User login
Treating obesity: Will new drugs end the crisis?
This is the second in a three-part series on the obesity crisis. Part one tackles a complicated question – why does the obesity rate keep rising despite our efforts to stop it? – and can be found here. Part three shows how doctors and patients can make treatment better and can be found here.
In the mid-1980s, Louis J. Aronne, MD, strolled into a lab at Rockefeller University in New York where a colleague was breeding mice. “I will never forget what he showed me,” said Dr. Aronne, now the director of obesity research and treatment at Weill Cornell Medicine in New York. “He had a cage with 10 mice, one severely obese and the others normal weight. He took blood from one of the thin mice and gave it to the fat mouse.”
When Dr. Aronne returned 3 days later, that obese mouse had turned thin.
It was proof of something Dr. Aronne already suspected: Obesity had biological causes and wasn’t just a failure of willpower.
Years later, in 1994, that research led to the discovery of leptin, a hormone released from fat cells that’s involved in the regulation of body weight. It was a watershed moment in obesity research.
Since then, Dr. Aronne and others have worked to build the clinical field of obesity medicine, attempting to shift the public and medical view of obesity from a purely behavioral issue to a disease worthy of medical treatment.
All the while, the U.S. obesity rate soared.
Now, another watershed moment: We finally have highly effective obesity drugs. The hype is real, and so are the weight loss results.
“I’ve been saying for 30 years that when we find treatments that really work, people aren’t going to believe the results,” Dr. Aronne said. “It took longer than I expected, but it’s gratifying now to see.”
The big question
The emerging class of obesity medications known as GLP-1 agonists is indeed a game changer. The weight loss drug semaglutide (Ozempic, Wegovy) showed groundbreaking results, and studies suggest a parade of even more impressive drugs is on the way.
Yes, the drugs offer new hope to millions with obesity complications. But to truly turn the tide on our 42% obesity rate, much more work remains to be done, researchers said, including answering a big question:
How do these weight loss drugs work?
“We have new blockbuster drugs, and we don’t even know why they reduce body weight,” said Samuel Klein, MD, professor of medicine and nutritional science at Washington University in St. Louis. “It was by accident that this was discovered.”
Oops, we created a weight loss drug
Developed to treat diabetes, the GLP-1 drugs’ weight loss effects were a surprise. Now that those effects are confirmed, pharmaceutical companies and researchers are racing to figure out how these drugs work.
In the 1960s, scientists discovered the incretin effect – when you eat glucose (sugar), your body makes more insulin than it does if glucose is given intravenously. Glucose passes through the GI tract and the gut releases hormones that stimulate insulin secretion. It’s “essentially a feed-forward signal to your pancreas to tell it, ‘By the way, you need to be ready because there’s a bunch of glucose coming,’ ” said Randy Seeley, MD, director of the Michigan Nutrition Obesity Research Center, funded by the National Institutes of Health.
One of these hormones – or “incretins” – is GLP-1. In experiments, people with type 2 diabetes who were hooked up to GLP-1 saw their blood sugar go down.
“That led to the idea that if we could take this native hormone and make it last longer, we’d have a therapy for type 2 diabetes,” said Dr. Seeley. Thanks to a GLP-1-like compound in the saliva of the Gila monster, that idea became reality in the 2000s.
Along the way, a surprising side finding came to light: In early trials, diabetes patients on these drugs dropped weight.
Both Ozempic and Wegovy – brand names for semaglutide – are once-weekly injections (pill forms to treat obesity are on the way), but the latter is a higher dose.
“That dose results in about 40% of patients in the clinical trials achieving a 20% weight loss. We’ve just had nothing like that in terms of efficacy before,” said Dr. Seeley, who has worked with some of the drug companies (including Novo Nordisk, the maker of Ozempic and Wegovy, and Eli Lilly, maker of Mounjaro) that market the GLP-1s.
By contrast, semaglutide’s once-a-day predecessor liraglutide (Saxenda, made by Novo Nordisk) can lead to about 10% weight loss.
“And one of the ironies is, we don’t really know why,” Dr. Seeley said. “We don’t know why semaglutide is a better molecule for weight loss than liraglutide.”
Initially, scientists believed that the drugs, in addition to telling the pancreas to secrete more insulin, were also signaling the brain that you’re full. “Turns out that’s not really the way it works,” Dr. Seeley said. “GLP-1 made from your gut probably doesn’t get into your brain very much. But you make GLP-1 in your brain as well.”
For weight loss, it’s the brain’s GLP-1 system, not the gut’s, that the drugs are thought to hijack. But exactly which parts of the brain they affect and how is unknown. “That’s something lots of people are working on, including our own lab,” Dr. Seeley said. (Another surprise: The drugs may have potential as an anti-addiction treatment.)
The diabetes medication tirzepatide (Mounjaro), expected to be approved for weight loss as early as this year, is also a weekly injection, but it has a unique feature: It starts a response not just for GLP-1 but also for another incretin called GIP. Turns out, two is better than one: Trial participants on tirzepatide lost up to 22.5% of their body weight.
More of these hybrid drugs are on the way, Dr. Seeley said. In mid-stage clinical trials, the drug retatrutide, which targets three hormones, led to 24% weight loss. “The idea is the more bullets we can load into the gun, the more we can push the biology into a place where it’s easier to lose weight.”
Shifting from prevention to damage control
Less invasive and more scalable than surgery (only 1% of the eligible population gets bariatric surgery), the drugs offer doctors a safe, effective way to treat many patients with obesity. That’s cause for excitement, but concerns remain because they are expensive, costing about $800 to $1,300 per month out of pocket. Many health insurers, including Medicare, do not cover them for weight loss.
“You have this significant advance in obesity treatment, but very few will be able to access it,” said Gary Foster, PhD, adjunct professor of psychology in psychiatry at the University of Pennsylvania, Philadelphia, and chief scientific officer at WW (formerly Weight Watchers).
There is a push, including a proposed bill, to get Medicare to cover obesity medication. But given the expense of the drugs, the health economics do not support that move, according to an editorial in the New England Journal of Medicine. If Medicare were to cover obesity meds, the budget impact would likely be huge, potentially driving up premiums. If other payers followed suit, the impact could be felt across the U.S. health care system.
Other drawbacks include side effects – including nausea, diarrhea, stomach pain, and vomiting – that can be so bad that some patients can’t tolerate them.
And critically, the drugs do not deal with the root cause of the problem, said Robert Lustig, MD, an endocrinologist and pediatrician at the University of California, San Francisco, who has suggested that excess insulin is driving obesity. “No one has the disease that these drugs are treating. No one has GLP-1 deficiency. They’re bypassing the problem. They’re band-aiding the problem.”
Because the drugs work by mimicking starvation – they appear to curb hunger, so you eat less – people on them lose not just fat but also healthy lean mass, Dr. Lustig said.
Concerns about pancreatitis did not really bear out in postmarketing reports. (The drugs are still not recommended in people with pancreatitis or multiple endocrine neoplasia.) But predicting longer-term outcomes can be difficult, noted Dr. Lustig.
Then there are philosophical questions, said James Hill, PhD, director of the Nutrition Obesity Research Center at the University of Alabama at Birmingham.. “If you’re continuing to not exercise and eat not healthy foods and take a medication, is that success? Have we won when people are at a lower weight but not doing a healthy behavior?”
‘We can’t treat our way out of this’
The fact is, ending the obesity epidemic is a tall order, even for drugs as impressive as these.
“We can’t treat our way out of this,” said Jamy Ard, MD, codirector of Wake Forest Baptist Health Weight Management Center in Winston-Salem, N.C. “The treatments we have now are great, and there will be more coming. But we do need to figure out the prevention side of things.”
Dr. Seeley agreed but added that we can’t diet-and-exercise our way out either.
“There’s no switch to be flipped,” Dr. Seeley said. “If you told me we shouldn’t spend all this money on these drugs, we should spend it on prevention – great! What would we do?”
And prevention efforts won’t help the millions already living with health problems from obesity, Dr. Aronne said.
“Getting people to stop smoking prevents lung cancer. But stopping smoking doesn’t treat lung cancer,” Dr. Aronne said. “Once the physical changes occur in the lung that cause a tumor to grow, it’s too late. You have to think of obesity the same way.”
Dr. Seeley pointed out that “fearmongering” around the drugs highlights our lingering bias that obesity is a lifestyle issue that should not be medically treated.
“People say, ‘When you stop taking it, you’re going to gain the weight back,’ ” Dr. Seeley said. “There’s truth to that, but when you stop taking your hypertension medication, your blood pressure goes up. We don’t think of that as a [reason] for why you shouldn’t take your blood pressure medication. But that gets trumpeted into all these conversations about whether people [with obesity] should be treated at all.”
Like obesity, blood pressure was once thought to be a behavioral problem, Dr. Aronne said. But blood pressure meds prevent heart attacks and strokes. And it’s likely obesity meds will do the same.
One 55-year-old patient on the road to kidney failure lost weight on obesity medications, including semaglutide, Dr. Aronne said. Now, 6 years later, his kidney function is back to normal. “Normally, we think of kidney disease as irreversible,” Dr. Aronne said.
In that respect, these drugs should save money in the long run by virtue of heading off those health care costs, said Dr. Seeley, who imagines a future where obesity is not gone but better managed, like high blood pressure is now.
In the end, the drugs are another step toward what Dr. Aronne and many others have always pushed for: Treating obesity as a disease.
A version of this article originally appeared on WebMD.com.
This is the second in a three-part series on the obesity crisis. Part one tackles a complicated question – why does the obesity rate keep rising despite our efforts to stop it? – and can be found here. Part three shows how doctors and patients can make treatment better and can be found here.
In the mid-1980s, Louis J. Aronne, MD, strolled into a lab at Rockefeller University in New York where a colleague was breeding mice. “I will never forget what he showed me,” said Dr. Aronne, now the director of obesity research and treatment at Weill Cornell Medicine in New York. “He had a cage with 10 mice, one severely obese and the others normal weight. He took blood from one of the thin mice and gave it to the fat mouse.”
When Dr. Aronne returned 3 days later, that obese mouse had turned thin.
It was proof of something Dr. Aronne already suspected: Obesity had biological causes and wasn’t just a failure of willpower.
Years later, in 1994, that research led to the discovery of leptin, a hormone released from fat cells that’s involved in the regulation of body weight. It was a watershed moment in obesity research.
Since then, Dr. Aronne and others have worked to build the clinical field of obesity medicine, attempting to shift the public and medical view of obesity from a purely behavioral issue to a disease worthy of medical treatment.
All the while, the U.S. obesity rate soared.
Now, another watershed moment: We finally have highly effective obesity drugs. The hype is real, and so are the weight loss results.
“I’ve been saying for 30 years that when we find treatments that really work, people aren’t going to believe the results,” Dr. Aronne said. “It took longer than I expected, but it’s gratifying now to see.”
The big question
The emerging class of obesity medications known as GLP-1 agonists is indeed a game changer. The weight loss drug semaglutide (Ozempic, Wegovy) showed groundbreaking results, and studies suggest a parade of even more impressive drugs is on the way.
Yes, the drugs offer new hope to millions with obesity complications. But to truly turn the tide on our 42% obesity rate, much more work remains to be done, researchers said, including answering a big question:
How do these weight loss drugs work?
“We have new blockbuster drugs, and we don’t even know why they reduce body weight,” said Samuel Klein, MD, professor of medicine and nutritional science at Washington University in St. Louis. “It was by accident that this was discovered.”
Oops, we created a weight loss drug
Developed to treat diabetes, the GLP-1 drugs’ weight loss effects were a surprise. Now that those effects are confirmed, pharmaceutical companies and researchers are racing to figure out how these drugs work.
In the 1960s, scientists discovered the incretin effect – when you eat glucose (sugar), your body makes more insulin than it does if glucose is given intravenously. Glucose passes through the GI tract and the gut releases hormones that stimulate insulin secretion. It’s “essentially a feed-forward signal to your pancreas to tell it, ‘By the way, you need to be ready because there’s a bunch of glucose coming,’ ” said Randy Seeley, MD, director of the Michigan Nutrition Obesity Research Center, funded by the National Institutes of Health.
One of these hormones – or “incretins” – is GLP-1. In experiments, people with type 2 diabetes who were hooked up to GLP-1 saw their blood sugar go down.
“That led to the idea that if we could take this native hormone and make it last longer, we’d have a therapy for type 2 diabetes,” said Dr. Seeley. Thanks to a GLP-1-like compound in the saliva of the Gila monster, that idea became reality in the 2000s.
Along the way, a surprising side finding came to light: In early trials, diabetes patients on these drugs dropped weight.
Both Ozempic and Wegovy – brand names for semaglutide – are once-weekly injections (pill forms to treat obesity are on the way), but the latter is a higher dose.
“That dose results in about 40% of patients in the clinical trials achieving a 20% weight loss. We’ve just had nothing like that in terms of efficacy before,” said Dr. Seeley, who has worked with some of the drug companies (including Novo Nordisk, the maker of Ozempic and Wegovy, and Eli Lilly, maker of Mounjaro) that market the GLP-1s.
By contrast, semaglutide’s once-a-day predecessor liraglutide (Saxenda, made by Novo Nordisk) can lead to about 10% weight loss.
“And one of the ironies is, we don’t really know why,” Dr. Seeley said. “We don’t know why semaglutide is a better molecule for weight loss than liraglutide.”
Initially, scientists believed that the drugs, in addition to telling the pancreas to secrete more insulin, were also signaling the brain that you’re full. “Turns out that’s not really the way it works,” Dr. Seeley said. “GLP-1 made from your gut probably doesn’t get into your brain very much. But you make GLP-1 in your brain as well.”
For weight loss, it’s the brain’s GLP-1 system, not the gut’s, that the drugs are thought to hijack. But exactly which parts of the brain they affect and how is unknown. “That’s something lots of people are working on, including our own lab,” Dr. Seeley said. (Another surprise: The drugs may have potential as an anti-addiction treatment.)
The diabetes medication tirzepatide (Mounjaro), expected to be approved for weight loss as early as this year, is also a weekly injection, but it has a unique feature: It starts a response not just for GLP-1 but also for another incretin called GIP. Turns out, two is better than one: Trial participants on tirzepatide lost up to 22.5% of their body weight.
More of these hybrid drugs are on the way, Dr. Seeley said. In mid-stage clinical trials, the drug retatrutide, which targets three hormones, led to 24% weight loss. “The idea is the more bullets we can load into the gun, the more we can push the biology into a place where it’s easier to lose weight.”
Shifting from prevention to damage control
Less invasive and more scalable than surgery (only 1% of the eligible population gets bariatric surgery), the drugs offer doctors a safe, effective way to treat many patients with obesity. That’s cause for excitement, but concerns remain because they are expensive, costing about $800 to $1,300 per month out of pocket. Many health insurers, including Medicare, do not cover them for weight loss.
“You have this significant advance in obesity treatment, but very few will be able to access it,” said Gary Foster, PhD, adjunct professor of psychology in psychiatry at the University of Pennsylvania, Philadelphia, and chief scientific officer at WW (formerly Weight Watchers).
There is a push, including a proposed bill, to get Medicare to cover obesity medication. But given the expense of the drugs, the health economics do not support that move, according to an editorial in the New England Journal of Medicine. If Medicare were to cover obesity meds, the budget impact would likely be huge, potentially driving up premiums. If other payers followed suit, the impact could be felt across the U.S. health care system.
Other drawbacks include side effects – including nausea, diarrhea, stomach pain, and vomiting – that can be so bad that some patients can’t tolerate them.
And critically, the drugs do not deal with the root cause of the problem, said Robert Lustig, MD, an endocrinologist and pediatrician at the University of California, San Francisco, who has suggested that excess insulin is driving obesity. “No one has the disease that these drugs are treating. No one has GLP-1 deficiency. They’re bypassing the problem. They’re band-aiding the problem.”
Because the drugs work by mimicking starvation – they appear to curb hunger, so you eat less – people on them lose not just fat but also healthy lean mass, Dr. Lustig said.
Concerns about pancreatitis did not really bear out in postmarketing reports. (The drugs are still not recommended in people with pancreatitis or multiple endocrine neoplasia.) But predicting longer-term outcomes can be difficult, noted Dr. Lustig.
Then there are philosophical questions, said James Hill, PhD, director of the Nutrition Obesity Research Center at the University of Alabama at Birmingham.. “If you’re continuing to not exercise and eat not healthy foods and take a medication, is that success? Have we won when people are at a lower weight but not doing a healthy behavior?”
‘We can’t treat our way out of this’
The fact is, ending the obesity epidemic is a tall order, even for drugs as impressive as these.
“We can’t treat our way out of this,” said Jamy Ard, MD, codirector of Wake Forest Baptist Health Weight Management Center in Winston-Salem, N.C. “The treatments we have now are great, and there will be more coming. But we do need to figure out the prevention side of things.”
Dr. Seeley agreed but added that we can’t diet-and-exercise our way out either.
“There’s no switch to be flipped,” Dr. Seeley said. “If you told me we shouldn’t spend all this money on these drugs, we should spend it on prevention – great! What would we do?”
And prevention efforts won’t help the millions already living with health problems from obesity, Dr. Aronne said.
“Getting people to stop smoking prevents lung cancer. But stopping smoking doesn’t treat lung cancer,” Dr. Aronne said. “Once the physical changes occur in the lung that cause a tumor to grow, it’s too late. You have to think of obesity the same way.”
Dr. Seeley pointed out that “fearmongering” around the drugs highlights our lingering bias that obesity is a lifestyle issue that should not be medically treated.
“People say, ‘When you stop taking it, you’re going to gain the weight back,’ ” Dr. Seeley said. “There’s truth to that, but when you stop taking your hypertension medication, your blood pressure goes up. We don’t think of that as a [reason] for why you shouldn’t take your blood pressure medication. But that gets trumpeted into all these conversations about whether people [with obesity] should be treated at all.”
Like obesity, blood pressure was once thought to be a behavioral problem, Dr. Aronne said. But blood pressure meds prevent heart attacks and strokes. And it’s likely obesity meds will do the same.
One 55-year-old patient on the road to kidney failure lost weight on obesity medications, including semaglutide, Dr. Aronne said. Now, 6 years later, his kidney function is back to normal. “Normally, we think of kidney disease as irreversible,” Dr. Aronne said.
In that respect, these drugs should save money in the long run by virtue of heading off those health care costs, said Dr. Seeley, who imagines a future where obesity is not gone but better managed, like high blood pressure is now.
In the end, the drugs are another step toward what Dr. Aronne and many others have always pushed for: Treating obesity as a disease.
A version of this article originally appeared on WebMD.com.
This is the second in a three-part series on the obesity crisis. Part one tackles a complicated question – why does the obesity rate keep rising despite our efforts to stop it? – and can be found here. Part three shows how doctors and patients can make treatment better and can be found here.
In the mid-1980s, Louis J. Aronne, MD, strolled into a lab at Rockefeller University in New York where a colleague was breeding mice. “I will never forget what he showed me,” said Dr. Aronne, now the director of obesity research and treatment at Weill Cornell Medicine in New York. “He had a cage with 10 mice, one severely obese and the others normal weight. He took blood from one of the thin mice and gave it to the fat mouse.”
When Dr. Aronne returned 3 days later, that obese mouse had turned thin.
It was proof of something Dr. Aronne already suspected: Obesity had biological causes and wasn’t just a failure of willpower.
Years later, in 1994, that research led to the discovery of leptin, a hormone released from fat cells that’s involved in the regulation of body weight. It was a watershed moment in obesity research.
Since then, Dr. Aronne and others have worked to build the clinical field of obesity medicine, attempting to shift the public and medical view of obesity from a purely behavioral issue to a disease worthy of medical treatment.
All the while, the U.S. obesity rate soared.
Now, another watershed moment: We finally have highly effective obesity drugs. The hype is real, and so are the weight loss results.
“I’ve been saying for 30 years that when we find treatments that really work, people aren’t going to believe the results,” Dr. Aronne said. “It took longer than I expected, but it’s gratifying now to see.”
The big question
The emerging class of obesity medications known as GLP-1 agonists is indeed a game changer. The weight loss drug semaglutide (Ozempic, Wegovy) showed groundbreaking results, and studies suggest a parade of even more impressive drugs is on the way.
Yes, the drugs offer new hope to millions with obesity complications. But to truly turn the tide on our 42% obesity rate, much more work remains to be done, researchers said, including answering a big question:
How do these weight loss drugs work?
“We have new blockbuster drugs, and we don’t even know why they reduce body weight,” said Samuel Klein, MD, professor of medicine and nutritional science at Washington University in St. Louis. “It was by accident that this was discovered.”
Oops, we created a weight loss drug
Developed to treat diabetes, the GLP-1 drugs’ weight loss effects were a surprise. Now that those effects are confirmed, pharmaceutical companies and researchers are racing to figure out how these drugs work.
In the 1960s, scientists discovered the incretin effect – when you eat glucose (sugar), your body makes more insulin than it does if glucose is given intravenously. Glucose passes through the GI tract and the gut releases hormones that stimulate insulin secretion. It’s “essentially a feed-forward signal to your pancreas to tell it, ‘By the way, you need to be ready because there’s a bunch of glucose coming,’ ” said Randy Seeley, MD, director of the Michigan Nutrition Obesity Research Center, funded by the National Institutes of Health.
One of these hormones – or “incretins” – is GLP-1. In experiments, people with type 2 diabetes who were hooked up to GLP-1 saw their blood sugar go down.
“That led to the idea that if we could take this native hormone and make it last longer, we’d have a therapy for type 2 diabetes,” said Dr. Seeley. Thanks to a GLP-1-like compound in the saliva of the Gila monster, that idea became reality in the 2000s.
Along the way, a surprising side finding came to light: In early trials, diabetes patients on these drugs dropped weight.
Both Ozempic and Wegovy – brand names for semaglutide – are once-weekly injections (pill forms to treat obesity are on the way), but the latter is a higher dose.
“That dose results in about 40% of patients in the clinical trials achieving a 20% weight loss. We’ve just had nothing like that in terms of efficacy before,” said Dr. Seeley, who has worked with some of the drug companies (including Novo Nordisk, the maker of Ozempic and Wegovy, and Eli Lilly, maker of Mounjaro) that market the GLP-1s.
By contrast, semaglutide’s once-a-day predecessor liraglutide (Saxenda, made by Novo Nordisk) can lead to about 10% weight loss.
“And one of the ironies is, we don’t really know why,” Dr. Seeley said. “We don’t know why semaglutide is a better molecule for weight loss than liraglutide.”
Initially, scientists believed that the drugs, in addition to telling the pancreas to secrete more insulin, were also signaling the brain that you’re full. “Turns out that’s not really the way it works,” Dr. Seeley said. “GLP-1 made from your gut probably doesn’t get into your brain very much. But you make GLP-1 in your brain as well.”
For weight loss, it’s the brain’s GLP-1 system, not the gut’s, that the drugs are thought to hijack. But exactly which parts of the brain they affect and how is unknown. “That’s something lots of people are working on, including our own lab,” Dr. Seeley said. (Another surprise: The drugs may have potential as an anti-addiction treatment.)
The diabetes medication tirzepatide (Mounjaro), expected to be approved for weight loss as early as this year, is also a weekly injection, but it has a unique feature: It starts a response not just for GLP-1 but also for another incretin called GIP. Turns out, two is better than one: Trial participants on tirzepatide lost up to 22.5% of their body weight.
More of these hybrid drugs are on the way, Dr. Seeley said. In mid-stage clinical trials, the drug retatrutide, which targets three hormones, led to 24% weight loss. “The idea is the more bullets we can load into the gun, the more we can push the biology into a place where it’s easier to lose weight.”
Shifting from prevention to damage control
Less invasive and more scalable than surgery (only 1% of the eligible population gets bariatric surgery), the drugs offer doctors a safe, effective way to treat many patients with obesity. That’s cause for excitement, but concerns remain because they are expensive, costing about $800 to $1,300 per month out of pocket. Many health insurers, including Medicare, do not cover them for weight loss.
“You have this significant advance in obesity treatment, but very few will be able to access it,” said Gary Foster, PhD, adjunct professor of psychology in psychiatry at the University of Pennsylvania, Philadelphia, and chief scientific officer at WW (formerly Weight Watchers).
There is a push, including a proposed bill, to get Medicare to cover obesity medication. But given the expense of the drugs, the health economics do not support that move, according to an editorial in the New England Journal of Medicine. If Medicare were to cover obesity meds, the budget impact would likely be huge, potentially driving up premiums. If other payers followed suit, the impact could be felt across the U.S. health care system.
Other drawbacks include side effects – including nausea, diarrhea, stomach pain, and vomiting – that can be so bad that some patients can’t tolerate them.
And critically, the drugs do not deal with the root cause of the problem, said Robert Lustig, MD, an endocrinologist and pediatrician at the University of California, San Francisco, who has suggested that excess insulin is driving obesity. “No one has the disease that these drugs are treating. No one has GLP-1 deficiency. They’re bypassing the problem. They’re band-aiding the problem.”
Because the drugs work by mimicking starvation – they appear to curb hunger, so you eat less – people on them lose not just fat but also healthy lean mass, Dr. Lustig said.
Concerns about pancreatitis did not really bear out in postmarketing reports. (The drugs are still not recommended in people with pancreatitis or multiple endocrine neoplasia.) But predicting longer-term outcomes can be difficult, noted Dr. Lustig.
Then there are philosophical questions, said James Hill, PhD, director of the Nutrition Obesity Research Center at the University of Alabama at Birmingham.. “If you’re continuing to not exercise and eat not healthy foods and take a medication, is that success? Have we won when people are at a lower weight but not doing a healthy behavior?”
‘We can’t treat our way out of this’
The fact is, ending the obesity epidemic is a tall order, even for drugs as impressive as these.
“We can’t treat our way out of this,” said Jamy Ard, MD, codirector of Wake Forest Baptist Health Weight Management Center in Winston-Salem, N.C. “The treatments we have now are great, and there will be more coming. But we do need to figure out the prevention side of things.”
Dr. Seeley agreed but added that we can’t diet-and-exercise our way out either.
“There’s no switch to be flipped,” Dr. Seeley said. “If you told me we shouldn’t spend all this money on these drugs, we should spend it on prevention – great! What would we do?”
And prevention efforts won’t help the millions already living with health problems from obesity, Dr. Aronne said.
“Getting people to stop smoking prevents lung cancer. But stopping smoking doesn’t treat lung cancer,” Dr. Aronne said. “Once the physical changes occur in the lung that cause a tumor to grow, it’s too late. You have to think of obesity the same way.”
Dr. Seeley pointed out that “fearmongering” around the drugs highlights our lingering bias that obesity is a lifestyle issue that should not be medically treated.
“People say, ‘When you stop taking it, you’re going to gain the weight back,’ ” Dr. Seeley said. “There’s truth to that, but when you stop taking your hypertension medication, your blood pressure goes up. We don’t think of that as a [reason] for why you shouldn’t take your blood pressure medication. But that gets trumpeted into all these conversations about whether people [with obesity] should be treated at all.”
Like obesity, blood pressure was once thought to be a behavioral problem, Dr. Aronne said. But blood pressure meds prevent heart attacks and strokes. And it’s likely obesity meds will do the same.
One 55-year-old patient on the road to kidney failure lost weight on obesity medications, including semaglutide, Dr. Aronne said. Now, 6 years later, his kidney function is back to normal. “Normally, we think of kidney disease as irreversible,” Dr. Aronne said.
In that respect, these drugs should save money in the long run by virtue of heading off those health care costs, said Dr. Seeley, who imagines a future where obesity is not gone but better managed, like high blood pressure is now.
In the end, the drugs are another step toward what Dr. Aronne and many others have always pushed for: Treating obesity as a disease.
A version of this article originally appeared on WebMD.com.
GLP-1 agonists offer multiple benefits in type 2 diabetes with liver cirrhosis
Topline
, new observational data show.
Methodology
- Population-based cohort study using data from the National Health Insurance Research Database of Taiwan.
- Propensity-score matching was used to construct 467 matched pairs of GLP-1 RA users and nonusers (mean age, 57) with T2D and compensated liver cirrhosis.
- All-cause mortality, cardiovascular events, decompensated cirrhosis, and other key outcomes were compared using multivariable-adjusted Cox proportional hazards models.
Takeaway
- During mean follow-up of about 3 years, rates of death per 1,000 person-years were 27.5 in GLP-1 RA users versus 55.9 in nonusers.
- GLP-1 RA users had a significantly lower risk for mortality (adjusted hazard ratio [aHR], 0.47), cardiovascular events (aHR, 0.6), decompensated cirrhosis (aHR, 0.7), hepatic encephalopathy (aHR, 0.59), and liver failure (aHR, 0.54).
- A longer cumulative duration of GLP-1 RA use was associated with lower risk for these outcomes compared with no use.
In practice
“GLP-1 RAs may be a treatment option for diabetes patients with liver cirrhosis. However, additional studies are needed to confirm our results and to explore the mechanisms of GLP-1 RAs, cirrhotic decompensation and hepatic encephalopathy,” the researchers concluded.
Study details
The study was led by Fu-Shun Yen, Dr Yen’s Clinic, Taoyuan, Taiwan. It was published online June 16, 2023, in Clinical Gastroenterology and Hepatology. Funding was provided in part by the Taiwan Ministry of Health and Welfare Clinical Trial Center, China Medical University Hospital, Taipei Veterans General Hospital, and the Ministry of Science and Technology.
Limitations
Limitations of the study include a lack of complete information on family history, diet, body weight, and physical activity, as well as biochemical tests, hemoglobin A1c, pathology, and imaging findings that could potentially influence the results.
Disclosures
The authors disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Topline
, new observational data show.
Methodology
- Population-based cohort study using data from the National Health Insurance Research Database of Taiwan.
- Propensity-score matching was used to construct 467 matched pairs of GLP-1 RA users and nonusers (mean age, 57) with T2D and compensated liver cirrhosis.
- All-cause mortality, cardiovascular events, decompensated cirrhosis, and other key outcomes were compared using multivariable-adjusted Cox proportional hazards models.
Takeaway
- During mean follow-up of about 3 years, rates of death per 1,000 person-years were 27.5 in GLP-1 RA users versus 55.9 in nonusers.
- GLP-1 RA users had a significantly lower risk for mortality (adjusted hazard ratio [aHR], 0.47), cardiovascular events (aHR, 0.6), decompensated cirrhosis (aHR, 0.7), hepatic encephalopathy (aHR, 0.59), and liver failure (aHR, 0.54).
- A longer cumulative duration of GLP-1 RA use was associated with lower risk for these outcomes compared with no use.
In practice
“GLP-1 RAs may be a treatment option for diabetes patients with liver cirrhosis. However, additional studies are needed to confirm our results and to explore the mechanisms of GLP-1 RAs, cirrhotic decompensation and hepatic encephalopathy,” the researchers concluded.
Study details
The study was led by Fu-Shun Yen, Dr Yen’s Clinic, Taoyuan, Taiwan. It was published online June 16, 2023, in Clinical Gastroenterology and Hepatology. Funding was provided in part by the Taiwan Ministry of Health and Welfare Clinical Trial Center, China Medical University Hospital, Taipei Veterans General Hospital, and the Ministry of Science and Technology.
Limitations
Limitations of the study include a lack of complete information on family history, diet, body weight, and physical activity, as well as biochemical tests, hemoglobin A1c, pathology, and imaging findings that could potentially influence the results.
Disclosures
The authors disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Topline
, new observational data show.
Methodology
- Population-based cohort study using data from the National Health Insurance Research Database of Taiwan.
- Propensity-score matching was used to construct 467 matched pairs of GLP-1 RA users and nonusers (mean age, 57) with T2D and compensated liver cirrhosis.
- All-cause mortality, cardiovascular events, decompensated cirrhosis, and other key outcomes were compared using multivariable-adjusted Cox proportional hazards models.
Takeaway
- During mean follow-up of about 3 years, rates of death per 1,000 person-years were 27.5 in GLP-1 RA users versus 55.9 in nonusers.
- GLP-1 RA users had a significantly lower risk for mortality (adjusted hazard ratio [aHR], 0.47), cardiovascular events (aHR, 0.6), decompensated cirrhosis (aHR, 0.7), hepatic encephalopathy (aHR, 0.59), and liver failure (aHR, 0.54).
- A longer cumulative duration of GLP-1 RA use was associated with lower risk for these outcomes compared with no use.
In practice
“GLP-1 RAs may be a treatment option for diabetes patients with liver cirrhosis. However, additional studies are needed to confirm our results and to explore the mechanisms of GLP-1 RAs, cirrhotic decompensation and hepatic encephalopathy,” the researchers concluded.
Study details
The study was led by Fu-Shun Yen, Dr Yen’s Clinic, Taoyuan, Taiwan. It was published online June 16, 2023, in Clinical Gastroenterology and Hepatology. Funding was provided in part by the Taiwan Ministry of Health and Welfare Clinical Trial Center, China Medical University Hospital, Taipei Veterans General Hospital, and the Ministry of Science and Technology.
Limitations
Limitations of the study include a lack of complete information on family history, diet, body weight, and physical activity, as well as biochemical tests, hemoglobin A1c, pathology, and imaging findings that could potentially influence the results.
Disclosures
The authors disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Education before Ramadan key to safe fasting with diabetes
SAN DIEGO – An assessment of people with diabetes before Ramadan is vital so they can learn whether it is safe for them to fast, and if it is, how to do so without jeopardizing their health.
“With correct advice and support” from knowledgeable health care professionals “most people with type 2 diabetes can fast safely during Ramadan,” Mohamed Hassanein, MBChB, said at the annual scientific sessions of the American Diabetes Association.
One of the most authoritative guidelines on how people with diabetes can safely fast during Ramadan has come from a collaboration between the International Diabetes Federation and the Diabetes & Ramadan International Alliance, an organization chaired by Dr. Hassanein. The groups issued a revised practical guide in 2021 for Ramadan fasting for people with diabetes, an update of the first edition released in 2016. Dr. Hassanein was lead author of the 2016 guidelines and edited the 2021 revision.
The 2021 guidelines also led to an update of a risk stratification app available for free from the DAR. The app provides risk stratification for people with diabetes and helps them access educational material to guide them through their fasts.
Although the latest guidelines address fasting for people with type 1 or type 2 diabetes, far more people with type 2 diabetes are at risk from fasting, and not only because of the higher prevalence of type 2 diabetes.
Results from a global survey of Muslims with diabetes in 2020 showed that 30% of those with type 1 diabetes did not do any fasting during Ramadan, but the percentage of those abstaining from fasting dropped to 16% among Muslims with type 2 diabetes, Dr. Hassanein explained. (Survey results in 2013 from about 38,000 Muslims in 39 countries showed a median of 7% of all adults did no fasting during Ramadan.)
Risk assessment by app
Currently, the DAR app is available in Arabic, English, French, and Urdu (the primary language of Pakistan), with more languages being added soon, said Dr. Hassanein, an endocrinologist at Dubai Hospital and professor at Mohammed Bin-Rashid University of Medicine & Health Sciences in Dubai, United Arab Emirates.
The app and screening protocol divides people with diabetes into low-, moderate-, and high-risk subgroups, and those at high risk are advised to refrain from fasting.
But the many other people with diabetes who potentially could fast still face risks for hypoglycemia, hyperglycemia (from overindulgent break-fast meals), diabetic ketoacidosis, dehydration, and thrombosis. Individual risk for these adverse events depends on many factors, including age, duration of diabetes, diabetes type, treatments received, history of hypoglycemia, and diabetes complications.
Dr. Hassanein and colleagues documented the high rate of complications from fasting in a 2020 survey of more than 5,800 Muslims with type 2 diabetes from 20 countries. The results showed that 72% of survey participants had to interrupt their 30 days of daily fasting for at least 1 day because of a diabetes-related event, and an additional 28% had diabetes-triggered interruptions that totaled more than 7 days. About 7% required hospitalization or an emergency department visit, and 16% developed at least one episode of daytime hypoglycemia.
Endorsement from Islamic clerics
The recommended risk assessment, and resulting exemptions from fasting, have been endorsed by the Mofty of Egypt, a group of religious scholars who issue legal opinions interpreting Islamic law.
The Mofty agreed that fasting should be interrupted for cases of hypoglycemia with blood glucose less than 70 mg/dL, hyperglycemia with blood glucose greater than 300 mg/dL, symptoms of hypo- or hyperglycemia, or symptoms of acute illness. The Mofty also endorsed that although fasting is obligatory for low-risk adults with diabetes and preferred for those with moderate-risk diabetes, the latter group may consider not fasting out of concern for their safety or to take prescribed medications. People at high risk were deemed by the Mofty as individuals who should not fast because of the potential for harm.
Other notable 2020 survey findings included pre-Ramadan education being received by just 43% of the respondents, and no self-monitoring of blood glucose performed by about a quarter of the respondents.
The 2021 guidelines also include treatment recommendations, such as avoiding older, longer-acting sulfonylurea agents in people with type 2 diabetes. And having people achieve stable, guideline-directed dosages of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide-1 (GLP-1) agonists before Ramadan starts, rather than trying to initiate these agents during Ramadan. The guidelines also recommend reducing usual insulin doses when fasting during Ramadan.
Despite summarizing findings from several observational studies and surveys, research to date on how to optimize the safety of diabetes management during Ramadan fasting “is all very basic,” Dr. Hassanein said in an interview.
“We need more randomized clinical trials. We need more [data and evidence] for every single aspect” of management, he added.
The 2021 Diabetes and Ramadan Practical Guidelines were supported by an educational grant from Sanofi and Servier. Dr. Hassanein has reported being a speaker on behalf of Abbott, AstraZeneca, Boehringer Ingelheim, Lilly, Novo Nordisk, Sanofi, and Servier.
A version of this article first appeared on Medscape.com.
SAN DIEGO – An assessment of people with diabetes before Ramadan is vital so they can learn whether it is safe for them to fast, and if it is, how to do so without jeopardizing their health.
“With correct advice and support” from knowledgeable health care professionals “most people with type 2 diabetes can fast safely during Ramadan,” Mohamed Hassanein, MBChB, said at the annual scientific sessions of the American Diabetes Association.
One of the most authoritative guidelines on how people with diabetes can safely fast during Ramadan has come from a collaboration between the International Diabetes Federation and the Diabetes & Ramadan International Alliance, an organization chaired by Dr. Hassanein. The groups issued a revised practical guide in 2021 for Ramadan fasting for people with diabetes, an update of the first edition released in 2016. Dr. Hassanein was lead author of the 2016 guidelines and edited the 2021 revision.
The 2021 guidelines also led to an update of a risk stratification app available for free from the DAR. The app provides risk stratification for people with diabetes and helps them access educational material to guide them through their fasts.
Although the latest guidelines address fasting for people with type 1 or type 2 diabetes, far more people with type 2 diabetes are at risk from fasting, and not only because of the higher prevalence of type 2 diabetes.
Results from a global survey of Muslims with diabetes in 2020 showed that 30% of those with type 1 diabetes did not do any fasting during Ramadan, but the percentage of those abstaining from fasting dropped to 16% among Muslims with type 2 diabetes, Dr. Hassanein explained. (Survey results in 2013 from about 38,000 Muslims in 39 countries showed a median of 7% of all adults did no fasting during Ramadan.)
Risk assessment by app
Currently, the DAR app is available in Arabic, English, French, and Urdu (the primary language of Pakistan), with more languages being added soon, said Dr. Hassanein, an endocrinologist at Dubai Hospital and professor at Mohammed Bin-Rashid University of Medicine & Health Sciences in Dubai, United Arab Emirates.
The app and screening protocol divides people with diabetes into low-, moderate-, and high-risk subgroups, and those at high risk are advised to refrain from fasting.
But the many other people with diabetes who potentially could fast still face risks for hypoglycemia, hyperglycemia (from overindulgent break-fast meals), diabetic ketoacidosis, dehydration, and thrombosis. Individual risk for these adverse events depends on many factors, including age, duration of diabetes, diabetes type, treatments received, history of hypoglycemia, and diabetes complications.
Dr. Hassanein and colleagues documented the high rate of complications from fasting in a 2020 survey of more than 5,800 Muslims with type 2 diabetes from 20 countries. The results showed that 72% of survey participants had to interrupt their 30 days of daily fasting for at least 1 day because of a diabetes-related event, and an additional 28% had diabetes-triggered interruptions that totaled more than 7 days. About 7% required hospitalization or an emergency department visit, and 16% developed at least one episode of daytime hypoglycemia.
Endorsement from Islamic clerics
The recommended risk assessment, and resulting exemptions from fasting, have been endorsed by the Mofty of Egypt, a group of religious scholars who issue legal opinions interpreting Islamic law.
The Mofty agreed that fasting should be interrupted for cases of hypoglycemia with blood glucose less than 70 mg/dL, hyperglycemia with blood glucose greater than 300 mg/dL, symptoms of hypo- or hyperglycemia, or symptoms of acute illness. The Mofty also endorsed that although fasting is obligatory for low-risk adults with diabetes and preferred for those with moderate-risk diabetes, the latter group may consider not fasting out of concern for their safety or to take prescribed medications. People at high risk were deemed by the Mofty as individuals who should not fast because of the potential for harm.
Other notable 2020 survey findings included pre-Ramadan education being received by just 43% of the respondents, and no self-monitoring of blood glucose performed by about a quarter of the respondents.
The 2021 guidelines also include treatment recommendations, such as avoiding older, longer-acting sulfonylurea agents in people with type 2 diabetes. And having people achieve stable, guideline-directed dosages of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide-1 (GLP-1) agonists before Ramadan starts, rather than trying to initiate these agents during Ramadan. The guidelines also recommend reducing usual insulin doses when fasting during Ramadan.
Despite summarizing findings from several observational studies and surveys, research to date on how to optimize the safety of diabetes management during Ramadan fasting “is all very basic,” Dr. Hassanein said in an interview.
“We need more randomized clinical trials. We need more [data and evidence] for every single aspect” of management, he added.
The 2021 Diabetes and Ramadan Practical Guidelines were supported by an educational grant from Sanofi and Servier. Dr. Hassanein has reported being a speaker on behalf of Abbott, AstraZeneca, Boehringer Ingelheim, Lilly, Novo Nordisk, Sanofi, and Servier.
A version of this article first appeared on Medscape.com.
SAN DIEGO – An assessment of people with diabetes before Ramadan is vital so they can learn whether it is safe for them to fast, and if it is, how to do so without jeopardizing their health.
“With correct advice and support” from knowledgeable health care professionals “most people with type 2 diabetes can fast safely during Ramadan,” Mohamed Hassanein, MBChB, said at the annual scientific sessions of the American Diabetes Association.
One of the most authoritative guidelines on how people with diabetes can safely fast during Ramadan has come from a collaboration between the International Diabetes Federation and the Diabetes & Ramadan International Alliance, an organization chaired by Dr. Hassanein. The groups issued a revised practical guide in 2021 for Ramadan fasting for people with diabetes, an update of the first edition released in 2016. Dr. Hassanein was lead author of the 2016 guidelines and edited the 2021 revision.
The 2021 guidelines also led to an update of a risk stratification app available for free from the DAR. The app provides risk stratification for people with diabetes and helps them access educational material to guide them through their fasts.
Although the latest guidelines address fasting for people with type 1 or type 2 diabetes, far more people with type 2 diabetes are at risk from fasting, and not only because of the higher prevalence of type 2 diabetes.
Results from a global survey of Muslims with diabetes in 2020 showed that 30% of those with type 1 diabetes did not do any fasting during Ramadan, but the percentage of those abstaining from fasting dropped to 16% among Muslims with type 2 diabetes, Dr. Hassanein explained. (Survey results in 2013 from about 38,000 Muslims in 39 countries showed a median of 7% of all adults did no fasting during Ramadan.)
Risk assessment by app
Currently, the DAR app is available in Arabic, English, French, and Urdu (the primary language of Pakistan), with more languages being added soon, said Dr. Hassanein, an endocrinologist at Dubai Hospital and professor at Mohammed Bin-Rashid University of Medicine & Health Sciences in Dubai, United Arab Emirates.
The app and screening protocol divides people with diabetes into low-, moderate-, and high-risk subgroups, and those at high risk are advised to refrain from fasting.
But the many other people with diabetes who potentially could fast still face risks for hypoglycemia, hyperglycemia (from overindulgent break-fast meals), diabetic ketoacidosis, dehydration, and thrombosis. Individual risk for these adverse events depends on many factors, including age, duration of diabetes, diabetes type, treatments received, history of hypoglycemia, and diabetes complications.
Dr. Hassanein and colleagues documented the high rate of complications from fasting in a 2020 survey of more than 5,800 Muslims with type 2 diabetes from 20 countries. The results showed that 72% of survey participants had to interrupt their 30 days of daily fasting for at least 1 day because of a diabetes-related event, and an additional 28% had diabetes-triggered interruptions that totaled more than 7 days. About 7% required hospitalization or an emergency department visit, and 16% developed at least one episode of daytime hypoglycemia.
Endorsement from Islamic clerics
The recommended risk assessment, and resulting exemptions from fasting, have been endorsed by the Mofty of Egypt, a group of religious scholars who issue legal opinions interpreting Islamic law.
The Mofty agreed that fasting should be interrupted for cases of hypoglycemia with blood glucose less than 70 mg/dL, hyperglycemia with blood glucose greater than 300 mg/dL, symptoms of hypo- or hyperglycemia, or symptoms of acute illness. The Mofty also endorsed that although fasting is obligatory for low-risk adults with diabetes and preferred for those with moderate-risk diabetes, the latter group may consider not fasting out of concern for their safety or to take prescribed medications. People at high risk were deemed by the Mofty as individuals who should not fast because of the potential for harm.
Other notable 2020 survey findings included pre-Ramadan education being received by just 43% of the respondents, and no self-monitoring of blood glucose performed by about a quarter of the respondents.
The 2021 guidelines also include treatment recommendations, such as avoiding older, longer-acting sulfonylurea agents in people with type 2 diabetes. And having people achieve stable, guideline-directed dosages of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide-1 (GLP-1) agonists before Ramadan starts, rather than trying to initiate these agents during Ramadan. The guidelines also recommend reducing usual insulin doses when fasting during Ramadan.
Despite summarizing findings from several observational studies and surveys, research to date on how to optimize the safety of diabetes management during Ramadan fasting “is all very basic,” Dr. Hassanein said in an interview.
“We need more randomized clinical trials. We need more [data and evidence] for every single aspect” of management, he added.
The 2021 Diabetes and Ramadan Practical Guidelines were supported by an educational grant from Sanofi and Servier. Dr. Hassanein has reported being a speaker on behalf of Abbott, AstraZeneca, Boehringer Ingelheim, Lilly, Novo Nordisk, Sanofi, and Servier.
A version of this article first appeared on Medscape.com.
AT ADA 2023
COORDINATE-Diabetes: A ‘wake-up call’ for many specialties
SAN DIEGO – at the annual scientific sessions of the American Diabetes Association.
A symposium there focused on the recent randomized, controlled COORDINATE-Diabetes trial, which investigated a multipronged educational intervention in 43 U.S. cardiology clinics aimed at improving prescribing of guideline-recommended treatments for people with both type 2 diabetes and cardiovascular disease. Compared with clinics that were randomly assigned to offer usual care, the intervention significantly increased recommended prescribing of high-intensity statins, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ARBs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors and/or glucagonlike peptide 1 receptor agonists (GLP-1 agonists).
COORDINATE-Diabetes was aimed at cardiologists, who typically see these patients more often than do endocrinologists. However, the results are relevant to all health care providers involved in the care of those with type 2 diabetes, speakers argued at the ADA symposium.
“This is a cardiology study. I think it’s safe to say that not too many of you in the room are cardiologists. So why would you care about the results of the COORDINATE study?” said Ildiko Lingvay, MD, of the University of Texas Southwestern Medical Center, Dallas.
Dr. Lingvay went on to outline reasons that the COORDINATE findings apply to endocrinologists and primary care clinicians, as well as cardiologists. For one, a study from her institution that was presented at a recent internal medicine meeting showed that, among more than 10,000 patients with type 2 diabetes and cardiovascular disease, heart failure, and/or chronic kidney disease, the proportion of patients who were prescribed the appropriate guideline-indicated medications was 20.1% for those seen in primary care, 24.8% in endocrinology, 20.3% in cardiology, and 18.3% in nephrology.
“So, we [endocrinologists are] not that much better [than other specialties]” at prescribing, she noted.
Mikhail N. Kosiborod, MD, in independent commentary called the COORDINATE trial and other similar initiatives “the beginning of care transformation.”
The COORDINATE-Diabetes results were originally presented in March at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The study was simultaneously published in JAMA.
‘They’ve shown we can do better’
Asked to comment, Robert H. Eckel, MD, said in an interview, “I look at COORDINATE as a wake-up call to the need for multispecialty approaches to people with type 2 diabetes and cardiovascular disease. ... I think it’s a step in the door.”
Dr. Eckel, who has long advocated for a new “cardiometabolic” physician subspecialty, noted that COORDINATE-Diabetes “stopped short of training health care providers in the science and medicine of cardio-renal-metabolic disease.”
Nonetheless, regarding the efforts toward a more coordinated system of care, Dr. Eckel said, “I support the concept, unequivocally.” He is associated with the division of endocrinology, metabolism, and diabetes, University of Colorado at Denver, Aurora.
But the cost-effectiveness of the intervention “requires time to assess,” he added. “We don’t know anything yet other than [that] managing drug administration to meet goals that relate to outcomes in people with diabetes can be accomplished. They’ve shown that we can do better.”
Why should you care about a cardiology study?
In COORDINATE-Diabetes, 20 of the centers were randomly assigned to provide five interventions: assess local barriers, develop care pathways, coordinate care, educate clinicians, report data back to the clinics, and provide tools for the 459 participants. The other 23 clinics, with 590 participants, were randomly assigned to provide usual care per practice guidelines.
The primary outcome was the proportion of participants that prescribed all three groups of the recommended therapies at 6-12 months after enrollment; 37.9% prescribed the intervention, and 14.5% provided usual care, a significant 23% difference (P < .001). The rate of prescriptions of each of the three individual drug groups was also significantly higher with the intervention. No differences were seen in cardiovascular risk factors or outcomes.
Dr. Lingvay pointed out that the interventions tested in COORDINATE – such as fact sheets and medication passports for patients, system audits and feedback, and provider grand rounds – can be extrapolated to any specialist setting.
She added that the long-held model of team-based care means that “everyone involved in the care of these patients is responsible for ensuring best practices are followed.” Part of that, she said, is helping other specialists prescribe the same medications and communicate across the team.
For all specialists, she recommends using the resources available on the COORDINATE website.
‘It’s not a silver bullet; additional solutions are needed’
In his commentary, Dr. Kosiborod, executive director of the Cardiometabolic Center Alliance, noted, “The treatments studied in COORDINATE represent the biggest advances in a generation when it comes to improving outcomes in this population. ... We’re living in a renaissance age with the number of tools we have available. ... It’s getting better every day.”
Moreover, all the relevant professional society guidelines now recommend GLP-1 agonists and SGLT2 inhibitors. “And yet, when we look, less than 1 in 10 patients with type 2 diabetes and atherosclerotic cardiovascular disease are getting appropriate recommended care. One of the lessons of COORDINATE is that this needs to change if we’re really going to improve our patients’ lives.”
The barriers aren’t simply financial, Dr. Kosiborod said. He pointed to two studies that show that even reducing out-of-pocket costs resulted in only modest increases in adherence.
Educational gaps on the part of both clinicians and patients also factor in, as do misaligned incentives.
“Clinicians get paid for how many things they do, not necessarily how well they do them. Everyone wants to do the right thing, but ultimately, incentives do matter,” he emphasized.
While the COORDINATE-Diabetes interventions addressed several of the barriers, two-thirds of the participants still did not receive optimal therapy.
“It’s not a silver bullet. ... Additional solutions are needed,” Dr. Kosiborod observed.
Transformation occurs ‘when the status quo is no longer acceptable’
Enter his institution, the Cardiometabolic Center Alliance, part of Saint Luke’s Mid-America Heart Institute. The nonprofit system, which currently has 16 subscribing clinics around the country, offers patient-centered “team-based, coordinated, comprehensive care” for people with both type 2 diabetes and cardiovascular disease.
The model is led by preventive cardiology in collaboration with endocrinology and primary care. Support staff includes advance practice providers, nurse navigators, certified diabetes educators, dietitians, and pharmacists. Individualized treatment plans aim for “aggressive secondary risk reduction,” Dr. Kosiborod noted.
Six-month data from the Cardiometabolic Center Alliance show an increase from 28.2% at baseline to 67.1% (P < .0001) in prescribing of a four-agent guideline-directed medical therapy “bundle,” including the three from COORDINATE-Diabetes plus an antiplatelet or anticoagulant agent. Dr. Kosiborod presented these data during the ADA meeting in a poster.
Remaining questions involve sustainability, scalability, and system transformation, which require buy-in from multiple stakeholders, he noted.
He contends that it can be done. A prior example of “rapid and lasting care transformation” occurred in November 2006 with the launch of the “Door to Balloon (D2B) Alliance for Quality,” which dramatically increased the proportion of patients who received primary angioplasty within 90 minutes at hospitals around the United States. From January 2005 to September 2010, those proportions rose from 27.3% to 70.4%.
“Patients were coming into the emergency department with myocardial infarctions and waiting for hours before the interventional cardiologist came. The community said we needed a nationwide quality improvement initiative. ... Almost every hospital in the country changed their systems of care. It was a huge national effort. ... When we no longer consider the status quo acceptable, we can actually make something very special happen very quickly.”
After the session, Dr. Kosiborod said in an interview that the Cardiometabolic Center Alliance is now gathering data to make the financial case for the approach.
“We’re trying to develop a model that tells the admins which patients will save money, because, of course, if you can create a financial incentive, it only makes it go faster. ... We want to synchronize it in the best way possible.”
Dr. Lingvay has receiving nonfinancial support and grants from Novo Nordisk, personal fees or nonfinancial support from Sanofi, Lilly, Boehringer Ingelheim, Merck/Pfizer, Mylan, AstraZeneca, Johnson & Johnson, Intercept, Target Pharma, Zealand, Shionogi, Carmot, Structure, Bayer, Mediflix, WebMD, GI Dynamics, Intarcia Therapeutics, Mannkind, Novartis, Structure Therapeutics, and Valeritas. Dr. Kosiborod is a consultant for Alnylam Pharmaceuticals, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, ESPERION Therapeutics, Janssen Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Novo Nordisk, Pharmacosmos, Pfizer, Sanofi, Vifor Pharma Management, and Youngene Therapeutics. He also receives research support from AstraZeneca and Boehringer Ingelheim. Dr. Eckel serves on consulting/advisory boards for Amgen, Arrowhead, Better, Ionis, Kowa, Lexicon, Novo Nordisk, Precision BioSciences, The Healthy Aging Company, Tolmar, and Weight Watchers.
A version of this article first appeared on Medscape.com.
SAN DIEGO – at the annual scientific sessions of the American Diabetes Association.
A symposium there focused on the recent randomized, controlled COORDINATE-Diabetes trial, which investigated a multipronged educational intervention in 43 U.S. cardiology clinics aimed at improving prescribing of guideline-recommended treatments for people with both type 2 diabetes and cardiovascular disease. Compared with clinics that were randomly assigned to offer usual care, the intervention significantly increased recommended prescribing of high-intensity statins, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ARBs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors and/or glucagonlike peptide 1 receptor agonists (GLP-1 agonists).
COORDINATE-Diabetes was aimed at cardiologists, who typically see these patients more often than do endocrinologists. However, the results are relevant to all health care providers involved in the care of those with type 2 diabetes, speakers argued at the ADA symposium.
“This is a cardiology study. I think it’s safe to say that not too many of you in the room are cardiologists. So why would you care about the results of the COORDINATE study?” said Ildiko Lingvay, MD, of the University of Texas Southwestern Medical Center, Dallas.
Dr. Lingvay went on to outline reasons that the COORDINATE findings apply to endocrinologists and primary care clinicians, as well as cardiologists. For one, a study from her institution that was presented at a recent internal medicine meeting showed that, among more than 10,000 patients with type 2 diabetes and cardiovascular disease, heart failure, and/or chronic kidney disease, the proportion of patients who were prescribed the appropriate guideline-indicated medications was 20.1% for those seen in primary care, 24.8% in endocrinology, 20.3% in cardiology, and 18.3% in nephrology.
“So, we [endocrinologists are] not that much better [than other specialties]” at prescribing, she noted.
Mikhail N. Kosiborod, MD, in independent commentary called the COORDINATE trial and other similar initiatives “the beginning of care transformation.”
The COORDINATE-Diabetes results were originally presented in March at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The study was simultaneously published in JAMA.
‘They’ve shown we can do better’
Asked to comment, Robert H. Eckel, MD, said in an interview, “I look at COORDINATE as a wake-up call to the need for multispecialty approaches to people with type 2 diabetes and cardiovascular disease. ... I think it’s a step in the door.”
Dr. Eckel, who has long advocated for a new “cardiometabolic” physician subspecialty, noted that COORDINATE-Diabetes “stopped short of training health care providers in the science and medicine of cardio-renal-metabolic disease.”
Nonetheless, regarding the efforts toward a more coordinated system of care, Dr. Eckel said, “I support the concept, unequivocally.” He is associated with the division of endocrinology, metabolism, and diabetes, University of Colorado at Denver, Aurora.
But the cost-effectiveness of the intervention “requires time to assess,” he added. “We don’t know anything yet other than [that] managing drug administration to meet goals that relate to outcomes in people with diabetes can be accomplished. They’ve shown that we can do better.”
Why should you care about a cardiology study?
In COORDINATE-Diabetes, 20 of the centers were randomly assigned to provide five interventions: assess local barriers, develop care pathways, coordinate care, educate clinicians, report data back to the clinics, and provide tools for the 459 participants. The other 23 clinics, with 590 participants, were randomly assigned to provide usual care per practice guidelines.
The primary outcome was the proportion of participants that prescribed all three groups of the recommended therapies at 6-12 months after enrollment; 37.9% prescribed the intervention, and 14.5% provided usual care, a significant 23% difference (P < .001). The rate of prescriptions of each of the three individual drug groups was also significantly higher with the intervention. No differences were seen in cardiovascular risk factors or outcomes.
Dr. Lingvay pointed out that the interventions tested in COORDINATE – such as fact sheets and medication passports for patients, system audits and feedback, and provider grand rounds – can be extrapolated to any specialist setting.
She added that the long-held model of team-based care means that “everyone involved in the care of these patients is responsible for ensuring best practices are followed.” Part of that, she said, is helping other specialists prescribe the same medications and communicate across the team.
For all specialists, she recommends using the resources available on the COORDINATE website.
‘It’s not a silver bullet; additional solutions are needed’
In his commentary, Dr. Kosiborod, executive director of the Cardiometabolic Center Alliance, noted, “The treatments studied in COORDINATE represent the biggest advances in a generation when it comes to improving outcomes in this population. ... We’re living in a renaissance age with the number of tools we have available. ... It’s getting better every day.”
Moreover, all the relevant professional society guidelines now recommend GLP-1 agonists and SGLT2 inhibitors. “And yet, when we look, less than 1 in 10 patients with type 2 diabetes and atherosclerotic cardiovascular disease are getting appropriate recommended care. One of the lessons of COORDINATE is that this needs to change if we’re really going to improve our patients’ lives.”
The barriers aren’t simply financial, Dr. Kosiborod said. He pointed to two studies that show that even reducing out-of-pocket costs resulted in only modest increases in adherence.
Educational gaps on the part of both clinicians and patients also factor in, as do misaligned incentives.
“Clinicians get paid for how many things they do, not necessarily how well they do them. Everyone wants to do the right thing, but ultimately, incentives do matter,” he emphasized.
While the COORDINATE-Diabetes interventions addressed several of the barriers, two-thirds of the participants still did not receive optimal therapy.
“It’s not a silver bullet. ... Additional solutions are needed,” Dr. Kosiborod observed.
Transformation occurs ‘when the status quo is no longer acceptable’
Enter his institution, the Cardiometabolic Center Alliance, part of Saint Luke’s Mid-America Heart Institute. The nonprofit system, which currently has 16 subscribing clinics around the country, offers patient-centered “team-based, coordinated, comprehensive care” for people with both type 2 diabetes and cardiovascular disease.
The model is led by preventive cardiology in collaboration with endocrinology and primary care. Support staff includes advance practice providers, nurse navigators, certified diabetes educators, dietitians, and pharmacists. Individualized treatment plans aim for “aggressive secondary risk reduction,” Dr. Kosiborod noted.
Six-month data from the Cardiometabolic Center Alliance show an increase from 28.2% at baseline to 67.1% (P < .0001) in prescribing of a four-agent guideline-directed medical therapy “bundle,” including the three from COORDINATE-Diabetes plus an antiplatelet or anticoagulant agent. Dr. Kosiborod presented these data during the ADA meeting in a poster.
Remaining questions involve sustainability, scalability, and system transformation, which require buy-in from multiple stakeholders, he noted.
He contends that it can be done. A prior example of “rapid and lasting care transformation” occurred in November 2006 with the launch of the “Door to Balloon (D2B) Alliance for Quality,” which dramatically increased the proportion of patients who received primary angioplasty within 90 minutes at hospitals around the United States. From January 2005 to September 2010, those proportions rose from 27.3% to 70.4%.
“Patients were coming into the emergency department with myocardial infarctions and waiting for hours before the interventional cardiologist came. The community said we needed a nationwide quality improvement initiative. ... Almost every hospital in the country changed their systems of care. It was a huge national effort. ... When we no longer consider the status quo acceptable, we can actually make something very special happen very quickly.”
After the session, Dr. Kosiborod said in an interview that the Cardiometabolic Center Alliance is now gathering data to make the financial case for the approach.
“We’re trying to develop a model that tells the admins which patients will save money, because, of course, if you can create a financial incentive, it only makes it go faster. ... We want to synchronize it in the best way possible.”
Dr. Lingvay has receiving nonfinancial support and grants from Novo Nordisk, personal fees or nonfinancial support from Sanofi, Lilly, Boehringer Ingelheim, Merck/Pfizer, Mylan, AstraZeneca, Johnson & Johnson, Intercept, Target Pharma, Zealand, Shionogi, Carmot, Structure, Bayer, Mediflix, WebMD, GI Dynamics, Intarcia Therapeutics, Mannkind, Novartis, Structure Therapeutics, and Valeritas. Dr. Kosiborod is a consultant for Alnylam Pharmaceuticals, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, ESPERION Therapeutics, Janssen Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Novo Nordisk, Pharmacosmos, Pfizer, Sanofi, Vifor Pharma Management, and Youngene Therapeutics. He also receives research support from AstraZeneca and Boehringer Ingelheim. Dr. Eckel serves on consulting/advisory boards for Amgen, Arrowhead, Better, Ionis, Kowa, Lexicon, Novo Nordisk, Precision BioSciences, The Healthy Aging Company, Tolmar, and Weight Watchers.
A version of this article first appeared on Medscape.com.
SAN DIEGO – at the annual scientific sessions of the American Diabetes Association.
A symposium there focused on the recent randomized, controlled COORDINATE-Diabetes trial, which investigated a multipronged educational intervention in 43 U.S. cardiology clinics aimed at improving prescribing of guideline-recommended treatments for people with both type 2 diabetes and cardiovascular disease. Compared with clinics that were randomly assigned to offer usual care, the intervention significantly increased recommended prescribing of high-intensity statins, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ARBs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors and/or glucagonlike peptide 1 receptor agonists (GLP-1 agonists).
COORDINATE-Diabetes was aimed at cardiologists, who typically see these patients more often than do endocrinologists. However, the results are relevant to all health care providers involved in the care of those with type 2 diabetes, speakers argued at the ADA symposium.
“This is a cardiology study. I think it’s safe to say that not too many of you in the room are cardiologists. So why would you care about the results of the COORDINATE study?” said Ildiko Lingvay, MD, of the University of Texas Southwestern Medical Center, Dallas.
Dr. Lingvay went on to outline reasons that the COORDINATE findings apply to endocrinologists and primary care clinicians, as well as cardiologists. For one, a study from her institution that was presented at a recent internal medicine meeting showed that, among more than 10,000 patients with type 2 diabetes and cardiovascular disease, heart failure, and/or chronic kidney disease, the proportion of patients who were prescribed the appropriate guideline-indicated medications was 20.1% for those seen in primary care, 24.8% in endocrinology, 20.3% in cardiology, and 18.3% in nephrology.
“So, we [endocrinologists are] not that much better [than other specialties]” at prescribing, she noted.
Mikhail N. Kosiborod, MD, in independent commentary called the COORDINATE trial and other similar initiatives “the beginning of care transformation.”
The COORDINATE-Diabetes results were originally presented in March at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The study was simultaneously published in JAMA.
‘They’ve shown we can do better’
Asked to comment, Robert H. Eckel, MD, said in an interview, “I look at COORDINATE as a wake-up call to the need for multispecialty approaches to people with type 2 diabetes and cardiovascular disease. ... I think it’s a step in the door.”
Dr. Eckel, who has long advocated for a new “cardiometabolic” physician subspecialty, noted that COORDINATE-Diabetes “stopped short of training health care providers in the science and medicine of cardio-renal-metabolic disease.”
Nonetheless, regarding the efforts toward a more coordinated system of care, Dr. Eckel said, “I support the concept, unequivocally.” He is associated with the division of endocrinology, metabolism, and diabetes, University of Colorado at Denver, Aurora.
But the cost-effectiveness of the intervention “requires time to assess,” he added. “We don’t know anything yet other than [that] managing drug administration to meet goals that relate to outcomes in people with diabetes can be accomplished. They’ve shown that we can do better.”
Why should you care about a cardiology study?
In COORDINATE-Diabetes, 20 of the centers were randomly assigned to provide five interventions: assess local barriers, develop care pathways, coordinate care, educate clinicians, report data back to the clinics, and provide tools for the 459 participants. The other 23 clinics, with 590 participants, were randomly assigned to provide usual care per practice guidelines.
The primary outcome was the proportion of participants that prescribed all three groups of the recommended therapies at 6-12 months after enrollment; 37.9% prescribed the intervention, and 14.5% provided usual care, a significant 23% difference (P < .001). The rate of prescriptions of each of the three individual drug groups was also significantly higher with the intervention. No differences were seen in cardiovascular risk factors or outcomes.
Dr. Lingvay pointed out that the interventions tested in COORDINATE – such as fact sheets and medication passports for patients, system audits and feedback, and provider grand rounds – can be extrapolated to any specialist setting.
She added that the long-held model of team-based care means that “everyone involved in the care of these patients is responsible for ensuring best practices are followed.” Part of that, she said, is helping other specialists prescribe the same medications and communicate across the team.
For all specialists, she recommends using the resources available on the COORDINATE website.
‘It’s not a silver bullet; additional solutions are needed’
In his commentary, Dr. Kosiborod, executive director of the Cardiometabolic Center Alliance, noted, “The treatments studied in COORDINATE represent the biggest advances in a generation when it comes to improving outcomes in this population. ... We’re living in a renaissance age with the number of tools we have available. ... It’s getting better every day.”
Moreover, all the relevant professional society guidelines now recommend GLP-1 agonists and SGLT2 inhibitors. “And yet, when we look, less than 1 in 10 patients with type 2 diabetes and atherosclerotic cardiovascular disease are getting appropriate recommended care. One of the lessons of COORDINATE is that this needs to change if we’re really going to improve our patients’ lives.”
The barriers aren’t simply financial, Dr. Kosiborod said. He pointed to two studies that show that even reducing out-of-pocket costs resulted in only modest increases in adherence.
Educational gaps on the part of both clinicians and patients also factor in, as do misaligned incentives.
“Clinicians get paid for how many things they do, not necessarily how well they do them. Everyone wants to do the right thing, but ultimately, incentives do matter,” he emphasized.
While the COORDINATE-Diabetes interventions addressed several of the barriers, two-thirds of the participants still did not receive optimal therapy.
“It’s not a silver bullet. ... Additional solutions are needed,” Dr. Kosiborod observed.
Transformation occurs ‘when the status quo is no longer acceptable’
Enter his institution, the Cardiometabolic Center Alliance, part of Saint Luke’s Mid-America Heart Institute. The nonprofit system, which currently has 16 subscribing clinics around the country, offers patient-centered “team-based, coordinated, comprehensive care” for people with both type 2 diabetes and cardiovascular disease.
The model is led by preventive cardiology in collaboration with endocrinology and primary care. Support staff includes advance practice providers, nurse navigators, certified diabetes educators, dietitians, and pharmacists. Individualized treatment plans aim for “aggressive secondary risk reduction,” Dr. Kosiborod noted.
Six-month data from the Cardiometabolic Center Alliance show an increase from 28.2% at baseline to 67.1% (P < .0001) in prescribing of a four-agent guideline-directed medical therapy “bundle,” including the three from COORDINATE-Diabetes plus an antiplatelet or anticoagulant agent. Dr. Kosiborod presented these data during the ADA meeting in a poster.
Remaining questions involve sustainability, scalability, and system transformation, which require buy-in from multiple stakeholders, he noted.
He contends that it can be done. A prior example of “rapid and lasting care transformation” occurred in November 2006 with the launch of the “Door to Balloon (D2B) Alliance for Quality,” which dramatically increased the proportion of patients who received primary angioplasty within 90 minutes at hospitals around the United States. From January 2005 to September 2010, those proportions rose from 27.3% to 70.4%.
“Patients were coming into the emergency department with myocardial infarctions and waiting for hours before the interventional cardiologist came. The community said we needed a nationwide quality improvement initiative. ... Almost every hospital in the country changed their systems of care. It was a huge national effort. ... When we no longer consider the status quo acceptable, we can actually make something very special happen very quickly.”
After the session, Dr. Kosiborod said in an interview that the Cardiometabolic Center Alliance is now gathering data to make the financial case for the approach.
“We’re trying to develop a model that tells the admins which patients will save money, because, of course, if you can create a financial incentive, it only makes it go faster. ... We want to synchronize it in the best way possible.”
Dr. Lingvay has receiving nonfinancial support and grants from Novo Nordisk, personal fees or nonfinancial support from Sanofi, Lilly, Boehringer Ingelheim, Merck/Pfizer, Mylan, AstraZeneca, Johnson & Johnson, Intercept, Target Pharma, Zealand, Shionogi, Carmot, Structure, Bayer, Mediflix, WebMD, GI Dynamics, Intarcia Therapeutics, Mannkind, Novartis, Structure Therapeutics, and Valeritas. Dr. Kosiborod is a consultant for Alnylam Pharmaceuticals, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, ESPERION Therapeutics, Janssen Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Novo Nordisk, Pharmacosmos, Pfizer, Sanofi, Vifor Pharma Management, and Youngene Therapeutics. He also receives research support from AstraZeneca and Boehringer Ingelheim. Dr. Eckel serves on consulting/advisory boards for Amgen, Arrowhead, Better, Ionis, Kowa, Lexicon, Novo Nordisk, Precision BioSciences, The Healthy Aging Company, Tolmar, and Weight Watchers.
A version of this article first appeared on Medscape.com.
AT ADA 2023
‘Artificial pancreas’ for all type 1 diabetes pregnancies?
In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.
Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.
The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.
CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”
The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.
Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”
However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
Two experts weigh in
Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.
“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.
“If a woman is on an AID system – except for DIY loop – I have them stop the automation and adjust manually,” she said in an email. “My [patients] do amazingly well in pregnancy – most can get their A1cs below 6%,” she noted. “But if someone can’t do that and their A1cs are higher, automation can help.
“It is always about individualizing care,” said Dr. Peters. “The one thing that helps the most is continuous glucose monitoring (CGM). And I do have patients who remain on [insulin] injections throughout pregnancy.”
And Sarit Polsky, MD, MPH, who was also not involved with the current study, agrees that “AID with CamAPS, which has an option to customize the glucose target in the pregnancy-specific range, appears to be safe and effective in pregnancy and should be offered” to patients in Europe and the United Kingdom.
“Whether other AID systems should be recommended in pregnancy is still unclear, said Dr. Polsky, associate professor of medicine and pediatrics at Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus.
“Around 48% of [global] pregnancies are unplanned,” Dr. Polsky said in an interview. “Many women do indeed become pregnant while using AID systems and many opt to continue use of these systems.
“Off-label use of these products can be beneficial in pregnancy in select cases, but the systems generally need the use of assistive techniques, which we previously published, to help get glucose levels to pregnancy-specific targets,” she noted in an email.
Study rationale, method, and findings
Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.
“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.
Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin.
As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.
Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.
They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.
A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).
Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.
The effect was consistent across clinical sites and maternal age and A1c categories.
Ongoing studies, off-label use
Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”
There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.
The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.
“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.
“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.
The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.
A version of this article first appeared on Medscape.com.
In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.
Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.
The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.
CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”
The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.
Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”
However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
Two experts weigh in
Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.
“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.
“If a woman is on an AID system – except for DIY loop – I have them stop the automation and adjust manually,” she said in an email. “My [patients] do amazingly well in pregnancy – most can get their A1cs below 6%,” she noted. “But if someone can’t do that and their A1cs are higher, automation can help.
“It is always about individualizing care,” said Dr. Peters. “The one thing that helps the most is continuous glucose monitoring (CGM). And I do have patients who remain on [insulin] injections throughout pregnancy.”
And Sarit Polsky, MD, MPH, who was also not involved with the current study, agrees that “AID with CamAPS, which has an option to customize the glucose target in the pregnancy-specific range, appears to be safe and effective in pregnancy and should be offered” to patients in Europe and the United Kingdom.
“Whether other AID systems should be recommended in pregnancy is still unclear, said Dr. Polsky, associate professor of medicine and pediatrics at Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus.
“Around 48% of [global] pregnancies are unplanned,” Dr. Polsky said in an interview. “Many women do indeed become pregnant while using AID systems and many opt to continue use of these systems.
“Off-label use of these products can be beneficial in pregnancy in select cases, but the systems generally need the use of assistive techniques, which we previously published, to help get glucose levels to pregnancy-specific targets,” she noted in an email.
Study rationale, method, and findings
Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.
“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.
Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin.
As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.
Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.
They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.
A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).
Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.
The effect was consistent across clinical sites and maternal age and A1c categories.
Ongoing studies, off-label use
Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”
There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.
The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.
“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.
“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.
The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.
A version of this article first appeared on Medscape.com.
In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.
Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.
The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.
CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”
The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.
Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”
However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
Two experts weigh in
Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.
“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.
“If a woman is on an AID system – except for DIY loop – I have them stop the automation and adjust manually,” she said in an email. “My [patients] do amazingly well in pregnancy – most can get their A1cs below 6%,” she noted. “But if someone can’t do that and their A1cs are higher, automation can help.
“It is always about individualizing care,” said Dr. Peters. “The one thing that helps the most is continuous glucose monitoring (CGM). And I do have patients who remain on [insulin] injections throughout pregnancy.”
And Sarit Polsky, MD, MPH, who was also not involved with the current study, agrees that “AID with CamAPS, which has an option to customize the glucose target in the pregnancy-specific range, appears to be safe and effective in pregnancy and should be offered” to patients in Europe and the United Kingdom.
“Whether other AID systems should be recommended in pregnancy is still unclear, said Dr. Polsky, associate professor of medicine and pediatrics at Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus.
“Around 48% of [global] pregnancies are unplanned,” Dr. Polsky said in an interview. “Many women do indeed become pregnant while using AID systems and many opt to continue use of these systems.
“Off-label use of these products can be beneficial in pregnancy in select cases, but the systems generally need the use of assistive techniques, which we previously published, to help get glucose levels to pregnancy-specific targets,” she noted in an email.
Study rationale, method, and findings
Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.
“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.
Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin.
As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.
Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.
They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.
A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).
Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.
The effect was consistent across clinical sites and maternal age and A1c categories.
Ongoing studies, off-label use
Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”
There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.
The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.
“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.
“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.
The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.
A version of this article first appeared on Medscape.com.
FROM ADA 2023
Thirty-three percent of type 1 diabetes patients insulin free with stem cells
SAN DIEGO – An investigational allogeneic stem cell–derived pancreatic islet cell replacement therapy (VX-880, Vertex Pharmaceuticals) continues to show promise as a treatment for type 1 diabetes, according to the latest data, from six patients thus far.
Two of the six are insulin-independent beyond 1 year after receiving the VX-880 infusions, and three others who received them more recently are on a similar trajectory. One dropped out because of reasons unrelated to the therapy. The remaining five are continuing to receive immunosuppressive treatment to prevent rejection of the islets. The six all had undetectable insulin secretion, impaired hypoglycemic awareness, and severe hypoglycemia as the criterion to enter the phase 1/2 study.
“These new findings demonstrate the potential of stem cell–derived islets as a future treatment for patients with type 1 diabetes, signaling a new era that could potentially remove the need for exogenously administered insulin to achieve glycemic control,” said lead investigator Trevor W. Reichman, MD, PhD, surgical director of Pancreas and Islet Cell Transplantation at the University of Toronto.
Dr. Reichman presented the data at the annual scientific sessions of the American Diabetes Association, as an update to the report of the first two patients at last year’s ADA meeting. “We are hopeful that this first-of-its-kind research could be a game-changer for the treatment of type 1 diabetes,” he emphasized.
Co-investigator Maria Cristina Nostro, PhD, senior scientist at McEwen Stem Cell Institute, Toronto, told this news organization: “The clinical trial data are extremely exciting ... I think what was very beautiful is the glucose tolerance test where the insulin secretion was almost like a person without type 1 diabetes. For someone who is in the lab doing basic science research ... all the work we’ve put into this, it’s a labor of love. We’ve been trying to generate the cells for so long, and now to see this, it’s fantastic.”
Two meet primary endpoint, three more on the right path
The six patients had a mean age of 44 years and mean 23 years’ diabetes duration. Three each were male and female. Their mean baseline A1c was 8.1%, and fasting C-peptide was undetectable. They had experienced a mean of 3.3 severe hypoglycemia episodes in the year prior to receiving the infusion, which was delivered to the portal vein similarly to the procedure with cadaveric donor islets, Dr. Reichman said.
The first two patients, including the one who dropped out, received half target doses of VX-880 (trial part A), while the rest, enrolled sequentially (part B), were each administered the full target dose of VX-880 given as a single infusion.
Induction with anti-thymocyte globulin and maintenance immunosuppressants, tacrolimus/sirolimus, was used to protect the cells from the recipient’s immune system. After the infusion, all six participants had C-peptide production, reduction in A1c despite reduced insulin use, and no severe hypoglycemia episodes from day 90 onwards.
Both participants with at least a year of follow-up met the criteria for the primary endpoint of A1c less than 7% with no severe hypoglycemic episodes. The first participant had an A1c of 5.3% at month 21, and the second 6.0% at 12 months. Both had sustained glucose-responsive insulin production with a mixed-meal tolerance test and exceeded the ADA target of more than 70% time-in blood glucose range assessed with continuous glucose monitoring.
Safety: No major concerns thus far
Among all six, adverse events included elevations in the liver enzyme transaminase, occurring shortly after VX-880 infusion that were transient and resolved. No serious adverse events were considered related to the therapy.
Regarding safety, Dr. Nostro said, “With this trial, I have no concerns, because they’re using immunosuppression, so should anything go bad, you remove immunosuppression and the cells would be destroyed by the immune system. So it’s a perfect trial in a way.”
However, she noted, “Moving forward, as we develop something that will be genetically modified ... I think this is the future, because if you’re going to treat people with type 1 diabetes, we have to eliminate the immune suppression. I think the concern would be making sure the genetically modified cells are safe.”
Dr. Nostro, who gave an introductory presentation at the beginning of the symposium where the VX-880 data were presented, explained that in a current trial of genetically modified cells, “they’re placing the product inside a device so that the cells would be retrievable. It might not be perfect, but at least it’s going to tell us whether the genetically modified product is safe, which I think is what we need to use.”
In her talk, Dr. Nostro also summarized ongoing work in this field involving efforts to improve the generation of stem cell–derived islets with no “off target” non-beta cells to ensure consistency, optimization of engraftment, and elimination of immunosuppression. “[VX-880] is the beginning. This is the first product that’s going to be in the clinic, but I can imagine how 5, 10 years from now we will have different and more enhanced solutions for type 1 diabetes and who knows, maybe even for type 2.”
Based on the data so far, the VX-880 trial is now moving to part C, in which 10 concurrently enrolled participants will receive the full target dose of the product. The trial, previously exclusively in the United States, has now expanded to additional sites in Norway, Switzerland, and the Netherlands.
The study was funded by Vertex. Dr. Reichman is on advisory boards for Vertex and Sernova. Dr. Nostro was a consultant for Sigilon Therapeutics from 2018-2022, currently receives research support from Universal Cells, and has a patent licensed to Sernova.
A version of this article originally appeared on Medscape.com.
SAN DIEGO – An investigational allogeneic stem cell–derived pancreatic islet cell replacement therapy (VX-880, Vertex Pharmaceuticals) continues to show promise as a treatment for type 1 diabetes, according to the latest data, from six patients thus far.
Two of the six are insulin-independent beyond 1 year after receiving the VX-880 infusions, and three others who received them more recently are on a similar trajectory. One dropped out because of reasons unrelated to the therapy. The remaining five are continuing to receive immunosuppressive treatment to prevent rejection of the islets. The six all had undetectable insulin secretion, impaired hypoglycemic awareness, and severe hypoglycemia as the criterion to enter the phase 1/2 study.
“These new findings demonstrate the potential of stem cell–derived islets as a future treatment for patients with type 1 diabetes, signaling a new era that could potentially remove the need for exogenously administered insulin to achieve glycemic control,” said lead investigator Trevor W. Reichman, MD, PhD, surgical director of Pancreas and Islet Cell Transplantation at the University of Toronto.
Dr. Reichman presented the data at the annual scientific sessions of the American Diabetes Association, as an update to the report of the first two patients at last year’s ADA meeting. “We are hopeful that this first-of-its-kind research could be a game-changer for the treatment of type 1 diabetes,” he emphasized.
Co-investigator Maria Cristina Nostro, PhD, senior scientist at McEwen Stem Cell Institute, Toronto, told this news organization: “The clinical trial data are extremely exciting ... I think what was very beautiful is the glucose tolerance test where the insulin secretion was almost like a person without type 1 diabetes. For someone who is in the lab doing basic science research ... all the work we’ve put into this, it’s a labor of love. We’ve been trying to generate the cells for so long, and now to see this, it’s fantastic.”
Two meet primary endpoint, three more on the right path
The six patients had a mean age of 44 years and mean 23 years’ diabetes duration. Three each were male and female. Their mean baseline A1c was 8.1%, and fasting C-peptide was undetectable. They had experienced a mean of 3.3 severe hypoglycemia episodes in the year prior to receiving the infusion, which was delivered to the portal vein similarly to the procedure with cadaveric donor islets, Dr. Reichman said.
The first two patients, including the one who dropped out, received half target doses of VX-880 (trial part A), while the rest, enrolled sequentially (part B), were each administered the full target dose of VX-880 given as a single infusion.
Induction with anti-thymocyte globulin and maintenance immunosuppressants, tacrolimus/sirolimus, was used to protect the cells from the recipient’s immune system. After the infusion, all six participants had C-peptide production, reduction in A1c despite reduced insulin use, and no severe hypoglycemia episodes from day 90 onwards.
Both participants with at least a year of follow-up met the criteria for the primary endpoint of A1c less than 7% with no severe hypoglycemic episodes. The first participant had an A1c of 5.3% at month 21, and the second 6.0% at 12 months. Both had sustained glucose-responsive insulin production with a mixed-meal tolerance test and exceeded the ADA target of more than 70% time-in blood glucose range assessed with continuous glucose monitoring.
Safety: No major concerns thus far
Among all six, adverse events included elevations in the liver enzyme transaminase, occurring shortly after VX-880 infusion that were transient and resolved. No serious adverse events were considered related to the therapy.
Regarding safety, Dr. Nostro said, “With this trial, I have no concerns, because they’re using immunosuppression, so should anything go bad, you remove immunosuppression and the cells would be destroyed by the immune system. So it’s a perfect trial in a way.”
However, she noted, “Moving forward, as we develop something that will be genetically modified ... I think this is the future, because if you’re going to treat people with type 1 diabetes, we have to eliminate the immune suppression. I think the concern would be making sure the genetically modified cells are safe.”
Dr. Nostro, who gave an introductory presentation at the beginning of the symposium where the VX-880 data were presented, explained that in a current trial of genetically modified cells, “they’re placing the product inside a device so that the cells would be retrievable. It might not be perfect, but at least it’s going to tell us whether the genetically modified product is safe, which I think is what we need to use.”
In her talk, Dr. Nostro also summarized ongoing work in this field involving efforts to improve the generation of stem cell–derived islets with no “off target” non-beta cells to ensure consistency, optimization of engraftment, and elimination of immunosuppression. “[VX-880] is the beginning. This is the first product that’s going to be in the clinic, but I can imagine how 5, 10 years from now we will have different and more enhanced solutions for type 1 diabetes and who knows, maybe even for type 2.”
Based on the data so far, the VX-880 trial is now moving to part C, in which 10 concurrently enrolled participants will receive the full target dose of the product. The trial, previously exclusively in the United States, has now expanded to additional sites in Norway, Switzerland, and the Netherlands.
The study was funded by Vertex. Dr. Reichman is on advisory boards for Vertex and Sernova. Dr. Nostro was a consultant for Sigilon Therapeutics from 2018-2022, currently receives research support from Universal Cells, and has a patent licensed to Sernova.
A version of this article originally appeared on Medscape.com.
SAN DIEGO – An investigational allogeneic stem cell–derived pancreatic islet cell replacement therapy (VX-880, Vertex Pharmaceuticals) continues to show promise as a treatment for type 1 diabetes, according to the latest data, from six patients thus far.
Two of the six are insulin-independent beyond 1 year after receiving the VX-880 infusions, and three others who received them more recently are on a similar trajectory. One dropped out because of reasons unrelated to the therapy. The remaining five are continuing to receive immunosuppressive treatment to prevent rejection of the islets. The six all had undetectable insulin secretion, impaired hypoglycemic awareness, and severe hypoglycemia as the criterion to enter the phase 1/2 study.
“These new findings demonstrate the potential of stem cell–derived islets as a future treatment for patients with type 1 diabetes, signaling a new era that could potentially remove the need for exogenously administered insulin to achieve glycemic control,” said lead investigator Trevor W. Reichman, MD, PhD, surgical director of Pancreas and Islet Cell Transplantation at the University of Toronto.
Dr. Reichman presented the data at the annual scientific sessions of the American Diabetes Association, as an update to the report of the first two patients at last year’s ADA meeting. “We are hopeful that this first-of-its-kind research could be a game-changer for the treatment of type 1 diabetes,” he emphasized.
Co-investigator Maria Cristina Nostro, PhD, senior scientist at McEwen Stem Cell Institute, Toronto, told this news organization: “The clinical trial data are extremely exciting ... I think what was very beautiful is the glucose tolerance test where the insulin secretion was almost like a person without type 1 diabetes. For someone who is in the lab doing basic science research ... all the work we’ve put into this, it’s a labor of love. We’ve been trying to generate the cells for so long, and now to see this, it’s fantastic.”
Two meet primary endpoint, three more on the right path
The six patients had a mean age of 44 years and mean 23 years’ diabetes duration. Three each were male and female. Their mean baseline A1c was 8.1%, and fasting C-peptide was undetectable. They had experienced a mean of 3.3 severe hypoglycemia episodes in the year prior to receiving the infusion, which was delivered to the portal vein similarly to the procedure with cadaveric donor islets, Dr. Reichman said.
The first two patients, including the one who dropped out, received half target doses of VX-880 (trial part A), while the rest, enrolled sequentially (part B), were each administered the full target dose of VX-880 given as a single infusion.
Induction with anti-thymocyte globulin and maintenance immunosuppressants, tacrolimus/sirolimus, was used to protect the cells from the recipient’s immune system. After the infusion, all six participants had C-peptide production, reduction in A1c despite reduced insulin use, and no severe hypoglycemia episodes from day 90 onwards.
Both participants with at least a year of follow-up met the criteria for the primary endpoint of A1c less than 7% with no severe hypoglycemic episodes. The first participant had an A1c of 5.3% at month 21, and the second 6.0% at 12 months. Both had sustained glucose-responsive insulin production with a mixed-meal tolerance test and exceeded the ADA target of more than 70% time-in blood glucose range assessed with continuous glucose monitoring.
Safety: No major concerns thus far
Among all six, adverse events included elevations in the liver enzyme transaminase, occurring shortly after VX-880 infusion that were transient and resolved. No serious adverse events were considered related to the therapy.
Regarding safety, Dr. Nostro said, “With this trial, I have no concerns, because they’re using immunosuppression, so should anything go bad, you remove immunosuppression and the cells would be destroyed by the immune system. So it’s a perfect trial in a way.”
However, she noted, “Moving forward, as we develop something that will be genetically modified ... I think this is the future, because if you’re going to treat people with type 1 diabetes, we have to eliminate the immune suppression. I think the concern would be making sure the genetically modified cells are safe.”
Dr. Nostro, who gave an introductory presentation at the beginning of the symposium where the VX-880 data were presented, explained that in a current trial of genetically modified cells, “they’re placing the product inside a device so that the cells would be retrievable. It might not be perfect, but at least it’s going to tell us whether the genetically modified product is safe, which I think is what we need to use.”
In her talk, Dr. Nostro also summarized ongoing work in this field involving efforts to improve the generation of stem cell–derived islets with no “off target” non-beta cells to ensure consistency, optimization of engraftment, and elimination of immunosuppression. “[VX-880] is the beginning. This is the first product that’s going to be in the clinic, but I can imagine how 5, 10 years from now we will have different and more enhanced solutions for type 1 diabetes and who knows, maybe even for type 2.”
Based on the data so far, the VX-880 trial is now moving to part C, in which 10 concurrently enrolled participants will receive the full target dose of the product. The trial, previously exclusively in the United States, has now expanded to additional sites in Norway, Switzerland, and the Netherlands.
The study was funded by Vertex. Dr. Reichman is on advisory boards for Vertex and Sernova. Dr. Nostro was a consultant for Sigilon Therapeutics from 2018-2022, currently receives research support from Universal Cells, and has a patent licensed to Sernova.
A version of this article originally appeared on Medscape.com.
AT ADA 2023
WHO plans to declare common sweetener as possible carcinogen
The World Health Organization is set to list the artificial sweetener aspartame as a possible carcinogen.
The move, reported by multiple media sources, is expected during a July 14 meeting of WHO research experts – the International Agency for Research on Cancer. Reuters cited two unnamed sources “with knowledge of the process,” noting that aspartame is one of the world’s most commonly used sweeteners.
Aspartame is 200 times sweeter than sugar and was first approved by the Food and Drug Administration in 1974 for use as a tabletop sweetener and in chewing gum and cold breakfast cereals, as well as instant coffee, gelatins, puddings and fillings, and dairy products. Up to 95% of carbonated soft drinks that have a sweetener use aspartame, and the substance is often added by consumers to beverages (it’s the blue packet of sweetener in the array of packets that appear on diner and restaurant tables), The Washington Post reported.
The WHO currently lists 126 agents as known to be carcinogenic to humans, ranging from alcohol and tobacco to outdoor air pollution. The WHO also lists 94 agents as “probably” carcinogenic to humans and 322 agents as “possibly” carcinogenic to humans. Aspartame would join the “possibly” group, which includes gasoline engine exhaust and working as a dry cleaner.
Earlier this year, the WHO warned that people should not use nonsugar sweeteners to control their weight because of potential health risks.
A version of this article originally appeared on WebMD.com.
The World Health Organization is set to list the artificial sweetener aspartame as a possible carcinogen.
The move, reported by multiple media sources, is expected during a July 14 meeting of WHO research experts – the International Agency for Research on Cancer. Reuters cited two unnamed sources “with knowledge of the process,” noting that aspartame is one of the world’s most commonly used sweeteners.
Aspartame is 200 times sweeter than sugar and was first approved by the Food and Drug Administration in 1974 for use as a tabletop sweetener and in chewing gum and cold breakfast cereals, as well as instant coffee, gelatins, puddings and fillings, and dairy products. Up to 95% of carbonated soft drinks that have a sweetener use aspartame, and the substance is often added by consumers to beverages (it’s the blue packet of sweetener in the array of packets that appear on diner and restaurant tables), The Washington Post reported.
The WHO currently lists 126 agents as known to be carcinogenic to humans, ranging from alcohol and tobacco to outdoor air pollution. The WHO also lists 94 agents as “probably” carcinogenic to humans and 322 agents as “possibly” carcinogenic to humans. Aspartame would join the “possibly” group, which includes gasoline engine exhaust and working as a dry cleaner.
Earlier this year, the WHO warned that people should not use nonsugar sweeteners to control their weight because of potential health risks.
A version of this article originally appeared on WebMD.com.
The World Health Organization is set to list the artificial sweetener aspartame as a possible carcinogen.
The move, reported by multiple media sources, is expected during a July 14 meeting of WHO research experts – the International Agency for Research on Cancer. Reuters cited two unnamed sources “with knowledge of the process,” noting that aspartame is one of the world’s most commonly used sweeteners.
Aspartame is 200 times sweeter than sugar and was first approved by the Food and Drug Administration in 1974 for use as a tabletop sweetener and in chewing gum and cold breakfast cereals, as well as instant coffee, gelatins, puddings and fillings, and dairy products. Up to 95% of carbonated soft drinks that have a sweetener use aspartame, and the substance is often added by consumers to beverages (it’s the blue packet of sweetener in the array of packets that appear on diner and restaurant tables), The Washington Post reported.
The WHO currently lists 126 agents as known to be carcinogenic to humans, ranging from alcohol and tobacco to outdoor air pollution. The WHO also lists 94 agents as “probably” carcinogenic to humans and 322 agents as “possibly” carcinogenic to humans. Aspartame would join the “possibly” group, which includes gasoline engine exhaust and working as a dry cleaner.
Earlier this year, the WHO warned that people should not use nonsugar sweeteners to control their weight because of potential health risks.
A version of this article originally appeared on WebMD.com.
Tirzepatide: Therapeutic titan or costly cure?
As a general practitioner with a specialist interest in diabetes, I am increasingly diagnosing younger people living with type 2 diabetes and obesity. Sadly, my youngest patient living with type 2 diabetes and obesity is only in her early 20s.
In fact, in England, there are now more people under the age of 40 years living with type 2 diabetes than type 1 diabetes. These younger individuals tend to present with very high hemoglobin A1c levels; I am routinely seeing double-digit A1c percentage levels in my practice. Indeed, the patient mentioned above presented with an A1c of more than 13%.
The lifetime cardiometabolic risk of individuals like her is considerable and very worrying: Younger adults with type 2 diabetes often have adverse cardiometabolic risk profiles at diagnosis, with higher body mass indices, marked dyslipidemia, hypertension, and abnormal liver profiles suggesting nonalcoholic fatty liver disease. The cumulative impact of this risk profile is a significant impact on quality and quantity of life. Evidence tells us that a younger age of diagnosis with type 2 diabetes is associated with an increased risk for premature death, especially from cardiovascular disease.
Early treatment intensification is warranted in younger individuals living with type 2 diabetes and obesity. My patient above is now on triple therapy with metformin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and a glucagonlike peptide–1 (GLP-1) receptor agonist. I gave her an urgent referral to my local weight management service for weight, nutritional, and psychological support. I have also issued her a real-time continuous glucose monitoring (rt-CGM) device: Whilst she does not meet any current U.K. criteria for using rt-CGM, I feel that the role of CGM as an educational tool for her is invaluable and equally important to her pharmacologic therapies. We are in desperate need of effective pharmacologic and lifestyle interventions to tackle this epidemic of cardiometabolic disease in the young.
I attended the recent ADA 2023 congress in San Diego, including the presentation of the SURMOUNT-2 trial data. SURMOUNT-2 explored the efficacy and safety of the dual GLP-GIP agonist tirzepatide for weight management in patients with obesity and type 2 diabetes. Tirzepatide was associated with significant reductions in weight (average weight loss, 14-16 kg after 72 weeks) and glycemia (2.1% reduction in A1c after 72 weeks), as well as reductions in clinically meaningful cardiometabolic risk factors, including systolic blood pressure, liver enzymes, and fasting non–HDL cholesterol levels. The overall safety profile of tirzepatide was also reassuring and consistent with the GLP-1 class. Most adverse effects were gastrointestinal and of mild to moderate severity. These adverse effects decreased over time.
These results perfectly position tirzepatide for my younger patients like the young woman mentioned above. The significant improvements in weight, glycemia, and cardiometabolic risk factors will not only help mitigate her future cardiometabolic risk but also help the sustainability of the U.K.’s National Health System. The cost of diabetes to the NHS in the United Kingdom is more than 10% of the entire NHS budget for England and Wales. More than 80% of this cost, however, is related not to the medications and devices we prescribe for diabetes but to the downstream complications of diabetes, such as hospital admissions for cardiovascular events and amputations, as well as regular hospital attendance for dialysis for end-stage kidney disease.
There is no doubt, however, that modern obesity medications such as semaglutide and tirzepatide are expensive, and demand has been astronomical. This demand has been driven by private weight-management services and celebrity influencers, and has resulted in major U.K.-wide GLP-1 shortages.
This situation is tragically widening health inequalities, as many of my patients who have been on GLP-1 receptor agonists for many years are unable to obtain them. I am having to consider switching therapies, often to less efficacious options without the compelling cardiorenal benefits. Furthermore, the GLP-1 shortages have prevented GLP-1 initiation for my other high-risk younger patients, potentially increasing future cardiometabolic risk.
There remain unanswered questions for tirzepatide: What is the durability of effect of tirzepatide after 72 weeks (that is, the trial duration of SURMOUNT-2)? Crucially, what is the effect of withdrawal of tirzepatide on weight loss maintenance? Previous evidence has suggested weight regain after discontinuation of a GLP-1 receptor agonist for obesity. This, of course, has further financial and sustainability implications for health care systems such as the NHS.
Finally, we are increasingly seeing younger women of childbearing age with or at risk for cardiometabolic disease. Again, my patient above is one example. Many of the therapies we use for cardiometabolic disease management, including GLP-1 receptor agonists and tirzepatide, have not been studied, and hence have not been licensed in pregnant women. Therefore, frank discussions are required with patients about future family plans and the importance of contraception. Often, the significant weight loss seen with GLP-1 receptor agonists can improve hormonal profiles and fertility in women and result in unexpected pregnancies if robust contraception is not in place.
Tirzepatide has yet to be made commercially available in the United Kingdom, and its price has also yet to be set. But I already envision a clear role for tirzepatide in my treatment armamentarium. I will be positioning tirzepatide as my first injectable of choice after oral treatment escalation with metformin and an SGLT2 inhibitor in all my patients who require treatment intensification – not just my younger, higher-risk individuals. This may remain an aspirational goal until supply chains and cost are defined. There is no doubt, however, that the compelling weight and glycemic benefits of tirzepatide alongside individualized lifestyle interventions can help improve the quality and quantity of life of my patients living with type 2 diabetes and obesity.
Dr. Fernando is a general practitioner near Edinburgh. He reported receiving speaker fees from Eli Lilly and Novo Nordisk..
A version of this article first appeared on Medscape.com.
As a general practitioner with a specialist interest in diabetes, I am increasingly diagnosing younger people living with type 2 diabetes and obesity. Sadly, my youngest patient living with type 2 diabetes and obesity is only in her early 20s.
In fact, in England, there are now more people under the age of 40 years living with type 2 diabetes than type 1 diabetes. These younger individuals tend to present with very high hemoglobin A1c levels; I am routinely seeing double-digit A1c percentage levels in my practice. Indeed, the patient mentioned above presented with an A1c of more than 13%.
The lifetime cardiometabolic risk of individuals like her is considerable and very worrying: Younger adults with type 2 diabetes often have adverse cardiometabolic risk profiles at diagnosis, with higher body mass indices, marked dyslipidemia, hypertension, and abnormal liver profiles suggesting nonalcoholic fatty liver disease. The cumulative impact of this risk profile is a significant impact on quality and quantity of life. Evidence tells us that a younger age of diagnosis with type 2 diabetes is associated with an increased risk for premature death, especially from cardiovascular disease.
Early treatment intensification is warranted in younger individuals living with type 2 diabetes and obesity. My patient above is now on triple therapy with metformin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and a glucagonlike peptide–1 (GLP-1) receptor agonist. I gave her an urgent referral to my local weight management service for weight, nutritional, and psychological support. I have also issued her a real-time continuous glucose monitoring (rt-CGM) device: Whilst she does not meet any current U.K. criteria for using rt-CGM, I feel that the role of CGM as an educational tool for her is invaluable and equally important to her pharmacologic therapies. We are in desperate need of effective pharmacologic and lifestyle interventions to tackle this epidemic of cardiometabolic disease in the young.
I attended the recent ADA 2023 congress in San Diego, including the presentation of the SURMOUNT-2 trial data. SURMOUNT-2 explored the efficacy and safety of the dual GLP-GIP agonist tirzepatide for weight management in patients with obesity and type 2 diabetes. Tirzepatide was associated with significant reductions in weight (average weight loss, 14-16 kg after 72 weeks) and glycemia (2.1% reduction in A1c after 72 weeks), as well as reductions in clinically meaningful cardiometabolic risk factors, including systolic blood pressure, liver enzymes, and fasting non–HDL cholesterol levels. The overall safety profile of tirzepatide was also reassuring and consistent with the GLP-1 class. Most adverse effects were gastrointestinal and of mild to moderate severity. These adverse effects decreased over time.
These results perfectly position tirzepatide for my younger patients like the young woman mentioned above. The significant improvements in weight, glycemia, and cardiometabolic risk factors will not only help mitigate her future cardiometabolic risk but also help the sustainability of the U.K.’s National Health System. The cost of diabetes to the NHS in the United Kingdom is more than 10% of the entire NHS budget for England and Wales. More than 80% of this cost, however, is related not to the medications and devices we prescribe for diabetes but to the downstream complications of diabetes, such as hospital admissions for cardiovascular events and amputations, as well as regular hospital attendance for dialysis for end-stage kidney disease.
There is no doubt, however, that modern obesity medications such as semaglutide and tirzepatide are expensive, and demand has been astronomical. This demand has been driven by private weight-management services and celebrity influencers, and has resulted in major U.K.-wide GLP-1 shortages.
This situation is tragically widening health inequalities, as many of my patients who have been on GLP-1 receptor agonists for many years are unable to obtain them. I am having to consider switching therapies, often to less efficacious options without the compelling cardiorenal benefits. Furthermore, the GLP-1 shortages have prevented GLP-1 initiation for my other high-risk younger patients, potentially increasing future cardiometabolic risk.
There remain unanswered questions for tirzepatide: What is the durability of effect of tirzepatide after 72 weeks (that is, the trial duration of SURMOUNT-2)? Crucially, what is the effect of withdrawal of tirzepatide on weight loss maintenance? Previous evidence has suggested weight regain after discontinuation of a GLP-1 receptor agonist for obesity. This, of course, has further financial and sustainability implications for health care systems such as the NHS.
Finally, we are increasingly seeing younger women of childbearing age with or at risk for cardiometabolic disease. Again, my patient above is one example. Many of the therapies we use for cardiometabolic disease management, including GLP-1 receptor agonists and tirzepatide, have not been studied, and hence have not been licensed in pregnant women. Therefore, frank discussions are required with patients about future family plans and the importance of contraception. Often, the significant weight loss seen with GLP-1 receptor agonists can improve hormonal profiles and fertility in women and result in unexpected pregnancies if robust contraception is not in place.
Tirzepatide has yet to be made commercially available in the United Kingdom, and its price has also yet to be set. But I already envision a clear role for tirzepatide in my treatment armamentarium. I will be positioning tirzepatide as my first injectable of choice after oral treatment escalation with metformin and an SGLT2 inhibitor in all my patients who require treatment intensification – not just my younger, higher-risk individuals. This may remain an aspirational goal until supply chains and cost are defined. There is no doubt, however, that the compelling weight and glycemic benefits of tirzepatide alongside individualized lifestyle interventions can help improve the quality and quantity of life of my patients living with type 2 diabetes and obesity.
Dr. Fernando is a general practitioner near Edinburgh. He reported receiving speaker fees from Eli Lilly and Novo Nordisk..
A version of this article first appeared on Medscape.com.
As a general practitioner with a specialist interest in diabetes, I am increasingly diagnosing younger people living with type 2 diabetes and obesity. Sadly, my youngest patient living with type 2 diabetes and obesity is only in her early 20s.
In fact, in England, there are now more people under the age of 40 years living with type 2 diabetes than type 1 diabetes. These younger individuals tend to present with very high hemoglobin A1c levels; I am routinely seeing double-digit A1c percentage levels in my practice. Indeed, the patient mentioned above presented with an A1c of more than 13%.
The lifetime cardiometabolic risk of individuals like her is considerable and very worrying: Younger adults with type 2 diabetes often have adverse cardiometabolic risk profiles at diagnosis, with higher body mass indices, marked dyslipidemia, hypertension, and abnormal liver profiles suggesting nonalcoholic fatty liver disease. The cumulative impact of this risk profile is a significant impact on quality and quantity of life. Evidence tells us that a younger age of diagnosis with type 2 diabetes is associated with an increased risk for premature death, especially from cardiovascular disease.
Early treatment intensification is warranted in younger individuals living with type 2 diabetes and obesity. My patient above is now on triple therapy with metformin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and a glucagonlike peptide–1 (GLP-1) receptor agonist. I gave her an urgent referral to my local weight management service for weight, nutritional, and psychological support. I have also issued her a real-time continuous glucose monitoring (rt-CGM) device: Whilst she does not meet any current U.K. criteria for using rt-CGM, I feel that the role of CGM as an educational tool for her is invaluable and equally important to her pharmacologic therapies. We are in desperate need of effective pharmacologic and lifestyle interventions to tackle this epidemic of cardiometabolic disease in the young.
I attended the recent ADA 2023 congress in San Diego, including the presentation of the SURMOUNT-2 trial data. SURMOUNT-2 explored the efficacy and safety of the dual GLP-GIP agonist tirzepatide for weight management in patients with obesity and type 2 diabetes. Tirzepatide was associated with significant reductions in weight (average weight loss, 14-16 kg after 72 weeks) and glycemia (2.1% reduction in A1c after 72 weeks), as well as reductions in clinically meaningful cardiometabolic risk factors, including systolic blood pressure, liver enzymes, and fasting non–HDL cholesterol levels. The overall safety profile of tirzepatide was also reassuring and consistent with the GLP-1 class. Most adverse effects were gastrointestinal and of mild to moderate severity. These adverse effects decreased over time.
These results perfectly position tirzepatide for my younger patients like the young woman mentioned above. The significant improvements in weight, glycemia, and cardiometabolic risk factors will not only help mitigate her future cardiometabolic risk but also help the sustainability of the U.K.’s National Health System. The cost of diabetes to the NHS in the United Kingdom is more than 10% of the entire NHS budget for England and Wales. More than 80% of this cost, however, is related not to the medications and devices we prescribe for diabetes but to the downstream complications of diabetes, such as hospital admissions for cardiovascular events and amputations, as well as regular hospital attendance for dialysis for end-stage kidney disease.
There is no doubt, however, that modern obesity medications such as semaglutide and tirzepatide are expensive, and demand has been astronomical. This demand has been driven by private weight-management services and celebrity influencers, and has resulted in major U.K.-wide GLP-1 shortages.
This situation is tragically widening health inequalities, as many of my patients who have been on GLP-1 receptor agonists for many years are unable to obtain them. I am having to consider switching therapies, often to less efficacious options without the compelling cardiorenal benefits. Furthermore, the GLP-1 shortages have prevented GLP-1 initiation for my other high-risk younger patients, potentially increasing future cardiometabolic risk.
There remain unanswered questions for tirzepatide: What is the durability of effect of tirzepatide after 72 weeks (that is, the trial duration of SURMOUNT-2)? Crucially, what is the effect of withdrawal of tirzepatide on weight loss maintenance? Previous evidence has suggested weight regain after discontinuation of a GLP-1 receptor agonist for obesity. This, of course, has further financial and sustainability implications for health care systems such as the NHS.
Finally, we are increasingly seeing younger women of childbearing age with or at risk for cardiometabolic disease. Again, my patient above is one example. Many of the therapies we use for cardiometabolic disease management, including GLP-1 receptor agonists and tirzepatide, have not been studied, and hence have not been licensed in pregnant women. Therefore, frank discussions are required with patients about future family plans and the importance of contraception. Often, the significant weight loss seen with GLP-1 receptor agonists can improve hormonal profiles and fertility in women and result in unexpected pregnancies if robust contraception is not in place.
Tirzepatide has yet to be made commercially available in the United Kingdom, and its price has also yet to be set. But I already envision a clear role for tirzepatide in my treatment armamentarium. I will be positioning tirzepatide as my first injectable of choice after oral treatment escalation with metformin and an SGLT2 inhibitor in all my patients who require treatment intensification – not just my younger, higher-risk individuals. This may remain an aspirational goal until supply chains and cost are defined. There is no doubt, however, that the compelling weight and glycemic benefits of tirzepatide alongside individualized lifestyle interventions can help improve the quality and quantity of life of my patients living with type 2 diabetes and obesity.
Dr. Fernando is a general practitioner near Edinburgh. He reported receiving speaker fees from Eli Lilly and Novo Nordisk..
A version of this article first appeared on Medscape.com.
CGM alarm fatigue in youth?
Teenagers with diabetes who use a continuous glucose monitor (CGM) employ a wide variety of alarm settings to alert them when their blood sugar may be too high or too low. But sometimes those thresholds generate too many alarms – which in turn might lead patients to ignore the devices, according to a study presented at the 2023 annual meeting of the Endocrine Society.
“These alarms alert people with diabetes and their caregivers of pending glycemic changes. However, little work has been done studying CGM alarm settings in pediatric clinical populations,” said Victoria Ochs, BS, a medical student at the Indiana University, Indianapolis, who helped conduct the study.
Ms. Ochs and colleagues analyzed 2 weeks of real-time CGM alarm settings from 150 children with diabetes treated at Indiana. Their average age was 14 years; 47% were female, 89% of were White, 9.5% were Black, and 1.5% were Asian. Approximately half the patients used insulin pumps (51%) in addition to the monitoring devices.
For both alarms that indicated blood sugar was too low or too high, settings among the children often varied widely from thresholds recommended by the University of Colorado’s Barbara Davis Center for Diabetes, Aurora. Those thresholds are 70 mg/dL of glucose for low and 180 mg/dL for high glucose. At Indiana, the median alert level for low was set to 74 mg/dL (range: 60-100), while the median for high was 242 mg/dL (range: 120-400).
“If we have it set at 100, what exactly is the purpose of that? Is it just to make you more anxious that you’re going to drop low at some point?” asked Cari Berget, MPH, RN, CDE, who specializes in pediatric diabetes at the University of Colorado, speaking of the low blood sugar alarm. Setting this alarm at 70 md/dL instead could lead to concrete action when it does go off – such as consuming carbohydrates to boost blood sugar, she said.
“Alarms should result in action most of the time,” said Ms. Berget, associate director of Colorado’s PANTHER program, which established the alarm thresholds used in the Indiana study. Alarm setting is not one-size-fits-all, Ms. Berget noted: Some people might want 70 mg/dL to warn of low blood sugar, whereas others prefer 75 or 80 mg/dL.
As for alerts about hyperglycemia, Ms. Berget said patients often exceed the high range of 180 mg/dL immediately after a meal. Ideally these sugars will subside on their own within 3 hours, a process aided by insulin shots or pumps. Setting a threshold for high blood sugar too low, such as 120 mg/dL, could result in ceaseless alarms even if the person is not at risk for harm.
“If you receive an alarm and there’s no action for you to take, then we need to change how we’re setting these alarms,” Ms. Berget said. She advised parents and children to be thoughtful about setting their CGM alarm thresholds to be most useful to them.
Ms. Ochs said in some cases families have CGM devices shipped directly to their homes and never consult with anyone about optimal alarm settings.
“It would be useful to talk to families about what baseline information they had,” Ms. Ochs told this news organization. “It would be nice to talk to diabetes educators, and I think it would be nice to talk to physicians.”
Ms. Ochs reports no relevant financial relationships. Ms. Berget has consulted for Dexcom and Insulet.
A version of this article originally appeared on Medscape.com.
Teenagers with diabetes who use a continuous glucose monitor (CGM) employ a wide variety of alarm settings to alert them when their blood sugar may be too high or too low. But sometimes those thresholds generate too many alarms – which in turn might lead patients to ignore the devices, according to a study presented at the 2023 annual meeting of the Endocrine Society.
“These alarms alert people with diabetes and their caregivers of pending glycemic changes. However, little work has been done studying CGM alarm settings in pediatric clinical populations,” said Victoria Ochs, BS, a medical student at the Indiana University, Indianapolis, who helped conduct the study.
Ms. Ochs and colleagues analyzed 2 weeks of real-time CGM alarm settings from 150 children with diabetes treated at Indiana. Their average age was 14 years; 47% were female, 89% of were White, 9.5% were Black, and 1.5% were Asian. Approximately half the patients used insulin pumps (51%) in addition to the monitoring devices.
For both alarms that indicated blood sugar was too low or too high, settings among the children often varied widely from thresholds recommended by the University of Colorado’s Barbara Davis Center for Diabetes, Aurora. Those thresholds are 70 mg/dL of glucose for low and 180 mg/dL for high glucose. At Indiana, the median alert level for low was set to 74 mg/dL (range: 60-100), while the median for high was 242 mg/dL (range: 120-400).
“If we have it set at 100, what exactly is the purpose of that? Is it just to make you more anxious that you’re going to drop low at some point?” asked Cari Berget, MPH, RN, CDE, who specializes in pediatric diabetes at the University of Colorado, speaking of the low blood sugar alarm. Setting this alarm at 70 md/dL instead could lead to concrete action when it does go off – such as consuming carbohydrates to boost blood sugar, she said.
“Alarms should result in action most of the time,” said Ms. Berget, associate director of Colorado’s PANTHER program, which established the alarm thresholds used in the Indiana study. Alarm setting is not one-size-fits-all, Ms. Berget noted: Some people might want 70 mg/dL to warn of low blood sugar, whereas others prefer 75 or 80 mg/dL.
As for alerts about hyperglycemia, Ms. Berget said patients often exceed the high range of 180 mg/dL immediately after a meal. Ideally these sugars will subside on their own within 3 hours, a process aided by insulin shots or pumps. Setting a threshold for high blood sugar too low, such as 120 mg/dL, could result in ceaseless alarms even if the person is not at risk for harm.
“If you receive an alarm and there’s no action for you to take, then we need to change how we’re setting these alarms,” Ms. Berget said. She advised parents and children to be thoughtful about setting their CGM alarm thresholds to be most useful to them.
Ms. Ochs said in some cases families have CGM devices shipped directly to their homes and never consult with anyone about optimal alarm settings.
“It would be useful to talk to families about what baseline information they had,” Ms. Ochs told this news organization. “It would be nice to talk to diabetes educators, and I think it would be nice to talk to physicians.”
Ms. Ochs reports no relevant financial relationships. Ms. Berget has consulted for Dexcom and Insulet.
A version of this article originally appeared on Medscape.com.
Teenagers with diabetes who use a continuous glucose monitor (CGM) employ a wide variety of alarm settings to alert them when their blood sugar may be too high or too low. But sometimes those thresholds generate too many alarms – which in turn might lead patients to ignore the devices, according to a study presented at the 2023 annual meeting of the Endocrine Society.
“These alarms alert people with diabetes and their caregivers of pending glycemic changes. However, little work has been done studying CGM alarm settings in pediatric clinical populations,” said Victoria Ochs, BS, a medical student at the Indiana University, Indianapolis, who helped conduct the study.
Ms. Ochs and colleagues analyzed 2 weeks of real-time CGM alarm settings from 150 children with diabetes treated at Indiana. Their average age was 14 years; 47% were female, 89% of were White, 9.5% were Black, and 1.5% were Asian. Approximately half the patients used insulin pumps (51%) in addition to the monitoring devices.
For both alarms that indicated blood sugar was too low or too high, settings among the children often varied widely from thresholds recommended by the University of Colorado’s Barbara Davis Center for Diabetes, Aurora. Those thresholds are 70 mg/dL of glucose for low and 180 mg/dL for high glucose. At Indiana, the median alert level for low was set to 74 mg/dL (range: 60-100), while the median for high was 242 mg/dL (range: 120-400).
“If we have it set at 100, what exactly is the purpose of that? Is it just to make you more anxious that you’re going to drop low at some point?” asked Cari Berget, MPH, RN, CDE, who specializes in pediatric diabetes at the University of Colorado, speaking of the low blood sugar alarm. Setting this alarm at 70 md/dL instead could lead to concrete action when it does go off – such as consuming carbohydrates to boost blood sugar, she said.
“Alarms should result in action most of the time,” said Ms. Berget, associate director of Colorado’s PANTHER program, which established the alarm thresholds used in the Indiana study. Alarm setting is not one-size-fits-all, Ms. Berget noted: Some people might want 70 mg/dL to warn of low blood sugar, whereas others prefer 75 or 80 mg/dL.
As for alerts about hyperglycemia, Ms. Berget said patients often exceed the high range of 180 mg/dL immediately after a meal. Ideally these sugars will subside on their own within 3 hours, a process aided by insulin shots or pumps. Setting a threshold for high blood sugar too low, such as 120 mg/dL, could result in ceaseless alarms even if the person is not at risk for harm.
“If you receive an alarm and there’s no action for you to take, then we need to change how we’re setting these alarms,” Ms. Berget said. She advised parents and children to be thoughtful about setting their CGM alarm thresholds to be most useful to them.
Ms. Ochs said in some cases families have CGM devices shipped directly to their homes and never consult with anyone about optimal alarm settings.
“It would be useful to talk to families about what baseline information they had,” Ms. Ochs told this news organization. “It would be nice to talk to diabetes educators, and I think it would be nice to talk to physicians.”
Ms. Ochs reports no relevant financial relationships. Ms. Berget has consulted for Dexcom and Insulet.
A version of this article originally appeared on Medscape.com.
Beta cells from stem cells: Nearing a cure for type 1 diabetes?
This transcript has been edited for clarity.
Those of us in the field of diabetes have long wanted to cure type 1 diabetes, and there are little steps making me feel like this might be a possibility. One of those steps is that a company named Vertex – I’m actually on the steering committee for Vertex in terms of this project – has made beta cells from stem cells. Now, instead of waiting for a cadaveric donor, we can make little beta cells. They started giving them to people in human trials. The Food and Drug Administration has been cautious because it’s new, and I get that.
In the first part of these trials, we could only give half a dose of these beta cells. The doses were determined based on what we know from giving beta-cell transplants from cadaveric donors. We gave half a dose of these stem cell–derived beta cells to two people who were having episodes of severe hypoglycemia.
In patient 1, these beta cells worked incredibly well. He became insulin independent, and now after over a year, he’s basically free of his type 1 diabetes. Patient 2 received half a dose, and she did get some activity of the beta cells, but not enough to achieve insulin independence, so she got a second dose. Shortly after the second dose, she decided she didn’t want to participate in the trial anymore and she was lost to follow-up.
Patient 2 didn’t get the same response as patient 1, but then we moved on to four more patients who got a full dose to start with. Now, there’s a total of six patients. Of those additional four patients, one of them has now been followed for a year. Just like patient 1, he’s off insulin. It’s as though his body has normal beta cells and he’s doing great. For the next three patients, we don’t have enough follow-up data to tell you what’s going to happen to them at a year.
I can tell you that, in all six patients, the beta cells worked. They basically were producing insulin, they had positive C-peptide levels, and it showed that these beta cells work when given to human beings. Now the trial is going to start giving more patients these stem cell–derived beta cells.
One of the things that’s important to realize is that this is a very small sample size, at just six individuals. Even within those six individuals, there was variation in terms of the response to the treatment. Probably, just like with all things in medicine, there will be different doses, different ways in which people do respond, people who get off of insulin completely, and people who may require some ongoing insulin therapy. I have no idea what this is going to look like as we test this in more people.
Everybody did start making C-peptide, they were having an effect of these beta cells, and it was working. We’ll have to see how well it works, how well it works in whom, and how we’re going to be able to use these types of therapies in the future.
In terms of side effects, they were really related to immunosuppression. There were no real surprises, but again, this is a very small sample size.
In summary, I think this is really hopeful. I don’t like to give false hope, but each step of this development process has shown that these beta cells derived from stem cells do seem to work in human beings as native beta cells might. Hopefully, this portends a future of newer therapies in the treatment of people with type 1 diabetes. Thank you.
Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen.
A version of this article originally appeared on Medscape.com.
This transcript has been edited for clarity.
Those of us in the field of diabetes have long wanted to cure type 1 diabetes, and there are little steps making me feel like this might be a possibility. One of those steps is that a company named Vertex – I’m actually on the steering committee for Vertex in terms of this project – has made beta cells from stem cells. Now, instead of waiting for a cadaveric donor, we can make little beta cells. They started giving them to people in human trials. The Food and Drug Administration has been cautious because it’s new, and I get that.
In the first part of these trials, we could only give half a dose of these beta cells. The doses were determined based on what we know from giving beta-cell transplants from cadaveric donors. We gave half a dose of these stem cell–derived beta cells to two people who were having episodes of severe hypoglycemia.
In patient 1, these beta cells worked incredibly well. He became insulin independent, and now after over a year, he’s basically free of his type 1 diabetes. Patient 2 received half a dose, and she did get some activity of the beta cells, but not enough to achieve insulin independence, so she got a second dose. Shortly after the second dose, she decided she didn’t want to participate in the trial anymore and she was lost to follow-up.
Patient 2 didn’t get the same response as patient 1, but then we moved on to four more patients who got a full dose to start with. Now, there’s a total of six patients. Of those additional four patients, one of them has now been followed for a year. Just like patient 1, he’s off insulin. It’s as though his body has normal beta cells and he’s doing great. For the next three patients, we don’t have enough follow-up data to tell you what’s going to happen to them at a year.
I can tell you that, in all six patients, the beta cells worked. They basically were producing insulin, they had positive C-peptide levels, and it showed that these beta cells work when given to human beings. Now the trial is going to start giving more patients these stem cell–derived beta cells.
One of the things that’s important to realize is that this is a very small sample size, at just six individuals. Even within those six individuals, there was variation in terms of the response to the treatment. Probably, just like with all things in medicine, there will be different doses, different ways in which people do respond, people who get off of insulin completely, and people who may require some ongoing insulin therapy. I have no idea what this is going to look like as we test this in more people.
Everybody did start making C-peptide, they were having an effect of these beta cells, and it was working. We’ll have to see how well it works, how well it works in whom, and how we’re going to be able to use these types of therapies in the future.
In terms of side effects, they were really related to immunosuppression. There were no real surprises, but again, this is a very small sample size.
In summary, I think this is really hopeful. I don’t like to give false hope, but each step of this development process has shown that these beta cells derived from stem cells do seem to work in human beings as native beta cells might. Hopefully, this portends a future of newer therapies in the treatment of people with type 1 diabetes. Thank you.
Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen.
A version of this article originally appeared on Medscape.com.
This transcript has been edited for clarity.
Those of us in the field of diabetes have long wanted to cure type 1 diabetes, and there are little steps making me feel like this might be a possibility. One of those steps is that a company named Vertex – I’m actually on the steering committee for Vertex in terms of this project – has made beta cells from stem cells. Now, instead of waiting for a cadaveric donor, we can make little beta cells. They started giving them to people in human trials. The Food and Drug Administration has been cautious because it’s new, and I get that.
In the first part of these trials, we could only give half a dose of these beta cells. The doses were determined based on what we know from giving beta-cell transplants from cadaveric donors. We gave half a dose of these stem cell–derived beta cells to two people who were having episodes of severe hypoglycemia.
In patient 1, these beta cells worked incredibly well. He became insulin independent, and now after over a year, he’s basically free of his type 1 diabetes. Patient 2 received half a dose, and she did get some activity of the beta cells, but not enough to achieve insulin independence, so she got a second dose. Shortly after the second dose, she decided she didn’t want to participate in the trial anymore and she was lost to follow-up.
Patient 2 didn’t get the same response as patient 1, but then we moved on to four more patients who got a full dose to start with. Now, there’s a total of six patients. Of those additional four patients, one of them has now been followed for a year. Just like patient 1, he’s off insulin. It’s as though his body has normal beta cells and he’s doing great. For the next three patients, we don’t have enough follow-up data to tell you what’s going to happen to them at a year.
I can tell you that, in all six patients, the beta cells worked. They basically were producing insulin, they had positive C-peptide levels, and it showed that these beta cells work when given to human beings. Now the trial is going to start giving more patients these stem cell–derived beta cells.
One of the things that’s important to realize is that this is a very small sample size, at just six individuals. Even within those six individuals, there was variation in terms of the response to the treatment. Probably, just like with all things in medicine, there will be different doses, different ways in which people do respond, people who get off of insulin completely, and people who may require some ongoing insulin therapy. I have no idea what this is going to look like as we test this in more people.
Everybody did start making C-peptide, they were having an effect of these beta cells, and it was working. We’ll have to see how well it works, how well it works in whom, and how we’re going to be able to use these types of therapies in the future.
In terms of side effects, they were really related to immunosuppression. There were no real surprises, but again, this is a very small sample size.
In summary, I think this is really hopeful. I don’t like to give false hope, but each step of this development process has shown that these beta cells derived from stem cells do seem to work in human beings as native beta cells might. Hopefully, this portends a future of newer therapies in the treatment of people with type 1 diabetes. Thank you.
Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen.
A version of this article originally appeared on Medscape.com.