blood flow to the baby, and 10 weeks of progesterone in oil shots later and we’re days away from welcoming our first baby into our lives.

In short, there’s more than one way to define “miracle baby.”

Global estimates say 48 million couples and 186 million individuals struggle with infertility. On average, 2 million infants born in the United States each year are conceived through assisted reproductive technology and the demand for treatments like IVF have doubled in the last decade.

Now the need for treatments outweighs clinician availability. “We have about 1,250 practicing fertility physicians in the U.S. to serve the whole country, which is highly inadequate,” said Eduardo Hariton, MD, a reproductive endocrinology physician in San Francisco and managing director of the U.S. Fertility Innovation Fund. “We have people that want to get care waiting 1 to 3 months to be seen.”

Dr. Hariton explains that U.S. IVF clinics are performing around 250,000 to 300,000 IVF cycles per year and need to be doing a million-plus to meet demand. This, plus the cost of fertility treatments – an average IVF cycle runs $23,500 and the majority of patients need multiple cycles to conceive – keeps the barrier to entry high.

Enter technology: New advances are on the way to help the assisted fertility process to run smoother and be less costly. “The field is really coming into an age of great progress and innovation,” added S. Zev Williams, MD, PhD, chief of the division of reproductive endocrinology and Infertility at Columbia University Irving Medical Center, New York City.

I’m personally grateful that such technology exists. Here is a look at some recent game changers in reproductive tech and what the future may hold.
 

AI will help, of course

Fertility treatments involve endless analysis, diagnosis, and recommendations – dozens if not hundreds of decisions from each physician for each patient. Human action and reaction can affect this process, Dr. Hariton explained.

For example, if he hyperstimulated a woman during the follicle growing stage of her egg retrieval and ended up with eggs too large to retrieve, Dr. Hariton said he may subconsciously be more inclined to be extra cautious with his patients the week after, and vice versa.

This is where AI can help. “Rather than me making decisions from a couple of thousands of cycles of experience, I get to leverage hundreds of thousands of cycles from different providers over different people,” said Dr. Hariton. “I get to use all the data from that patient today – her age, her weight, what happened last cycle, how she’s doing – and make a very objective decision about the optimal time to give that woman or that couple the best outcome possible.”

AI can also assist with tasks like embryo grading. “Once our embryos are made in the lab, we usually have an embryologist looking at those embryos, grading them on a three-variable scale, and then picking the nicest one for transfer,” said Dr. Hariton. Machine learning computer vision software can help doctors select the best embryo.

Many of these AI products are in trials in the United States and some AI-based technology is already being used in fertility labs, especially in other countries. “ALife recently launched a suite of products to help with their decisions during stimulation that can help with the quality KPIs [key performance indicators] in the lab,” said Dr. Hariton. “There’s also a company that does AI-based predictions of success to give patients a better estimate called Univfy.” More AI products are still in development or awaiting Food and Drug Administration clearance.
 

Robots lend a hand

Like artificial intelligence, robots can be a big help in the IVF lab. Columbia University Fertility Center recently became the first to use an articulated (ART) robot to handle precise and highly repetitive work.

“IVF, from the initial point, involves creating these special plates where embryos can grow, and you do that by making little droplets,” said Dr. Williams. “It’s very time-consuming to create tons of these little droplets for the embryos to grow.” Thus, the lab created a robot to help squirt drops of the media substance required to sustain embryos in a way that is 10 times more precise than that of a trained embryologist.

“It’s a win-win because you allow the robots to do things better than a human can and this allows the humans to do things that a robot just can’t do,” explained Dr. Williams. He and his team began using this technology in the beginning of November 2022.

Dr. Williams sees ART robots being used in many more parts of the fertility treatment journey along the way, like preparing eggs after they are retrieved and performing intracytoplasmic sperm injection (ICSI), with the robot injecting the sperm into the egg.

Launching with the plate making, said Dr. Williams, is a low stakes entry point for robotic technology in the lab. “It allows us to introduce robotics to automate and optimize each step along the way, but to do so in the safest possible way.”

Dr. Williams estimates that robots will have their hands on actual eggs and sperm in 5 years.
 

Updates in genetic testing

Currently, if a couple wants to have their embryos genetically tested, also known as preimplantation genetic testing, each embryo must be frozen, then a biopsy of that embryo is performed and sent to the lab.

“It takes time to get the results,” said Dr. Williams. “The whole time you’re waiting, you don’t know if you’re going to have any embryos that are transferable or if next month you’re going to have to do another IVF cycle.”

Columbia researchers recently developed a new in-house test that can determine if a fetus or embryo has the right number of chromosomes. This STORK (Short-read Transpore Rapid Karyotyping) can be performed without freezing embryos and sending them out, which Dr. Williams said can save couples money and time, as they won’t necessarily need to do a separate embryo transfer cycle and can transfer an embryo in the same cycle. “You can test in the morning and transfer in the afternoon,” said Dr. Williams.

The test is currently awaiting approval and will first be used to test miscarriage samples to see if embryos were genetically normal or not, which he said should cost around $200 vs. the $2,000 to $4,000 it can cost to have fetal tissue sent to the lab – and insurance doesn’t cover the procedure until after a second or third miscarriage.

This, said Dr. Williams, should be in the field in less than a year, and he estimates that the test will be used for fresh embryos in about a year and a half.
 

Sperm collection made simpler

Typically, a man delivers a sperm sample in a room at an IVF clinic or by collecting a sample at home and rushing it to the clinic before it degrades, which Dr. Williams said can happen in as little as 15 minutes.

In 2020, Dr. Williams and his team began using a custom at-home sperm collection box that houses sperm in a recyclable foam container that holds a sample cup, which is filled with special sperm-supporting media, at an angle that prevents evaporation and maintains temperature and pH. This allows patients to collect samples in the comfort of their homes and increases the clock to 3 hours.

“It’s great for the patients because it’s much more comfortable,” said Dr. Williams, who notes that having to “perform” on site can be stressful for men. Studies the team has conducted have shown sperm collected in this manner have a better success rate than those collected in the lab, and 90% of Columbia’s Fertility Center patients are now providing sperm samples this way.

Similar innovations to deliver sperm, like Protex, are now on the market, while companies like myLabBox and Legacy are offering at-home sperm testing kits to mail in for a full semen analysis.
 

At-home monitoring: More and better

Wearable reproductive health devices are also helping more women get pregnant. “I am very excited about biometric data harnessed in wearables to predict periods, ovulation, and fertility,” said Amander Clark, PhD, director of the UCLA Center for Reproductive Science, Health, and Education, Los Angeles.

The Tempdrop Fertility and Ovulation Tracker, for instance, is a wearable sensor with an accompanying charting app that helps a woman identify her most fertile days to conceive. The Bellabeat Ivy is a women’s health smart bracelet with a strong focus on tracking a woman’s cycle and fertility, pregnancy, and postnatal symptoms. And Mirvie, which is currently in development, is a blood test that will be able to predict pregnancy complications earlier.

Physicians are also looking to move as much of the lab experience as they can into a patient’s home, which streamlines processes while offering privacy and comfort. For example, Dr. Hariton, who runs a strategic venture capital fund for physicians, said his team is currently working with a company that does remote ultrasounds.

And Mira, an at-home hormone monitor, uses patented AI algorithms to accurately measure the levels of major reproductive health hormones (E3G, LH, PdG, FSH) in urine, said Meir Olcha, MD, chief medical officer at Sama Fertility. The product recently completed a clinical trial, which showed it was a viable alternative to blood serum for patients undergoing IVF.
 

Stem cells could make eggs ageless

Research shows that a woman’s egg quality decreases gradually but significantly starting at age 32 and more rapidly after 37. Sperm quality may also decrease with age. A possible workaround: Scientists are actively researching how to create eggs and sperm from stem cells.

“I think getting eggs from stem cells will happen in the future,” said Dr. Hariton, who notes that this type of technology would be a game changer in his clinic. “It will make some of the hardest diagnoses that I have – which is on a daily basis, ‘I’m so sorry, you’re in premature menopause’ or ‘I don’t think we’re going to be successful getting you pregnant with your own eggs; here are some other options like donor eggs’ – much better,” he added. And stem cells are currently being used to research causes of infertility.

Clinics like UCLA have already been making strides. “We are using stem cells to identify new genes required for reproduction and to define the role of these genes in human fertility and infertility,” said Dr. Clark, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, who recently led a study in this arena. “In vitro gametogenesis (IVG), another stem cell technology, is currently used in the research lab to understand causes of infertility.”

These stem cell-based embryo models, she said, can help researchers understand the first few days of embryo development after an embryo implants and be used to provide critical information on causes of early pregnancy loss or birth defects.

A version of this article appeared on Medscape.com.

Fifth pregnancy, first baby.

After four pregnancies resulted in losses – and doing things as natural as possible and leaving it up to the birds, bees, and fate – my husband and I decided to explore in vitro fertilization (IVF).

Drugs to direct my follicles to produce more eggs, an egg retrieval procedure, genetic testing of our embryos, a quick procedure to remove a residual uterine septum from my uterus, drugs to thicken my endometrial lining to prepare my body to receive an embryo, an embryo transfer, steroids to suppress my immune system so my body would accept the pregnancy, blood thinner shots to promote blood flow to the baby, and 10 weeks of progesterone in oil shots later and we’re days away from welcoming our first baby into our lives.

In short, there’s more than one way to define “miracle baby.”

Global estimates say 48 million couples and 186 million individuals struggle with infertility. On average, 2 million infants born in the United States each year are conceived through assisted reproductive technology and the demand for treatments like IVF have doubled in the last decade.

Now the need for treatments outweighs clinician availability. “We have about 1,250 practicing fertility physicians in the U.S. to serve the whole country, which is highly inadequate,” said Eduardo Hariton, MD, a reproductive endocrinology physician in San Francisco and managing director of the U.S. Fertility Innovation Fund. “We have people that want to get care waiting 1 to 3 months to be seen.”

Dr. Hariton explains that U.S. IVF clinics are performing around 250,000 to 300,000 IVF cycles per year and need to be doing a million-plus to meet demand. This, plus the cost of fertility treatments – an average IVF cycle runs $23,500 and the majority of patients need multiple cycles to conceive – keeps the barrier to entry high.

Enter technology: New advances are on the way to help the assisted fertility process to run smoother and be less costly. “The field is really coming into an age of great progress and innovation,” added S. Zev Williams, MD, PhD, chief of the division of reproductive endocrinology and Infertility at Columbia University Irving Medical Center, New York City.

I’m personally grateful that such technology exists. Here is a look at some recent game changers in reproductive tech and what the future may hold.
 

AI will help, of course

Fertility treatments involve endless analysis, diagnosis, and recommendations – dozens if not hundreds of decisions from each physician for each patient. Human action and reaction can affect this process, Dr. Hariton explained.

For example, if he hyperstimulated a woman during the follicle growing stage of her egg retrieval and ended up with eggs too large to retrieve, Dr. Hariton said he may subconsciously be more inclined to be extra cautious with his patients the week after, and vice versa.

This is where AI can help. “Rather than me making decisions from a couple of thousands of cycles of experience, I get to leverage hundreds of thousands of cycles from different providers over different people,” said Dr. Hariton. “I get to use all the data from that patient today – her age, her weight, what happened last cycle, how she’s doing – and make a very objective decision about the optimal time to give that woman or that couple the best outcome possible.”

AI can also assist with tasks like embryo grading. “Once our embryos are made in the lab, we usually have an embryologist looking at those embryos, grading them on a three-variable scale, and then picking the nicest one for transfer,” said Dr. Hariton. Machine learning computer vision software can help doctors select the best embryo.

Many of these AI products are in trials in the United States and some AI-based technology is already being used in fertility labs, especially in other countries. “ALife recently launched a suite of products to help with their decisions during stimulation that can help with the quality KPIs [key performance indicators] in the lab,” said Dr. Hariton. “There’s also a company that does AI-based predictions of success to give patients a better estimate called Univfy.” More AI products are still in development or awaiting Food and Drug Administration clearance.
 

Robots lend a hand

Like artificial intelligence, robots can be a big help in the IVF lab. Columbia University Fertility Center recently became the first to use an articulated (ART) robot to handle precise and highly repetitive work.

“IVF, from the initial point, involves creating these special plates where embryos can grow, and you do that by making little droplets,” said Dr. Williams. “It’s very time-consuming to create tons of these little droplets for the embryos to grow.” Thus, the lab created a robot to help squirt drops of the media substance required to sustain embryos in a way that is 10 times more precise than that of a trained embryologist.

“It’s a win-win because you allow the robots to do things better than a human can and this allows the humans to do things that a robot just can’t do,” explained Dr. Williams. He and his team began using this technology in the beginning of November 2022.

Dr. Williams sees ART robots being used in many more parts of the fertility treatment journey along the way, like preparing eggs after they are retrieved and performing intracytoplasmic sperm injection (ICSI), with the robot injecting the sperm into the egg.

Launching with the plate making, said Dr. Williams, is a low stakes entry point for robotic technology in the lab. “It allows us to introduce robotics to automate and optimize each step along the way, but to do so in the safest possible way.”

Dr. Williams estimates that robots will have their hands on actual eggs and sperm in 5 years.
 

Updates in genetic testing

Currently, if a couple wants to have their embryos genetically tested, also known as preimplantation genetic testing, each embryo must be frozen, then a biopsy of that embryo is performed and sent to the lab.

“It takes time to get the results,” said Dr. Williams. “The whole time you’re waiting, you don’t know if you’re going to have any embryos that are transferable or if next month you’re going to have to do another IVF cycle.”

Columbia researchers recently developed a new in-house test that can determine if a fetus or embryo has the right number of chromosomes. This STORK (Short-read Transpore Rapid Karyotyping) can be performed without freezing embryos and sending them out, which Dr. Williams said can save couples money and time, as they won’t necessarily need to do a separate embryo transfer cycle and can transfer an embryo in the same cycle. “You can test in the morning and transfer in the afternoon,” said Dr. Williams.

The test is currently awaiting approval and will first be used to test miscarriage samples to see if embryos were genetically normal or not, which he said should cost around $200 vs. the $2,000 to $4,000 it can cost to have fetal tissue sent to the lab – and insurance doesn’t cover the procedure until after a second or third miscarriage.

This, said Dr. Williams, should be in the field in less than a year, and he estimates that the test will be used for fresh embryos in about a year and a half.
 

Sperm collection made simpler

Typically, a man delivers a sperm sample in a room at an IVF clinic or by collecting a sample at home and rushing it to the clinic before it degrades, which Dr. Williams said can happen in as little as 15 minutes.

In 2020, Dr. Williams and his team began using a custom at-home sperm collection box that houses sperm in a recyclable foam container that holds a sample cup, which is filled with special sperm-supporting media, at an angle that prevents evaporation and maintains temperature and pH. This allows patients to collect samples in the comfort of their homes and increases the clock to 3 hours.

“It’s great for the patients because it’s much more comfortable,” said Dr. Williams, who notes that having to “perform” on site can be stressful for men. Studies the team has conducted have shown sperm collected in this manner have a better success rate than those collected in the lab, and 90% of Columbia’s Fertility Center patients are now providing sperm samples this way.

Similar innovations to deliver sperm, like Protex, are now on the market, while companies like myLabBox and Legacy are offering at-home sperm testing kits to mail in for a full semen analysis.
 

At-home monitoring: More and better

Wearable reproductive health devices are also helping more women get pregnant. “I am very excited about biometric data harnessed in wearables to predict periods, ovulation, and fertility,” said Amander Clark, PhD, director of the UCLA Center for Reproductive Science, Health, and Education, Los Angeles.

The Tempdrop Fertility and Ovulation Tracker, for instance, is a wearable sensor with an accompanying charting app that helps a woman identify her most fertile days to conceive. The Bellabeat Ivy is a women’s health smart bracelet with a strong focus on tracking a woman’s cycle and fertility, pregnancy, and postnatal symptoms. And Mirvie, which is currently in development, is a blood test that will be able to predict pregnancy complications earlier.

Physicians are also looking to move as much of the lab experience as they can into a patient’s home, which streamlines processes while offering privacy and comfort. For example, Dr. Hariton, who runs a strategic venture capital fund for physicians, said his team is currently working with a company that does remote ultrasounds.

And Mira, an at-home hormone monitor, uses patented AI algorithms to accurately measure the levels of major reproductive health hormones (E3G, LH, PdG, FSH) in urine, said Meir Olcha, MD, chief medical officer at Sama Fertility. The product recently completed a clinical trial, which showed it was a viable alternative to blood serum for patients undergoing IVF.
 

Stem cells could make eggs ageless

Research shows that a woman’s egg quality decreases gradually but significantly starting at age 32 and more rapidly after 37. Sperm quality may also decrease with age. A possible workaround: Scientists are actively researching how to create eggs and sperm from stem cells.

“I think getting eggs from stem cells will happen in the future,” said Dr. Hariton, who notes that this type of technology would be a game changer in his clinic. “It will make some of the hardest diagnoses that I have – which is on a daily basis, ‘I’m so sorry, you’re in premature menopause’ or ‘I don’t think we’re going to be successful getting you pregnant with your own eggs; here are some other options like donor eggs’ – much better,” he added. And stem cells are currently being used to research causes of infertility.

Clinics like UCLA have already been making strides. “We are using stem cells to identify new genes required for reproduction and to define the role of these genes in human fertility and infertility,” said Dr. Clark, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, who recently led a study in this arena. “In vitro gametogenesis (IVG), another stem cell technology, is currently used in the research lab to understand causes of infertility.”

These stem cell-based embryo models, she said, can help researchers understand the first few days of embryo development after an embryo implants and be used to provide critical information on causes of early pregnancy loss or birth defects.

A version of this article appeared on Medscape.com.

Fifth pregnancy, first baby.

After four pregnancies resulted in losses – and doing things as natural as possible and leaving it up to the birds, bees, and fate – my husband and I decided to explore in vitro fertilization (IVF).

Drugs to direct my follicles to produce more eggs, an egg retrieval procedure, genetic testing of our embryos, a quick procedure to remove a residual uterine septum from my uterus, drugs to thicken my endometrial lining to prepare my body to receive an embryo, an embryo transfer, steroids to suppress my immune system so my body would accept the pregnancy, blood thinner shots to promote blood flow to the baby, and 10 weeks of progesterone in oil shots later and we’re days away from welcoming our first baby into our lives.

In short, there’s more than one way to define “miracle baby.”

Global estimates say 48 million couples and 186 million individuals struggle with infertility. On average, 2 million infants born in the United States each year are conceived through assisted reproductive technology and the demand for treatments like IVF have doubled in the last decade.

Now the need for treatments outweighs clinician availability. “We have about 1,250 practicing fertility physicians in the U.S. to serve the whole country, which is highly inadequate,” said Eduardo Hariton, MD, a reproductive endocrinology physician in San Francisco and managing director of the U.S. Fertility Innovation Fund. “We have people that want to get care waiting 1 to 3 months to be seen.”

Dr. Hariton explains that U.S. IVF clinics are performing around 250,000 to 300,000 IVF cycles per year and need to be doing a million-plus to meet demand. This, plus the cost of fertility treatments – an average IVF cycle runs $23,500 and the majority of patients need multiple cycles to conceive – keeps the barrier to entry high.

Enter technology: New advances are on the way to help the assisted fertility process to run smoother and be less costly. “The field is really coming into an age of great progress and innovation,” added S. Zev Williams, MD, PhD, chief of the division of reproductive endocrinology and Infertility at Columbia University Irving Medical Center, New York City.

I’m personally grateful that such technology exists. Here is a look at some recent game changers in reproductive tech and what the future may hold.
 

AI will help, of course

Fertility treatments involve endless analysis, diagnosis, and recommendations – dozens if not hundreds of decisions from each physician for each patient. Human action and reaction can affect this process, Dr. Hariton explained.

For example, if he hyperstimulated a woman during the follicle growing stage of her egg retrieval and ended up with eggs too large to retrieve, Dr. Hariton said he may subconsciously be more inclined to be extra cautious with his patients the week after, and vice versa.

This is where AI can help. “Rather than me making decisions from a couple of thousands of cycles of experience, I get to leverage hundreds of thousands of cycles from different providers over different people,” said Dr. Hariton. “I get to use all the data from that patient today – her age, her weight, what happened last cycle, how she’s doing – and make a very objective decision about the optimal time to give that woman or that couple the best outcome possible.”

AI can also assist with tasks like embryo grading. “Once our embryos are made in the lab, we usually have an embryologist looking at those embryos, grading them on a three-variable scale, and then picking the nicest one for transfer,” said Dr. Hariton. Machine learning computer vision software can help doctors select the best embryo.

Many of these AI products are in trials in the United States and some AI-based technology is already being used in fertility labs, especially in other countries. “ALife recently launched a suite of products to help with their decisions during stimulation that can help with the quality KPIs [key performance indicators] in the lab,” said Dr. Hariton. “There’s also a company that does AI-based predictions of success to give patients a better estimate called Univfy.” More AI products are still in development or awaiting Food and Drug Administration clearance.
 

Robots lend a hand

Like artificial intelligence, robots can be a big help in the IVF lab. Columbia University Fertility Center recently became the first to use an articulated (ART) robot to handle precise and highly repetitive work.

“IVF, from the initial point, involves creating these special plates where embryos can grow, and you do that by making little droplets,” said Dr. Williams. “It’s very time-consuming to create tons of these little droplets for the embryos to grow.” Thus, the lab created a robot to help squirt drops of the media substance required to sustain embryos in a way that is 10 times more precise than that of a trained embryologist.

“It’s a win-win because you allow the robots to do things better than a human can and this allows the humans to do things that a robot just can’t do,” explained Dr. Williams. He and his team began using this technology in the beginning of November 2022.

Dr. Williams sees ART robots being used in many more parts of the fertility treatment journey along the way, like preparing eggs after they are retrieved and performing intracytoplasmic sperm injection (ICSI), with the robot injecting the sperm into the egg.

Launching with the plate making, said Dr. Williams, is a low stakes entry point for robotic technology in the lab. “It allows us to introduce robotics to automate and optimize each step along the way, but to do so in the safest possible way.”

Dr. Williams estimates that robots will have their hands on actual eggs and sperm in 5 years.
 

Updates in genetic testing

Currently, if a couple wants to have their embryos genetically tested, also known as preimplantation genetic testing, each embryo must be frozen, then a biopsy of that embryo is performed and sent to the lab.

“It takes time to get the results,” said Dr. Williams. “The whole time you’re waiting, you don’t know if you’re going to have any embryos that are transferable or if next month you’re going to have to do another IVF cycle.”

Columbia researchers recently developed a new in-house test that can determine if a fetus or embryo has the right number of chromosomes. This STORK (Short-read Transpore Rapid Karyotyping) can be performed without freezing embryos and sending them out, which Dr. Williams said can save couples money and time, as they won’t necessarily need to do a separate embryo transfer cycle and can transfer an embryo in the same cycle. “You can test in the morning and transfer in the afternoon,” said Dr. Williams.

The test is currently awaiting approval and will first be used to test miscarriage samples to see if embryos were genetically normal or not, which he said should cost around $200 vs. the $2,000 to $4,000 it can cost to have fetal tissue sent to the lab – and insurance doesn’t cover the procedure until after a second or third miscarriage.

This, said Dr. Williams, should be in the field in less than a year, and he estimates that the test will be used for fresh embryos in about a year and a half.
 

Sperm collection made simpler

Typically, a man delivers a sperm sample in a room at an IVF clinic or by collecting a sample at home and rushing it to the clinic before it degrades, which Dr. Williams said can happen in as little as 15 minutes.

In 2020, Dr. Williams and his team began using a custom at-home sperm collection box that houses sperm in a recyclable foam container that holds a sample cup, which is filled with special sperm-supporting media, at an angle that prevents evaporation and maintains temperature and pH. This allows patients to collect samples in the comfort of their homes and increases the clock to 3 hours.

“It’s great for the patients because it’s much more comfortable,” said Dr. Williams, who notes that having to “perform” on site can be stressful for men. Studies the team has conducted have shown sperm collected in this manner have a better success rate than those collected in the lab, and 90% of Columbia’s Fertility Center patients are now providing sperm samples this way.

Similar innovations to deliver sperm, like Protex, are now on the market, while companies like myLabBox and Legacy are offering at-home sperm testing kits to mail in for a full semen analysis.
 

At-home monitoring: More and better

Wearable reproductive health devices are also helping more women get pregnant. “I am very excited about biometric data harnessed in wearables to predict periods, ovulation, and fertility,” said Amander Clark, PhD, director of the UCLA Center for Reproductive Science, Health, and Education, Los Angeles.

The Tempdrop Fertility and Ovulation Tracker, for instance, is a wearable sensor with an accompanying charting app that helps a woman identify her most fertile days to conceive. The Bellabeat Ivy is a women’s health smart bracelet with a strong focus on tracking a woman’s cycle and fertility, pregnancy, and postnatal symptoms. And Mirvie, which is currently in development, is a blood test that will be able to predict pregnancy complications earlier.

Physicians are also looking to move as much of the lab experience as they can into a patient’s home, which streamlines processes while offering privacy and comfort. For example, Dr. Hariton, who runs a strategic venture capital fund for physicians, said his team is currently working with a company that does remote ultrasounds.

And Mira, an at-home hormone monitor, uses patented AI algorithms to accurately measure the levels of major reproductive health hormones (E3G, LH, PdG, FSH) in urine, said Meir Olcha, MD, chief medical officer at Sama Fertility. The product recently completed a clinical trial, which showed it was a viable alternative to blood serum for patients undergoing IVF.
 

Stem cells could make eggs ageless

Research shows that a woman’s egg quality decreases gradually but significantly starting at age 32 and more rapidly after 37. Sperm quality may also decrease with age. A possible workaround: Scientists are actively researching how to create eggs and sperm from stem cells.

“I think getting eggs from stem cells will happen in the future,” said Dr. Hariton, who notes that this type of technology would be a game changer in his clinic. “It will make some of the hardest diagnoses that I have – which is on a daily basis, ‘I’m so sorry, you’re in premature menopause’ or ‘I don’t think we’re going to be successful getting you pregnant with your own eggs; here are some other options like donor eggs’ – much better,” he added. And stem cells are currently being used to research causes of infertility.

Clinics like UCLA have already been making strides. “We are using stem cells to identify new genes required for reproduction and to define the role of these genes in human fertility and infertility,” said Dr. Clark, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, who recently led a study in this arena. “In vitro gametogenesis (IVG), another stem cell technology, is currently used in the research lab to understand causes of infertility.”

These stem cell-based embryo models, she said, can help researchers understand the first few days of embryo development after an embryo implants and be used to provide critical information on causes of early pregnancy loss or birth defects.

A version of this article appeared on Medscape.com.

Up to one in four patients who undergo metabolic/bariatric surgery have less than 20% weight loss and patients need additional strategies to help them reach their goals.

In the new BARI-OPTIMISE trial, patients with poor weight loss after such surgery were randomized to the glucagonlike peptide–1 (GLP-1) agonist liraglutide 3.0 mg/day or placebo. Liraglutide was safe and well-tolerated and led to a clinically meaningful 8% further reduction in bodyweight, compared with placebo, report Jessica Mok, BMBS, MPhil, University College London and colleagues, in their study published online in JAMA Surgery.

Weight loss in BARI-OPTIMISE (–9.2 kg or –20 lb) was greater than the weight loss in the earlier GRAVITAS trial of 80 patients with persistent or recurrent type 2 diabetes randomized to liraglutide 1.8 mg/day or placebo, Dr. Mok and colleagues note. And more patients in BARI-OPTIMISE than in GRAVITAS lost 5% or more of their baseline weight (72% vs. 46%).

“Our findings therefore suggest that liraglutide, 3.0 mg, may have a role in the treatment of people with poor weight loss following metabolic surgery,” they write.  

However, newer gut hormone–based therapies with greater efficacy than liraglutide 3.0 mg (for example, semaglutide and tirzepatide) are emerging, they add.

Therefore, “randomized clinical trials investigating the efficacy of novel pharmaceutical agents will be needed to generate the evidence required to deliver individualized precision-medicine approaches to patients with obesity and suboptimal weight loss following metabolic surgery,” the researchers urge.
 

‘Extremely welcome tools for severe obesity’

“The additional weight loss with associated favorable metabolic changes achieved with liraglutide reported in [the BARI-OPTIMISE and GRAVITAS trials] is extremely welcomed with the new antiobesity medications ... adding another effective tool in the toolbox for the treatment of severe obesity,” Paulina Salminen, MD, PhD, Turku (Finland) University Hospital, and Ali Aminian, MD, Cleveland Clinic, write in an accompanying editorial.

However, they also point to limitations of the current trial.

Almost all patients (65 of 70 [93%]) underwent laparoscopic sleeve gastrectomy in BARI-OPTIMISE. However, “there are safe and more effective surgical options that can be considered in patients with suboptimal initial clinical response or recurrent weight gain” after laparoscopic sleeve gastrectomy, such as “conversion to Roux-en-Y gastric bypass (RYGB), duodenal switch, or single-anastomosis duodeno-ileal bypass,” they note.

The small number of patients and low follow-up rate of 81% (57 of 70 patients) for the short intervention are other limitations.

“In treating a patient with ischemic heart disease, a combination of lifestyle intervention, risk factor modification, pharmacotherapy, coronary stenting, and open-heart surgery may be needed,” note the editorialists. “A very similar concept would be applicable in the management of severe obesity.”

In the past, they add, there was not much progress with combination therapies for obesity because of a lack of effective antiobesity medications.

However, “with the better availability of potent [antiobesity medications] now and in the near future, the practice of combination therapy will grow as [metabolic and bariatric surgery] and [antiobesity medications] work in synergy in both treating severe obesity and hopefully also in enabling increased access to effective obesity treatment,” Dr. Salminen and Dr. Aminian speculate.

“Hopefully, based on findings of future studies and the use of global uniform criteria for evaluating treatment outcomes,” the editorialists conclude, “we can develop practice guidelines to assist and optimize phenotype-tailored multimodal treatment of this heterogeneous chronic disease of severe obesity.”
 

Most patients had severe obesity, sleeve gastrectomy

Individuals with poor weight loss after surgery have increased appetite coupled with an unfavorable gut hormone profile, including lower circulating GLP-1 levels, Dr. Mok and colleagues note.

In 2018 and 2019, they recruited and randomized 70 adults who had had metabolic surgery at two hospitals in London at least a year earlier and had 20% or less weight loss, compared with the day of surgery, as well as a suboptimal nutrient-stimulated GLP-1 response.

Patients were excluded if they had type 1 diabetes or were taking a GLP-1 agonist, insulin, or other medications that can affect weight, among other criteria.

The mean age of patients was 48 years, and 74% were women; 13% had type 2 diabetes.

Participants had a mean weight of 120 kg, and a mean body mass index of 43 kg/m² (57% had a BMI ≥ 40 kg/m²). Almost all patients (93%) had had sleeve gastrectomy and 7% had RYGB.

On average, they had surgery 4.3 years earlier and had lost 7% of their initial weight.

Patients were randomized 1:1 to receive liraglutide 3.0 mg or placebo daily for 24 weeks. All patients received dietary counseling and aimed for a 500 kcal/day energy deficit. They were encouraged to do a minimum of 150 minutes of moderate to vigorous exercise each week.

The primary endpoint, percentage change in body weight from baseline to week 24, was –8.8% with liraglutide versus –0.53% with placebo.

Adverse effects were predominantly gastrointestinal in nature and were more frequent with liraglutide (80%) than placebo (57%). There were no serious adverse events.

This study was funded by the Sir Jules Thorn Charitable Trust and the National Institute for Health and Care Research. Novo Nordisk provided the liraglutide and placebo pens. Author disclosures are listed with the article. Dr. Salminen has reported receiving personal fees from Novo Nordisk. Dr. Aminian has reported receiving received grants and personal fees from Medtronic and Ethicon.

A version of this article appeared on Medscape.com.

Up to one in four patients who undergo metabolic/bariatric surgery have less than 20% weight loss and patients need additional strategies to help them reach their goals.

In the new BARI-OPTIMISE trial, patients with poor weight loss after such surgery were randomized to the glucagonlike peptide–1 (GLP-1) agonist liraglutide 3.0 mg/day or placebo. Liraglutide was safe and well-tolerated and led to a clinically meaningful 8% further reduction in bodyweight, compared with placebo, report Jessica Mok, BMBS, MPhil, University College London and colleagues, in their study published online in JAMA Surgery.

Weight loss in BARI-OPTIMISE (–9.2 kg or –20 lb) was greater than the weight loss in the earlier GRAVITAS trial of 80 patients with persistent or recurrent type 2 diabetes randomized to liraglutide 1.8 mg/day or placebo, Dr. Mok and colleagues note. And more patients in BARI-OPTIMISE than in GRAVITAS lost 5% or more of their baseline weight (72% vs. 46%).

“Our findings therefore suggest that liraglutide, 3.0 mg, may have a role in the treatment of people with poor weight loss following metabolic surgery,” they write.  

However, newer gut hormone–based therapies with greater efficacy than liraglutide 3.0 mg (for example, semaglutide and tirzepatide) are emerging, they add.

Therefore, “randomized clinical trials investigating the efficacy of novel pharmaceutical agents will be needed to generate the evidence required to deliver individualized precision-medicine approaches to patients with obesity and suboptimal weight loss following metabolic surgery,” the researchers urge.
 

‘Extremely welcome tools for severe obesity’

“The additional weight loss with associated favorable metabolic changes achieved with liraglutide reported in [the BARI-OPTIMISE and GRAVITAS trials] is extremely welcomed with the new antiobesity medications ... adding another effective tool in the toolbox for the treatment of severe obesity,” Paulina Salminen, MD, PhD, Turku (Finland) University Hospital, and Ali Aminian, MD, Cleveland Clinic, write in an accompanying editorial.

However, they also point to limitations of the current trial.

Almost all patients (65 of 70 [93%]) underwent laparoscopic sleeve gastrectomy in BARI-OPTIMISE. However, “there are safe and more effective surgical options that can be considered in patients with suboptimal initial clinical response or recurrent weight gain” after laparoscopic sleeve gastrectomy, such as “conversion to Roux-en-Y gastric bypass (RYGB), duodenal switch, or single-anastomosis duodeno-ileal bypass,” they note.

The small number of patients and low follow-up rate of 81% (57 of 70 patients) for the short intervention are other limitations.

“In treating a patient with ischemic heart disease, a combination of lifestyle intervention, risk factor modification, pharmacotherapy, coronary stenting, and open-heart surgery may be needed,” note the editorialists. “A very similar concept would be applicable in the management of severe obesity.”

In the past, they add, there was not much progress with combination therapies for obesity because of a lack of effective antiobesity medications.

However, “with the better availability of potent [antiobesity medications] now and in the near future, the practice of combination therapy will grow as [metabolic and bariatric surgery] and [antiobesity medications] work in synergy in both treating severe obesity and hopefully also in enabling increased access to effective obesity treatment,” Dr. Salminen and Dr. Aminian speculate.

“Hopefully, based on findings of future studies and the use of global uniform criteria for evaluating treatment outcomes,” the editorialists conclude, “we can develop practice guidelines to assist and optimize phenotype-tailored multimodal treatment of this heterogeneous chronic disease of severe obesity.”
 

Most patients had severe obesity, sleeve gastrectomy

Individuals with poor weight loss after surgery have increased appetite coupled with an unfavorable gut hormone profile, including lower circulating GLP-1 levels, Dr. Mok and colleagues note.

In 2018 and 2019, they recruited and randomized 70 adults who had had metabolic surgery at two hospitals in London at least a year earlier and had 20% or less weight loss, compared with the day of surgery, as well as a suboptimal nutrient-stimulated GLP-1 response.

Patients were excluded if they had type 1 diabetes or were taking a GLP-1 agonist, insulin, or other medications that can affect weight, among other criteria.

The mean age of patients was 48 years, and 74% were women; 13% had type 2 diabetes.

Participants had a mean weight of 120 kg, and a mean body mass index of 43 kg/m² (57% had a BMI ≥ 40 kg/m²). Almost all patients (93%) had had sleeve gastrectomy and 7% had RYGB.

On average, they had surgery 4.3 years earlier and had lost 7% of their initial weight.

Patients were randomized 1:1 to receive liraglutide 3.0 mg or placebo daily for 24 weeks. All patients received dietary counseling and aimed for a 500 kcal/day energy deficit. They were encouraged to do a minimum of 150 minutes of moderate to vigorous exercise each week.

The primary endpoint, percentage change in body weight from baseline to week 24, was –8.8% with liraglutide versus –0.53% with placebo.

Adverse effects were predominantly gastrointestinal in nature and were more frequent with liraglutide (80%) than placebo (57%). There were no serious adverse events.

This study was funded by the Sir Jules Thorn Charitable Trust and the National Institute for Health and Care Research. Novo Nordisk provided the liraglutide and placebo pens. Author disclosures are listed with the article. Dr. Salminen has reported receiving personal fees from Novo Nordisk. Dr. Aminian has reported receiving received grants and personal fees from Medtronic and Ethicon.

A version of this article appeared on Medscape.com.

Up to one in four patients who undergo metabolic/bariatric surgery have less than 20% weight loss and patients need additional strategies to help them reach their goals.

In the new BARI-OPTIMISE trial, patients with poor weight loss after such surgery were randomized to the glucagonlike peptide–1 (GLP-1) agonist liraglutide 3.0 mg/day or placebo. Liraglutide was safe and well-tolerated and led to a clinically meaningful 8% further reduction in bodyweight, compared with placebo, report Jessica Mok, BMBS, MPhil, University College London and colleagues, in their study published online in JAMA Surgery.

Weight loss in BARI-OPTIMISE (–9.2 kg or –20 lb) was greater than the weight loss in the earlier GRAVITAS trial of 80 patients with persistent or recurrent type 2 diabetes randomized to liraglutide 1.8 mg/day or placebo, Dr. Mok and colleagues note. And more patients in BARI-OPTIMISE than in GRAVITAS lost 5% or more of their baseline weight (72% vs. 46%).

“Our findings therefore suggest that liraglutide, 3.0 mg, may have a role in the treatment of people with poor weight loss following metabolic surgery,” they write.  

However, newer gut hormone–based therapies with greater efficacy than liraglutide 3.0 mg (for example, semaglutide and tirzepatide) are emerging, they add.

Therefore, “randomized clinical trials investigating the efficacy of novel pharmaceutical agents will be needed to generate the evidence required to deliver individualized precision-medicine approaches to patients with obesity and suboptimal weight loss following metabolic surgery,” the researchers urge.
 

‘Extremely welcome tools for severe obesity’

“The additional weight loss with associated favorable metabolic changes achieved with liraglutide reported in [the BARI-OPTIMISE and GRAVITAS trials] is extremely welcomed with the new antiobesity medications ... adding another effective tool in the toolbox for the treatment of severe obesity,” Paulina Salminen, MD, PhD, Turku (Finland) University Hospital, and Ali Aminian, MD, Cleveland Clinic, write in an accompanying editorial.

However, they also point to limitations of the current trial.

Almost all patients (65 of 70 [93%]) underwent laparoscopic sleeve gastrectomy in BARI-OPTIMISE. However, “there are safe and more effective surgical options that can be considered in patients with suboptimal initial clinical response or recurrent weight gain” after laparoscopic sleeve gastrectomy, such as “conversion to Roux-en-Y gastric bypass (RYGB), duodenal switch, or single-anastomosis duodeno-ileal bypass,” they note.

The small number of patients and low follow-up rate of 81% (57 of 70 patients) for the short intervention are other limitations.

“In treating a patient with ischemic heart disease, a combination of lifestyle intervention, risk factor modification, pharmacotherapy, coronary stenting, and open-heart surgery may be needed,” note the editorialists. “A very similar concept would be applicable in the management of severe obesity.”

In the past, they add, there was not much progress with combination therapies for obesity because of a lack of effective antiobesity medications.

However, “with the better availability of potent [antiobesity medications] now and in the near future, the practice of combination therapy will grow as [metabolic and bariatric surgery] and [antiobesity medications] work in synergy in both treating severe obesity and hopefully also in enabling increased access to effective obesity treatment,” Dr. Salminen and Dr. Aminian speculate.

“Hopefully, based on findings of future studies and the use of global uniform criteria for evaluating treatment outcomes,” the editorialists conclude, “we can develop practice guidelines to assist and optimize phenotype-tailored multimodal treatment of this heterogeneous chronic disease of severe obesity.”
 

Most patients had severe obesity, sleeve gastrectomy

Individuals with poor weight loss after surgery have increased appetite coupled with an unfavorable gut hormone profile, including lower circulating GLP-1 levels, Dr. Mok and colleagues note.

In 2018 and 2019, they recruited and randomized 70 adults who had had metabolic surgery at two hospitals in London at least a year earlier and had 20% or less weight loss, compared with the day of surgery, as well as a suboptimal nutrient-stimulated GLP-1 response.

Patients were excluded if they had type 1 diabetes or were taking a GLP-1 agonist, insulin, or other medications that can affect weight, among other criteria.

The mean age of patients was 48 years, and 74% were women; 13% had type 2 diabetes.

Participants had a mean weight of 120 kg, and a mean body mass index of 43 kg/m² (57% had a BMI ≥ 40 kg/m²). Almost all patients (93%) had had sleeve gastrectomy and 7% had RYGB.

On average, they had surgery 4.3 years earlier and had lost 7% of their initial weight.

Patients were randomized 1:1 to receive liraglutide 3.0 mg or placebo daily for 24 weeks. All patients received dietary counseling and aimed for a 500 kcal/day energy deficit. They were encouraged to do a minimum of 150 minutes of moderate to vigorous exercise each week.

The primary endpoint, percentage change in body weight from baseline to week 24, was –8.8% with liraglutide versus –0.53% with placebo.

Adverse effects were predominantly gastrointestinal in nature and were more frequent with liraglutide (80%) than placebo (57%). There were no serious adverse events.

This study was funded by the Sir Jules Thorn Charitable Trust and the National Institute for Health and Care Research. Novo Nordisk provided the liraglutide and placebo pens. Author disclosures are listed with the article. Dr. Salminen has reported receiving personal fees from Novo Nordisk. Dr. Aminian has reported receiving received grants and personal fees from Medtronic and Ethicon.

A version of this article appeared on Medscape.com.

Despite my best efforts to cultivate acquaintances across a broader age group, my social circle still has the somewhat musty odor of septuagenarians. We try to talk about things beyond the weather and grandchildren but pain scenarios surface with unfortunate frequency. Arthritic joints ache, body parts wear out or become diseased and have to be removed or replaced. That stuff can hurt.

There are two pain-related themes that seem to crop up more frequently than you might expect. The first is the unfortunate side effects of opioid medication – most often gastric distress and vomiting, then of course there’s constipation. They seem so common that a good many of my acquaintances just plain refuse to take opioids when they have been prescribed postoperatively because of their vivid memories of the consequences or horror stories friends have told.

The second theme is the general annoyance with the damn “Please rate your pain from one to ten” request issued by every well-intentioned nurse. Do you mean the pain I am having right now, this second, or last night, or the average over the last day and a half? Or should I be comparing it with when I gave birth 70 years ago, or when I stubbed my toe getting out of the shower last week? And then what are you going to do with my guesstimated number?

It may surprise some of you that 40 years ago there wasn’t a pain scale fetish. But a few observant health care professionals realized that many of our patients were suffering because we weren’t adequately managing their pain. In postoperative situations this was slowing recovery and effecting outcomes. Like good pseudoscientists, they realized that we should first quantify the pain and the notion that no pain should go unrated came into being. Nor should pain go untreated, which is too frequently interpreted as meaning unmedicated.

Pain is a complex, multifaceted phenomenon. Distilling a person’s pain experience to a single number doesn’t make sense, nor does reflexly reaching for a prescription.

For example a systematic review of 61 studies of juvenile idiopathic arthritis (JIA) published in the journal Pediatric Rheumatology found that there was positive relationship between pain and a child’s belief that pain causes harm, disability, and lack of control. Not surprisingly, stress was also associated with pain intensity.

It is a long paper and touches on numerous other associations of varying degrees of strength between parental, social, and other external factors. But, in general, they were not as consistent as those related to a child’s beliefs.

Before, or at least at the same time, we treat a patient’s pain, we should learn more about that patient – his or her concerns, beliefs, and stressors. You and I may have exactly the same hernia operation, but if you have a better understanding of why you are going to feel uncomfortable after the surgery, and understand that not every pain is the result of a complication, I suspect you are more likely to complain of less pain.

The recent JIA study doesn’t claim to suggest therapeutic methods. However, one wonders what the result would be if we could somehow alter a patient’s belief system so that he or she no longer sees pain as always harmful, nor does the patient see himself or herself as powerless to do anything about the pain. To do this experiment we must follow up our robotic request to “rate your pain” with a dialogue in which we learn more about the patient. Which means probing believes, fears, and stressors.

You can tell me this exercise would be unrealistic and time consuming. But I bet in the long run it will save time. Even if it doesn’t it is the better way to manage pain.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Despite my best efforts to cultivate acquaintances across a broader age group, my social circle still has the somewhat musty odor of septuagenarians. We try to talk about things beyond the weather and grandchildren but pain scenarios surface with unfortunate frequency. Arthritic joints ache, body parts wear out or become diseased and have to be removed or replaced. That stuff can hurt.

There are two pain-related themes that seem to crop up more frequently than you might expect. The first is the unfortunate side effects of opioid medication – most often gastric distress and vomiting, then of course there’s constipation. They seem so common that a good many of my acquaintances just plain refuse to take opioids when they have been prescribed postoperatively because of their vivid memories of the consequences or horror stories friends have told.

The second theme is the general annoyance with the damn “Please rate your pain from one to ten” request issued by every well-intentioned nurse. Do you mean the pain I am having right now, this second, or last night, or the average over the last day and a half? Or should I be comparing it with when I gave birth 70 years ago, or when I stubbed my toe getting out of the shower last week? And then what are you going to do with my guesstimated number?

It may surprise some of you that 40 years ago there wasn’t a pain scale fetish. But a few observant health care professionals realized that many of our patients were suffering because we weren’t adequately managing their pain. In postoperative situations this was slowing recovery and effecting outcomes. Like good pseudoscientists, they realized that we should first quantify the pain and the notion that no pain should go unrated came into being. Nor should pain go untreated, which is too frequently interpreted as meaning unmedicated.

Pain is a complex, multifaceted phenomenon. Distilling a person’s pain experience to a single number doesn’t make sense, nor does reflexly reaching for a prescription.

For example a systematic review of 61 studies of juvenile idiopathic arthritis (JIA) published in the journal Pediatric Rheumatology found that there was positive relationship between pain and a child’s belief that pain causes harm, disability, and lack of control. Not surprisingly, stress was also associated with pain intensity.

It is a long paper and touches on numerous other associations of varying degrees of strength between parental, social, and other external factors. But, in general, they were not as consistent as those related to a child’s beliefs.

Before, or at least at the same time, we treat a patient’s pain, we should learn more about that patient – his or her concerns, beliefs, and stressors. You and I may have exactly the same hernia operation, but if you have a better understanding of why you are going to feel uncomfortable after the surgery, and understand that not every pain is the result of a complication, I suspect you are more likely to complain of less pain.

The recent JIA study doesn’t claim to suggest therapeutic methods. However, one wonders what the result would be if we could somehow alter a patient’s belief system so that he or she no longer sees pain as always harmful, nor does the patient see himself or herself as powerless to do anything about the pain. To do this experiment we must follow up our robotic request to “rate your pain” with a dialogue in which we learn more about the patient. Which means probing believes, fears, and stressors.

You can tell me this exercise would be unrealistic and time consuming. But I bet in the long run it will save time. Even if it doesn’t it is the better way to manage pain.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Despite my best efforts to cultivate acquaintances across a broader age group, my social circle still has the somewhat musty odor of septuagenarians. We try to talk about things beyond the weather and grandchildren but pain scenarios surface with unfortunate frequency. Arthritic joints ache, body parts wear out or become diseased and have to be removed or replaced. That stuff can hurt.

There are two pain-related themes that seem to crop up more frequently than you might expect. The first is the unfortunate side effects of opioid medication – most often gastric distress and vomiting, then of course there’s constipation. They seem so common that a good many of my acquaintances just plain refuse to take opioids when they have been prescribed postoperatively because of their vivid memories of the consequences or horror stories friends have told.

The second theme is the general annoyance with the damn “Please rate your pain from one to ten” request issued by every well-intentioned nurse. Do you mean the pain I am having right now, this second, or last night, or the average over the last day and a half? Or should I be comparing it with when I gave birth 70 years ago, or when I stubbed my toe getting out of the shower last week? And then what are you going to do with my guesstimated number?

It may surprise some of you that 40 years ago there wasn’t a pain scale fetish. But a few observant health care professionals realized that many of our patients were suffering because we weren’t adequately managing their pain. In postoperative situations this was slowing recovery and effecting outcomes. Like good pseudoscientists, they realized that we should first quantify the pain and the notion that no pain should go unrated came into being. Nor should pain go untreated, which is too frequently interpreted as meaning unmedicated.

Pain is a complex, multifaceted phenomenon. Distilling a person’s pain experience to a single number doesn’t make sense, nor does reflexly reaching for a prescription.

For example a systematic review of 61 studies of juvenile idiopathic arthritis (JIA) published in the journal Pediatric Rheumatology found that there was positive relationship between pain and a child’s belief that pain causes harm, disability, and lack of control. Not surprisingly, stress was also associated with pain intensity.

It is a long paper and touches on numerous other associations of varying degrees of strength between parental, social, and other external factors. But, in general, they were not as consistent as those related to a child’s beliefs.

Before, or at least at the same time, we treat a patient’s pain, we should learn more about that patient – his or her concerns, beliefs, and stressors. You and I may have exactly the same hernia operation, but if you have a better understanding of why you are going to feel uncomfortable after the surgery, and understand that not every pain is the result of a complication, I suspect you are more likely to complain of less pain.

The recent JIA study doesn’t claim to suggest therapeutic methods. However, one wonders what the result would be if we could somehow alter a patient’s belief system so that he or she no longer sees pain as always harmful, nor does the patient see himself or herself as powerless to do anything about the pain. To do this experiment we must follow up our robotic request to “rate your pain” with a dialogue in which we learn more about the patient. Which means probing believes, fears, and stressors.

You can tell me this exercise would be unrealistic and time consuming. But I bet in the long run it will save time. Even if it doesn’t it is the better way to manage pain.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Daily use of low-dose aspirin offers no significant protection against stroke and was linked to a higher rate of bleeding in the brain, according to new research published in JAMA.

The research matches other evidence advising that healthy older adults without a history of heart conditions or warning signs of stroke should not take low-dose aspirin. 

The findings also support the recommendation from the U.S. Preventive Services Task Force that low-dose aspirin should not be prescribed for preventing a first heart attack or stroke in healthy older adults, The New York Times reported.

“We can be very emphatic that healthy people who are not on aspirin and do not have multiple risk factors should not be starting it now,” said Randall Stafford, MD, of Stanford (Calif.) University, who was not involved in the study, in the Times.

It’s not as clear for others, he said.

“The longer you’ve been on aspirin and the more risk factors you have for heart attacks and strokes, the murkier it gets,” he said.

Some cardiac and stroke experts say daily aspirin should remain part of the regimen for people who have had a heart attack or stroke.

The JAMA report was based on data from a randomized control trial of 19,000 people from Australia and America. Participants were over the age of 70 and did not have heart disease. 

The data covered an average of almost 4.7 years and revealed that aspirin lowered the rate of ischemic stroke but not significantly. An ischemic stroke happens when a clot forms in a blood vessel that sends blood to the brain. 

There was also a 38% higher rate of brain bleeds for people who took aspirin daily, compared with those who took a placebo.

The Times wrote, “In the past, some doctors regarded aspirin as something of a wonder drug, capable of protecting healthy patients against a future heart attack or stroke. But recent studies have shown that the powerful drug has limited protective power among people who have not yet had such an event, and it comes with dangerous side effects.”

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

Daily use of low-dose aspirin offers no significant protection against stroke and was linked to a higher rate of bleeding in the brain, according to new research published in JAMA.

The research matches other evidence advising that healthy older adults without a history of heart conditions or warning signs of stroke should not take low-dose aspirin. 

The findings also support the recommendation from the U.S. Preventive Services Task Force that low-dose aspirin should not be prescribed for preventing a first heart attack or stroke in healthy older adults, The New York Times reported.

“We can be very emphatic that healthy people who are not on aspirin and do not have multiple risk factors should not be starting it now,” said Randall Stafford, MD, of Stanford (Calif.) University, who was not involved in the study, in the Times.

It’s not as clear for others, he said.

“The longer you’ve been on aspirin and the more risk factors you have for heart attacks and strokes, the murkier it gets,” he said.

Some cardiac and stroke experts say daily aspirin should remain part of the regimen for people who have had a heart attack or stroke.

The JAMA report was based on data from a randomized control trial of 19,000 people from Australia and America. Participants were over the age of 70 and did not have heart disease. 

The data covered an average of almost 4.7 years and revealed that aspirin lowered the rate of ischemic stroke but not significantly. An ischemic stroke happens when a clot forms in a blood vessel that sends blood to the brain. 

There was also a 38% higher rate of brain bleeds for people who took aspirin daily, compared with those who took a placebo.

The Times wrote, “In the past, some doctors regarded aspirin as something of a wonder drug, capable of protecting healthy patients against a future heart attack or stroke. But recent studies have shown that the powerful drug has limited protective power among people who have not yet had such an event, and it comes with dangerous side effects.”

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

Daily use of low-dose aspirin offers no significant protection against stroke and was linked to a higher rate of bleeding in the brain, according to new research published in JAMA.

The research matches other evidence advising that healthy older adults without a history of heart conditions or warning signs of stroke should not take low-dose aspirin. 

The findings also support the recommendation from the U.S. Preventive Services Task Force that low-dose aspirin should not be prescribed for preventing a first heart attack or stroke in healthy older adults, The New York Times reported.

“We can be very emphatic that healthy people who are not on aspirin and do not have multiple risk factors should not be starting it now,” said Randall Stafford, MD, of Stanford (Calif.) University, who was not involved in the study, in the Times.

It’s not as clear for others, he said.

“The longer you’ve been on aspirin and the more risk factors you have for heart attacks and strokes, the murkier it gets,” he said.

Some cardiac and stroke experts say daily aspirin should remain part of the regimen for people who have had a heart attack or stroke.

The JAMA report was based on data from a randomized control trial of 19,000 people from Australia and America. Participants were over the age of 70 and did not have heart disease. 

The data covered an average of almost 4.7 years and revealed that aspirin lowered the rate of ischemic stroke but not significantly. An ischemic stroke happens when a clot forms in a blood vessel that sends blood to the brain. 

There was also a 38% higher rate of brain bleeds for people who took aspirin daily, compared with those who took a placebo.

The Times wrote, “In the past, some doctors regarded aspirin as something of a wonder drug, capable of protecting healthy patients against a future heart attack or stroke. But recent studies have shown that the powerful drug has limited protective power among people who have not yet had such an event, and it comes with dangerous side effects.”

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

If you’ve ever felt an urge to scratch after witnessing someone else relieve their own itch, you’re certainly not alone. Itching can be contagious and the phenomenon is so common it doesn’t just affect humans. Now researchers may understand why.

Some background: In a 2007 study led by Zhou-Feng Chen, PhD, professor of anesthesiology, psychiatry, and developmental biology at the Washington University in St. Louis, researchers discovered a specific gene, the GRPR (gastrin-releasing peptide receptor), in the spinal cord and a corresponding neuropeptide, GRP (gastrin-releasing peptide). Together, the GRP system was found to transmit the “itch information” from one’s skin to the spinal cord.

This discovery was further backed by 2017 findings when Dr. Chen and his colleagues closely observed the molecular and neural basis of contagious itch behavior in mice. “We played a video that showed a mouse scratching at a very high frequency to other mice,” said Dr. Chen. “We found that, indeed, the mice who watched the video also scratched.”

To determine the inner workings at play, the researchers used molecular mapping to reveal increased neuronal activity in the suprachiasmatic nucleus (SCN), a bilateral structure found in the hypothalamus of the mouse’s brain. In other words, this part of the mouse’s brain “lit up” when a mouse displayed contagious scratching behavior.

The researchers then decided to take this one step further by manipulating the amount of GRP in the hypothalamus. “When we deleted the GRP in the SCN, the mice stopped imitating the scratch,” Dr. Chen said. “When we injected more GRP into the SCN, the mice started scratching like crazy.”

Now, after more investigating and research published in 2022 in Cell Reports, Dr. Chen and his team suspect contagious itching may have just as much to do with our eyeballs as our skin and spinal cord. Why? The phenomenon begins with a visual component: Someone seeing another person scratching.

The researchers targeted mice’s retinal ganglion cells, a type of light-capturing neuron found near the inner surface of the retina. When those cells were disabled, all scratching stopped.

This recent study argues that a previously undiscovered visual pathway may exist between the retina and the brain – bypassing the visual cortex – to provide more immediate physical reactions to potential adverse situations.

There’s more (and it could be quite relatable to some people): After the mice watched a video of another mouse scratching for half an hour, the researchers measured the mice’s stress hormone levels, finding a significant increase. This suggested that exposure to impulsive, contagious scratching behavior may have caused heightened anxiety in the mice.

“This is an important discovery that helps answer the psychological question of why animals and people scratch all the time,” said Dr. Chen. “We humans also scratch a lot, sometimes as a way to unconsciously express our internal anxiety.”

The mice may have interpreted the scratching video as a sudden negative change to their environment that they had to prepare for. “Contagious behavior is actually a very efficient way to inform other animals of what’s coming,” Dr. Chen said. “When we see other people running in a panic, there is no time to think. You just run as fast as you can. This is another example of contagious behavior that is in your own interest to survive.”

As a result, Dr. Chen believes it’s fair to infer that contagious behavior, including yawning and emotional contagion, is merely an expression of a fundamental survival mechanism that has evolved over time. “The human being is just an imitation machine. It’s often very difficult for people to act independently or as a minority because you would be working against evolution,” said Dr. Chen.

Scott Ira Krakower, DO, a child and adolescent psychiatrist at Northwell Health in Glen Oaks, N.Y., (and not party to this research), seconds this sentiment. “In regard to the physical benefits of contagion, it acts as a permanent defense and helps build collective immunity,” he said. “The social benefits when it comes to empathy or social media contagion are also important to our development. It helps us understand, adapt, and connect with others.”

Observing how empathy operates as a socially contagious behavior is something Dr. Chen and his colleagues are interested in looking into in the future.

“The definition of empathy is the sharing of emotions,” Dr. Chen said. “Shared feelings are crucial for social bonding and mental health, and for other animals, like mice, this is also the case.” Previous studies have shown that mice do, in fact, experience empathy and share feelings of pain and fear with one another.

There is still much to be explored in the study of contagious behaviors and the components of the brain that are activated during such behavior. Dr. Chen and his team intend to, ahem, scratch that particular itch.

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

If you’ve ever felt an urge to scratch after witnessing someone else relieve their own itch, you’re certainly not alone. Itching can be contagious and the phenomenon is so common it doesn’t just affect humans. Now researchers may understand why.

Some background: In a 2007 study led by Zhou-Feng Chen, PhD, professor of anesthesiology, psychiatry, and developmental biology at the Washington University in St. Louis, researchers discovered a specific gene, the GRPR (gastrin-releasing peptide receptor), in the spinal cord and a corresponding neuropeptide, GRP (gastrin-releasing peptide). Together, the GRP system was found to transmit the “itch information” from one’s skin to the spinal cord.

This discovery was further backed by 2017 findings when Dr. Chen and his colleagues closely observed the molecular and neural basis of contagious itch behavior in mice. “We played a video that showed a mouse scratching at a very high frequency to other mice,” said Dr. Chen. “We found that, indeed, the mice who watched the video also scratched.”

To determine the inner workings at play, the researchers used molecular mapping to reveal increased neuronal activity in the suprachiasmatic nucleus (SCN), a bilateral structure found in the hypothalamus of the mouse’s brain. In other words, this part of the mouse’s brain “lit up” when a mouse displayed contagious scratching behavior.

The researchers then decided to take this one step further by manipulating the amount of GRP in the hypothalamus. “When we deleted the GRP in the SCN, the mice stopped imitating the scratch,” Dr. Chen said. “When we injected more GRP into the SCN, the mice started scratching like crazy.”

Now, after more investigating and research published in 2022 in Cell Reports, Dr. Chen and his team suspect contagious itching may have just as much to do with our eyeballs as our skin and spinal cord. Why? The phenomenon begins with a visual component: Someone seeing another person scratching.

The researchers targeted mice’s retinal ganglion cells, a type of light-capturing neuron found near the inner surface of the retina. When those cells were disabled, all scratching stopped.

This recent study argues that a previously undiscovered visual pathway may exist between the retina and the brain – bypassing the visual cortex – to provide more immediate physical reactions to potential adverse situations.

There’s more (and it could be quite relatable to some people): After the mice watched a video of another mouse scratching for half an hour, the researchers measured the mice’s stress hormone levels, finding a significant increase. This suggested that exposure to impulsive, contagious scratching behavior may have caused heightened anxiety in the mice.

“This is an important discovery that helps answer the psychological question of why animals and people scratch all the time,” said Dr. Chen. “We humans also scratch a lot, sometimes as a way to unconsciously express our internal anxiety.”

The mice may have interpreted the scratching video as a sudden negative change to their environment that they had to prepare for. “Contagious behavior is actually a very efficient way to inform other animals of what’s coming,” Dr. Chen said. “When we see other people running in a panic, there is no time to think. You just run as fast as you can. This is another example of contagious behavior that is in your own interest to survive.”

As a result, Dr. Chen believes it’s fair to infer that contagious behavior, including yawning and emotional contagion, is merely an expression of a fundamental survival mechanism that has evolved over time. “The human being is just an imitation machine. It’s often very difficult for people to act independently or as a minority because you would be working against evolution,” said Dr. Chen.

Scott Ira Krakower, DO, a child and adolescent psychiatrist at Northwell Health in Glen Oaks, N.Y., (and not party to this research), seconds this sentiment. “In regard to the physical benefits of contagion, it acts as a permanent defense and helps build collective immunity,” he said. “The social benefits when it comes to empathy or social media contagion are also important to our development. It helps us understand, adapt, and connect with others.”

Observing how empathy operates as a socially contagious behavior is something Dr. Chen and his colleagues are interested in looking into in the future.

“The definition of empathy is the sharing of emotions,” Dr. Chen said. “Shared feelings are crucial for social bonding and mental health, and for other animals, like mice, this is also the case.” Previous studies have shown that mice do, in fact, experience empathy and share feelings of pain and fear with one another.

There is still much to be explored in the study of contagious behaviors and the components of the brain that are activated during such behavior. Dr. Chen and his team intend to, ahem, scratch that particular itch.

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

If you’ve ever felt an urge to scratch after witnessing someone else relieve their own itch, you’re certainly not alone. Itching can be contagious and the phenomenon is so common it doesn’t just affect humans. Now researchers may understand why.

Some background: In a 2007 study led by Zhou-Feng Chen, PhD, professor of anesthesiology, psychiatry, and developmental biology at the Washington University in St. Louis, researchers discovered a specific gene, the GRPR (gastrin-releasing peptide receptor), in the spinal cord and a corresponding neuropeptide, GRP (gastrin-releasing peptide). Together, the GRP system was found to transmit the “itch information” from one’s skin to the spinal cord.

This discovery was further backed by 2017 findings when Dr. Chen and his colleagues closely observed the molecular and neural basis of contagious itch behavior in mice. “We played a video that showed a mouse scratching at a very high frequency to other mice,” said Dr. Chen. “We found that, indeed, the mice who watched the video also scratched.”

To determine the inner workings at play, the researchers used molecular mapping to reveal increased neuronal activity in the suprachiasmatic nucleus (SCN), a bilateral structure found in the hypothalamus of the mouse’s brain. In other words, this part of the mouse’s brain “lit up” when a mouse displayed contagious scratching behavior.

The researchers then decided to take this one step further by manipulating the amount of GRP in the hypothalamus. “When we deleted the GRP in the SCN, the mice stopped imitating the scratch,” Dr. Chen said. “When we injected more GRP into the SCN, the mice started scratching like crazy.”

Now, after more investigating and research published in 2022 in Cell Reports, Dr. Chen and his team suspect contagious itching may have just as much to do with our eyeballs as our skin and spinal cord. Why? The phenomenon begins with a visual component: Someone seeing another person scratching.

The researchers targeted mice’s retinal ganglion cells, a type of light-capturing neuron found near the inner surface of the retina. When those cells were disabled, all scratching stopped.

This recent study argues that a previously undiscovered visual pathway may exist between the retina and the brain – bypassing the visual cortex – to provide more immediate physical reactions to potential adverse situations.

There’s more (and it could be quite relatable to some people): After the mice watched a video of another mouse scratching for half an hour, the researchers measured the mice’s stress hormone levels, finding a significant increase. This suggested that exposure to impulsive, contagious scratching behavior may have caused heightened anxiety in the mice.

“This is an important discovery that helps answer the psychological question of why animals and people scratch all the time,” said Dr. Chen. “We humans also scratch a lot, sometimes as a way to unconsciously express our internal anxiety.”

The mice may have interpreted the scratching video as a sudden negative change to their environment that they had to prepare for. “Contagious behavior is actually a very efficient way to inform other animals of what’s coming,” Dr. Chen said. “When we see other people running in a panic, there is no time to think. You just run as fast as you can. This is another example of contagious behavior that is in your own interest to survive.”

As a result, Dr. Chen believes it’s fair to infer that contagious behavior, including yawning and emotional contagion, is merely an expression of a fundamental survival mechanism that has evolved over time. “The human being is just an imitation machine. It’s often very difficult for people to act independently or as a minority because you would be working against evolution,” said Dr. Chen.

Scott Ira Krakower, DO, a child and adolescent psychiatrist at Northwell Health in Glen Oaks, N.Y., (and not party to this research), seconds this sentiment. “In regard to the physical benefits of contagion, it acts as a permanent defense and helps build collective immunity,” he said. “The social benefits when it comes to empathy or social media contagion are also important to our development. It helps us understand, adapt, and connect with others.”

Observing how empathy operates as a socially contagious behavior is something Dr. Chen and his colleagues are interested in looking into in the future.

“The definition of empathy is the sharing of emotions,” Dr. Chen said. “Shared feelings are crucial for social bonding and mental health, and for other animals, like mice, this is also the case.” Previous studies have shown that mice do, in fact, experience empathy and share feelings of pain and fear with one another.

There is still much to be explored in the study of contagious behaviors and the components of the brain that are activated during such behavior. Dr. Chen and his team intend to, ahem, scratch that particular itch.

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

This transcript has been edited for clarity.

Dr. Jain: I’m Akshay Jain, an endocrinologist in Vancouver. This is Dr. Christopher Gardner, a nutritional scientist at Stanford. He is the author of many publications, including the widely cited SWAP-MEAT study. He was also a presenter at the American Diabetes Association conference in San Diego in 2023.

We’ll be talking about his work and the presentation that he did classifying different kinds of diets as well as the pluses and minuses of a plant-based diet versus an animal-based diet. Welcome, Dr Gardner.

Dr. Gardner: Glad to be here.

Dr. Jain: Let’s get right into this. There’s obviously been a large amount of talk, both in the lay media and in the scientific literature, on plant-based diets versus animal-based diets. When it comes to an individual living with diabetes, does one diet make more sense than the other?

Dr. Gardner: I think this is one of those false dichotomies. It’s really not all one or all the other. Two of my favorite sayings are “with what” and “instead of what.” You may be thinking, I’m really going to go for animal based. I know it’s low carb. I have diabetes. I know animal foods have few carbs in them.

That’s true. But think of some of the more and the less healthy animal foods. Yogurt is a great choice for an animal food. Fish is a great choice for an animal food with omega-3s. Chicken McNuggets, not so much.

Then, you switch to the plant side and say: “I’ve heard all these people talking about a whole-food, plant-based diet. That sounds great. I’m thinking broccoli and chickpeas.”

I know there’s somebody out there saying: “I just had a Coke. Isn’t that plant based? I just had a pastry. Isn’t that full of plants?” It doesn’t really take much to think about this, but it’s not as dichotomous as animal versus plant.

Dr. Jain: There is, obviously, a good understanding regarding what actually constitutes the diet. Initially, people were saying that animal-based diets are really bad from a cardiovascular perspective. But now, some studies are suggesting that it may not be true. What’s your take on that?

Dr. Gardner: Again, if you think “with what” or “instead of what,” microbiome is a super-hot topic. That’s really fiber and fermented food, which are only plants. Saturated fat, despite all the controversy, raises your blood cholesterol. It’s more prevalent in animal foods than in plant foods.

Are there any great nutrients in animal foods? Sure. There’s calcium in dairy products for osteoporosis. There’s iron. Actually, people can get too much iron, which can be a pro-oxidant in levels that are too high.

The American Heart Association, in particular, which I’m very involved with, came out with new guidelines in 2021. It was very plant focused. The top of the list was vegetables, fruits, whole grains, and protein. When it came to protein, it was mostly from lentils, beans, and grains.

Dr. Jain: That’s good to know. Let’s talk about protein. We often hear about how somebody on a plant-based diet only can never have all the essential amino acids and the amount of protein that one needs. Whether it’s for general everyday individuals or even more so for athletes or bodybuilders, you cannot get enough good-quality protein from a plant-based diet.

Is there any truth to that? If not, what would you suggest for everyday individuals on a plant-based diet?

Dr. Gardner: This one drives me nuts. Please stop obsessing about protein. This isn’t a very scientific answer, but go watch the documentary Game Changers, which is all about vegan athletes. There are some pretty hokey things in that film that are very unscientific.

Let’s go back to basics, since we only have a couple of minutes together. It is a myth that plants don’t have all the amino acids, including all nine essential amino acids. I have several YouTube rants about this if anybody wants to search “Gardner Stanford protein.” All plant foods have all nine essential amino acids and all 20 amino acids.

There is a modest difference. Grains tend to be a little low in lysine, and beans tend to be a little low in methionine. Part of this has to do with how much of a difference is a little low. If you go to protein requirements that were written up in 2005 by the Institute of Medicine, you’ll see that the estimated average requirement for adults is 0.66 g/kg of body weight.

If we recommended the estimated average requirement for everyone, and everyone got it, by definition, half the population would be deficient. We have recommended daily allowances. The recommended daily allowances include two standard deviations above the estimated average requirement. Why would we do that? It’s a population approach.

If that’s the goal and everybody got it, you’d actually still have the tail of the normal distribution that would be deficient, which would be about 2.5%. The flip side of that argument is how many would exceed their requirement? That’s 97.5% of the population who would exceed their requirement if they got the recommended daily allowance.

The recommended daily allowance translates to about 45 g of protein per day for women and about 55 g of protein per day for men. Today, men and women in the United States get 80 g, 90 g, and 100 g of protein per day. What I hear them say is: “I’m not sure if I need the recommended daily allowance. I feel like I’m extra special or I’m above the curve and I want to make sure I’m getting enough.”

The recommended daily allowance already has a safety buffer in it. It was designed that way.

Let’s flip to athletes just for a second. Athletes want to be more muscular and make sure they’re supporting their activity. Americans get 1.2-1.5 g of protein per kg of body weight per day, which is almost double.

Athletes don’t eat as many calories as the average American does. If they’re working out to be muscular, they’re not eating 2,000 or 2,500 calories per day. I have a Rose Bowl football player teaching assistant from a Human Nutrition class at Stanford. He logged what he was eating for his football workouts. He was eating 5,000 calories per day. He was getting 250 g of protein per day, without any supplements or shakes.

I really do think this whole protein thing is a myth. As long as you get a reasonable amount of variety in your diet, there is no problem meeting your protein needs. Vegetarians? Absolutely no problem because they’re getting dairy and some eggs and things. Even vegans are likely fine. They would have to pay a little more attention to this, but I know many very strong, healthy vegans.

Dr. Jain: This is so helpful, Dr Gardner. I know that many clinicians, including myself, will find this very helpful, including when we talk to our patients and counsel them on their requirements. Thanks for sharing that.

Final question for you. We know people who are on either side of the extreme: either completely plant based or completely animal based. For a majority of us that have some kind of a happy medium, what would your suggestions be as far as the macronutrient distribution that you would recommend from a mixed animal- and plant-based diet? What would be the ideal recommendations here?

Dr. Gardner: We did a huge weight loss study with people with prediabetes. It was as low in carbs as people could go and as low in fat as people could go. That didn’t end up being the ketogenic level or the low-fat, vegan level. That ended up being much more moderate.

We found that people were successful either on low carb or low fat. Interestingly, on both diets, protein was very similar. Let’s not get into that since we just did a lot of protein. The key was a healthy low carb or a healthy low fat. I actually think we have a lot of wiggle room there. Let me build on what you said just a moment ago.

I really don’t think you need to be vegan to be healthy. We prefer the term whole food, plant based. If you’re getting 70% or 80% of your food from plants, you’re fine. If you really want to get the last 5%, 10%, or 15% all from plants, the additional benefit is not going to be large. You might want to do that for the environment or animal rights and welfare, but from a health perspective, a whole-food, plant-based diet leaves room for some yogurt, fish, and maybe some eggs for breakfast instead of those silly high-carb breakfasts that most Americans eat.

I will say that animal foods have no fiber. Given what a hot topic the microbiome is these days, the higher and higher you get in animal food, it’s going to be really hard to get antioxidants, most of which are in plants, and very hard to get enough fiber, which is good for the microbiome.

That’s why I tend to follow along the lines of a whole-food, plant-based diet that leaves some room for meat and animal-sourced foods, which you could leave out and be fine. I wouldn’t go in the opposite direction to the all-animal side.

Dr. Jain: That was awesome. Thank you so much, Dr Gardner. Final pearl of wisdom here. When clinicians like us see patients with diabetes, what should be the final take-home message that we can counsel our patients about?

Dr. Gardner: That’s a great question. I don’t think it’s really so much animal or plants; it’s actually type of carbohydrate. There’s a great paper out of JAMA in 2019 or 2020 by Shan and colleagues. They looked at the proportion of calories from proteins, carbs, and fats over about 20 years, and they looked at the subtypes.

Very interestingly, protein from animal foods is about 10% of calories; from plants, about 5%; mono-, poly-, and saturated fats are all about 10% of calories; and high-quality carbohydrates are about 10% of calories. What’s left is 40% of calories from crappy carbohydrates. We eat so many calories from added sugars and refined grains, and those are plant-based. Added sugars and refined grains are plant-based.

In terms of a lower-carbohydrate diet, there is an immense amount of room for cutting back on that 40%. What would you do with that? Would you eat more animal food? Would you eat more plant food? This is where I think we have a large amount of wiggle room. If the patients could get rid of all or most of that 40%, they could pick some eggs, yogurt, fish, and some high-fat foods. They could pick avocados, nuts, seeds, and olive oil or they could have more broccoli, chickpeas, tempeh, and tofu.

There really is a large amount of wiggle room. The key – can we please get rid of the elephant in the room, which is plant food – is all that added sugar and refined grain.

Dr. Jain is an endocrinologist and clinical instructor University of British Columbia, Vancouver. Dr. Gardner is a professor of medicine at Stanford (Calif.) University. Dr. Jain reported numerous conflicts of interest with various companies; Dr. Gardner reported receiving research funding from Beyond Meat.


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

This transcript has been edited for clarity.

Dr. Jain: I’m Akshay Jain, an endocrinologist in Vancouver. This is Dr. Christopher Gardner, a nutritional scientist at Stanford. He is the author of many publications, including the widely cited SWAP-MEAT study. He was also a presenter at the American Diabetes Association conference in San Diego in 2023.

We’ll be talking about his work and the presentation that he did classifying different kinds of diets as well as the pluses and minuses of a plant-based diet versus an animal-based diet. Welcome, Dr Gardner.

Dr. Gardner: Glad to be here.

Dr. Jain: Let’s get right into this. There’s obviously been a large amount of talk, both in the lay media and in the scientific literature, on plant-based diets versus animal-based diets. When it comes to an individual living with diabetes, does one diet make more sense than the other?

Dr. Gardner: I think this is one of those false dichotomies. It’s really not all one or all the other. Two of my favorite sayings are “with what” and “instead of what.” You may be thinking, I’m really going to go for animal based. I know it’s low carb. I have diabetes. I know animal foods have few carbs in them.

That’s true. But think of some of the more and the less healthy animal foods. Yogurt is a great choice for an animal food. Fish is a great choice for an animal food with omega-3s. Chicken McNuggets, not so much.

Then, you switch to the plant side and say: “I’ve heard all these people talking about a whole-food, plant-based diet. That sounds great. I’m thinking broccoli and chickpeas.”

I know there’s somebody out there saying: “I just had a Coke. Isn’t that plant based? I just had a pastry. Isn’t that full of plants?” It doesn’t really take much to think about this, but it’s not as dichotomous as animal versus plant.

Dr. Jain: There is, obviously, a good understanding regarding what actually constitutes the diet. Initially, people were saying that animal-based diets are really bad from a cardiovascular perspective. But now, some studies are suggesting that it may not be true. What’s your take on that?

Dr. Gardner: Again, if you think “with what” or “instead of what,” microbiome is a super-hot topic. That’s really fiber and fermented food, which are only plants. Saturated fat, despite all the controversy, raises your blood cholesterol. It’s more prevalent in animal foods than in plant foods.

Are there any great nutrients in animal foods? Sure. There’s calcium in dairy products for osteoporosis. There’s iron. Actually, people can get too much iron, which can be a pro-oxidant in levels that are too high.

The American Heart Association, in particular, which I’m very involved with, came out with new guidelines in 2021. It was very plant focused. The top of the list was vegetables, fruits, whole grains, and protein. When it came to protein, it was mostly from lentils, beans, and grains.

Dr. Jain: That’s good to know. Let’s talk about protein. We often hear about how somebody on a plant-based diet only can never have all the essential amino acids and the amount of protein that one needs. Whether it’s for general everyday individuals or even more so for athletes or bodybuilders, you cannot get enough good-quality protein from a plant-based diet.

Is there any truth to that? If not, what would you suggest for everyday individuals on a plant-based diet?

Dr. Gardner: This one drives me nuts. Please stop obsessing about protein. This isn’t a very scientific answer, but go watch the documentary Game Changers, which is all about vegan athletes. There are some pretty hokey things in that film that are very unscientific.

Let’s go back to basics, since we only have a couple of minutes together. It is a myth that plants don’t have all the amino acids, including all nine essential amino acids. I have several YouTube rants about this if anybody wants to search “Gardner Stanford protein.” All plant foods have all nine essential amino acids and all 20 amino acids.

There is a modest difference. Grains tend to be a little low in lysine, and beans tend to be a little low in methionine. Part of this has to do with how much of a difference is a little low. If you go to protein requirements that were written up in 2005 by the Institute of Medicine, you’ll see that the estimated average requirement for adults is 0.66 g/kg of body weight.

If we recommended the estimated average requirement for everyone, and everyone got it, by definition, half the population would be deficient. We have recommended daily allowances. The recommended daily allowances include two standard deviations above the estimated average requirement. Why would we do that? It’s a population approach.

If that’s the goal and everybody got it, you’d actually still have the tail of the normal distribution that would be deficient, which would be about 2.5%. The flip side of that argument is how many would exceed their requirement? That’s 97.5% of the population who would exceed their requirement if they got the recommended daily allowance.

The recommended daily allowance translates to about 45 g of protein per day for women and about 55 g of protein per day for men. Today, men and women in the United States get 80 g, 90 g, and 100 g of protein per day. What I hear them say is: “I’m not sure if I need the recommended daily allowance. I feel like I’m extra special or I’m above the curve and I want to make sure I’m getting enough.”

The recommended daily allowance already has a safety buffer in it. It was designed that way.

Let’s flip to athletes just for a second. Athletes want to be more muscular and make sure they’re supporting their activity. Americans get 1.2-1.5 g of protein per kg of body weight per day, which is almost double.

Athletes don’t eat as many calories as the average American does. If they’re working out to be muscular, they’re not eating 2,000 or 2,500 calories per day. I have a Rose Bowl football player teaching assistant from a Human Nutrition class at Stanford. He logged what he was eating for his football workouts. He was eating 5,000 calories per day. He was getting 250 g of protein per day, without any supplements or shakes.

I really do think this whole protein thing is a myth. As long as you get a reasonable amount of variety in your diet, there is no problem meeting your protein needs. Vegetarians? Absolutely no problem because they’re getting dairy and some eggs and things. Even vegans are likely fine. They would have to pay a little more attention to this, but I know many very strong, healthy vegans.

Dr. Jain: This is so helpful, Dr Gardner. I know that many clinicians, including myself, will find this very helpful, including when we talk to our patients and counsel them on their requirements. Thanks for sharing that.

Final question for you. We know people who are on either side of the extreme: either completely plant based or completely animal based. For a majority of us that have some kind of a happy medium, what would your suggestions be as far as the macronutrient distribution that you would recommend from a mixed animal- and plant-based diet? What would be the ideal recommendations here?

Dr. Gardner: We did a huge weight loss study with people with prediabetes. It was as low in carbs as people could go and as low in fat as people could go. That didn’t end up being the ketogenic level or the low-fat, vegan level. That ended up being much more moderate.

We found that people were successful either on low carb or low fat. Interestingly, on both diets, protein was very similar. Let’s not get into that since we just did a lot of protein. The key was a healthy low carb or a healthy low fat. I actually think we have a lot of wiggle room there. Let me build on what you said just a moment ago.

I really don’t think you need to be vegan to be healthy. We prefer the term whole food, plant based. If you’re getting 70% or 80% of your food from plants, you’re fine. If you really want to get the last 5%, 10%, or 15% all from plants, the additional benefit is not going to be large. You might want to do that for the environment or animal rights and welfare, but from a health perspective, a whole-food, plant-based diet leaves room for some yogurt, fish, and maybe some eggs for breakfast instead of those silly high-carb breakfasts that most Americans eat.

I will say that animal foods have no fiber. Given what a hot topic the microbiome is these days, the higher and higher you get in animal food, it’s going to be really hard to get antioxidants, most of which are in plants, and very hard to get enough fiber, which is good for the microbiome.

That’s why I tend to follow along the lines of a whole-food, plant-based diet that leaves some room for meat and animal-sourced foods, which you could leave out and be fine. I wouldn’t go in the opposite direction to the all-animal side.

Dr. Jain: That was awesome. Thank you so much, Dr Gardner. Final pearl of wisdom here. When clinicians like us see patients with diabetes, what should be the final take-home message that we can counsel our patients about?

Dr. Gardner: That’s a great question. I don’t think it’s really so much animal or plants; it’s actually type of carbohydrate. There’s a great paper out of JAMA in 2019 or 2020 by Shan and colleagues. They looked at the proportion of calories from proteins, carbs, and fats over about 20 years, and they looked at the subtypes.

Very interestingly, protein from animal foods is about 10% of calories; from plants, about 5%; mono-, poly-, and saturated fats are all about 10% of calories; and high-quality carbohydrates are about 10% of calories. What’s left is 40% of calories from crappy carbohydrates. We eat so many calories from added sugars and refined grains, and those are plant-based. Added sugars and refined grains are plant-based.

In terms of a lower-carbohydrate diet, there is an immense amount of room for cutting back on that 40%. What would you do with that? Would you eat more animal food? Would you eat more plant food? This is where I think we have a large amount of wiggle room. If the patients could get rid of all or most of that 40%, they could pick some eggs, yogurt, fish, and some high-fat foods. They could pick avocados, nuts, seeds, and olive oil or they could have more broccoli, chickpeas, tempeh, and tofu.

There really is a large amount of wiggle room. The key – can we please get rid of the elephant in the room, which is plant food – is all that added sugar and refined grain.

Dr. Jain is an endocrinologist and clinical instructor University of British Columbia, Vancouver. Dr. Gardner is a professor of medicine at Stanford (Calif.) University. Dr. Jain reported numerous conflicts of interest with various companies; Dr. Gardner reported receiving research funding from Beyond Meat.


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

This transcript has been edited for clarity.

Dr. Jain: I’m Akshay Jain, an endocrinologist in Vancouver. This is Dr. Christopher Gardner, a nutritional scientist at Stanford. He is the author of many publications, including the widely cited SWAP-MEAT study. He was also a presenter at the American Diabetes Association conference in San Diego in 2023.

We’ll be talking about his work and the presentation that he did classifying different kinds of diets as well as the pluses and minuses of a plant-based diet versus an animal-based diet. Welcome, Dr Gardner.

Dr. Gardner: Glad to be here.

Dr. Jain: Let’s get right into this. There’s obviously been a large amount of talk, both in the lay media and in the scientific literature, on plant-based diets versus animal-based diets. When it comes to an individual living with diabetes, does one diet make more sense than the other?

Dr. Gardner: I think this is one of those false dichotomies. It’s really not all one or all the other. Two of my favorite sayings are “with what” and “instead of what.” You may be thinking, I’m really going to go for animal based. I know it’s low carb. I have diabetes. I know animal foods have few carbs in them.

That’s true. But think of some of the more and the less healthy animal foods. Yogurt is a great choice for an animal food. Fish is a great choice for an animal food with omega-3s. Chicken McNuggets, not so much.

Then, you switch to the plant side and say: “I’ve heard all these people talking about a whole-food, plant-based diet. That sounds great. I’m thinking broccoli and chickpeas.”

I know there’s somebody out there saying: “I just had a Coke. Isn’t that plant based? I just had a pastry. Isn’t that full of plants?” It doesn’t really take much to think about this, but it’s not as dichotomous as animal versus plant.

Dr. Jain: There is, obviously, a good understanding regarding what actually constitutes the diet. Initially, people were saying that animal-based diets are really bad from a cardiovascular perspective. But now, some studies are suggesting that it may not be true. What’s your take on that?

Dr. Gardner: Again, if you think “with what” or “instead of what,” microbiome is a super-hot topic. That’s really fiber and fermented food, which are only plants. Saturated fat, despite all the controversy, raises your blood cholesterol. It’s more prevalent in animal foods than in plant foods.

Are there any great nutrients in animal foods? Sure. There’s calcium in dairy products for osteoporosis. There’s iron. Actually, people can get too much iron, which can be a pro-oxidant in levels that are too high.

The American Heart Association, in particular, which I’m very involved with, came out with new guidelines in 2021. It was very plant focused. The top of the list was vegetables, fruits, whole grains, and protein. When it came to protein, it was mostly from lentils, beans, and grains.

Dr. Jain: That’s good to know. Let’s talk about protein. We often hear about how somebody on a plant-based diet only can never have all the essential amino acids and the amount of protein that one needs. Whether it’s for general everyday individuals or even more so for athletes or bodybuilders, you cannot get enough good-quality protein from a plant-based diet.

Is there any truth to that? If not, what would you suggest for everyday individuals on a plant-based diet?

Dr. Gardner: This one drives me nuts. Please stop obsessing about protein. This isn’t a very scientific answer, but go watch the documentary Game Changers, which is all about vegan athletes. There are some pretty hokey things in that film that are very unscientific.

Let’s go back to basics, since we only have a couple of minutes together. It is a myth that plants don’t have all the amino acids, including all nine essential amino acids. I have several YouTube rants about this if anybody wants to search “Gardner Stanford protein.” All plant foods have all nine essential amino acids and all 20 amino acids.

There is a modest difference. Grains tend to be a little low in lysine, and beans tend to be a little low in methionine. Part of this has to do with how much of a difference is a little low. If you go to protein requirements that were written up in 2005 by the Institute of Medicine, you’ll see that the estimated average requirement for adults is 0.66 g/kg of body weight.

If we recommended the estimated average requirement for everyone, and everyone got it, by definition, half the population would be deficient. We have recommended daily allowances. The recommended daily allowances include two standard deviations above the estimated average requirement. Why would we do that? It’s a population approach.

If that’s the goal and everybody got it, you’d actually still have the tail of the normal distribution that would be deficient, which would be about 2.5%. The flip side of that argument is how many would exceed their requirement? That’s 97.5% of the population who would exceed their requirement if they got the recommended daily allowance.

The recommended daily allowance translates to about 45 g of protein per day for women and about 55 g of protein per day for men. Today, men and women in the United States get 80 g, 90 g, and 100 g of protein per day. What I hear them say is: “I’m not sure if I need the recommended daily allowance. I feel like I’m extra special or I’m above the curve and I want to make sure I’m getting enough.”

The recommended daily allowance already has a safety buffer in it. It was designed that way.

Let’s flip to athletes just for a second. Athletes want to be more muscular and make sure they’re supporting their activity. Americans get 1.2-1.5 g of protein per kg of body weight per day, which is almost double.

Athletes don’t eat as many calories as the average American does. If they’re working out to be muscular, they’re not eating 2,000 or 2,500 calories per day. I have a Rose Bowl football player teaching assistant from a Human Nutrition class at Stanford. He logged what he was eating for his football workouts. He was eating 5,000 calories per day. He was getting 250 g of protein per day, without any supplements or shakes.

I really do think this whole protein thing is a myth. As long as you get a reasonable amount of variety in your diet, there is no problem meeting your protein needs. Vegetarians? Absolutely no problem because they’re getting dairy and some eggs and things. Even vegans are likely fine. They would have to pay a little more attention to this, but I know many very strong, healthy vegans.

Dr. Jain: This is so helpful, Dr Gardner. I know that many clinicians, including myself, will find this very helpful, including when we talk to our patients and counsel them on their requirements. Thanks for sharing that.

Final question for you. We know people who are on either side of the extreme: either completely plant based or completely animal based. For a majority of us that have some kind of a happy medium, what would your suggestions be as far as the macronutrient distribution that you would recommend from a mixed animal- and plant-based diet? What would be the ideal recommendations here?

Dr. Gardner: We did a huge weight loss study with people with prediabetes. It was as low in carbs as people could go and as low in fat as people could go. That didn’t end up being the ketogenic level or the low-fat, vegan level. That ended up being much more moderate.

We found that people were successful either on low carb or low fat. Interestingly, on both diets, protein was very similar. Let’s not get into that since we just did a lot of protein. The key was a healthy low carb or a healthy low fat. I actually think we have a lot of wiggle room there. Let me build on what you said just a moment ago.

I really don’t think you need to be vegan to be healthy. We prefer the term whole food, plant based. If you’re getting 70% or 80% of your food from plants, you’re fine. If you really want to get the last 5%, 10%, or 15% all from plants, the additional benefit is not going to be large. You might want to do that for the environment or animal rights and welfare, but from a health perspective, a whole-food, plant-based diet leaves room for some yogurt, fish, and maybe some eggs for breakfast instead of those silly high-carb breakfasts that most Americans eat.

I will say that animal foods have no fiber. Given what a hot topic the microbiome is these days, the higher and higher you get in animal food, it’s going to be really hard to get antioxidants, most of which are in plants, and very hard to get enough fiber, which is good for the microbiome.

That’s why I tend to follow along the lines of a whole-food, plant-based diet that leaves some room for meat and animal-sourced foods, which you could leave out and be fine. I wouldn’t go in the opposite direction to the all-animal side.

Dr. Jain: That was awesome. Thank you so much, Dr Gardner. Final pearl of wisdom here. When clinicians like us see patients with diabetes, what should be the final take-home message that we can counsel our patients about?

Dr. Gardner: That’s a great question. I don’t think it’s really so much animal or plants; it’s actually type of carbohydrate. There’s a great paper out of JAMA in 2019 or 2020 by Shan and colleagues. They looked at the proportion of calories from proteins, carbs, and fats over about 20 years, and they looked at the subtypes.

Very interestingly, protein from animal foods is about 10% of calories; from plants, about 5%; mono-, poly-, and saturated fats are all about 10% of calories; and high-quality carbohydrates are about 10% of calories. What’s left is 40% of calories from crappy carbohydrates. We eat so many calories from added sugars and refined grains, and those are plant-based. Added sugars and refined grains are plant-based.

In terms of a lower-carbohydrate diet, there is an immense amount of room for cutting back on that 40%. What would you do with that? Would you eat more animal food? Would you eat more plant food? This is where I think we have a large amount of wiggle room. If the patients could get rid of all or most of that 40%, they could pick some eggs, yogurt, fish, and some high-fat foods. They could pick avocados, nuts, seeds, and olive oil or they could have more broccoli, chickpeas, tempeh, and tofu.

There really is a large amount of wiggle room. The key – can we please get rid of the elephant in the room, which is plant food – is all that added sugar and refined grain.

Dr. Jain is an endocrinologist and clinical instructor University of British Columbia, Vancouver. Dr. Gardner is a professor of medicine at Stanford (Calif.) University. Dr. Jain reported numerous conflicts of interest with various companies; Dr. Gardner reported receiving research funding from Beyond Meat.


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

Use of glucagonlike peptide–1 (GLP-1) agonists, such as semaglutide, surged among U.S. adults with type 2 diabetes in recent years, through March 2022, and dethroned dipeptidyl peptidase–4 (DPP-4) inhibitors as the top incretin-based drug class, according to a retrospective analysis of insurance claims data from more than 1 million individuals.

By January–March 2022, 56.6% of U.S. adults with type 2 diabetes prescribed an incretin-based treatment were taking a GLP-1 agonist and 38.7% were taking a DPP-4 inhibitor, Elisabetta Patorno, MD, and colleagues reported in an abstract released in advance of the annual meeting of the European Association for the Study of Diabetes.

These usage rates sharply diverged from the earliest period the researchers examined – 4 years earlier in January–March 2018 – when DPP-4 inhibitors were used by 62.4% of adults with type 2 diabetes on any incretin-based regimen and 37.6% were taking a GLP-1 agonist.

This shift was largely driven by accumulating evidence for clinically meaningful weight loss with GLP-1 agonists, especially semaglutide when used for people with type 2 diabetes as Ozempic (Novo Nordisk) or for treating people with obesity as Wegovy (Novo Nordisk).
 

Market share of GLP-1 agonists ‘likely to expand’ further

“The importance of the DPP-4 inhibitor class will further decrease when effective alternatives such as GLP-1 agonists and sodium-glucose cotransporter 2 inhibitors can be used,” said Alexander Kutz, MD, a coauthor of the report, in a statement released by EASD.

“The market share of GLP-1 agonists is likely to expand in patients with type 2 diabetes,” especially those who also have obesity, said Dr. Kutz, who like Dr. Patorno is a pharmacoepidemiologist at Brigham and Women’s Hospital in Boston.

Incretin-based agents currently account for roughly a third of all medications prescribed to people with type 2 diabetes, the authors said. GLP-1 is an incretin hormone, and receptor agonists mimic its action. The DPP-4 enzyme inactivates incretin hormones, and so inhibiting the enzyme boosts incretin activity.

The obesity-driven shift in positioning of agents for people with type 2 diabetes will likely extend to tirzepatide (Mounjaro), which acts as both a GLP-1 agonist and has agonist activity on the receptor for another incretin, glucose-dependent insulinotropic polypeptide. The Food and Drug Administration approved tirzepatide for type 2 diabetes in May 2022, too late for inclusion in the data the researchers reviewed. Plus, tirzepatide prescribing may lag for a few years as clinicians gain experience, and some might await results from the cardiovascular outcomes trial SURPASS-CVOT , said Dr. Kutz. SURPASS-CVOT has enrolled more than 13,000 adults with type 2 diabetes and is currently scheduled to finish by October 2024.
 

Injected semaglutide had the biggest gain

The study by Dr. Patorno and colleagues included 1,065,592 U.S. adults with type 2 diabetes taking an incretin-based medication in the Clinformatics Data Mart database maintained by Optum on claims it processed on behalf of various U.S. commercial insurers, including insurers that service certain Medicare beneficiaries.

The claims data had granularity for specific agents in the GLP-1 agonist class. Injected semaglutide, given once weekly, spiked from no use early in 2018 to a third of GLP-1 agonist use by the start of 2022.

However, use of liraglutide (Victoza, Novo Nordisk), a daily subcutaneous injection, dropped from a 44.2% share in early 2018 to 10.0% in early 2022. Dulaglutide (Trulicity, Lilly), a weekly injection, showed a small increase, from a 35.2% share in 2018 to 42.1% in 2022, and oral semaglutide (Rybelsus, Novo Nordisk) jumped from no use in 2018 to a 7.7% share in 2022. Among the DPP-4 inhibitors, sitagliptin (Januvia, Merck) was most commonly used, followed by linagliptin (Tradjenta, Boehringer Ingelheim) and saxagliptin (Onglyza, AstraZeneca). Use of all three DPP-4 inhibitors fell from 2018 to 2022.

Additional analyses showed that, compared with people starting a DPP-4 inhibitor during the period examined, those who started a GLP-1 agonist were 54%-64% more likely to have obesity and 18%-46% more likely to receive care from an endocrinologist. Those starting a GLP-1 agonist were also significantly less likely to have chronic kidney disease or dementia.

Although Dr. Kutz and Dr. Patorno foresee continued increases in the use of agents that act as GLP-1 agonists in U.S. adults with type 2 diabetes, they also stressed the ongoing role for sitagliptin and other DPP-4 inhibitors.

This class “may still be preferred in older and multimorbid patients at higher risk for frailty,” such as patients who live in nursing homes, they said in the EASD statement. 

The study received no commercial funding. Dr. Patorno reported no relevant financial relationships. Dr. Kutz reported receiving an educational grant from Novo Nordisk, the company that markets semaglutide and liraglutide.

A version of this article appeared on Medscape.com.

Use of glucagonlike peptide–1 (GLP-1) agonists, such as semaglutide, surged among U.S. adults with type 2 diabetes in recent years, through March 2022, and dethroned dipeptidyl peptidase–4 (DPP-4) inhibitors as the top incretin-based drug class, according to a retrospective analysis of insurance claims data from more than 1 million individuals.

By January–March 2022, 56.6% of U.S. adults with type 2 diabetes prescribed an incretin-based treatment were taking a GLP-1 agonist and 38.7% were taking a DPP-4 inhibitor, Elisabetta Patorno, MD, and colleagues reported in an abstract released in advance of the annual meeting of the European Association for the Study of Diabetes.

These usage rates sharply diverged from the earliest period the researchers examined – 4 years earlier in January–March 2018 – when DPP-4 inhibitors were used by 62.4% of adults with type 2 diabetes on any incretin-based regimen and 37.6% were taking a GLP-1 agonist.

This shift was largely driven by accumulating evidence for clinically meaningful weight loss with GLP-1 agonists, especially semaglutide when used for people with type 2 diabetes as Ozempic (Novo Nordisk) or for treating people with obesity as Wegovy (Novo Nordisk).
 

Market share of GLP-1 agonists ‘likely to expand’ further

“The importance of the DPP-4 inhibitor class will further decrease when effective alternatives such as GLP-1 agonists and sodium-glucose cotransporter 2 inhibitors can be used,” said Alexander Kutz, MD, a coauthor of the report, in a statement released by EASD.

“The market share of GLP-1 agonists is likely to expand in patients with type 2 diabetes,” especially those who also have obesity, said Dr. Kutz, who like Dr. Patorno is a pharmacoepidemiologist at Brigham and Women’s Hospital in Boston.

Incretin-based agents currently account for roughly a third of all medications prescribed to people with type 2 diabetes, the authors said. GLP-1 is an incretin hormone, and receptor agonists mimic its action. The DPP-4 enzyme inactivates incretin hormones, and so inhibiting the enzyme boosts incretin activity.

The obesity-driven shift in positioning of agents for people with type 2 diabetes will likely extend to tirzepatide (Mounjaro), which acts as both a GLP-1 agonist and has agonist activity on the receptor for another incretin, glucose-dependent insulinotropic polypeptide. The Food and Drug Administration approved tirzepatide for type 2 diabetes in May 2022, too late for inclusion in the data the researchers reviewed. Plus, tirzepatide prescribing may lag for a few years as clinicians gain experience, and some might await results from the cardiovascular outcomes trial SURPASS-CVOT , said Dr. Kutz. SURPASS-CVOT has enrolled more than 13,000 adults with type 2 diabetes and is currently scheduled to finish by October 2024.
 

Injected semaglutide had the biggest gain

The study by Dr. Patorno and colleagues included 1,065,592 U.S. adults with type 2 diabetes taking an incretin-based medication in the Clinformatics Data Mart database maintained by Optum on claims it processed on behalf of various U.S. commercial insurers, including insurers that service certain Medicare beneficiaries.

The claims data had granularity for specific agents in the GLP-1 agonist class. Injected semaglutide, given once weekly, spiked from no use early in 2018 to a third of GLP-1 agonist use by the start of 2022.

However, use of liraglutide (Victoza, Novo Nordisk), a daily subcutaneous injection, dropped from a 44.2% share in early 2018 to 10.0% in early 2022. Dulaglutide (Trulicity, Lilly), a weekly injection, showed a small increase, from a 35.2% share in 2018 to 42.1% in 2022, and oral semaglutide (Rybelsus, Novo Nordisk) jumped from no use in 2018 to a 7.7% share in 2022. Among the DPP-4 inhibitors, sitagliptin (Januvia, Merck) was most commonly used, followed by linagliptin (Tradjenta, Boehringer Ingelheim) and saxagliptin (Onglyza, AstraZeneca). Use of all three DPP-4 inhibitors fell from 2018 to 2022.

Additional analyses showed that, compared with people starting a DPP-4 inhibitor during the period examined, those who started a GLP-1 agonist were 54%-64% more likely to have obesity and 18%-46% more likely to receive care from an endocrinologist. Those starting a GLP-1 agonist were also significantly less likely to have chronic kidney disease or dementia.

Although Dr. Kutz and Dr. Patorno foresee continued increases in the use of agents that act as GLP-1 agonists in U.S. adults with type 2 diabetes, they also stressed the ongoing role for sitagliptin and other DPP-4 inhibitors.

This class “may still be preferred in older and multimorbid patients at higher risk for frailty,” such as patients who live in nursing homes, they said in the EASD statement. 

The study received no commercial funding. Dr. Patorno reported no relevant financial relationships. Dr. Kutz reported receiving an educational grant from Novo Nordisk, the company that markets semaglutide and liraglutide.

A version of this article appeared on Medscape.com.

Use of glucagonlike peptide–1 (GLP-1) agonists, such as semaglutide, surged among U.S. adults with type 2 diabetes in recent years, through March 2022, and dethroned dipeptidyl peptidase–4 (DPP-4) inhibitors as the top incretin-based drug class, according to a retrospective analysis of insurance claims data from more than 1 million individuals.

By January–March 2022, 56.6% of U.S. adults with type 2 diabetes prescribed an incretin-based treatment were taking a GLP-1 agonist and 38.7% were taking a DPP-4 inhibitor, Elisabetta Patorno, MD, and colleagues reported in an abstract released in advance of the annual meeting of the European Association for the Study of Diabetes.

These usage rates sharply diverged from the earliest period the researchers examined – 4 years earlier in January–March 2018 – when DPP-4 inhibitors were used by 62.4% of adults with type 2 diabetes on any incretin-based regimen and 37.6% were taking a GLP-1 agonist.

This shift was largely driven by accumulating evidence for clinically meaningful weight loss with GLP-1 agonists, especially semaglutide when used for people with type 2 diabetes as Ozempic (Novo Nordisk) or for treating people with obesity as Wegovy (Novo Nordisk).
 

Market share of GLP-1 agonists ‘likely to expand’ further

“The importance of the DPP-4 inhibitor class will further decrease when effective alternatives such as GLP-1 agonists and sodium-glucose cotransporter 2 inhibitors can be used,” said Alexander Kutz, MD, a coauthor of the report, in a statement released by EASD.

“The market share of GLP-1 agonists is likely to expand in patients with type 2 diabetes,” especially those who also have obesity, said Dr. Kutz, who like Dr. Patorno is a pharmacoepidemiologist at Brigham and Women’s Hospital in Boston.

Incretin-based agents currently account for roughly a third of all medications prescribed to people with type 2 diabetes, the authors said. GLP-1 is an incretin hormone, and receptor agonists mimic its action. The DPP-4 enzyme inactivates incretin hormones, and so inhibiting the enzyme boosts incretin activity.

The obesity-driven shift in positioning of agents for people with type 2 diabetes will likely extend to tirzepatide (Mounjaro), which acts as both a GLP-1 agonist and has agonist activity on the receptor for another incretin, glucose-dependent insulinotropic polypeptide. The Food and Drug Administration approved tirzepatide for type 2 diabetes in May 2022, too late for inclusion in the data the researchers reviewed. Plus, tirzepatide prescribing may lag for a few years as clinicians gain experience, and some might await results from the cardiovascular outcomes trial SURPASS-CVOT , said Dr. Kutz. SURPASS-CVOT has enrolled more than 13,000 adults with type 2 diabetes and is currently scheduled to finish by October 2024.
 

Injected semaglutide had the biggest gain

The study by Dr. Patorno and colleagues included 1,065,592 U.S. adults with type 2 diabetes taking an incretin-based medication in the Clinformatics Data Mart database maintained by Optum on claims it processed on behalf of various U.S. commercial insurers, including insurers that service certain Medicare beneficiaries.

The claims data had granularity for specific agents in the GLP-1 agonist class. Injected semaglutide, given once weekly, spiked from no use early in 2018 to a third of GLP-1 agonist use by the start of 2022.

However, use of liraglutide (Victoza, Novo Nordisk), a daily subcutaneous injection, dropped from a 44.2% share in early 2018 to 10.0% in early 2022. Dulaglutide (Trulicity, Lilly), a weekly injection, showed a small increase, from a 35.2% share in 2018 to 42.1% in 2022, and oral semaglutide (Rybelsus, Novo Nordisk) jumped from no use in 2018 to a 7.7% share in 2022. Among the DPP-4 inhibitors, sitagliptin (Januvia, Merck) was most commonly used, followed by linagliptin (Tradjenta, Boehringer Ingelheim) and saxagliptin (Onglyza, AstraZeneca). Use of all three DPP-4 inhibitors fell from 2018 to 2022.

Additional analyses showed that, compared with people starting a DPP-4 inhibitor during the period examined, those who started a GLP-1 agonist were 54%-64% more likely to have obesity and 18%-46% more likely to receive care from an endocrinologist. Those starting a GLP-1 agonist were also significantly less likely to have chronic kidney disease or dementia.

Although Dr. Kutz and Dr. Patorno foresee continued increases in the use of agents that act as GLP-1 agonists in U.S. adults with type 2 diabetes, they also stressed the ongoing role for sitagliptin and other DPP-4 inhibitors.

This class “may still be preferred in older and multimorbid patients at higher risk for frailty,” such as patients who live in nursing homes, they said in the EASD statement. 

The study received no commercial funding. Dr. Patorno reported no relevant financial relationships. Dr. Kutz reported receiving an educational grant from Novo Nordisk, the company that markets semaglutide and liraglutide.

A version of this article appeared on Medscape.com.

The former owner of a South Florida nursing school at the heart of a federal investigation into a multistate fraud scheme awarding at least 7,600 fake diplomas will have to serve nearly 2 years and repay millions.

U.S. District Judge Rodney Smith of the Southern District of Florida in Fort Lauderdale recently sentenced Johanah Napoleon, former president of the Palm Beach School of Nursing, to 21 months in prison, according to the Miami Herald . The judge also ordered Ms. Napoleon to pay about $3.5 million. She already paid $2.6 million of it, the Herald reports.

The sentence is “indicative of the seriousness of this crime,” shared Willa Fuller, BSN, RN, executive director of the Florida Nurses Association. “Hopefully, this decision will deter potential perpetrators in the future,” Ms. Fuller said in an email.

Ms. Napoleon was charged in 2021 along with two owners of nursing schools in Maryland and Virginia who worked with her. All pled guilty to selling fake degrees for $6,000-$18,000. The Florida Board of Nursing had previously shut down the Palm Beach school in 2017 as a result of its students’ low passing rate on the national licensing exam.

A tip related to the Maryland case led to federal charges in January against 25 owners, operators, and employees of the Palm Beach School of Nursing and two other Florida nursing schools for selling thousands of fake nursing degrees. Those who were charged operated in Delaware, New York, New Jersey, Texas, and Florida.

Five of those 25 defendants will be sentenced on July 27 in a federal district court in Fort Lauderdale after pleading guilty in May to wire fraud conspiracy, according to the U.S. Attorney for the Southern District of Florida. They each face up to 20 years in federal prison.

Purchasers of the fake associate or bachelor’s degrees received transcripts showing that they completed coursework. Some 2,800 of the buyers passed the national nursing licensing exam to become registered nurses and licensed practice nurses/vocational nurses in hospitals, nursing homes, and Veterans Affairs medical centers around the country, according to The New York Times.

Ms. Napoleon’s attorney, Joel DeFabio, said in an interview that he requested a lower sentence than the 4 years recommended in sentencing guidelines because Ms. Napoleon pled guilty quickly and cooperated with the federal investigation.

Mr. DeFabio said that Ms. Napoleon will appear as the government’s witness in a trial in November against Gail Russ, who is one defendant, along with 13 others in the case involving the Palm Beach School of Nursing.

Meanwhile, state nursing boards have been trying to locate nurses who received the fake degrees. In March, the New York nursing board told 903 nurses to either surrender their licenses or prove they had the appropriate education. The board estimated that another 2,300 licensees from the Florida schools had pending applications.

Some nurses who received fake diplomas are pushing back. Attorneys for nurses in Georgia and Pennsylvania claim that their clients were either victims or in some cases, have legitimate credentials.

“The quality of nursing education as well as protection of applicants from these harmful schemes is essential to maintaining the strict standards of the nursing profession,” Ms. Fuller said.

A version of this article appeared on Medscape.com.

The former owner of a South Florida nursing school at the heart of a federal investigation into a multistate fraud scheme awarding at least 7,600 fake diplomas will have to serve nearly 2 years and repay millions.

U.S. District Judge Rodney Smith of the Southern District of Florida in Fort Lauderdale recently sentenced Johanah Napoleon, former president of the Palm Beach School of Nursing, to 21 months in prison, according to the Miami Herald . The judge also ordered Ms. Napoleon to pay about $3.5 million. She already paid $2.6 million of it, the Herald reports.

The sentence is “indicative of the seriousness of this crime,” shared Willa Fuller, BSN, RN, executive director of the Florida Nurses Association. “Hopefully, this decision will deter potential perpetrators in the future,” Ms. Fuller said in an email.

Ms. Napoleon was charged in 2021 along with two owners of nursing schools in Maryland and Virginia who worked with her. All pled guilty to selling fake degrees for $6,000-$18,000. The Florida Board of Nursing had previously shut down the Palm Beach school in 2017 as a result of its students’ low passing rate on the national licensing exam.

A tip related to the Maryland case led to federal charges in January against 25 owners, operators, and employees of the Palm Beach School of Nursing and two other Florida nursing schools for selling thousands of fake nursing degrees. Those who were charged operated in Delaware, New York, New Jersey, Texas, and Florida.

Five of those 25 defendants will be sentenced on July 27 in a federal district court in Fort Lauderdale after pleading guilty in May to wire fraud conspiracy, according to the U.S. Attorney for the Southern District of Florida. They each face up to 20 years in federal prison.

Purchasers of the fake associate or bachelor’s degrees received transcripts showing that they completed coursework. Some 2,800 of the buyers passed the national nursing licensing exam to become registered nurses and licensed practice nurses/vocational nurses in hospitals, nursing homes, and Veterans Affairs medical centers around the country, according to The New York Times.

Ms. Napoleon’s attorney, Joel DeFabio, said in an interview that he requested a lower sentence than the 4 years recommended in sentencing guidelines because Ms. Napoleon pled guilty quickly and cooperated with the federal investigation.

Mr. DeFabio said that Ms. Napoleon will appear as the government’s witness in a trial in November against Gail Russ, who is one defendant, along with 13 others in the case involving the Palm Beach School of Nursing.

Meanwhile, state nursing boards have been trying to locate nurses who received the fake degrees. In March, the New York nursing board told 903 nurses to either surrender their licenses or prove they had the appropriate education. The board estimated that another 2,300 licensees from the Florida schools had pending applications.

Some nurses who received fake diplomas are pushing back. Attorneys for nurses in Georgia and Pennsylvania claim that their clients were either victims or in some cases, have legitimate credentials.

“The quality of nursing education as well as protection of applicants from these harmful schemes is essential to maintaining the strict standards of the nursing profession,” Ms. Fuller said.

A version of this article appeared on Medscape.com.

The former owner of a South Florida nursing school at the heart of a federal investigation into a multistate fraud scheme awarding at least 7,600 fake diplomas will have to serve nearly 2 years and repay millions.

U.S. District Judge Rodney Smith of the Southern District of Florida in Fort Lauderdale recently sentenced Johanah Napoleon, former president of the Palm Beach School of Nursing, to 21 months in prison, according to the Miami Herald . The judge also ordered Ms. Napoleon to pay about $3.5 million. She already paid $2.6 million of it, the Herald reports.

The sentence is “indicative of the seriousness of this crime,” shared Willa Fuller, BSN, RN, executive director of the Florida Nurses Association. “Hopefully, this decision will deter potential perpetrators in the future,” Ms. Fuller said in an email.

Ms. Napoleon was charged in 2021 along with two owners of nursing schools in Maryland and Virginia who worked with her. All pled guilty to selling fake degrees for $6,000-$18,000. The Florida Board of Nursing had previously shut down the Palm Beach school in 2017 as a result of its students’ low passing rate on the national licensing exam.

A tip related to the Maryland case led to federal charges in January against 25 owners, operators, and employees of the Palm Beach School of Nursing and two other Florida nursing schools for selling thousands of fake nursing degrees. Those who were charged operated in Delaware, New York, New Jersey, Texas, and Florida.

Five of those 25 defendants will be sentenced on July 27 in a federal district court in Fort Lauderdale after pleading guilty in May to wire fraud conspiracy, according to the U.S. Attorney for the Southern District of Florida. They each face up to 20 years in federal prison.

Purchasers of the fake associate or bachelor’s degrees received transcripts showing that they completed coursework. Some 2,800 of the buyers passed the national nursing licensing exam to become registered nurses and licensed practice nurses/vocational nurses in hospitals, nursing homes, and Veterans Affairs medical centers around the country, according to The New York Times.

Ms. Napoleon’s attorney, Joel DeFabio, said in an interview that he requested a lower sentence than the 4 years recommended in sentencing guidelines because Ms. Napoleon pled guilty quickly and cooperated with the federal investigation.

Mr. DeFabio said that Ms. Napoleon will appear as the government’s witness in a trial in November against Gail Russ, who is one defendant, along with 13 others in the case involving the Palm Beach School of Nursing.

Meanwhile, state nursing boards have been trying to locate nurses who received the fake degrees. In March, the New York nursing board told 903 nurses to either surrender their licenses or prove they had the appropriate education. The board estimated that another 2,300 licensees from the Florida schools had pending applications.

Some nurses who received fake diplomas are pushing back. Attorneys for nurses in Georgia and Pennsylvania claim that their clients were either victims or in some cases, have legitimate credentials.

“The quality of nursing education as well as protection of applicants from these harmful schemes is essential to maintaining the strict standards of the nursing profession,” Ms. Fuller said.

A version of this article appeared on Medscape.com.

The tirzepatide weight-loss juggernaut barreled forward with a report on July 27 of positive top-line results from a pair of pivotal trials in adults with obesity or overweight but without diabetes.

The primary weight-loss results from the SURMOUNT-3 and SURMOUNT-4 studies in a combined total of 1,249 randomized adults add to positive data previously reported from more than 3,400 randomized patients in SURMOUNT-1 and SURMOUNT-2, also in people with overweight or obesity. The results from these four trials collectively create a compelling picture of safety and efficacy as tirzepatide (Mounjaro, Lilly) nears a decision, expected later in 2023, from the U.S. Food and Drug Administration for approval as a weight-loss agent in people with or without type 2 diabetes.

Tirzepatide received FDA approval in May 2022 for the indication of improving glycemic control in people with type 2 diabetes.
 

SURMOUNT-3 included intensive lifestyle management

SURMOUNT-3 initially enrolled 806 adults with obesity or overweight plus one or more weight-related comorbidities who received a 12-week intensive lifestyle-intervention program. People who lost at least 5% of their baseline weight could continue, and in the second phase, investigators randomized 579 people to 72 weeks of treatment with weekly injections of tirzepatide or placebo while they continued the lifestyle intervention. In the intervention group, tirzepatide was gradually up-titrated to a 10-mg or 15-mg weekly dose, depending on tolerance.

People taking tirzepatide lost an average of 21.1% of body weight after 72 weeks from time of randomization, compared with an average weight gain of 3.3% among controls, an overall incremental loss of 24.5% of body weight with tirzepatide, compared with placebo, one of the trial’s two primary endpoints. The second primary endpoint was the percentage of people achieving at least a 5% weight loss from time of randomization, which occurred in 94.4% of people taking tirzepatide and 10.7% of controls.
 

SURMOUNT-4 tested tirzepatide discontinuation

SURMOUNT-4 started with a 36-week lead-in period during which 783 adults with obesity or overweight plus comorbidities received weekly injections of tirzepatide, which led to an average weight loss of 21.1% from baseline. Researchers then randomized 670 of these participants to continue weekly tirzepatide for another 52 weeks or continue placebo injections. At the end of the 1-year randomized phase, those who continued tirzepatide had an average additional weight loss of 6.7%, while those who switched to placebo had an average 14.8% weight gain during the 52-week phase, producing a placebo-adjusted weight loss with tirzepatide of 21.4% for this phase.

As a secondary endpoint, those who received tirzepatide continuously for 88 weeks (the 36-week run-in plus the 52-week randomized phase) had an overall average weight loss from baseline of 26.0%. In SURMOUNT-3, participants randomized to receive tirzepatide during the second phase had an overall average weight loss, compared with baseline, before the lifestyle-intervention lead-in of 26.6% during 84 total weeks of treatment. These weight-loss levels, 26.0% and 26.6%, were “the highest level of weight loss observed in the SURMOUNT program to date,” said a Lilly official in a written statement. The findings from this trial also highlighted the importance of ongoing tirzepatide treatment to maintain weight loss.

Safety findings from both trials were consistent with prior studies of tirzepatide, as well as other agents that act by mimicking the action of human incretin hormones, the glucagonlike peptide-1 (GLP-1) receptor agonists. The most common adverse effects with tirzepatide were gastrointestinal and were generally mild to moderate in severity. Tirzepatide is a twincretin that has agonist activity for both the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide receptor.

According to Lilly’s announcement, the SURMOUNT-3 results will be reported at Obesity Week, being held Oct. 14-17 in Dallas, and the SURMOUNT-4 findings will be reported at the European Association for the Study of Diabetes 2023 annual meeting, being held Oct. 2-6 in Hamburg, Germany. 

The SURMOUNT trials have been funded by Lilly, the company that markets tirzepatide (Mounjaro).

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

The tirzepatide weight-loss juggernaut barreled forward with a report on July 27 of positive top-line results from a pair of pivotal trials in adults with obesity or overweight but without diabetes.

The primary weight-loss results from the SURMOUNT-3 and SURMOUNT-4 studies in a combined total of 1,249 randomized adults add to positive data previously reported from more than 3,400 randomized patients in SURMOUNT-1 and SURMOUNT-2, also in people with overweight or obesity. The results from these four trials collectively create a compelling picture of safety and efficacy as tirzepatide (Mounjaro, Lilly) nears a decision, expected later in 2023, from the U.S. Food and Drug Administration for approval as a weight-loss agent in people with or without type 2 diabetes.

Tirzepatide received FDA approval in May 2022 for the indication of improving glycemic control in people with type 2 diabetes.
 

SURMOUNT-3 included intensive lifestyle management

SURMOUNT-3 initially enrolled 806 adults with obesity or overweight plus one or more weight-related comorbidities who received a 12-week intensive lifestyle-intervention program. People who lost at least 5% of their baseline weight could continue, and in the second phase, investigators randomized 579 people to 72 weeks of treatment with weekly injections of tirzepatide or placebo while they continued the lifestyle intervention. In the intervention group, tirzepatide was gradually up-titrated to a 10-mg or 15-mg weekly dose, depending on tolerance.

People taking tirzepatide lost an average of 21.1% of body weight after 72 weeks from time of randomization, compared with an average weight gain of 3.3% among controls, an overall incremental loss of 24.5% of body weight with tirzepatide, compared with placebo, one of the trial’s two primary endpoints. The second primary endpoint was the percentage of people achieving at least a 5% weight loss from time of randomization, which occurred in 94.4% of people taking tirzepatide and 10.7% of controls.
 

SURMOUNT-4 tested tirzepatide discontinuation

SURMOUNT-4 started with a 36-week lead-in period during which 783 adults with obesity or overweight plus comorbidities received weekly injections of tirzepatide, which led to an average weight loss of 21.1% from baseline. Researchers then randomized 670 of these participants to continue weekly tirzepatide for another 52 weeks or continue placebo injections. At the end of the 1-year randomized phase, those who continued tirzepatide had an average additional weight loss of 6.7%, while those who switched to placebo had an average 14.8% weight gain during the 52-week phase, producing a placebo-adjusted weight loss with tirzepatide of 21.4% for this phase.

As a secondary endpoint, those who received tirzepatide continuously for 88 weeks (the 36-week run-in plus the 52-week randomized phase) had an overall average weight loss from baseline of 26.0%. In SURMOUNT-3, participants randomized to receive tirzepatide during the second phase had an overall average weight loss, compared with baseline, before the lifestyle-intervention lead-in of 26.6% during 84 total weeks of treatment. These weight-loss levels, 26.0% and 26.6%, were “the highest level of weight loss observed in the SURMOUNT program to date,” said a Lilly official in a written statement. The findings from this trial also highlighted the importance of ongoing tirzepatide treatment to maintain weight loss.

Safety findings from both trials were consistent with prior studies of tirzepatide, as well as other agents that act by mimicking the action of human incretin hormones, the glucagonlike peptide-1 (GLP-1) receptor agonists. The most common adverse effects with tirzepatide were gastrointestinal and were generally mild to moderate in severity. Tirzepatide is a twincretin that has agonist activity for both the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide receptor.

According to Lilly’s announcement, the SURMOUNT-3 results will be reported at Obesity Week, being held Oct. 14-17 in Dallas, and the SURMOUNT-4 findings will be reported at the European Association for the Study of Diabetes 2023 annual meeting, being held Oct. 2-6 in Hamburg, Germany. 

The SURMOUNT trials have been funded by Lilly, the company that markets tirzepatide (Mounjaro).

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

The tirzepatide weight-loss juggernaut barreled forward with a report on July 27 of positive top-line results from a pair of pivotal trials in adults with obesity or overweight but without diabetes.

The primary weight-loss results from the SURMOUNT-3 and SURMOUNT-4 studies in a combined total of 1,249 randomized adults add to positive data previously reported from more than 3,400 randomized patients in SURMOUNT-1 and SURMOUNT-2, also in people with overweight or obesity. The results from these four trials collectively create a compelling picture of safety and efficacy as tirzepatide (Mounjaro, Lilly) nears a decision, expected later in 2023, from the U.S. Food and Drug Administration for approval as a weight-loss agent in people with or without type 2 diabetes.

Tirzepatide received FDA approval in May 2022 for the indication of improving glycemic control in people with type 2 diabetes.
 

SURMOUNT-3 included intensive lifestyle management

SURMOUNT-3 initially enrolled 806 adults with obesity or overweight plus one or more weight-related comorbidities who received a 12-week intensive lifestyle-intervention program. People who lost at least 5% of their baseline weight could continue, and in the second phase, investigators randomized 579 people to 72 weeks of treatment with weekly injections of tirzepatide or placebo while they continued the lifestyle intervention. In the intervention group, tirzepatide was gradually up-titrated to a 10-mg or 15-mg weekly dose, depending on tolerance.

People taking tirzepatide lost an average of 21.1% of body weight after 72 weeks from time of randomization, compared with an average weight gain of 3.3% among controls, an overall incremental loss of 24.5% of body weight with tirzepatide, compared with placebo, one of the trial’s two primary endpoints. The second primary endpoint was the percentage of people achieving at least a 5% weight loss from time of randomization, which occurred in 94.4% of people taking tirzepatide and 10.7% of controls.
 

SURMOUNT-4 tested tirzepatide discontinuation

SURMOUNT-4 started with a 36-week lead-in period during which 783 adults with obesity or overweight plus comorbidities received weekly injections of tirzepatide, which led to an average weight loss of 21.1% from baseline. Researchers then randomized 670 of these participants to continue weekly tirzepatide for another 52 weeks or continue placebo injections. At the end of the 1-year randomized phase, those who continued tirzepatide had an average additional weight loss of 6.7%, while those who switched to placebo had an average 14.8% weight gain during the 52-week phase, producing a placebo-adjusted weight loss with tirzepatide of 21.4% for this phase.

As a secondary endpoint, those who received tirzepatide continuously for 88 weeks (the 36-week run-in plus the 52-week randomized phase) had an overall average weight loss from baseline of 26.0%. In SURMOUNT-3, participants randomized to receive tirzepatide during the second phase had an overall average weight loss, compared with baseline, before the lifestyle-intervention lead-in of 26.6% during 84 total weeks of treatment. These weight-loss levels, 26.0% and 26.6%, were “the highest level of weight loss observed in the SURMOUNT program to date,” said a Lilly official in a written statement. The findings from this trial also highlighted the importance of ongoing tirzepatide treatment to maintain weight loss.

Safety findings from both trials were consistent with prior studies of tirzepatide, as well as other agents that act by mimicking the action of human incretin hormones, the glucagonlike peptide-1 (GLP-1) receptor agonists. The most common adverse effects with tirzepatide were gastrointestinal and were generally mild to moderate in severity. Tirzepatide is a twincretin that has agonist activity for both the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide receptor.

According to Lilly’s announcement, the SURMOUNT-3 results will be reported at Obesity Week, being held Oct. 14-17 in Dallas, and the SURMOUNT-4 findings will be reported at the European Association for the Study of Diabetes 2023 annual meeting, being held Oct. 2-6 in Hamburg, Germany. 

The SURMOUNT trials have been funded by Lilly, the company that markets tirzepatide (Mounjaro).

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

Randomized controlled trials in oncology can make or break an investigational drug, with both patient lives and pharmaceutical company profits at stake.

These trials typically pit two options against each other, an investigational therapy and a control therapy – often a standard of care – to see which has greater benefit.

But there are ethical gray areas in trial designs that may, intentionally or inadvertently, tip the balance in favor of the experimental arm of a trial. These biases may result in substandard care for trial participants, even harm, and can invalidate or dilute scientific findings.

One major issue is whether participants in the control arm of a trial receive the standard of care or active therapy after disease progression. In clinical trial parlance, this practice is called crossover.

Patients who do not receive standard-of-care therapy after disease progression may be “unfairly disadvantaged,” experts wrote in a commentary published in late June.What’s worse, optimal crossover does not always happen, commentary author Edward R. Scheffer Cliff, MBBS, MPH, from Brigham and Women’s Hospital in Boston said in an interview.

A recent example comes from the ADAURA trial comparing adjuvant therapy with osimertinib (Tagrisso) to placebo following complete resection of localized or locally advanced stage IB-IIIA non–small cell lung cancer (NSCLC) harboring EGFR mutations.

The trial, which began in November 2015, was unblinded early and halted on the recommendation of the independent data-monitoring committee because osimertinib was associated with a nearly 80% reduction in the risk of disease recurrence or death. These data led to the Food and Drug Administration’s 2018 approval of osimertinib as first-line treatment in this setting.

The recent overall survival data from ADAURA, presented at the 2023 American Society of Clinical Oncology annual meeting, helped confirm the drug’s benefit: Osimertinib was associated with a 51% reduced risk for death, compared with placebo.

But critics of this report were troubled by the fact that, despite the reported benefits of osimertinib, only 79 of 205 patients (38.5%) in the control arm who relapsed received the drug – now considered standard of care in this setting.

The low rate of osimertinib crossover represents a serious flaw in the trial design and potentially an ethical problem. 

In the commentary, Dr. Cliff, alongside colleagues Aaron S. Kesselheim, MD, JD, MPH, and William B. Feldman, MD, DPhil, MPH, detailed the ethical issues associated with substandard crossover in clinical trials.

“In the ethical design of clinical trials, patients make important sacrifices to participate, and in exchange, the academic and clinical communities owe them optimal treatment both during the intervention part of the trial and, if they progress, after progression, especially when it is directly in the control of the trial sponsor as to whether a drug that they produce is made available to a clinical trial participant,” Dr. Cliff and colleagues wrote.

The authors highlighted 10 clinical trials – including SHINE, ZUMA-7, CLL14, ALCYONE, and JAVELIN 100 –  that had problematic crossover. In the SHINE trial, for instance, 39% of control arm patients with mantle cell lymphoma received BTKi therapy post progression, while in the ALCYONE trial of multiple myeloma, only 10% of control patients received daratumumab at first progression. The VISION trial had the lowest crossover rate, with only one control arm patient (0.5%) with metastatic castration-resistant prostate cancer receiving lutetium-PSMA-617 after progression.

“Depriving control arm patients access to standard-of-care post-RCT therapy also has important scientific implications,” Dr. Cliff and colleagues wrote. In oncology, “if patients in the control arm do not receive standard-of-care therapy after disease progression, then they are unfairly disadvantaged, and it becomes difficult to assess whether the intervention has indeed improved quality of life or survival.”

Clinical trials should be designed with both ethical behavior and scientific integrity in mind, Dr. Cliff told this news organization. It’s incumbent on everyone directly or peripherally involved in randomized trials to ensure that they are designed with mandatory unblinding at the time of disease progression, and that crossover is both allowed and funded by the trial sponsor and mandated by the trial investigators and FDA.

When it comes to clinical trials and the sacrifices patients make to participate, “I think everyone needs to lift their game,” Dr. Cliff said.

The commentary by Dr. Cliff and colleagues was supported by Arnold Ventures. Dr. Cliff disclosed institutional funding from the firm. Dr. Kesselheim reported reimbursement for expert testimony. Dr. Feldman reported consulting for Alosa Health and Aetion, and expert testimony on litigation.

A version of this article appeared on Medscape.com.

Randomized controlled trials in oncology can make or break an investigational drug, with both patient lives and pharmaceutical company profits at stake.

These trials typically pit two options against each other, an investigational therapy and a control therapy – often a standard of care – to see which has greater benefit.

But there are ethical gray areas in trial designs that may, intentionally or inadvertently, tip the balance in favor of the experimental arm of a trial. These biases may result in substandard care for trial participants, even harm, and can invalidate or dilute scientific findings.

One major issue is whether participants in the control arm of a trial receive the standard of care or active therapy after disease progression. In clinical trial parlance, this practice is called crossover.

Patients who do not receive standard-of-care therapy after disease progression may be “unfairly disadvantaged,” experts wrote in a commentary published in late June.What’s worse, optimal crossover does not always happen, commentary author Edward R. Scheffer Cliff, MBBS, MPH, from Brigham and Women’s Hospital in Boston said in an interview.

A recent example comes from the ADAURA trial comparing adjuvant therapy with osimertinib (Tagrisso) to placebo following complete resection of localized or locally advanced stage IB-IIIA non–small cell lung cancer (NSCLC) harboring EGFR mutations.

The trial, which began in November 2015, was unblinded early and halted on the recommendation of the independent data-monitoring committee because osimertinib was associated with a nearly 80% reduction in the risk of disease recurrence or death. These data led to the Food and Drug Administration’s 2018 approval of osimertinib as first-line treatment in this setting.

The recent overall survival data from ADAURA, presented at the 2023 American Society of Clinical Oncology annual meeting, helped confirm the drug’s benefit: Osimertinib was associated with a 51% reduced risk for death, compared with placebo.

But critics of this report were troubled by the fact that, despite the reported benefits of osimertinib, only 79 of 205 patients (38.5%) in the control arm who relapsed received the drug – now considered standard of care in this setting.

The low rate of osimertinib crossover represents a serious flaw in the trial design and potentially an ethical problem. 

In the commentary, Dr. Cliff, alongside colleagues Aaron S. Kesselheim, MD, JD, MPH, and William B. Feldman, MD, DPhil, MPH, detailed the ethical issues associated with substandard crossover in clinical trials.

“In the ethical design of clinical trials, patients make important sacrifices to participate, and in exchange, the academic and clinical communities owe them optimal treatment both during the intervention part of the trial and, if they progress, after progression, especially when it is directly in the control of the trial sponsor as to whether a drug that they produce is made available to a clinical trial participant,” Dr. Cliff and colleagues wrote.

The authors highlighted 10 clinical trials – including SHINE, ZUMA-7, CLL14, ALCYONE, and JAVELIN 100 –  that had problematic crossover. In the SHINE trial, for instance, 39% of control arm patients with mantle cell lymphoma received BTKi therapy post progression, while in the ALCYONE trial of multiple myeloma, only 10% of control patients received daratumumab at first progression. The VISION trial had the lowest crossover rate, with only one control arm patient (0.5%) with metastatic castration-resistant prostate cancer receiving lutetium-PSMA-617 after progression.

“Depriving control arm patients access to standard-of-care post-RCT therapy also has important scientific implications,” Dr. Cliff and colleagues wrote. In oncology, “if patients in the control arm do not receive standard-of-care therapy after disease progression, then they are unfairly disadvantaged, and it becomes difficult to assess whether the intervention has indeed improved quality of life or survival.”

Clinical trials should be designed with both ethical behavior and scientific integrity in mind, Dr. Cliff told this news organization. It’s incumbent on everyone directly or peripherally involved in randomized trials to ensure that they are designed with mandatory unblinding at the time of disease progression, and that crossover is both allowed and funded by the trial sponsor and mandated by the trial investigators and FDA.

When it comes to clinical trials and the sacrifices patients make to participate, “I think everyone needs to lift their game,” Dr. Cliff said.

The commentary by Dr. Cliff and colleagues was supported by Arnold Ventures. Dr. Cliff disclosed institutional funding from the firm. Dr. Kesselheim reported reimbursement for expert testimony. Dr. Feldman reported consulting for Alosa Health and Aetion, and expert testimony on litigation.

A version of this article appeared on Medscape.com.

Randomized controlled trials in oncology can make or break an investigational drug, with both patient lives and pharmaceutical company profits at stake.

These trials typically pit two options against each other, an investigational therapy and a control therapy – often a standard of care – to see which has greater benefit.

But there are ethical gray areas in trial designs that may, intentionally or inadvertently, tip the balance in favor of the experimental arm of a trial. These biases may result in substandard care for trial participants, even harm, and can invalidate or dilute scientific findings.

One major issue is whether participants in the control arm of a trial receive the standard of care or active therapy after disease progression. In clinical trial parlance, this practice is called crossover.

Patients who do not receive standard-of-care therapy after disease progression may be “unfairly disadvantaged,” experts wrote in a commentary published in late June.What’s worse, optimal crossover does not always happen, commentary author Edward R. Scheffer Cliff, MBBS, MPH, from Brigham and Women’s Hospital in Boston said in an interview.

A recent example comes from the ADAURA trial comparing adjuvant therapy with osimertinib (Tagrisso) to placebo following complete resection of localized or locally advanced stage IB-IIIA non–small cell lung cancer (NSCLC) harboring EGFR mutations.

The trial, which began in November 2015, was unblinded early and halted on the recommendation of the independent data-monitoring committee because osimertinib was associated with a nearly 80% reduction in the risk of disease recurrence or death. These data led to the Food and Drug Administration’s 2018 approval of osimertinib as first-line treatment in this setting.

The recent overall survival data from ADAURA, presented at the 2023 American Society of Clinical Oncology annual meeting, helped confirm the drug’s benefit: Osimertinib was associated with a 51% reduced risk for death, compared with placebo.

But critics of this report were troubled by the fact that, despite the reported benefits of osimertinib, only 79 of 205 patients (38.5%) in the control arm who relapsed received the drug – now considered standard of care in this setting.

The low rate of osimertinib crossover represents a serious flaw in the trial design and potentially an ethical problem. 

In the commentary, Dr. Cliff, alongside colleagues Aaron S. Kesselheim, MD, JD, MPH, and William B. Feldman, MD, DPhil, MPH, detailed the ethical issues associated with substandard crossover in clinical trials.

“In the ethical design of clinical trials, patients make important sacrifices to participate, and in exchange, the academic and clinical communities owe them optimal treatment both during the intervention part of the trial and, if they progress, after progression, especially when it is directly in the control of the trial sponsor as to whether a drug that they produce is made available to a clinical trial participant,” Dr. Cliff and colleagues wrote.

The authors highlighted 10 clinical trials – including SHINE, ZUMA-7, CLL14, ALCYONE, and JAVELIN 100 –  that had problematic crossover. In the SHINE trial, for instance, 39% of control arm patients with mantle cell lymphoma received BTKi therapy post progression, while in the ALCYONE trial of multiple myeloma, only 10% of control patients received daratumumab at first progression. The VISION trial had the lowest crossover rate, with only one control arm patient (0.5%) with metastatic castration-resistant prostate cancer receiving lutetium-PSMA-617 after progression.

“Depriving control arm patients access to standard-of-care post-RCT therapy also has important scientific implications,” Dr. Cliff and colleagues wrote. In oncology, “if patients in the control arm do not receive standard-of-care therapy after disease progression, then they are unfairly disadvantaged, and it becomes difficult to assess whether the intervention has indeed improved quality of life or survival.”

Clinical trials should be designed with both ethical behavior and scientific integrity in mind, Dr. Cliff told this news organization. It’s incumbent on everyone directly or peripherally involved in randomized trials to ensure that they are designed with mandatory unblinding at the time of disease progression, and that crossover is both allowed and funded by the trial sponsor and mandated by the trial investigators and FDA.

When it comes to clinical trials and the sacrifices patients make to participate, “I think everyone needs to lift their game,” Dr. Cliff said.

The commentary by Dr. Cliff and colleagues was supported by Arnold Ventures. Dr. Cliff disclosed institutional funding from the firm. Dr. Kesselheim reported reimbursement for expert testimony. Dr. Feldman reported consulting for Alosa Health and Aetion, and expert testimony on litigation.

A version of this article appeared on Medscape.com.