User login
In Medicare, insulin costs more for patients who use pumps
Under the U.S. Medicare system, the cost of insulin is about 50% higher for beneficiaries who use insulin pumps than those who inject insulin, a new analysis reveals.
Robert A. Vigersky, MD, chief medical officer of Medtronic Diabetes, Washington, is senior author. Medtronic estimates that 60,000-70,000 fee-for-service Medicare beneficiaries with type 1 diabetes use insulin pumps.
Under Medicare, insulin delivered via syringe or pen is reimbursed under Part D, the drug benefit, whereas insulin infused by pump falls under Part B, as durable medical equipment (DME).
The price differential arose in 2017, with a rule change to the 21st Century Cures Act regarding reimbursement for infused drugs under Part B, and further worsened with subsequent overall increases in the price of insulin.
Only 29% of Medicare beneficiaries have supplemental Medigap insurance to help lower out-of-pocket costs, the authors of the commentary noted.
“Our patients who are using insulin pumps noticed a big increase in the cost of their insulin when the 21st Century Cures Act took place in January 2017. Without any notification from Medicare, the amount of money out of pocket and the total cost of insulin rose for patients who are using insulin pumps. … There were anecdotal reports; then we looked into it,” Dr. Vigersky, who is also professor of medicine at the Uniformed Services University for the Health Sciences, Bethesda, Md., said in an interview.
Physicians should be aware of the situation in order to counsel patients – who are either aging into Medicare with an insulin pump or who are already in Medicare and want to switch from injections to a pump – that they may encounter higher copays for insulin, he said.
In addition, Dr. Vigersky advised, concerned patients should be encouraged to call their representatives in Congress. But, “this shouldn’t dissuade clinicians from prescribing pumps, because they provide a huge benefit in terms of patients’ overall ability to control their diabetes.”
A call to action as price of insulin rose, suddenly shifted, in 2017
In the article, the authors call for the Centers for Medicare & Medicaid Services to fix the situation with a series of actions, including better aligning the cost of insulin under Parts B and D, and determining reimbursement rates on a drug-by-drug basis, rather than lumping together all infused drugs.
The CMS said in a statement: “As with all relevant and topical research, CMS appreciates the input of the journal authors and considers external research in all potential future policymaking and initiatives.”
As outlined by the authors, the overall price of insulin in the United States has dramatically increased in the past 2 decades. For example, the average list price of one vial of insulin rose from $9.61 to $25.38 between January 2013 and July 2018, a 164% increase.
A provision in the 21st Century Cures Act, which went into effect Jan. 1, 2017, attempted to remedy past overpayment for DME-infused drugs covered under Medicare Part B by changing the pricing methodology. Prior to 2017, the drugs had been reimbursed based on 95% of the 2003 average wholesale price. With the new law, payments have been set to average sales price plus 6%.
As a result, the price of insulin rose by 251% overnight from Dec. 31, 2016, to Jan. 1, 2017, for Medicare beneficiaries using insulin pumps, whereas there was no change for those injecting their insulin.
And then in 2018, insulin manufacturers raised the price by another 53%, resulting in an overall 304% price increase under Part B over 2 years.
Meanwhile, on March 11, 2020, CMS announced a cap on insulin copays in Part D to $35 a month, which doesn’t apply to pump users.
Thus, as of now, the average monthly copay for insulin for pump users in Medicare is about $54.26, about 50% more than the $35 maximum for those who inject insulin.
“This is in the setting of patients skimping on insulin anyway because of the high cost. There’s reasonably good evidence that patients stretch out their insulin because of cost, including those in Medicare,” Dr. Vigersky emphasized.
What can be done?
The problem could have been avoided, the authors wrote in their commentary, if payments had simply been adjusted for the two pre-2017 most highly overpaid DME-infused drugs, milrinone lactate and immune globulin, rather than all of them. Doing that would have addressed 95% of the overpayments and saved $267 million without affecting insulin cost.
Unlike insulin, nearly all of the other infused drugs are used only for short periods of time, such as pain medications, antibiotics, or chemotherapy.
“People get these for a few months, but not for years and years. Some aren’t used much at all. It was sort of a wholesale way to change things, and insulin got caught in it, with more extensive consequences,” Dr. Vigersky noted.
He and his coauthors advised the CMS to test pricing methodologies before implementation to prevent further unintended consequences going forward, to ask the Inspector General’s office to reanalyze costs to see if savings targets are being met, and to notify patients and health care providers in advance of a change so that they can better prepare for increased costs.
For now, Dr. Vigersky advised that, when considering pump therapy for a given patient, “from a clinical standpoint, this is a shared decision with the patient.
“As much as the reality of costs is shared with the patient, there is good evidence that pump therapy is cost-effective. The patient has to make the decision as to whether this extra amount is worth the benefits in the long run that they will get from pump therapy.”
A version of this article was originally published on Medscape.com.
Under the U.S. Medicare system, the cost of insulin is about 50% higher for beneficiaries who use insulin pumps than those who inject insulin, a new analysis reveals.
Robert A. Vigersky, MD, chief medical officer of Medtronic Diabetes, Washington, is senior author. Medtronic estimates that 60,000-70,000 fee-for-service Medicare beneficiaries with type 1 diabetes use insulin pumps.
Under Medicare, insulin delivered via syringe or pen is reimbursed under Part D, the drug benefit, whereas insulin infused by pump falls under Part B, as durable medical equipment (DME).
The price differential arose in 2017, with a rule change to the 21st Century Cures Act regarding reimbursement for infused drugs under Part B, and further worsened with subsequent overall increases in the price of insulin.
Only 29% of Medicare beneficiaries have supplemental Medigap insurance to help lower out-of-pocket costs, the authors of the commentary noted.
“Our patients who are using insulin pumps noticed a big increase in the cost of their insulin when the 21st Century Cures Act took place in January 2017. Without any notification from Medicare, the amount of money out of pocket and the total cost of insulin rose for patients who are using insulin pumps. … There were anecdotal reports; then we looked into it,” Dr. Vigersky, who is also professor of medicine at the Uniformed Services University for the Health Sciences, Bethesda, Md., said in an interview.
Physicians should be aware of the situation in order to counsel patients – who are either aging into Medicare with an insulin pump or who are already in Medicare and want to switch from injections to a pump – that they may encounter higher copays for insulin, he said.
In addition, Dr. Vigersky advised, concerned patients should be encouraged to call their representatives in Congress. But, “this shouldn’t dissuade clinicians from prescribing pumps, because they provide a huge benefit in terms of patients’ overall ability to control their diabetes.”
A call to action as price of insulin rose, suddenly shifted, in 2017
In the article, the authors call for the Centers for Medicare & Medicaid Services to fix the situation with a series of actions, including better aligning the cost of insulin under Parts B and D, and determining reimbursement rates on a drug-by-drug basis, rather than lumping together all infused drugs.
The CMS said in a statement: “As with all relevant and topical research, CMS appreciates the input of the journal authors and considers external research in all potential future policymaking and initiatives.”
As outlined by the authors, the overall price of insulin in the United States has dramatically increased in the past 2 decades. For example, the average list price of one vial of insulin rose from $9.61 to $25.38 between January 2013 and July 2018, a 164% increase.
A provision in the 21st Century Cures Act, which went into effect Jan. 1, 2017, attempted to remedy past overpayment for DME-infused drugs covered under Medicare Part B by changing the pricing methodology. Prior to 2017, the drugs had been reimbursed based on 95% of the 2003 average wholesale price. With the new law, payments have been set to average sales price plus 6%.
As a result, the price of insulin rose by 251% overnight from Dec. 31, 2016, to Jan. 1, 2017, for Medicare beneficiaries using insulin pumps, whereas there was no change for those injecting their insulin.
And then in 2018, insulin manufacturers raised the price by another 53%, resulting in an overall 304% price increase under Part B over 2 years.
Meanwhile, on March 11, 2020, CMS announced a cap on insulin copays in Part D to $35 a month, which doesn’t apply to pump users.
Thus, as of now, the average monthly copay for insulin for pump users in Medicare is about $54.26, about 50% more than the $35 maximum for those who inject insulin.
“This is in the setting of patients skimping on insulin anyway because of the high cost. There’s reasonably good evidence that patients stretch out their insulin because of cost, including those in Medicare,” Dr. Vigersky emphasized.
What can be done?
The problem could have been avoided, the authors wrote in their commentary, if payments had simply been adjusted for the two pre-2017 most highly overpaid DME-infused drugs, milrinone lactate and immune globulin, rather than all of them. Doing that would have addressed 95% of the overpayments and saved $267 million without affecting insulin cost.
Unlike insulin, nearly all of the other infused drugs are used only for short periods of time, such as pain medications, antibiotics, or chemotherapy.
“People get these for a few months, but not for years and years. Some aren’t used much at all. It was sort of a wholesale way to change things, and insulin got caught in it, with more extensive consequences,” Dr. Vigersky noted.
He and his coauthors advised the CMS to test pricing methodologies before implementation to prevent further unintended consequences going forward, to ask the Inspector General’s office to reanalyze costs to see if savings targets are being met, and to notify patients and health care providers in advance of a change so that they can better prepare for increased costs.
For now, Dr. Vigersky advised that, when considering pump therapy for a given patient, “from a clinical standpoint, this is a shared decision with the patient.
“As much as the reality of costs is shared with the patient, there is good evidence that pump therapy is cost-effective. The patient has to make the decision as to whether this extra amount is worth the benefits in the long run that they will get from pump therapy.”
A version of this article was originally published on Medscape.com.
Under the U.S. Medicare system, the cost of insulin is about 50% higher for beneficiaries who use insulin pumps than those who inject insulin, a new analysis reveals.
Robert A. Vigersky, MD, chief medical officer of Medtronic Diabetes, Washington, is senior author. Medtronic estimates that 60,000-70,000 fee-for-service Medicare beneficiaries with type 1 diabetes use insulin pumps.
Under Medicare, insulin delivered via syringe or pen is reimbursed under Part D, the drug benefit, whereas insulin infused by pump falls under Part B, as durable medical equipment (DME).
The price differential arose in 2017, with a rule change to the 21st Century Cures Act regarding reimbursement for infused drugs under Part B, and further worsened with subsequent overall increases in the price of insulin.
Only 29% of Medicare beneficiaries have supplemental Medigap insurance to help lower out-of-pocket costs, the authors of the commentary noted.
“Our patients who are using insulin pumps noticed a big increase in the cost of their insulin when the 21st Century Cures Act took place in January 2017. Without any notification from Medicare, the amount of money out of pocket and the total cost of insulin rose for patients who are using insulin pumps. … There were anecdotal reports; then we looked into it,” Dr. Vigersky, who is also professor of medicine at the Uniformed Services University for the Health Sciences, Bethesda, Md., said in an interview.
Physicians should be aware of the situation in order to counsel patients – who are either aging into Medicare with an insulin pump or who are already in Medicare and want to switch from injections to a pump – that they may encounter higher copays for insulin, he said.
In addition, Dr. Vigersky advised, concerned patients should be encouraged to call their representatives in Congress. But, “this shouldn’t dissuade clinicians from prescribing pumps, because they provide a huge benefit in terms of patients’ overall ability to control their diabetes.”
A call to action as price of insulin rose, suddenly shifted, in 2017
In the article, the authors call for the Centers for Medicare & Medicaid Services to fix the situation with a series of actions, including better aligning the cost of insulin under Parts B and D, and determining reimbursement rates on a drug-by-drug basis, rather than lumping together all infused drugs.
The CMS said in a statement: “As with all relevant and topical research, CMS appreciates the input of the journal authors and considers external research in all potential future policymaking and initiatives.”
As outlined by the authors, the overall price of insulin in the United States has dramatically increased in the past 2 decades. For example, the average list price of one vial of insulin rose from $9.61 to $25.38 between January 2013 and July 2018, a 164% increase.
A provision in the 21st Century Cures Act, which went into effect Jan. 1, 2017, attempted to remedy past overpayment for DME-infused drugs covered under Medicare Part B by changing the pricing methodology. Prior to 2017, the drugs had been reimbursed based on 95% of the 2003 average wholesale price. With the new law, payments have been set to average sales price plus 6%.
As a result, the price of insulin rose by 251% overnight from Dec. 31, 2016, to Jan. 1, 2017, for Medicare beneficiaries using insulin pumps, whereas there was no change for those injecting their insulin.
And then in 2018, insulin manufacturers raised the price by another 53%, resulting in an overall 304% price increase under Part B over 2 years.
Meanwhile, on March 11, 2020, CMS announced a cap on insulin copays in Part D to $35 a month, which doesn’t apply to pump users.
Thus, as of now, the average monthly copay for insulin for pump users in Medicare is about $54.26, about 50% more than the $35 maximum for those who inject insulin.
“This is in the setting of patients skimping on insulin anyway because of the high cost. There’s reasonably good evidence that patients stretch out their insulin because of cost, including those in Medicare,” Dr. Vigersky emphasized.
What can be done?
The problem could have been avoided, the authors wrote in their commentary, if payments had simply been adjusted for the two pre-2017 most highly overpaid DME-infused drugs, milrinone lactate and immune globulin, rather than all of them. Doing that would have addressed 95% of the overpayments and saved $267 million without affecting insulin cost.
Unlike insulin, nearly all of the other infused drugs are used only for short periods of time, such as pain medications, antibiotics, or chemotherapy.
“People get these for a few months, but not for years and years. Some aren’t used much at all. It was sort of a wholesale way to change things, and insulin got caught in it, with more extensive consequences,” Dr. Vigersky noted.
He and his coauthors advised the CMS to test pricing methodologies before implementation to prevent further unintended consequences going forward, to ask the Inspector General’s office to reanalyze costs to see if savings targets are being met, and to notify patients and health care providers in advance of a change so that they can better prepare for increased costs.
For now, Dr. Vigersky advised that, when considering pump therapy for a given patient, “from a clinical standpoint, this is a shared decision with the patient.
“As much as the reality of costs is shared with the patient, there is good evidence that pump therapy is cost-effective. The patient has to make the decision as to whether this extra amount is worth the benefits in the long run that they will get from pump therapy.”
A version of this article was originally published on Medscape.com.
FDA OKs new ‘artificial pancreas’ Medtronic 770G
The Food and Drug Administration has approved the MiniMed 770G (Medtronic) automated insulin delivery system for children aged 2-6 years.
The 770G system adds Bluetooth smartphone connectivity to the SmartGuard technology that is present in the hybrid closed-loop MiniMed 670G system, which has been available in the United States since 2016 for individuals aged 14 years and older who have type 1 diabetes. It has been available since 2018 for children aged 7 years.
The 770G will also be available to older children and adults once it has been launched.
As with other so-called artificial pancreas systems, the 770G is made up of an insulin pump and continuous glucose monitor that are connected via software that allows the pump to deliver or withhold insulin on the basis of glucose readings.
It is a “hybrid closed-loop” system in that users or caregivers must still manually signal carbohydrate consumption.
The 770G includes a “share” feature that allows health care providers, users, and caregivers to follow the user’s glucose levels remotely via smartphones. In-app notices indicate when glucose levels are out of range. The data can be uploaded prior to telehealth visits.
The approval was based on a 3-month study of 151 children aged 2-6 years who showed improvement in outcomes comparable with those seen in 124 older adolescents and adults with the 770G system as compared to patients who used manual (nonlooped) mode over a 2-week period. There were no episodes of severe hypoglycemia or diabetic ketoacidosis and no serious device-related adverse events while in hybrid closed-loop mode.
The FDA will require Medtronic to conduct a postmarketing study to evaluate the 770G in real-world settings. It is not approved for use in children younger than 2 years nor in any patient who requires less than 8 units of insulin per day.
The next-generation Medtronic closed-loop system, the 780G, has already been approved in Europe. It improves on the technology by delivering automated bolus correction doses in addition to basal insulin every 5 minutes. The company is preparing to submit the 780G for approval in the United States.
A version of this article originally appeared on Medscape.com.
The Food and Drug Administration has approved the MiniMed 770G (Medtronic) automated insulin delivery system for children aged 2-6 years.
The 770G system adds Bluetooth smartphone connectivity to the SmartGuard technology that is present in the hybrid closed-loop MiniMed 670G system, which has been available in the United States since 2016 for individuals aged 14 years and older who have type 1 diabetes. It has been available since 2018 for children aged 7 years.
The 770G will also be available to older children and adults once it has been launched.
As with other so-called artificial pancreas systems, the 770G is made up of an insulin pump and continuous glucose monitor that are connected via software that allows the pump to deliver or withhold insulin on the basis of glucose readings.
It is a “hybrid closed-loop” system in that users or caregivers must still manually signal carbohydrate consumption.
The 770G includes a “share” feature that allows health care providers, users, and caregivers to follow the user’s glucose levels remotely via smartphones. In-app notices indicate when glucose levels are out of range. The data can be uploaded prior to telehealth visits.
The approval was based on a 3-month study of 151 children aged 2-6 years who showed improvement in outcomes comparable with those seen in 124 older adolescents and adults with the 770G system as compared to patients who used manual (nonlooped) mode over a 2-week period. There were no episodes of severe hypoglycemia or diabetic ketoacidosis and no serious device-related adverse events while in hybrid closed-loop mode.
The FDA will require Medtronic to conduct a postmarketing study to evaluate the 770G in real-world settings. It is not approved for use in children younger than 2 years nor in any patient who requires less than 8 units of insulin per day.
The next-generation Medtronic closed-loop system, the 780G, has already been approved in Europe. It improves on the technology by delivering automated bolus correction doses in addition to basal insulin every 5 minutes. The company is preparing to submit the 780G for approval in the United States.
A version of this article originally appeared on Medscape.com.
The Food and Drug Administration has approved the MiniMed 770G (Medtronic) automated insulin delivery system for children aged 2-6 years.
The 770G system adds Bluetooth smartphone connectivity to the SmartGuard technology that is present in the hybrid closed-loop MiniMed 670G system, which has been available in the United States since 2016 for individuals aged 14 years and older who have type 1 diabetes. It has been available since 2018 for children aged 7 years.
The 770G will also be available to older children and adults once it has been launched.
As with other so-called artificial pancreas systems, the 770G is made up of an insulin pump and continuous glucose monitor that are connected via software that allows the pump to deliver or withhold insulin on the basis of glucose readings.
It is a “hybrid closed-loop” system in that users or caregivers must still manually signal carbohydrate consumption.
The 770G includes a “share” feature that allows health care providers, users, and caregivers to follow the user’s glucose levels remotely via smartphones. In-app notices indicate when glucose levels are out of range. The data can be uploaded prior to telehealth visits.
The approval was based on a 3-month study of 151 children aged 2-6 years who showed improvement in outcomes comparable with those seen in 124 older adolescents and adults with the 770G system as compared to patients who used manual (nonlooped) mode over a 2-week period. There were no episodes of severe hypoglycemia or diabetic ketoacidosis and no serious device-related adverse events while in hybrid closed-loop mode.
The FDA will require Medtronic to conduct a postmarketing study to evaluate the 770G in real-world settings. It is not approved for use in children younger than 2 years nor in any patient who requires less than 8 units of insulin per day.
The next-generation Medtronic closed-loop system, the 780G, has already been approved in Europe. It improves on the technology by delivering automated bolus correction doses in addition to basal insulin every 5 minutes. The company is preparing to submit the 780G for approval in the United States.
A version of this article originally appeared on Medscape.com.
Black diabetics lose limbs at triple the rate of others. Here’s how health care leaders are starting to act.
Prompted by a ProPublica story that detailed how Black Americans with diabetes lose limbs at a rate triple that of others, the American Diabetes Association has included an initiative to prevent unnecessary amputations as part of an unprecedented campaign to reduce racial disparities in diabetes care.
“The ProPublica article raised the consciousness of what the problem is,” said Tracey Brown, the CEO of the ADA. “Every four minutes, someone is losing a limb from diabetic complications. That’s ridiculous. We have got to find a way to drive change.”
The story highlighted obstacles to equitable care for diabetic patients at risk of amputation, from the government’s decision not to endorse screening at-risk patients for vascular disease in the legs, to the inadequate incentives for certain specialists to move to underserved areas, to the health system’s failure to consider limb-saving options before permitting surgeons to apply a blade.
In the weeks that followed publication, several congressional and state legislative offices reached out to the association to ask for guidance on drafting policy to reduce disparities in diabetic amputations. In response, the organization decided to build an agenda around the issue.
The ADA’s Health Equity Now campaign, which addresses the cost of diabetes care, nutrition, discrimination, and more, was motivated by the racial health disparities that have been exposed by COVID-19, which has hit Black Americans with diabetes particularly hard. As part of the project, the association has built a Health Equity Bill of Rights, asserting that all diabetes patients are entitled to affordable drugs, healthy food, the latest medical advances, and other protections.
The right to avoid preventable amputations is the only complication of uncontrolled diabetes that is included in the list. The organization is sharing the document with policymakers, practitioners, and patients as it begins to look toward policy change. It is also encouraging members of the public to ask their governors to support the project.
Dr. Ronald Dalman, president of the Society for Vascular Surgery, said: “I commend the ADA for doubling down on this particular complication of poorly managed diabetes. It’s a long overdue prioritization.” He added that it’s a “moment in time where we can leverage this concern about health care disparities to call out a very specific problem: the prevalence of amputation in certain subsets of the population.”
Dr. Gary Puckrein, head of the National Minority Quality Forum, a nonprofit focused on reducing health care disparities, said that the ADA’s efforts are just a step. “The American health care system was organized during an era when inequality was acceptable and mainstream in American society,” he said. “It’s not that African Americans are sicker, it’s that the health care delivered is unequal.”
He said he hopes that the national conversation on health disparities will mirror the conversation about police violence against Black Americans. “You, in effect, have your knees on their neck in the health care system as well when you don’t provide them with the care that they need.”
Two weeks after publication of the story, Rep. Bennie Thompson, a Democrat from Mississippi, honored Dr. Foluso Fakorede, the main subject of the ProPublica article, for his work in reducing unnecessary amputations in Bolivar County, Mississippi. The acknowledgment, made in the House of Representatives, referenced ProPublica’s findings.
The co-chairs of the Congressional Peripheral Artery Disease Caucus — Rep. Donald M. Payne Jr., a Democrat from New Jersey, and Rep. Gus Bilirakis, a Republican from Florida — have also begun work on a bill to address disparities in amputations, particularly for people with peripheral artery disease, a condition in which clogged arteries in the legs limit the flow of blood.
“The ProPublica article has brought strong awareness and real interest from a variety of parties — from the medical field and from patients and from potentially future patients,” said a spokesman for Payne. “We have been working with Bilirakis and other members to move this forward, with the ultimate goal of introducing legislation.”
Summer Blevins, deputy chief of staff for Bilirakis, added that their legislative ambition “is based on the basic principle that prevention, education and early intervention is best for the patient and also saves money.”
This story was originally published by ProPublica.
Prompted by a ProPublica story that detailed how Black Americans with diabetes lose limbs at a rate triple that of others, the American Diabetes Association has included an initiative to prevent unnecessary amputations as part of an unprecedented campaign to reduce racial disparities in diabetes care.
“The ProPublica article raised the consciousness of what the problem is,” said Tracey Brown, the CEO of the ADA. “Every four minutes, someone is losing a limb from diabetic complications. That’s ridiculous. We have got to find a way to drive change.”
The story highlighted obstacles to equitable care for diabetic patients at risk of amputation, from the government’s decision not to endorse screening at-risk patients for vascular disease in the legs, to the inadequate incentives for certain specialists to move to underserved areas, to the health system’s failure to consider limb-saving options before permitting surgeons to apply a blade.
In the weeks that followed publication, several congressional and state legislative offices reached out to the association to ask for guidance on drafting policy to reduce disparities in diabetic amputations. In response, the organization decided to build an agenda around the issue.
The ADA’s Health Equity Now campaign, which addresses the cost of diabetes care, nutrition, discrimination, and more, was motivated by the racial health disparities that have been exposed by COVID-19, which has hit Black Americans with diabetes particularly hard. As part of the project, the association has built a Health Equity Bill of Rights, asserting that all diabetes patients are entitled to affordable drugs, healthy food, the latest medical advances, and other protections.
The right to avoid preventable amputations is the only complication of uncontrolled diabetes that is included in the list. The organization is sharing the document with policymakers, practitioners, and patients as it begins to look toward policy change. It is also encouraging members of the public to ask their governors to support the project.
Dr. Ronald Dalman, president of the Society for Vascular Surgery, said: “I commend the ADA for doubling down on this particular complication of poorly managed diabetes. It’s a long overdue prioritization.” He added that it’s a “moment in time where we can leverage this concern about health care disparities to call out a very specific problem: the prevalence of amputation in certain subsets of the population.”
Dr. Gary Puckrein, head of the National Minority Quality Forum, a nonprofit focused on reducing health care disparities, said that the ADA’s efforts are just a step. “The American health care system was organized during an era when inequality was acceptable and mainstream in American society,” he said. “It’s not that African Americans are sicker, it’s that the health care delivered is unequal.”
He said he hopes that the national conversation on health disparities will mirror the conversation about police violence against Black Americans. “You, in effect, have your knees on their neck in the health care system as well when you don’t provide them with the care that they need.”
Two weeks after publication of the story, Rep. Bennie Thompson, a Democrat from Mississippi, honored Dr. Foluso Fakorede, the main subject of the ProPublica article, for his work in reducing unnecessary amputations in Bolivar County, Mississippi. The acknowledgment, made in the House of Representatives, referenced ProPublica’s findings.
The co-chairs of the Congressional Peripheral Artery Disease Caucus — Rep. Donald M. Payne Jr., a Democrat from New Jersey, and Rep. Gus Bilirakis, a Republican from Florida — have also begun work on a bill to address disparities in amputations, particularly for people with peripheral artery disease, a condition in which clogged arteries in the legs limit the flow of blood.
“The ProPublica article has brought strong awareness and real interest from a variety of parties — from the medical field and from patients and from potentially future patients,” said a spokesman for Payne. “We have been working with Bilirakis and other members to move this forward, with the ultimate goal of introducing legislation.”
Summer Blevins, deputy chief of staff for Bilirakis, added that their legislative ambition “is based on the basic principle that prevention, education and early intervention is best for the patient and also saves money.”
This story was originally published by ProPublica.
Prompted by a ProPublica story that detailed how Black Americans with diabetes lose limbs at a rate triple that of others, the American Diabetes Association has included an initiative to prevent unnecessary amputations as part of an unprecedented campaign to reduce racial disparities in diabetes care.
“The ProPublica article raised the consciousness of what the problem is,” said Tracey Brown, the CEO of the ADA. “Every four minutes, someone is losing a limb from diabetic complications. That’s ridiculous. We have got to find a way to drive change.”
The story highlighted obstacles to equitable care for diabetic patients at risk of amputation, from the government’s decision not to endorse screening at-risk patients for vascular disease in the legs, to the inadequate incentives for certain specialists to move to underserved areas, to the health system’s failure to consider limb-saving options before permitting surgeons to apply a blade.
In the weeks that followed publication, several congressional and state legislative offices reached out to the association to ask for guidance on drafting policy to reduce disparities in diabetic amputations. In response, the organization decided to build an agenda around the issue.
The ADA’s Health Equity Now campaign, which addresses the cost of diabetes care, nutrition, discrimination, and more, was motivated by the racial health disparities that have been exposed by COVID-19, which has hit Black Americans with diabetes particularly hard. As part of the project, the association has built a Health Equity Bill of Rights, asserting that all diabetes patients are entitled to affordable drugs, healthy food, the latest medical advances, and other protections.
The right to avoid preventable amputations is the only complication of uncontrolled diabetes that is included in the list. The organization is sharing the document with policymakers, practitioners, and patients as it begins to look toward policy change. It is also encouraging members of the public to ask their governors to support the project.
Dr. Ronald Dalman, president of the Society for Vascular Surgery, said: “I commend the ADA for doubling down on this particular complication of poorly managed diabetes. It’s a long overdue prioritization.” He added that it’s a “moment in time where we can leverage this concern about health care disparities to call out a very specific problem: the prevalence of amputation in certain subsets of the population.”
Dr. Gary Puckrein, head of the National Minority Quality Forum, a nonprofit focused on reducing health care disparities, said that the ADA’s efforts are just a step. “The American health care system was organized during an era when inequality was acceptable and mainstream in American society,” he said. “It’s not that African Americans are sicker, it’s that the health care delivered is unequal.”
He said he hopes that the national conversation on health disparities will mirror the conversation about police violence against Black Americans. “You, in effect, have your knees on their neck in the health care system as well when you don’t provide them with the care that they need.”
Two weeks after publication of the story, Rep. Bennie Thompson, a Democrat from Mississippi, honored Dr. Foluso Fakorede, the main subject of the ProPublica article, for his work in reducing unnecessary amputations in Bolivar County, Mississippi. The acknowledgment, made in the House of Representatives, referenced ProPublica’s findings.
The co-chairs of the Congressional Peripheral Artery Disease Caucus — Rep. Donald M. Payne Jr., a Democrat from New Jersey, and Rep. Gus Bilirakis, a Republican from Florida — have also begun work on a bill to address disparities in amputations, particularly for people with peripheral artery disease, a condition in which clogged arteries in the legs limit the flow of blood.
“The ProPublica article has brought strong awareness and real interest from a variety of parties — from the medical field and from patients and from potentially future patients,” said a spokesman for Payne. “We have been working with Bilirakis and other members to move this forward, with the ultimate goal of introducing legislation.”
Summer Blevins, deputy chief of staff for Bilirakis, added that their legislative ambition “is based on the basic principle that prevention, education and early intervention is best for the patient and also saves money.”
This story was originally published by ProPublica.
Gut bacteria linked to cardiovascular, other health conditions
Microorganisms in the human digestive tract are linked to 29 specific health conditions, including chronic obstructive pulmonary disease, high blood pressure, and type 2 diabetes, according to a genome analysis in more than 400,000 individuals.
Although previous studies have suggested a link between gut microbiota and diseases in humans, “the extent to which the human gut microbiome can be considered a determinant of disease and healthy aging remains unknown,” Hilde E. Groot, MD, of the University of Groningen (The Netherlands), said in a presentation at the virtual annual congress of the European Society of Cardiology.
To identify the spectrum of diseases linked to the gut microbiome, the researchers identified 422,417 unrelated adults of White British ancestry with genotype and matching genetic data. The average age of the participants was 57 years and 46% were male.
The researchers conducted a phenomewide association study including 35 distinct single-nucleotide polymorphisms (SNPs) that are known to influence the microbiome of the human gut.
Overall, seven SNPs were significantly associated with 29 disease outcomes including hypertension, type 2 diabetes, hypercholesterolemia, heart failure, renal failure, and osteoarthritis.
In addition, after a further sensitivity analysis using a Mendelian randomization (MR) approach, associations between Ruminococcus flavefaciens and hypertension and between Clostridium and platelet count might point to a causal link, the researchers said.
“Over the past few years, the amount of research concerning the human gut microbiome and the associations with health and disease has tremendously increased. However, most studies investigated one or a few traits. The strength of our study is the possibility to cover a wide range of traits simultaneously within one population,” Dr. Groot said in an interview.
“Our data support the hypothesis that the human gut microbiome is a complex system, involved in many pathophysiological mechanisms in the human body. So, our results are additional to earlier research and strengthen this hypothesis,” Dr. Groot added.
“Microbiota and their metabolites might be of importance in the interplay between overlapping pathophysiological processes, and could serve as potential therapeutic targets for the maintenance of health and prevention and treatment of cardiovascular diseases. However, before it is possible to give advice for the public and medical practice, further research is needed to study causality,” she emphasized.
“Currently, it is too soon to advise patients concerning their microbiome,” Dr. Groot noted. “However, genetic studies like ours might help other researchers to study causality between the gut microbiome and particular traits, which might potentially lead to new therapeutic targets. Next to genetic variants as a proxy, we’re currently studying the gut microbiome composition in myocardial infarction patients and healthy controls in a longitudinal setting.”
“Previous studies have suggested a potential link between the gut microbiome and the development of cardiovascular disease, type 2 diabetes mellitus, and other chronic disorders,” Carol Ann Remme, MD, of the Amsterdam University Medical Center, said in an interview. “However, it is challenging to study the effect of gut microbiome composition in large patient cohorts. As an alternative approach, the study authors showed in a very large population that genetic variants previously shown to influence gut microbiome composition were significantly associated with conditions such as hypertension, type 2 diabetes, hypercholesterolemia, and heart failure.”
The study is unique in that it employed a very large cohort of more than 400,000 individuals, which is typically required to be able to draw clear conclusions, Dr. Remme continued. “The authors were able to further refine their findings by linking genetic variants known to influence specific gut bacteria to some particular disorders,” she noted.
“It is becoming increasingly clear that an individual’s gut microbiome composition, which is defined by both genetic and environmental factors such as diet, may affect his/her susceptibility to certain diseases – including cardiovascular – in addition to disease progression and outcome,” said Dr. Remme. “This may ultimately lead to development of novel, personalized strategies for risk stratification in addition to potential preventive measures targeting the gut microbiome. I expect this area of research will become increasingly important in the coming years.”
The study received no outside funding. Dr. Groot and colleagues had no financial conflicts to disclose. Dr. Remme had no financial conflicts to disclose.
Microorganisms in the human digestive tract are linked to 29 specific health conditions, including chronic obstructive pulmonary disease, high blood pressure, and type 2 diabetes, according to a genome analysis in more than 400,000 individuals.
Although previous studies have suggested a link between gut microbiota and diseases in humans, “the extent to which the human gut microbiome can be considered a determinant of disease and healthy aging remains unknown,” Hilde E. Groot, MD, of the University of Groningen (The Netherlands), said in a presentation at the virtual annual congress of the European Society of Cardiology.
To identify the spectrum of diseases linked to the gut microbiome, the researchers identified 422,417 unrelated adults of White British ancestry with genotype and matching genetic data. The average age of the participants was 57 years and 46% were male.
The researchers conducted a phenomewide association study including 35 distinct single-nucleotide polymorphisms (SNPs) that are known to influence the microbiome of the human gut.
Overall, seven SNPs were significantly associated with 29 disease outcomes including hypertension, type 2 diabetes, hypercholesterolemia, heart failure, renal failure, and osteoarthritis.
In addition, after a further sensitivity analysis using a Mendelian randomization (MR) approach, associations between Ruminococcus flavefaciens and hypertension and between Clostridium and platelet count might point to a causal link, the researchers said.
“Over the past few years, the amount of research concerning the human gut microbiome and the associations with health and disease has tremendously increased. However, most studies investigated one or a few traits. The strength of our study is the possibility to cover a wide range of traits simultaneously within one population,” Dr. Groot said in an interview.
“Our data support the hypothesis that the human gut microbiome is a complex system, involved in many pathophysiological mechanisms in the human body. So, our results are additional to earlier research and strengthen this hypothesis,” Dr. Groot added.
“Microbiota and their metabolites might be of importance in the interplay between overlapping pathophysiological processes, and could serve as potential therapeutic targets for the maintenance of health and prevention and treatment of cardiovascular diseases. However, before it is possible to give advice for the public and medical practice, further research is needed to study causality,” she emphasized.
“Currently, it is too soon to advise patients concerning their microbiome,” Dr. Groot noted. “However, genetic studies like ours might help other researchers to study causality between the gut microbiome and particular traits, which might potentially lead to new therapeutic targets. Next to genetic variants as a proxy, we’re currently studying the gut microbiome composition in myocardial infarction patients and healthy controls in a longitudinal setting.”
“Previous studies have suggested a potential link between the gut microbiome and the development of cardiovascular disease, type 2 diabetes mellitus, and other chronic disorders,” Carol Ann Remme, MD, of the Amsterdam University Medical Center, said in an interview. “However, it is challenging to study the effect of gut microbiome composition in large patient cohorts. As an alternative approach, the study authors showed in a very large population that genetic variants previously shown to influence gut microbiome composition were significantly associated with conditions such as hypertension, type 2 diabetes, hypercholesterolemia, and heart failure.”
The study is unique in that it employed a very large cohort of more than 400,000 individuals, which is typically required to be able to draw clear conclusions, Dr. Remme continued. “The authors were able to further refine their findings by linking genetic variants known to influence specific gut bacteria to some particular disorders,” she noted.
“It is becoming increasingly clear that an individual’s gut microbiome composition, which is defined by both genetic and environmental factors such as diet, may affect his/her susceptibility to certain diseases – including cardiovascular – in addition to disease progression and outcome,” said Dr. Remme. “This may ultimately lead to development of novel, personalized strategies for risk stratification in addition to potential preventive measures targeting the gut microbiome. I expect this area of research will become increasingly important in the coming years.”
The study received no outside funding. Dr. Groot and colleagues had no financial conflicts to disclose. Dr. Remme had no financial conflicts to disclose.
Microorganisms in the human digestive tract are linked to 29 specific health conditions, including chronic obstructive pulmonary disease, high blood pressure, and type 2 diabetes, according to a genome analysis in more than 400,000 individuals.
Although previous studies have suggested a link between gut microbiota and diseases in humans, “the extent to which the human gut microbiome can be considered a determinant of disease and healthy aging remains unknown,” Hilde E. Groot, MD, of the University of Groningen (The Netherlands), said in a presentation at the virtual annual congress of the European Society of Cardiology.
To identify the spectrum of diseases linked to the gut microbiome, the researchers identified 422,417 unrelated adults of White British ancestry with genotype and matching genetic data. The average age of the participants was 57 years and 46% were male.
The researchers conducted a phenomewide association study including 35 distinct single-nucleotide polymorphisms (SNPs) that are known to influence the microbiome of the human gut.
Overall, seven SNPs were significantly associated with 29 disease outcomes including hypertension, type 2 diabetes, hypercholesterolemia, heart failure, renal failure, and osteoarthritis.
In addition, after a further sensitivity analysis using a Mendelian randomization (MR) approach, associations between Ruminococcus flavefaciens and hypertension and between Clostridium and platelet count might point to a causal link, the researchers said.
“Over the past few years, the amount of research concerning the human gut microbiome and the associations with health and disease has tremendously increased. However, most studies investigated one or a few traits. The strength of our study is the possibility to cover a wide range of traits simultaneously within one population,” Dr. Groot said in an interview.
“Our data support the hypothesis that the human gut microbiome is a complex system, involved in many pathophysiological mechanisms in the human body. So, our results are additional to earlier research and strengthen this hypothesis,” Dr. Groot added.
“Microbiota and their metabolites might be of importance in the interplay between overlapping pathophysiological processes, and could serve as potential therapeutic targets for the maintenance of health and prevention and treatment of cardiovascular diseases. However, before it is possible to give advice for the public and medical practice, further research is needed to study causality,” she emphasized.
“Currently, it is too soon to advise patients concerning their microbiome,” Dr. Groot noted. “However, genetic studies like ours might help other researchers to study causality between the gut microbiome and particular traits, which might potentially lead to new therapeutic targets. Next to genetic variants as a proxy, we’re currently studying the gut microbiome composition in myocardial infarction patients and healthy controls in a longitudinal setting.”
“Previous studies have suggested a potential link between the gut microbiome and the development of cardiovascular disease, type 2 diabetes mellitus, and other chronic disorders,” Carol Ann Remme, MD, of the Amsterdam University Medical Center, said in an interview. “However, it is challenging to study the effect of gut microbiome composition in large patient cohorts. As an alternative approach, the study authors showed in a very large population that genetic variants previously shown to influence gut microbiome composition were significantly associated with conditions such as hypertension, type 2 diabetes, hypercholesterolemia, and heart failure.”
The study is unique in that it employed a very large cohort of more than 400,000 individuals, which is typically required to be able to draw clear conclusions, Dr. Remme continued. “The authors were able to further refine their findings by linking genetic variants known to influence specific gut bacteria to some particular disorders,” she noted.
“It is becoming increasingly clear that an individual’s gut microbiome composition, which is defined by both genetic and environmental factors such as diet, may affect his/her susceptibility to certain diseases – including cardiovascular – in addition to disease progression and outcome,” said Dr. Remme. “This may ultimately lead to development of novel, personalized strategies for risk stratification in addition to potential preventive measures targeting the gut microbiome. I expect this area of research will become increasingly important in the coming years.”
The study received no outside funding. Dr. Groot and colleagues had no financial conflicts to disclose. Dr. Remme had no financial conflicts to disclose.
FROM ESC CONGRESS 2020
DAPA-CKD: SGLT2 inhibitor benefit extends to chronic kidney disease without diabetes
In the DAPA-CKD trial, treatment with the SGLT2 inhibitor dapagliflozin (Farxiga) cut the incidence of substantially worsened chronic kidney disease by an average of 39% compared with placebo when added to standard treatment, with a number needed to treat of 19 to prevent one primary outcome event after a median of 2.4 years.
The level of benefit was similar in both the one-third of enrolled patients without diabetes and in the two-thirds with diabetes, showing a statistically significant 50% cut in the primary endpoint among patients without diabetes, Hiddo J.L. Heerspink, MD, reported at the virtual annual congress of the European Society of Cardiology.
“We found that dapagliflozin delayed the initiation of dialysis, and reduced the number of deaths,” regardless of diabetes status, Dr. Heerspink, of University Medical Centre Groningen, the Netherlands, said during a press conference. “DAPA-CKD trial has shown dapagliflozin’s potential as a long-awaited new treatment for patients with chronic kidney disease.”
This finding ushers in a “completely new era in chronic kidney disease management,” said Janani Rangaswami, MD, a nephrologist and cardiorenal syndrome specialist at Einstein Medical Center in Philadelphia. “It’s good news” for these patients.
The results showed that dapagliflozin is the first “game changing” drug for chronic kidney disease in 2 decades, following the introduction of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, she said in an interview. And given the consistency of the findings with the results from several other studies that documented meaningful renal protection by several different SGLT2 inhibitors, the results from this single trial also convincingly establish dapagliflozin as a standard-of-care agent to use on the types of patients the study enrolled, she said in an interview.
Representing many real-world patients
The DAPA-CKD trial enrolled 4,304 patients with albuminuria based on having a urinary albumin-to-creatinine ratio of at least 200 mg/g, and an estimated glomerular filtration rate (eGFR) of 25-75 mL/min per 1.73 m2 (with 90% of patients having an eGFR of less than 60 mL/min per 1.73 m2), and 97% were on treatment with a renin-angiotensin system–blocking drug. The primary endpoint was the combined rate of a drop in eGFR of at least 50% from baseline, progression to end stage renal disease, or renal or cardiovascular death; the between-group difference in this composite was driven primarily by both preserved eGFR and by prevention of end stage renal disease.
This represents both an appropriate target population, and meaningful endpoints, Dr. Rangaswami said. The study was “very representative of who we see in real-world practice,” a group that likely includes “hundreds of thousands” of U.S. patients with nondiabetic chronic kidney disease, she estimated.
Another notable finding was that 14% of the enrolled patients had eGFR values at baseline of 25-29 mL/min per 1.73 m2, pegging them as having stage 4 chronic kidney disease, and the median baseline eGFR was 43 mL/min per 1.73 m2, but dapagliflozin treatment was as safe and effective in these patients as it was in enrolled patients with a higher level of retained renal activity. This experience should give clinicians greater confidence about using dapagliflozin and other drugs in the sodium-glucose cotransporter (SGLT) 2 inhibitor class in patients with substantially depressed renal function, Dr. Rangaswami said.
“We now need to be more proactive about treating patients with more advanced kidney disease who can still benefit” from dapagliflozin treatment. “The sooner you intervene the better,” to slow further progression, but the new findings show “benefit even when treating patients with lower eGFRs. There is still hope to prevent or delay dialysis.”
A heart-kidney connection
Dapagliflozin treatment also cut all-cause mortality by a statistically significant, relative 31%, and another secondary-endpoint analysis showed a statistically significant 29% relative reduction in the rate of cardiovascular death or heart failure hospitalization, a benefit seen consistently in several prior studies of SGLT2 inhibitors, but possibly unexpected here because enrolled patients underwent no selection for a history of heart failure or any other cardiovascular disease. But the finding shouldn’t surprise, because “chronic kidney disease is an independent risk factor for cardiovascular disease across the board, and especially for heart failure,” noted Dr. Rangaswami.
“Heart and kidney disease is one big spectrum,” and the collected experience of several trials that have now proven the efficacy of SGLT2 inhibitors among patients with heart failure with reduced ejection fraction or with chronic kidney disease, regardless of their glycemic control, shows how broadly this drug class can benefit patients across the breadth of this spectrum, she said.
DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Heerspink has been a consultant to and received research funding from AstraZeneca and from several other companies. Dr. Rangaswami had no disclosures.
In the DAPA-CKD trial, treatment with the SGLT2 inhibitor dapagliflozin (Farxiga) cut the incidence of substantially worsened chronic kidney disease by an average of 39% compared with placebo when added to standard treatment, with a number needed to treat of 19 to prevent one primary outcome event after a median of 2.4 years.
The level of benefit was similar in both the one-third of enrolled patients without diabetes and in the two-thirds with diabetes, showing a statistically significant 50% cut in the primary endpoint among patients without diabetes, Hiddo J.L. Heerspink, MD, reported at the virtual annual congress of the European Society of Cardiology.
“We found that dapagliflozin delayed the initiation of dialysis, and reduced the number of deaths,” regardless of diabetes status, Dr. Heerspink, of University Medical Centre Groningen, the Netherlands, said during a press conference. “DAPA-CKD trial has shown dapagliflozin’s potential as a long-awaited new treatment for patients with chronic kidney disease.”
This finding ushers in a “completely new era in chronic kidney disease management,” said Janani Rangaswami, MD, a nephrologist and cardiorenal syndrome specialist at Einstein Medical Center in Philadelphia. “It’s good news” for these patients.
The results showed that dapagliflozin is the first “game changing” drug for chronic kidney disease in 2 decades, following the introduction of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, she said in an interview. And given the consistency of the findings with the results from several other studies that documented meaningful renal protection by several different SGLT2 inhibitors, the results from this single trial also convincingly establish dapagliflozin as a standard-of-care agent to use on the types of patients the study enrolled, she said in an interview.
Representing many real-world patients
The DAPA-CKD trial enrolled 4,304 patients with albuminuria based on having a urinary albumin-to-creatinine ratio of at least 200 mg/g, and an estimated glomerular filtration rate (eGFR) of 25-75 mL/min per 1.73 m2 (with 90% of patients having an eGFR of less than 60 mL/min per 1.73 m2), and 97% were on treatment with a renin-angiotensin system–blocking drug. The primary endpoint was the combined rate of a drop in eGFR of at least 50% from baseline, progression to end stage renal disease, or renal or cardiovascular death; the between-group difference in this composite was driven primarily by both preserved eGFR and by prevention of end stage renal disease.
This represents both an appropriate target population, and meaningful endpoints, Dr. Rangaswami said. The study was “very representative of who we see in real-world practice,” a group that likely includes “hundreds of thousands” of U.S. patients with nondiabetic chronic kidney disease, she estimated.
Another notable finding was that 14% of the enrolled patients had eGFR values at baseline of 25-29 mL/min per 1.73 m2, pegging them as having stage 4 chronic kidney disease, and the median baseline eGFR was 43 mL/min per 1.73 m2, but dapagliflozin treatment was as safe and effective in these patients as it was in enrolled patients with a higher level of retained renal activity. This experience should give clinicians greater confidence about using dapagliflozin and other drugs in the sodium-glucose cotransporter (SGLT) 2 inhibitor class in patients with substantially depressed renal function, Dr. Rangaswami said.
“We now need to be more proactive about treating patients with more advanced kidney disease who can still benefit” from dapagliflozin treatment. “The sooner you intervene the better,” to slow further progression, but the new findings show “benefit even when treating patients with lower eGFRs. There is still hope to prevent or delay dialysis.”
A heart-kidney connection
Dapagliflozin treatment also cut all-cause mortality by a statistically significant, relative 31%, and another secondary-endpoint analysis showed a statistically significant 29% relative reduction in the rate of cardiovascular death or heart failure hospitalization, a benefit seen consistently in several prior studies of SGLT2 inhibitors, but possibly unexpected here because enrolled patients underwent no selection for a history of heart failure or any other cardiovascular disease. But the finding shouldn’t surprise, because “chronic kidney disease is an independent risk factor for cardiovascular disease across the board, and especially for heart failure,” noted Dr. Rangaswami.
“Heart and kidney disease is one big spectrum,” and the collected experience of several trials that have now proven the efficacy of SGLT2 inhibitors among patients with heart failure with reduced ejection fraction or with chronic kidney disease, regardless of their glycemic control, shows how broadly this drug class can benefit patients across the breadth of this spectrum, she said.
DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Heerspink has been a consultant to and received research funding from AstraZeneca and from several other companies. Dr. Rangaswami had no disclosures.
In the DAPA-CKD trial, treatment with the SGLT2 inhibitor dapagliflozin (Farxiga) cut the incidence of substantially worsened chronic kidney disease by an average of 39% compared with placebo when added to standard treatment, with a number needed to treat of 19 to prevent one primary outcome event after a median of 2.4 years.
The level of benefit was similar in both the one-third of enrolled patients without diabetes and in the two-thirds with diabetes, showing a statistically significant 50% cut in the primary endpoint among patients without diabetes, Hiddo J.L. Heerspink, MD, reported at the virtual annual congress of the European Society of Cardiology.
“We found that dapagliflozin delayed the initiation of dialysis, and reduced the number of deaths,” regardless of diabetes status, Dr. Heerspink, of University Medical Centre Groningen, the Netherlands, said during a press conference. “DAPA-CKD trial has shown dapagliflozin’s potential as a long-awaited new treatment for patients with chronic kidney disease.”
This finding ushers in a “completely new era in chronic kidney disease management,” said Janani Rangaswami, MD, a nephrologist and cardiorenal syndrome specialist at Einstein Medical Center in Philadelphia. “It’s good news” for these patients.
The results showed that dapagliflozin is the first “game changing” drug for chronic kidney disease in 2 decades, following the introduction of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, she said in an interview. And given the consistency of the findings with the results from several other studies that documented meaningful renal protection by several different SGLT2 inhibitors, the results from this single trial also convincingly establish dapagliflozin as a standard-of-care agent to use on the types of patients the study enrolled, she said in an interview.
Representing many real-world patients
The DAPA-CKD trial enrolled 4,304 patients with albuminuria based on having a urinary albumin-to-creatinine ratio of at least 200 mg/g, and an estimated glomerular filtration rate (eGFR) of 25-75 mL/min per 1.73 m2 (with 90% of patients having an eGFR of less than 60 mL/min per 1.73 m2), and 97% were on treatment with a renin-angiotensin system–blocking drug. The primary endpoint was the combined rate of a drop in eGFR of at least 50% from baseline, progression to end stage renal disease, or renal or cardiovascular death; the between-group difference in this composite was driven primarily by both preserved eGFR and by prevention of end stage renal disease.
This represents both an appropriate target population, and meaningful endpoints, Dr. Rangaswami said. The study was “very representative of who we see in real-world practice,” a group that likely includes “hundreds of thousands” of U.S. patients with nondiabetic chronic kidney disease, she estimated.
Another notable finding was that 14% of the enrolled patients had eGFR values at baseline of 25-29 mL/min per 1.73 m2, pegging them as having stage 4 chronic kidney disease, and the median baseline eGFR was 43 mL/min per 1.73 m2, but dapagliflozin treatment was as safe and effective in these patients as it was in enrolled patients with a higher level of retained renal activity. This experience should give clinicians greater confidence about using dapagliflozin and other drugs in the sodium-glucose cotransporter (SGLT) 2 inhibitor class in patients with substantially depressed renal function, Dr. Rangaswami said.
“We now need to be more proactive about treating patients with more advanced kidney disease who can still benefit” from dapagliflozin treatment. “The sooner you intervene the better,” to slow further progression, but the new findings show “benefit even when treating patients with lower eGFRs. There is still hope to prevent or delay dialysis.”
A heart-kidney connection
Dapagliflozin treatment also cut all-cause mortality by a statistically significant, relative 31%, and another secondary-endpoint analysis showed a statistically significant 29% relative reduction in the rate of cardiovascular death or heart failure hospitalization, a benefit seen consistently in several prior studies of SGLT2 inhibitors, but possibly unexpected here because enrolled patients underwent no selection for a history of heart failure or any other cardiovascular disease. But the finding shouldn’t surprise, because “chronic kidney disease is an independent risk factor for cardiovascular disease across the board, and especially for heart failure,” noted Dr. Rangaswami.
“Heart and kidney disease is one big spectrum,” and the collected experience of several trials that have now proven the efficacy of SGLT2 inhibitors among patients with heart failure with reduced ejection fraction or with chronic kidney disease, regardless of their glycemic control, shows how broadly this drug class can benefit patients across the breadth of this spectrum, she said.
DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Heerspink has been a consultant to and received research funding from AstraZeneca and from several other companies. Dr. Rangaswami had no disclosures.
FROM ESC CONGRESS 2020
EMPEROR-Reduced: Empagliflozin’s HFrEF benefit solidifies class effects
The SGLT2 inhibitor drug class solidified its role as a major, new treatment for patients with heart failure with reduced ejection fraction and no diabetes, with results from a second large, controlled trial showing clear efficacy and safety in this population.
Patients with heart failure with reduced ejection fraction (HFrEF) treated with the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) had a statistically significant 25% relative cut in their incidence of cardiovascular death or first heart failure hospitalization, compared with placebo-treated controls when added on top of standard HFrEF treatment, and this benefit was consistent regardless of whether the treated patients also had type 2 diabetes, Milton Packer, MD, reported at the virtual annual congress of the European Society of Cardiology.
This 25% drop in the primary endpoint with empagliflozin treatment in the EMPEROR-Reduced trial exactly matched the cut in incidence of cardiovascular death or heart failure hospitalization produced by treatment with a another SGLT2 inhibitor, dapagliflozin (Farxiga), in the DAPA-HF trial (N Engl J Med. 2019 Nov 21;381[21]:1995-2008).
The performance of these two SGLT2 inhibitors was “incredibly consistent” across the their respective trials run in HFrEF patients with and without type 2 diabetes, and the combined evidence base of the two trials makes for “really compelling evidence” of both safety and efficacy that should prompt a change to U.S. practice, with both of these drugs forming a new cornerstone of HFrEF treatment, Dr. Packer said.
Results plant drug class firmly as HFrEF treatment
Dr. Packer stressed in his presentation that optimal treatment of patients with HFrEF now demands use of one of these two SGLT2 inhibitors, as well as sacubitril plus valsartan (Entresto), a beta-blocker, and a mineralocorticoid receptor antagonist, plus a diuretic as a fifth drug class for the many HFrEF patients who also need treatment for fluid overload. He further advocated for rapid introduction of these four cornerstone agents with proven survival benefits once a patient receives a HFrEF diagnosis, suggesting that sacubitril plus valsartan, an SGLT2 inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist could all be initiated within 6 weeks or less while acknowledging that optimal up-titration of the beta-blocker would likely take longer.
The order in which a patient starts these drugs shouldn’t matter, and there currently seems to be no evidence that clearly points toward using either dapagliflozin or empagliflozin over the other, Dr. Packer added.
In recognition of the importance of sending a message to heart failure clinicians about the newly proven efficacy of SGLT2 inhibitors in HFrEF patients, the American College of Cardiology and American Heart Association are now drafting an “expert decision pathway” to help clinicians as they enter this new prescribing space. This interim guidance should come out before the end of 2020, prior to release of fully revised HFrEF management guidelines in 2021, said Athena Poppas, MD, president of the ACC, in an interview.
“There is clearly need for education” that can help guide physicians who care for HFrEF patients on how to introduce an SGLT2 inhibitor along with the additional, lengthy list of drug classes proven to benefit these patients, noted Dr. Poppas, who is also a professor and chief of cardiology at the Brown University in Providence, R.I. Physicians may find that they need extra backup for successfully starting both sacubitril plus valsartan and an SGLT2 inhibitor in HFrEF patients because recent history has shown substantial pushback from third-party payers in reimbursing for these relatively expensive drugs, Dr. Poppas noted. She added that this is a problem that may be compounded when patients should ideally get both drug classes.
Physicians who care for heart failure patients have their own history of dragging their feet when adding new drugs to the regimens HFrEF patients receive. The angiotensin converting enzyme inhibitors and beta-blockers took about 17 years each to start reaching a majority of U.S. HFrEF patients, and sacubitril plus valsartan is now used on perhaps a quarter to a third of HFrEF patients despite receiving Food and Drug Administration approval for these patients in mid 2015, noted Christopher M. O’Connor, MD, a heart failure specialist and president of the Inova Heart and Vascular Institute in Fairfax, Va.
Despite dapagliflozin receiving FDA approval in May 2020 for treating HFrEF in patients without diabetes, early uptake in U.S. practice has been very slow, with findings from large U.S. patient registries suggesting that perhaps 1% of suitable HFrEF patients currently get the drug, estimated Dr. O’Connor in an interview.
Given how strong the evidence now is for benefit and safety from dapagliflozin and empagliflozin, it may take as little as 5 years to reach greater than 50% penetration of one of these drugs into U.S. HFrEF patient populations, suggested Dr. Packer, a distinguished scholar in cardiovascular science at Baylor University Medical Center in Dallas.
EMPEROR-Reduced outcomes
The road to routine use of these SGLT2 inhibitor drugs should be hastened by empagliflozin’s impressive performance in EMPEROR-Reduced, in which the drug scored highly significant benefits over placebo for the prespecified primary and two major secondary endpoints, one of which was a measure of preserved renal function.
The trial randomized 3,730 patients at 520 sites in 20 countries during 2017-2019 and followed them on treatment for a median of 16 months. All patients had a left ventricular ejection fraction of 40% or less, and roughly three-quarters had New York Heart Association (NYHA) class II function, nearly one-quarter had class III function, and fewer than 1% of patients fell into the class IV category.
The primary endpoint occurred in 19% of the empagliflozin-treated patients and in 25% of those who received placebo. Among the half of patients with diabetes in the trial, the relative risk reduction by empagliflozin compared with placebo was a statistically significant 28%; among those without diabetes, it was a statistically significant 22%. Concurrently with Dr. Packer’s report, the results appeared in an article posted online (N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190).
The study also had two main prespecified secondary endpoints: the incidence of total hospitalizations for heart failure, both first and recurrent, which fell by 30% in the empagliflozin-treated patients, compared with placebo, and the rate of declining renal function during the 16 months of the study as measured by estimated glomerular filtration rate, which dropped by roughly 1 mL/min per 1.73 m2 among the empagliflozin recipients and by about 4 mL/min/ per 1.73 m2 in the placebo patients.
Treatment with empagliflozin also achieved a notable, statistically significant 50% drop in major adverse renal events, consistent with the performance of other drugs in the class.
“Renal protection is a big plus” of empagliflozin in this trial and from the other SGLT2 inhibitors in prior studies, noted Dr. O’Connor.
The EMPEROR-Reduced results also showed an important benefit for HFrEF patients from empagliflozin not previously seen as quickly with any other drug class, noted Dr. Packer. The SGLT2 inhibitor led to statistically a significant slowing in the progression of patients from NYHA class II function to class III, compared with placebo, and it also significantly promoted the recovery of patients from NYHA class III to class II, an effect that became apparent within the first month on treatment and a benefit that is a “big deal” for patients because it represents a “significant change in functional capacity.” This additional dimension of empagliflozin’s benefit “really impressed me,” Dr. Packer said.
EMPEROR-Reduced was funded by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin. Dr. Packer has received personal fees from Boehringer Ingelheim and Eli Lilly and from several other companies. Dr. Poppas and Dr. O’Connor had no relevant disclosures.
SOURCE: Packer M. ESC 2020. N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190.
The SGLT2 inhibitor drug class solidified its role as a major, new treatment for patients with heart failure with reduced ejection fraction and no diabetes, with results from a second large, controlled trial showing clear efficacy and safety in this population.
Patients with heart failure with reduced ejection fraction (HFrEF) treated with the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) had a statistically significant 25% relative cut in their incidence of cardiovascular death or first heart failure hospitalization, compared with placebo-treated controls when added on top of standard HFrEF treatment, and this benefit was consistent regardless of whether the treated patients also had type 2 diabetes, Milton Packer, MD, reported at the virtual annual congress of the European Society of Cardiology.
This 25% drop in the primary endpoint with empagliflozin treatment in the EMPEROR-Reduced trial exactly matched the cut in incidence of cardiovascular death or heart failure hospitalization produced by treatment with a another SGLT2 inhibitor, dapagliflozin (Farxiga), in the DAPA-HF trial (N Engl J Med. 2019 Nov 21;381[21]:1995-2008).
The performance of these two SGLT2 inhibitors was “incredibly consistent” across the their respective trials run in HFrEF patients with and without type 2 diabetes, and the combined evidence base of the two trials makes for “really compelling evidence” of both safety and efficacy that should prompt a change to U.S. practice, with both of these drugs forming a new cornerstone of HFrEF treatment, Dr. Packer said.
Results plant drug class firmly as HFrEF treatment
Dr. Packer stressed in his presentation that optimal treatment of patients with HFrEF now demands use of one of these two SGLT2 inhibitors, as well as sacubitril plus valsartan (Entresto), a beta-blocker, and a mineralocorticoid receptor antagonist, plus a diuretic as a fifth drug class for the many HFrEF patients who also need treatment for fluid overload. He further advocated for rapid introduction of these four cornerstone agents with proven survival benefits once a patient receives a HFrEF diagnosis, suggesting that sacubitril plus valsartan, an SGLT2 inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist could all be initiated within 6 weeks or less while acknowledging that optimal up-titration of the beta-blocker would likely take longer.
The order in which a patient starts these drugs shouldn’t matter, and there currently seems to be no evidence that clearly points toward using either dapagliflozin or empagliflozin over the other, Dr. Packer added.
In recognition of the importance of sending a message to heart failure clinicians about the newly proven efficacy of SGLT2 inhibitors in HFrEF patients, the American College of Cardiology and American Heart Association are now drafting an “expert decision pathway” to help clinicians as they enter this new prescribing space. This interim guidance should come out before the end of 2020, prior to release of fully revised HFrEF management guidelines in 2021, said Athena Poppas, MD, president of the ACC, in an interview.
“There is clearly need for education” that can help guide physicians who care for HFrEF patients on how to introduce an SGLT2 inhibitor along with the additional, lengthy list of drug classes proven to benefit these patients, noted Dr. Poppas, who is also a professor and chief of cardiology at the Brown University in Providence, R.I. Physicians may find that they need extra backup for successfully starting both sacubitril plus valsartan and an SGLT2 inhibitor in HFrEF patients because recent history has shown substantial pushback from third-party payers in reimbursing for these relatively expensive drugs, Dr. Poppas noted. She added that this is a problem that may be compounded when patients should ideally get both drug classes.
Physicians who care for heart failure patients have their own history of dragging their feet when adding new drugs to the regimens HFrEF patients receive. The angiotensin converting enzyme inhibitors and beta-blockers took about 17 years each to start reaching a majority of U.S. HFrEF patients, and sacubitril plus valsartan is now used on perhaps a quarter to a third of HFrEF patients despite receiving Food and Drug Administration approval for these patients in mid 2015, noted Christopher M. O’Connor, MD, a heart failure specialist and president of the Inova Heart and Vascular Institute in Fairfax, Va.
Despite dapagliflozin receiving FDA approval in May 2020 for treating HFrEF in patients without diabetes, early uptake in U.S. practice has been very slow, with findings from large U.S. patient registries suggesting that perhaps 1% of suitable HFrEF patients currently get the drug, estimated Dr. O’Connor in an interview.
Given how strong the evidence now is for benefit and safety from dapagliflozin and empagliflozin, it may take as little as 5 years to reach greater than 50% penetration of one of these drugs into U.S. HFrEF patient populations, suggested Dr. Packer, a distinguished scholar in cardiovascular science at Baylor University Medical Center in Dallas.
EMPEROR-Reduced outcomes
The road to routine use of these SGLT2 inhibitor drugs should be hastened by empagliflozin’s impressive performance in EMPEROR-Reduced, in which the drug scored highly significant benefits over placebo for the prespecified primary and two major secondary endpoints, one of which was a measure of preserved renal function.
The trial randomized 3,730 patients at 520 sites in 20 countries during 2017-2019 and followed them on treatment for a median of 16 months. All patients had a left ventricular ejection fraction of 40% or less, and roughly three-quarters had New York Heart Association (NYHA) class II function, nearly one-quarter had class III function, and fewer than 1% of patients fell into the class IV category.
The primary endpoint occurred in 19% of the empagliflozin-treated patients and in 25% of those who received placebo. Among the half of patients with diabetes in the trial, the relative risk reduction by empagliflozin compared with placebo was a statistically significant 28%; among those without diabetes, it was a statistically significant 22%. Concurrently with Dr. Packer’s report, the results appeared in an article posted online (N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190).
The study also had two main prespecified secondary endpoints: the incidence of total hospitalizations for heart failure, both first and recurrent, which fell by 30% in the empagliflozin-treated patients, compared with placebo, and the rate of declining renal function during the 16 months of the study as measured by estimated glomerular filtration rate, which dropped by roughly 1 mL/min per 1.73 m2 among the empagliflozin recipients and by about 4 mL/min/ per 1.73 m2 in the placebo patients.
Treatment with empagliflozin also achieved a notable, statistically significant 50% drop in major adverse renal events, consistent with the performance of other drugs in the class.
“Renal protection is a big plus” of empagliflozin in this trial and from the other SGLT2 inhibitors in prior studies, noted Dr. O’Connor.
The EMPEROR-Reduced results also showed an important benefit for HFrEF patients from empagliflozin not previously seen as quickly with any other drug class, noted Dr. Packer. The SGLT2 inhibitor led to statistically a significant slowing in the progression of patients from NYHA class II function to class III, compared with placebo, and it also significantly promoted the recovery of patients from NYHA class III to class II, an effect that became apparent within the first month on treatment and a benefit that is a “big deal” for patients because it represents a “significant change in functional capacity.” This additional dimension of empagliflozin’s benefit “really impressed me,” Dr. Packer said.
EMPEROR-Reduced was funded by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin. Dr. Packer has received personal fees from Boehringer Ingelheim and Eli Lilly and from several other companies. Dr. Poppas and Dr. O’Connor had no relevant disclosures.
SOURCE: Packer M. ESC 2020. N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190.
The SGLT2 inhibitor drug class solidified its role as a major, new treatment for patients with heart failure with reduced ejection fraction and no diabetes, with results from a second large, controlled trial showing clear efficacy and safety in this population.
Patients with heart failure with reduced ejection fraction (HFrEF) treated with the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) had a statistically significant 25% relative cut in their incidence of cardiovascular death or first heart failure hospitalization, compared with placebo-treated controls when added on top of standard HFrEF treatment, and this benefit was consistent regardless of whether the treated patients also had type 2 diabetes, Milton Packer, MD, reported at the virtual annual congress of the European Society of Cardiology.
This 25% drop in the primary endpoint with empagliflozin treatment in the EMPEROR-Reduced trial exactly matched the cut in incidence of cardiovascular death or heart failure hospitalization produced by treatment with a another SGLT2 inhibitor, dapagliflozin (Farxiga), in the DAPA-HF trial (N Engl J Med. 2019 Nov 21;381[21]:1995-2008).
The performance of these two SGLT2 inhibitors was “incredibly consistent” across the their respective trials run in HFrEF patients with and without type 2 diabetes, and the combined evidence base of the two trials makes for “really compelling evidence” of both safety and efficacy that should prompt a change to U.S. practice, with both of these drugs forming a new cornerstone of HFrEF treatment, Dr. Packer said.
Results plant drug class firmly as HFrEF treatment
Dr. Packer stressed in his presentation that optimal treatment of patients with HFrEF now demands use of one of these two SGLT2 inhibitors, as well as sacubitril plus valsartan (Entresto), a beta-blocker, and a mineralocorticoid receptor antagonist, plus a diuretic as a fifth drug class for the many HFrEF patients who also need treatment for fluid overload. He further advocated for rapid introduction of these four cornerstone agents with proven survival benefits once a patient receives a HFrEF diagnosis, suggesting that sacubitril plus valsartan, an SGLT2 inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist could all be initiated within 6 weeks or less while acknowledging that optimal up-titration of the beta-blocker would likely take longer.
The order in which a patient starts these drugs shouldn’t matter, and there currently seems to be no evidence that clearly points toward using either dapagliflozin or empagliflozin over the other, Dr. Packer added.
In recognition of the importance of sending a message to heart failure clinicians about the newly proven efficacy of SGLT2 inhibitors in HFrEF patients, the American College of Cardiology and American Heart Association are now drafting an “expert decision pathway” to help clinicians as they enter this new prescribing space. This interim guidance should come out before the end of 2020, prior to release of fully revised HFrEF management guidelines in 2021, said Athena Poppas, MD, president of the ACC, in an interview.
“There is clearly need for education” that can help guide physicians who care for HFrEF patients on how to introduce an SGLT2 inhibitor along with the additional, lengthy list of drug classes proven to benefit these patients, noted Dr. Poppas, who is also a professor and chief of cardiology at the Brown University in Providence, R.I. Physicians may find that they need extra backup for successfully starting both sacubitril plus valsartan and an SGLT2 inhibitor in HFrEF patients because recent history has shown substantial pushback from third-party payers in reimbursing for these relatively expensive drugs, Dr. Poppas noted. She added that this is a problem that may be compounded when patients should ideally get both drug classes.
Physicians who care for heart failure patients have their own history of dragging their feet when adding new drugs to the regimens HFrEF patients receive. The angiotensin converting enzyme inhibitors and beta-blockers took about 17 years each to start reaching a majority of U.S. HFrEF patients, and sacubitril plus valsartan is now used on perhaps a quarter to a third of HFrEF patients despite receiving Food and Drug Administration approval for these patients in mid 2015, noted Christopher M. O’Connor, MD, a heart failure specialist and president of the Inova Heart and Vascular Institute in Fairfax, Va.
Despite dapagliflozin receiving FDA approval in May 2020 for treating HFrEF in patients without diabetes, early uptake in U.S. practice has been very slow, with findings from large U.S. patient registries suggesting that perhaps 1% of suitable HFrEF patients currently get the drug, estimated Dr. O’Connor in an interview.
Given how strong the evidence now is for benefit and safety from dapagliflozin and empagliflozin, it may take as little as 5 years to reach greater than 50% penetration of one of these drugs into U.S. HFrEF patient populations, suggested Dr. Packer, a distinguished scholar in cardiovascular science at Baylor University Medical Center in Dallas.
EMPEROR-Reduced outcomes
The road to routine use of these SGLT2 inhibitor drugs should be hastened by empagliflozin’s impressive performance in EMPEROR-Reduced, in which the drug scored highly significant benefits over placebo for the prespecified primary and two major secondary endpoints, one of which was a measure of preserved renal function.
The trial randomized 3,730 patients at 520 sites in 20 countries during 2017-2019 and followed them on treatment for a median of 16 months. All patients had a left ventricular ejection fraction of 40% or less, and roughly three-quarters had New York Heart Association (NYHA) class II function, nearly one-quarter had class III function, and fewer than 1% of patients fell into the class IV category.
The primary endpoint occurred in 19% of the empagliflozin-treated patients and in 25% of those who received placebo. Among the half of patients with diabetes in the trial, the relative risk reduction by empagliflozin compared with placebo was a statistically significant 28%; among those without diabetes, it was a statistically significant 22%. Concurrently with Dr. Packer’s report, the results appeared in an article posted online (N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190).
The study also had two main prespecified secondary endpoints: the incidence of total hospitalizations for heart failure, both first and recurrent, which fell by 30% in the empagliflozin-treated patients, compared with placebo, and the rate of declining renal function during the 16 months of the study as measured by estimated glomerular filtration rate, which dropped by roughly 1 mL/min per 1.73 m2 among the empagliflozin recipients and by about 4 mL/min/ per 1.73 m2 in the placebo patients.
Treatment with empagliflozin also achieved a notable, statistically significant 50% drop in major adverse renal events, consistent with the performance of other drugs in the class.
“Renal protection is a big plus” of empagliflozin in this trial and from the other SGLT2 inhibitors in prior studies, noted Dr. O’Connor.
The EMPEROR-Reduced results also showed an important benefit for HFrEF patients from empagliflozin not previously seen as quickly with any other drug class, noted Dr. Packer. The SGLT2 inhibitor led to statistically a significant slowing in the progression of patients from NYHA class II function to class III, compared with placebo, and it also significantly promoted the recovery of patients from NYHA class III to class II, an effect that became apparent within the first month on treatment and a benefit that is a “big deal” for patients because it represents a “significant change in functional capacity.” This additional dimension of empagliflozin’s benefit “really impressed me,” Dr. Packer said.
EMPEROR-Reduced was funded by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin. Dr. Packer has received personal fees from Boehringer Ingelheim and Eli Lilly and from several other companies. Dr. Poppas and Dr. O’Connor had no relevant disclosures.
SOURCE: Packer M. ESC 2020. N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190.
FROM ESC CONGRESS 2020
Vitamin D pearls
Case: A 56-year-old man with a history of type 2 diabetes, hypertension, hyperlipidemia, and obesity calls clinic to discuss concerns about COVID-19, stating: “I want to do everything I can to reduce my risk of infection.” In addition to physical distancing, mask wearing, hand hygiene, and control of chronic conditions, which of the following supplements would you recommend for this patient?
1. Coenzyme Q10 160 mg twice a day
2. Vitamin D 2,000 IU daily
3. Vitamin E 400 IU daily
4. Vitamin B12 1,000 mcg daily
Of these choices, vitamin D supplementation is likely the best option, based on the limited data that is available.
Risk factors for worse COVID-19 outcome, such as older age, obesity, and more pigmented skin are also risk factors for vitamin D deficiency. This makes the study of vitamin D and COVID-19 both challenging and relevant.
In a recent study of 7,807 people living in Israel, Merzon and colleagues found that low plasma vitamin D level was an independent risk factor for COVID-19 infection. Mean plasma vitamin D level was significantly lower among those who tested positive for COVID-19 (19.00 ng/mL) than negative (20.55 ng/ mL). After controlling for demographic variables and several medical conditions, the adjusted odds ratio of COVID-19 infection in those with lower vitamin D was 1.45 (95% confidence interval, 1.08-1.95; P < .001). However, the odds of hospitalization for COVID-19 was not significantly associated with vitamin D level.1
Prior studies have also looked at vitamin D and respiratory infection. Martineau and colleagues analyzed 25 randomized, controlled trials with a pooled number of 11,321 individuals, including healthy ones and those with comorbidities, and found that oral vitamin D supplementation in daily or weekly doses had a protective effect against acute respiratory infection (adjusted odds ratio, 0.88; 95% CI, 0.81-0.96; P < .001). Patients with vitamin D deficiency (less than 25 nmol/L) experienced the most protective benefit. Vitamin D did not influence respiratory infection outcome.2
These studies suggest an adequate vitamin D level may be protective against infection with COVID-19, but who will benefit from vitamin D supplementation, and in what dose? Per U.S. Preventive Services Task Force guidelines, there is insufficient evidence to recommend screening for vitamin D deficiency in asymptomatic adults. Regarding daily dietary intake, the Institute of Medicine recommends 600 IU for persons aged 1-70, and 800 IU for those aged over 70 years. Salmon (447 IU per 3 oz serving), tuna (154 IU), and fortified milk (116 IU) are among the most vitamin D–rich foods.3 The recommended upper level of intake is 4,000 IU/day.
Too much of a good thing?
Extra vitamin D is stored in adipose tissue. If it builds up over time, storage sites may be overwhelmed, causing a rise in serum D level. While one might expect a subsequent rise in calcium levels, studies have shown this happens inconsistently, and at very high vitamin D levels, over 120 ng/mL.4 Most people would have to take at least 50,000 IU daily for several months to see an effect. The main adverse outcome of vitamin D toxicity is kidney stones, mediated by increased calcium in the blood and urine.
Several animal models have demonstrated hypervitaminosis D–induced aortic and coronary artery calcification. Like with kidney stones, the mechanism appears to be through increased calcium and phosphate levels. Shroff and colleagues studied serum vitamin D levels and vascular disease in children with renal disease on dialysis and found a U-shaped distribution: Children with both low and high vitamin D levels had significantly increased carotid artery intima-media thickness and calcification.5 Given the specialized nature of this population, it’s unclear whether these results can be generalized to most people. More studies are warranted on this topic.
Other benefits
Vitamin D is perhaps most famous for helping to build strong bones. Avenell and colleagues performed a Cochrane meta-analysis of vitamin D supplementation in older adults and found that vitamin D alone did not significantly reduce the risk of hip or other new fracture. Vitamin D plus calcium supplementation did reduce the risk of hip fracture (nine trials, pooled number of individuals was 49,853; relative risk, 0.84; P = .01).6
A lesser-known benefit of vitamin D is muscle protection. A prospective study out of the Jewish Hospital of Cincinnati followed 146 adults who were intolerant to two or more statins because of muscle side effects and found to have a vitamin D level below 32 ng per mL. Subjects were given vitamin D replacement (50,000 units weekly) and followed for 2 years. On statin rechallenge, 88-95% tolerated a statin with vitamin D levels 53-55 ng/mL.7
Pearl
Vitamin D supplementation may protect against COVID-19 infection and has very low chance of harm at daily doses at or below 4,000 IU. Other benefits of taking vitamin D include bone protection and reduction in statin-induced myopathy. The main adverse effect is kidney stones.
Ms. Sharninghausen is a medical student at the University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. Merzon E et al. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: An Israeli population‐based study. FEBS J. 2020. doi: 10.1111/febs.15495.
2. Martineau AR et al. Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. doi:10.1136/bmj.i6583
3. “How to Get More Vitamin D From Your Food,” Cleveland Clinic. 2019 Oct 23. https://health.clevelandclinic.org/how-to-get-more-vitamin-d-from-your-food/.
4. Galior K et al. Development of vitamin d toxicity from overcorrection of vitamin D Deficiency: A review of case reports. Nutrients. 2018;10(8):953. doi: 10.3390/nu10080953
5. Shroff R et al. A bimodal association of vitamin D levels and vascular disease in children on dialysis. J Am Soc Nephrol. 2008;19(6):1239-46. doi: 10.1681/ASN.2007090993.
6. Avenell A et al. Vitamin D and vitamin D analogues for preventing fractures in post‐menopausal women and older men. Cochrane Database Syst Rev. 2014 Apr 14;2014(4):CD000227. doi: 10.1002/14651858.CD000227.pub4.
7. Khayznikov M et al. Statin intolerance because of myalgia, myositis, myopathy, or myonecrosis can in most cases be safely resolved by vitamin D supplementation. N Am J Med Sci. 2015;7(3):86-93. doi:10.4103/1947-2714.153919
Case: A 56-year-old man with a history of type 2 diabetes, hypertension, hyperlipidemia, and obesity calls clinic to discuss concerns about COVID-19, stating: “I want to do everything I can to reduce my risk of infection.” In addition to physical distancing, mask wearing, hand hygiene, and control of chronic conditions, which of the following supplements would you recommend for this patient?
1. Coenzyme Q10 160 mg twice a day
2. Vitamin D 2,000 IU daily
3. Vitamin E 400 IU daily
4. Vitamin B12 1,000 mcg daily
Of these choices, vitamin D supplementation is likely the best option, based on the limited data that is available.
Risk factors for worse COVID-19 outcome, such as older age, obesity, and more pigmented skin are also risk factors for vitamin D deficiency. This makes the study of vitamin D and COVID-19 both challenging and relevant.
In a recent study of 7,807 people living in Israel, Merzon and colleagues found that low plasma vitamin D level was an independent risk factor for COVID-19 infection. Mean plasma vitamin D level was significantly lower among those who tested positive for COVID-19 (19.00 ng/mL) than negative (20.55 ng/ mL). After controlling for demographic variables and several medical conditions, the adjusted odds ratio of COVID-19 infection in those with lower vitamin D was 1.45 (95% confidence interval, 1.08-1.95; P < .001). However, the odds of hospitalization for COVID-19 was not significantly associated with vitamin D level.1
Prior studies have also looked at vitamin D and respiratory infection. Martineau and colleagues analyzed 25 randomized, controlled trials with a pooled number of 11,321 individuals, including healthy ones and those with comorbidities, and found that oral vitamin D supplementation in daily or weekly doses had a protective effect against acute respiratory infection (adjusted odds ratio, 0.88; 95% CI, 0.81-0.96; P < .001). Patients with vitamin D deficiency (less than 25 nmol/L) experienced the most protective benefit. Vitamin D did not influence respiratory infection outcome.2
These studies suggest an adequate vitamin D level may be protective against infection with COVID-19, but who will benefit from vitamin D supplementation, and in what dose? Per U.S. Preventive Services Task Force guidelines, there is insufficient evidence to recommend screening for vitamin D deficiency in asymptomatic adults. Regarding daily dietary intake, the Institute of Medicine recommends 600 IU for persons aged 1-70, and 800 IU for those aged over 70 years. Salmon (447 IU per 3 oz serving), tuna (154 IU), and fortified milk (116 IU) are among the most vitamin D–rich foods.3 The recommended upper level of intake is 4,000 IU/day.
Too much of a good thing?
Extra vitamin D is stored in adipose tissue. If it builds up over time, storage sites may be overwhelmed, causing a rise in serum D level. While one might expect a subsequent rise in calcium levels, studies have shown this happens inconsistently, and at very high vitamin D levels, over 120 ng/mL.4 Most people would have to take at least 50,000 IU daily for several months to see an effect. The main adverse outcome of vitamin D toxicity is kidney stones, mediated by increased calcium in the blood and urine.
Several animal models have demonstrated hypervitaminosis D–induced aortic and coronary artery calcification. Like with kidney stones, the mechanism appears to be through increased calcium and phosphate levels. Shroff and colleagues studied serum vitamin D levels and vascular disease in children with renal disease on dialysis and found a U-shaped distribution: Children with both low and high vitamin D levels had significantly increased carotid artery intima-media thickness and calcification.5 Given the specialized nature of this population, it’s unclear whether these results can be generalized to most people. More studies are warranted on this topic.
Other benefits
Vitamin D is perhaps most famous for helping to build strong bones. Avenell and colleagues performed a Cochrane meta-analysis of vitamin D supplementation in older adults and found that vitamin D alone did not significantly reduce the risk of hip or other new fracture. Vitamin D plus calcium supplementation did reduce the risk of hip fracture (nine trials, pooled number of individuals was 49,853; relative risk, 0.84; P = .01).6
A lesser-known benefit of vitamin D is muscle protection. A prospective study out of the Jewish Hospital of Cincinnati followed 146 adults who were intolerant to two or more statins because of muscle side effects and found to have a vitamin D level below 32 ng per mL. Subjects were given vitamin D replacement (50,000 units weekly) and followed for 2 years. On statin rechallenge, 88-95% tolerated a statin with vitamin D levels 53-55 ng/mL.7
Pearl
Vitamin D supplementation may protect against COVID-19 infection and has very low chance of harm at daily doses at or below 4,000 IU. Other benefits of taking vitamin D include bone protection and reduction in statin-induced myopathy. The main adverse effect is kidney stones.
Ms. Sharninghausen is a medical student at the University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. Merzon E et al. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: An Israeli population‐based study. FEBS J. 2020. doi: 10.1111/febs.15495.
2. Martineau AR et al. Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. doi:10.1136/bmj.i6583
3. “How to Get More Vitamin D From Your Food,” Cleveland Clinic. 2019 Oct 23. https://health.clevelandclinic.org/how-to-get-more-vitamin-d-from-your-food/.
4. Galior K et al. Development of vitamin d toxicity from overcorrection of vitamin D Deficiency: A review of case reports. Nutrients. 2018;10(8):953. doi: 10.3390/nu10080953
5. Shroff R et al. A bimodal association of vitamin D levels and vascular disease in children on dialysis. J Am Soc Nephrol. 2008;19(6):1239-46. doi: 10.1681/ASN.2007090993.
6. Avenell A et al. Vitamin D and vitamin D analogues for preventing fractures in post‐menopausal women and older men. Cochrane Database Syst Rev. 2014 Apr 14;2014(4):CD000227. doi: 10.1002/14651858.CD000227.pub4.
7. Khayznikov M et al. Statin intolerance because of myalgia, myositis, myopathy, or myonecrosis can in most cases be safely resolved by vitamin D supplementation. N Am J Med Sci. 2015;7(3):86-93. doi:10.4103/1947-2714.153919
Case: A 56-year-old man with a history of type 2 diabetes, hypertension, hyperlipidemia, and obesity calls clinic to discuss concerns about COVID-19, stating: “I want to do everything I can to reduce my risk of infection.” In addition to physical distancing, mask wearing, hand hygiene, and control of chronic conditions, which of the following supplements would you recommend for this patient?
1. Coenzyme Q10 160 mg twice a day
2. Vitamin D 2,000 IU daily
3. Vitamin E 400 IU daily
4. Vitamin B12 1,000 mcg daily
Of these choices, vitamin D supplementation is likely the best option, based on the limited data that is available.
Risk factors for worse COVID-19 outcome, such as older age, obesity, and more pigmented skin are also risk factors for vitamin D deficiency. This makes the study of vitamin D and COVID-19 both challenging and relevant.
In a recent study of 7,807 people living in Israel, Merzon and colleagues found that low plasma vitamin D level was an independent risk factor for COVID-19 infection. Mean plasma vitamin D level was significantly lower among those who tested positive for COVID-19 (19.00 ng/mL) than negative (20.55 ng/ mL). After controlling for demographic variables and several medical conditions, the adjusted odds ratio of COVID-19 infection in those with lower vitamin D was 1.45 (95% confidence interval, 1.08-1.95; P < .001). However, the odds of hospitalization for COVID-19 was not significantly associated with vitamin D level.1
Prior studies have also looked at vitamin D and respiratory infection. Martineau and colleagues analyzed 25 randomized, controlled trials with a pooled number of 11,321 individuals, including healthy ones and those with comorbidities, and found that oral vitamin D supplementation in daily or weekly doses had a protective effect against acute respiratory infection (adjusted odds ratio, 0.88; 95% CI, 0.81-0.96; P < .001). Patients with vitamin D deficiency (less than 25 nmol/L) experienced the most protective benefit. Vitamin D did not influence respiratory infection outcome.2
These studies suggest an adequate vitamin D level may be protective against infection with COVID-19, but who will benefit from vitamin D supplementation, and in what dose? Per U.S. Preventive Services Task Force guidelines, there is insufficient evidence to recommend screening for vitamin D deficiency in asymptomatic adults. Regarding daily dietary intake, the Institute of Medicine recommends 600 IU for persons aged 1-70, and 800 IU for those aged over 70 years. Salmon (447 IU per 3 oz serving), tuna (154 IU), and fortified milk (116 IU) are among the most vitamin D–rich foods.3 The recommended upper level of intake is 4,000 IU/day.
Too much of a good thing?
Extra vitamin D is stored in adipose tissue. If it builds up over time, storage sites may be overwhelmed, causing a rise in serum D level. While one might expect a subsequent rise in calcium levels, studies have shown this happens inconsistently, and at very high vitamin D levels, over 120 ng/mL.4 Most people would have to take at least 50,000 IU daily for several months to see an effect. The main adverse outcome of vitamin D toxicity is kidney stones, mediated by increased calcium in the blood and urine.
Several animal models have demonstrated hypervitaminosis D–induced aortic and coronary artery calcification. Like with kidney stones, the mechanism appears to be through increased calcium and phosphate levels. Shroff and colleagues studied serum vitamin D levels and vascular disease in children with renal disease on dialysis and found a U-shaped distribution: Children with both low and high vitamin D levels had significantly increased carotid artery intima-media thickness and calcification.5 Given the specialized nature of this population, it’s unclear whether these results can be generalized to most people. More studies are warranted on this topic.
Other benefits
Vitamin D is perhaps most famous for helping to build strong bones. Avenell and colleagues performed a Cochrane meta-analysis of vitamin D supplementation in older adults and found that vitamin D alone did not significantly reduce the risk of hip or other new fracture. Vitamin D plus calcium supplementation did reduce the risk of hip fracture (nine trials, pooled number of individuals was 49,853; relative risk, 0.84; P = .01).6
A lesser-known benefit of vitamin D is muscle protection. A prospective study out of the Jewish Hospital of Cincinnati followed 146 adults who were intolerant to two or more statins because of muscle side effects and found to have a vitamin D level below 32 ng per mL. Subjects were given vitamin D replacement (50,000 units weekly) and followed for 2 years. On statin rechallenge, 88-95% tolerated a statin with vitamin D levels 53-55 ng/mL.7
Pearl
Vitamin D supplementation may protect against COVID-19 infection and has very low chance of harm at daily doses at or below 4,000 IU. Other benefits of taking vitamin D include bone protection and reduction in statin-induced myopathy. The main adverse effect is kidney stones.
Ms. Sharninghausen is a medical student at the University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. Merzon E et al. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: An Israeli population‐based study. FEBS J. 2020. doi: 10.1111/febs.15495.
2. Martineau AR et al. Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. doi:10.1136/bmj.i6583
3. “How to Get More Vitamin D From Your Food,” Cleveland Clinic. 2019 Oct 23. https://health.clevelandclinic.org/how-to-get-more-vitamin-d-from-your-food/.
4. Galior K et al. Development of vitamin d toxicity from overcorrection of vitamin D Deficiency: A review of case reports. Nutrients. 2018;10(8):953. doi: 10.3390/nu10080953
5. Shroff R et al. A bimodal association of vitamin D levels and vascular disease in children on dialysis. J Am Soc Nephrol. 2008;19(6):1239-46. doi: 10.1681/ASN.2007090993.
6. Avenell A et al. Vitamin D and vitamin D analogues for preventing fractures in post‐menopausal women and older men. Cochrane Database Syst Rev. 2014 Apr 14;2014(4):CD000227. doi: 10.1002/14651858.CD000227.pub4.
7. Khayznikov M et al. Statin intolerance because of myalgia, myositis, myopathy, or myonecrosis can in most cases be safely resolved by vitamin D supplementation. N Am J Med Sci. 2015;7(3):86-93. doi:10.4103/1947-2714.153919
FDA pulls amputation boxed warning off canagliflozin label
The Food and Drug Administration has removed the boxed warning about the risk of leg and foot amputations for canagliflozin (Invokana, Invokamet, Janssen), a sodium-glucose cotransporter-2 (SGLT2) inhibitor for the treatment of type 2 diabetes, the agency announced Aug. 26.
As previously reported by Medscape Medical News, the FDA added the boxed warning to the canagliflozin label in May 2017, after an approximately doubled risk for lower-extremity amputations with the drug compared with placebo was seen during two trials.
The FDA said the decision to remove the boxed warning was made following a review of new data from three clinical trials, which demonstrated additional heart- and kidney-related benefits and led to additional approved uses for canagliflozin.
In 2018, canagliflozin was approved to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease.
In 2019, canagliflozin was approved to reduce the risk of end-stage kidney disease, worsening of kidney function, cardiovascular death, and heart failure hospitalization, in adults with type 2 diabetes and diabetic kidney disease.
“Collectively, these newly identified effects of canagliflozin on heart and kidney disease show significantly enhanced benefit of this medicine,” the FDA said.
The safety information from these trials, the FDA said, suggests that the risk of amputation, “while still increased with canagliflozin, is lower than previously described, particularly when appropriately monitored.”
The agency added: “Based upon these considerations, FDA concluded that the boxed warning should be removed.”
The FDA announcement said clinicians and patients should continue to be aware of the importance of preventive foot care and to monitor for new pain, tenderness, sores, ulcers, and infections in the legs and feet. Risk factors that may predispose patients to amputation should be considered when choosing antidiabetic medicines.
Health care professionals are encouraged to report adverse reactions with canagliflozin to the FDA’s MedWatch program.
A version of this article originally appeared on Medscape.com.
The Food and Drug Administration has removed the boxed warning about the risk of leg and foot amputations for canagliflozin (Invokana, Invokamet, Janssen), a sodium-glucose cotransporter-2 (SGLT2) inhibitor for the treatment of type 2 diabetes, the agency announced Aug. 26.
As previously reported by Medscape Medical News, the FDA added the boxed warning to the canagliflozin label in May 2017, after an approximately doubled risk for lower-extremity amputations with the drug compared with placebo was seen during two trials.
The FDA said the decision to remove the boxed warning was made following a review of new data from three clinical trials, which demonstrated additional heart- and kidney-related benefits and led to additional approved uses for canagliflozin.
In 2018, canagliflozin was approved to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease.
In 2019, canagliflozin was approved to reduce the risk of end-stage kidney disease, worsening of kidney function, cardiovascular death, and heart failure hospitalization, in adults with type 2 diabetes and diabetic kidney disease.
“Collectively, these newly identified effects of canagliflozin on heart and kidney disease show significantly enhanced benefit of this medicine,” the FDA said.
The safety information from these trials, the FDA said, suggests that the risk of amputation, “while still increased with canagliflozin, is lower than previously described, particularly when appropriately monitored.”
The agency added: “Based upon these considerations, FDA concluded that the boxed warning should be removed.”
The FDA announcement said clinicians and patients should continue to be aware of the importance of preventive foot care and to monitor for new pain, tenderness, sores, ulcers, and infections in the legs and feet. Risk factors that may predispose patients to amputation should be considered when choosing antidiabetic medicines.
Health care professionals are encouraged to report adverse reactions with canagliflozin to the FDA’s MedWatch program.
A version of this article originally appeared on Medscape.com.
The Food and Drug Administration has removed the boxed warning about the risk of leg and foot amputations for canagliflozin (Invokana, Invokamet, Janssen), a sodium-glucose cotransporter-2 (SGLT2) inhibitor for the treatment of type 2 diabetes, the agency announced Aug. 26.
As previously reported by Medscape Medical News, the FDA added the boxed warning to the canagliflozin label in May 2017, after an approximately doubled risk for lower-extremity amputations with the drug compared with placebo was seen during two trials.
The FDA said the decision to remove the boxed warning was made following a review of new data from three clinical trials, which demonstrated additional heart- and kidney-related benefits and led to additional approved uses for canagliflozin.
In 2018, canagliflozin was approved to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease.
In 2019, canagliflozin was approved to reduce the risk of end-stage kidney disease, worsening of kidney function, cardiovascular death, and heart failure hospitalization, in adults with type 2 diabetes and diabetic kidney disease.
“Collectively, these newly identified effects of canagliflozin on heart and kidney disease show significantly enhanced benefit of this medicine,” the FDA said.
The safety information from these trials, the FDA said, suggests that the risk of amputation, “while still increased with canagliflozin, is lower than previously described, particularly when appropriately monitored.”
The agency added: “Based upon these considerations, FDA concluded that the boxed warning should be removed.”
The FDA announcement said clinicians and patients should continue to be aware of the importance of preventive foot care and to monitor for new pain, tenderness, sores, ulcers, and infections in the legs and feet. Risk factors that may predispose patients to amputation should be considered when choosing antidiabetic medicines.
Health care professionals are encouraged to report adverse reactions with canagliflozin to the FDA’s MedWatch program.
A version of this article originally appeared on Medscape.com.
SGLT2 inhibitors with metformin look safe for bone
The combination of sodium-glucose transporter-2 (SGLT-2) inhibitors and metformin is not associated with an increase in fracture risk among patients with type 2 diabetes (T2D), according to a new meta-analysis of 25 randomized, controlled trials.
Researchers at The Second Clinical College of Dalian Medical University in Jiangsu, China, compared fracture risk associated with the metformin/SLGT2 combination to metformin alone as well as other T2D therapeutics, and found no differences in risk. The study was published online Aug. 11 in Osteoporosis International.
T2D is associated with an increased risk of fracture, though causative mechanisms remain uncertain. Some lines of evidence suggest multiple factors may contribute to fractures, including hyperglycemia, oxidative stress, toxic effects of advanced glycosylation end-products, altered insulin levels, and treatment-induced hypoglycemia, as well as an association between T2D and increased risk of falls.
Antidiabetes drugs can have positive or negative effects on bone. thiazolidinediones, insulin, and sulfonylureas may increase risk of fractures, while dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-2 (GLP-2) receptor agonists may be protective. Metformin may also reduce fracture risk.
SGLT-2 inhibitors interrupt glucose reabsorption in the kidney, leading to improved glycemic control. Other benefits include improved renal and cardiovascular outcomes, weight loss, and reduced blood pressure, liver fat, and serum uric acid levels.
These properties have made SGLT-2 inhibitors combined with metformin an important therapy for patients at high risk of atherosclerotic disease, or who have heart failure or chronic kidney disease.
But SGLT-2 inhibition increases osmotic diuresis, and this could alter the mineral balance within bone. Some studies also showed that SGLT-2 inhibitors led to changes in bone turnover markers, bone mineral density, and bone microarchitecture. Observational studies of the SGLT-2 inhibitor canagliflozin found associations with a higher rate of fracture risk in patients taking the drug.
Such studies carry the risk of confounding factors, so the researchers took advantage of the fact that many recent clinical trials have examined the impact of SGLT-2 inhibitors on T2D. They pooled data from 25 clinical trials with a total of 19,500 participants, 9,662 of whom received SGLT-2 inhibitors plus metformin; 9,838 received other active comparators.
The fracture rate was 0.91% in the SGLT-2 inhibitors/metformin group, and 0.80% among controls (odds ratio, 0.97; 95% CI, 0.71-1.32), with no heterogeneity. Metformin alone was not associated with a change in fracture rate (OR, 0.95; 95% CI, 0.44-2.08), nor were other forms of diabetes control (OR, 0.95; 95% CI, 0.69-1.31).
There were some differences in fracture risk among SGLT-2 inhibitors when studied individually, though none differed significantly from controls. The highest risk was associated with the canagliflozin/metformin (OR, 2.19; 95% CI, 0.66-7.27), followed by dapagliflozin/metformin (OR, 0.91; 95% CI, 0.50-1.64), empagliflozin/metformin (OR, 0.94; 95% CI, 0.59-1.50), and ertugliflozin/metformin (OR, 0.76; 95% CI, 0.38-1.54).
There were no differences with respect to hip or lumbar spine fractures, or other fractures. The researchers found no differences in bone mineral density or bone turnover markers.
The meta-analysis is limited by the relatively short average follow-up in the included studies, which was 61 weeks. Bone damage may occur over longer time periods. Bone fractures were also not a prespecified adverse event in most included studies.
The studies also did not provide detailed information on the types of fractures experienced, such as whether they were result of a fall, or the location of the fracture, or bone health parameters. Although the results support a belief that SGLT-2 inhibitors do not adversely affect bone health, “given limited information on bone health outcomes, further work is needed to validate this conclusion,” the authors wrote.
The authors did not disclose any funding and had no relevant conflicts of interest.
SOURCE: B-B Qian et al. Osteoporosis Int. 2020 Aug 11. doi: 10.1007/s00198-020-05590-y.
The combination of sodium-glucose transporter-2 (SGLT-2) inhibitors and metformin is not associated with an increase in fracture risk among patients with type 2 diabetes (T2D), according to a new meta-analysis of 25 randomized, controlled trials.
Researchers at The Second Clinical College of Dalian Medical University in Jiangsu, China, compared fracture risk associated with the metformin/SLGT2 combination to metformin alone as well as other T2D therapeutics, and found no differences in risk. The study was published online Aug. 11 in Osteoporosis International.
T2D is associated with an increased risk of fracture, though causative mechanisms remain uncertain. Some lines of evidence suggest multiple factors may contribute to fractures, including hyperglycemia, oxidative stress, toxic effects of advanced glycosylation end-products, altered insulin levels, and treatment-induced hypoglycemia, as well as an association between T2D and increased risk of falls.
Antidiabetes drugs can have positive or negative effects on bone. thiazolidinediones, insulin, and sulfonylureas may increase risk of fractures, while dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-2 (GLP-2) receptor agonists may be protective. Metformin may also reduce fracture risk.
SGLT-2 inhibitors interrupt glucose reabsorption in the kidney, leading to improved glycemic control. Other benefits include improved renal and cardiovascular outcomes, weight loss, and reduced blood pressure, liver fat, and serum uric acid levels.
These properties have made SGLT-2 inhibitors combined with metformin an important therapy for patients at high risk of atherosclerotic disease, or who have heart failure or chronic kidney disease.
But SGLT-2 inhibition increases osmotic diuresis, and this could alter the mineral balance within bone. Some studies also showed that SGLT-2 inhibitors led to changes in bone turnover markers, bone mineral density, and bone microarchitecture. Observational studies of the SGLT-2 inhibitor canagliflozin found associations with a higher rate of fracture risk in patients taking the drug.
Such studies carry the risk of confounding factors, so the researchers took advantage of the fact that many recent clinical trials have examined the impact of SGLT-2 inhibitors on T2D. They pooled data from 25 clinical trials with a total of 19,500 participants, 9,662 of whom received SGLT-2 inhibitors plus metformin; 9,838 received other active comparators.
The fracture rate was 0.91% in the SGLT-2 inhibitors/metformin group, and 0.80% among controls (odds ratio, 0.97; 95% CI, 0.71-1.32), with no heterogeneity. Metformin alone was not associated with a change in fracture rate (OR, 0.95; 95% CI, 0.44-2.08), nor were other forms of diabetes control (OR, 0.95; 95% CI, 0.69-1.31).
There were some differences in fracture risk among SGLT-2 inhibitors when studied individually, though none differed significantly from controls. The highest risk was associated with the canagliflozin/metformin (OR, 2.19; 95% CI, 0.66-7.27), followed by dapagliflozin/metformin (OR, 0.91; 95% CI, 0.50-1.64), empagliflozin/metformin (OR, 0.94; 95% CI, 0.59-1.50), and ertugliflozin/metformin (OR, 0.76; 95% CI, 0.38-1.54).
There were no differences with respect to hip or lumbar spine fractures, or other fractures. The researchers found no differences in bone mineral density or bone turnover markers.
The meta-analysis is limited by the relatively short average follow-up in the included studies, which was 61 weeks. Bone damage may occur over longer time periods. Bone fractures were also not a prespecified adverse event in most included studies.
The studies also did not provide detailed information on the types of fractures experienced, such as whether they were result of a fall, or the location of the fracture, or bone health parameters. Although the results support a belief that SGLT-2 inhibitors do not adversely affect bone health, “given limited information on bone health outcomes, further work is needed to validate this conclusion,” the authors wrote.
The authors did not disclose any funding and had no relevant conflicts of interest.
SOURCE: B-B Qian et al. Osteoporosis Int. 2020 Aug 11. doi: 10.1007/s00198-020-05590-y.
The combination of sodium-glucose transporter-2 (SGLT-2) inhibitors and metformin is not associated with an increase in fracture risk among patients with type 2 diabetes (T2D), according to a new meta-analysis of 25 randomized, controlled trials.
Researchers at The Second Clinical College of Dalian Medical University in Jiangsu, China, compared fracture risk associated with the metformin/SLGT2 combination to metformin alone as well as other T2D therapeutics, and found no differences in risk. The study was published online Aug. 11 in Osteoporosis International.
T2D is associated with an increased risk of fracture, though causative mechanisms remain uncertain. Some lines of evidence suggest multiple factors may contribute to fractures, including hyperglycemia, oxidative stress, toxic effects of advanced glycosylation end-products, altered insulin levels, and treatment-induced hypoglycemia, as well as an association between T2D and increased risk of falls.
Antidiabetes drugs can have positive or negative effects on bone. thiazolidinediones, insulin, and sulfonylureas may increase risk of fractures, while dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-2 (GLP-2) receptor agonists may be protective. Metformin may also reduce fracture risk.
SGLT-2 inhibitors interrupt glucose reabsorption in the kidney, leading to improved glycemic control. Other benefits include improved renal and cardiovascular outcomes, weight loss, and reduced blood pressure, liver fat, and serum uric acid levels.
These properties have made SGLT-2 inhibitors combined with metformin an important therapy for patients at high risk of atherosclerotic disease, or who have heart failure or chronic kidney disease.
But SGLT-2 inhibition increases osmotic diuresis, and this could alter the mineral balance within bone. Some studies also showed that SGLT-2 inhibitors led to changes in bone turnover markers, bone mineral density, and bone microarchitecture. Observational studies of the SGLT-2 inhibitor canagliflozin found associations with a higher rate of fracture risk in patients taking the drug.
Such studies carry the risk of confounding factors, so the researchers took advantage of the fact that many recent clinical trials have examined the impact of SGLT-2 inhibitors on T2D. They pooled data from 25 clinical trials with a total of 19,500 participants, 9,662 of whom received SGLT-2 inhibitors plus metformin; 9,838 received other active comparators.
The fracture rate was 0.91% in the SGLT-2 inhibitors/metformin group, and 0.80% among controls (odds ratio, 0.97; 95% CI, 0.71-1.32), with no heterogeneity. Metformin alone was not associated with a change in fracture rate (OR, 0.95; 95% CI, 0.44-2.08), nor were other forms of diabetes control (OR, 0.95; 95% CI, 0.69-1.31).
There were some differences in fracture risk among SGLT-2 inhibitors when studied individually, though none differed significantly from controls. The highest risk was associated with the canagliflozin/metformin (OR, 2.19; 95% CI, 0.66-7.27), followed by dapagliflozin/metformin (OR, 0.91; 95% CI, 0.50-1.64), empagliflozin/metformin (OR, 0.94; 95% CI, 0.59-1.50), and ertugliflozin/metformin (OR, 0.76; 95% CI, 0.38-1.54).
There were no differences with respect to hip or lumbar spine fractures, or other fractures. The researchers found no differences in bone mineral density or bone turnover markers.
The meta-analysis is limited by the relatively short average follow-up in the included studies, which was 61 weeks. Bone damage may occur over longer time periods. Bone fractures were also not a prespecified adverse event in most included studies.
The studies also did not provide detailed information on the types of fractures experienced, such as whether they were result of a fall, or the location of the fracture, or bone health parameters. Although the results support a belief that SGLT-2 inhibitors do not adversely affect bone health, “given limited information on bone health outcomes, further work is needed to validate this conclusion,” the authors wrote.
The authors did not disclose any funding and had no relevant conflicts of interest.
SOURCE: B-B Qian et al. Osteoporosis Int. 2020 Aug 11. doi: 10.1007/s00198-020-05590-y.
FROM OSTEOPOROSIS INTERNATIONAL
Diabetes plus weight loss equals increased risk of pancreatic cancer
A new study has linked recent-onset diabetes and subsequent weight loss to an increased risk of pancreatic cancer, indicating a distinct group of individuals to screen early for this deadly disease.
“The likelihood of a pancreatic cancer diagnosis was even further elevated among individuals with older age, healthy weight before weight loss, and unintentional weight loss,” wrote Chen Yuan, ScD, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston. The study was published in JAMA Oncology.
To determine whether an association exists between diabetes plus weight change and pancreatic cancer, the researchers analyzed decades of medical history data from the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). The study population from the NHS included 112,818 women with a mean age of 59 years; the population from the HPFS included 46,207 men with a mean age of 65 years. Since enrollment – the baseline was 1978 for the NHS and 1988 for the HPFS – participants have provided follow-up information via biennial questionnaires.
Recent diabetes onset, weight loss boost cancer risk
From those combined groups, 1,116 incident cases of pancreatic cancer (0.7%) were identified. Compared with patients with no diabetes, patients with recent-onset diabetes had triple the risk of pancreatic cancer (age-adjusted hazard ratio, 2.97; 95% confidence interval, 2.31-3.82) and patients with longstanding diabetes had more than double the risk (HR, 2.16; 95% CI, 1.78-2.60). Patients with longer disease duration also had more than twice the risk of pancreatic cancer, with HRs of 2.25 for those with diabetes for 4-10 years (95% CI, 1.74-2.92) and 2.07 for more than 10 years (95% CI, 1.61-2.66).
Compared with patients who hadn’t lost any weight, patients who reported a 1- to 4-pound weight loss (HR, 1.25; 95% CI, 1.03-1.52), a 5- to 8-pound weight loss (HR, 1.33; 95% CI, 1.06-1.66), and a more than 8-pound weight loss (HR, 1.92; 95% CI, 1.58-2.32) had higher risks of pancreatic cancer. Patients with recent-onset diabetes and a 1- to 8-pound weight loss (91 incident cases per 100,000 person-years; 95% CI, 55-151) or a weight loss of more than 8 pounds (164 incident cases per 100,000 person years; 95% CI, 114-238) had a much higher incidence of pancreatic cancer, compared with patients with neither (16 incident cases per 100,000 person-years; 95% CI, 14-17).
After stratified analyses of patients with both recent-onset diabetes and weight loss, rates of pancreatic cancer were also notably high in those 70 years or older (234 cases per 100,000 person years), those with a body mass index of less than 25 kg/m2 before weight loss (400 cases per 100,000 person years), and those with a low likelihood of intentional weight loss (334 cases per 100,000 person years).
“I like the study because it reminds us of the importance of not thinking everyone that presents with type 2 diabetes necessarily has garden-variety diabetes,” Paul Jellinger, MD, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., said in an interview. “I have always been concerned when a new-onset diabetic individual presents with no family history of diabetes or prediabetes, especially if they’re neither overweight nor obese. I have sometimes screened those individuals for pancreatic abnormalities.”
A call for screening
“This study highlights the consideration for further screening to those with weight loss at the time of diabetes diagnosis, which is very sensible given how unusual weight loss is as a presenting symptom at the time of diagnosis of typical type 2 diabetes,” Dr. Jellinger added. “The combination of weight loss and no family history of diabetes at the time of diagnosis should be an even stronger signal for pancreatic cancer screening and potential detection at a much earlier stage.”
The authors acknowledged their study’s limitations, including some patients with pancreatic cancer not returning their questionnaires and the timing of the questionnaires meaning that patients could’ve developed diabetes after returning it. In addition, they recognized that the participants were “predominantly White health professionals” and recommended a study of “additional patient populations” in the future.
The authors noted numerous potential conflicts of interest, including receiving grants and personal fees from various initiatives, organizations, and pharmaceutical companies.
SOURCE: Yuan C et al. JAMA Oncol. 2020 Aug 13. doi: 10.1001/jamaoncol.2020.2948.
A new study has linked recent-onset diabetes and subsequent weight loss to an increased risk of pancreatic cancer, indicating a distinct group of individuals to screen early for this deadly disease.
“The likelihood of a pancreatic cancer diagnosis was even further elevated among individuals with older age, healthy weight before weight loss, and unintentional weight loss,” wrote Chen Yuan, ScD, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston. The study was published in JAMA Oncology.
To determine whether an association exists between diabetes plus weight change and pancreatic cancer, the researchers analyzed decades of medical history data from the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). The study population from the NHS included 112,818 women with a mean age of 59 years; the population from the HPFS included 46,207 men with a mean age of 65 years. Since enrollment – the baseline was 1978 for the NHS and 1988 for the HPFS – participants have provided follow-up information via biennial questionnaires.
Recent diabetes onset, weight loss boost cancer risk
From those combined groups, 1,116 incident cases of pancreatic cancer (0.7%) were identified. Compared with patients with no diabetes, patients with recent-onset diabetes had triple the risk of pancreatic cancer (age-adjusted hazard ratio, 2.97; 95% confidence interval, 2.31-3.82) and patients with longstanding diabetes had more than double the risk (HR, 2.16; 95% CI, 1.78-2.60). Patients with longer disease duration also had more than twice the risk of pancreatic cancer, with HRs of 2.25 for those with diabetes for 4-10 years (95% CI, 1.74-2.92) and 2.07 for more than 10 years (95% CI, 1.61-2.66).
Compared with patients who hadn’t lost any weight, patients who reported a 1- to 4-pound weight loss (HR, 1.25; 95% CI, 1.03-1.52), a 5- to 8-pound weight loss (HR, 1.33; 95% CI, 1.06-1.66), and a more than 8-pound weight loss (HR, 1.92; 95% CI, 1.58-2.32) had higher risks of pancreatic cancer. Patients with recent-onset diabetes and a 1- to 8-pound weight loss (91 incident cases per 100,000 person-years; 95% CI, 55-151) or a weight loss of more than 8 pounds (164 incident cases per 100,000 person years; 95% CI, 114-238) had a much higher incidence of pancreatic cancer, compared with patients with neither (16 incident cases per 100,000 person-years; 95% CI, 14-17).
After stratified analyses of patients with both recent-onset diabetes and weight loss, rates of pancreatic cancer were also notably high in those 70 years or older (234 cases per 100,000 person years), those with a body mass index of less than 25 kg/m2 before weight loss (400 cases per 100,000 person years), and those with a low likelihood of intentional weight loss (334 cases per 100,000 person years).
“I like the study because it reminds us of the importance of not thinking everyone that presents with type 2 diabetes necessarily has garden-variety diabetes,” Paul Jellinger, MD, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., said in an interview. “I have always been concerned when a new-onset diabetic individual presents with no family history of diabetes or prediabetes, especially if they’re neither overweight nor obese. I have sometimes screened those individuals for pancreatic abnormalities.”
A call for screening
“This study highlights the consideration for further screening to those with weight loss at the time of diabetes diagnosis, which is very sensible given how unusual weight loss is as a presenting symptom at the time of diagnosis of typical type 2 diabetes,” Dr. Jellinger added. “The combination of weight loss and no family history of diabetes at the time of diagnosis should be an even stronger signal for pancreatic cancer screening and potential detection at a much earlier stage.”
The authors acknowledged their study’s limitations, including some patients with pancreatic cancer not returning their questionnaires and the timing of the questionnaires meaning that patients could’ve developed diabetes after returning it. In addition, they recognized that the participants were “predominantly White health professionals” and recommended a study of “additional patient populations” in the future.
The authors noted numerous potential conflicts of interest, including receiving grants and personal fees from various initiatives, organizations, and pharmaceutical companies.
SOURCE: Yuan C et al. JAMA Oncol. 2020 Aug 13. doi: 10.1001/jamaoncol.2020.2948.
A new study has linked recent-onset diabetes and subsequent weight loss to an increased risk of pancreatic cancer, indicating a distinct group of individuals to screen early for this deadly disease.
“The likelihood of a pancreatic cancer diagnosis was even further elevated among individuals with older age, healthy weight before weight loss, and unintentional weight loss,” wrote Chen Yuan, ScD, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston. The study was published in JAMA Oncology.
To determine whether an association exists between diabetes plus weight change and pancreatic cancer, the researchers analyzed decades of medical history data from the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). The study population from the NHS included 112,818 women with a mean age of 59 years; the population from the HPFS included 46,207 men with a mean age of 65 years. Since enrollment – the baseline was 1978 for the NHS and 1988 for the HPFS – participants have provided follow-up information via biennial questionnaires.
Recent diabetes onset, weight loss boost cancer risk
From those combined groups, 1,116 incident cases of pancreatic cancer (0.7%) were identified. Compared with patients with no diabetes, patients with recent-onset diabetes had triple the risk of pancreatic cancer (age-adjusted hazard ratio, 2.97; 95% confidence interval, 2.31-3.82) and patients with longstanding diabetes had more than double the risk (HR, 2.16; 95% CI, 1.78-2.60). Patients with longer disease duration also had more than twice the risk of pancreatic cancer, with HRs of 2.25 for those with diabetes for 4-10 years (95% CI, 1.74-2.92) and 2.07 for more than 10 years (95% CI, 1.61-2.66).
Compared with patients who hadn’t lost any weight, patients who reported a 1- to 4-pound weight loss (HR, 1.25; 95% CI, 1.03-1.52), a 5- to 8-pound weight loss (HR, 1.33; 95% CI, 1.06-1.66), and a more than 8-pound weight loss (HR, 1.92; 95% CI, 1.58-2.32) had higher risks of pancreatic cancer. Patients with recent-onset diabetes and a 1- to 8-pound weight loss (91 incident cases per 100,000 person-years; 95% CI, 55-151) or a weight loss of more than 8 pounds (164 incident cases per 100,000 person years; 95% CI, 114-238) had a much higher incidence of pancreatic cancer, compared with patients with neither (16 incident cases per 100,000 person-years; 95% CI, 14-17).
After stratified analyses of patients with both recent-onset diabetes and weight loss, rates of pancreatic cancer were also notably high in those 70 years or older (234 cases per 100,000 person years), those with a body mass index of less than 25 kg/m2 before weight loss (400 cases per 100,000 person years), and those with a low likelihood of intentional weight loss (334 cases per 100,000 person years).
“I like the study because it reminds us of the importance of not thinking everyone that presents with type 2 diabetes necessarily has garden-variety diabetes,” Paul Jellinger, MD, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., said in an interview. “I have always been concerned when a new-onset diabetic individual presents with no family history of diabetes or prediabetes, especially if they’re neither overweight nor obese. I have sometimes screened those individuals for pancreatic abnormalities.”
A call for screening
“This study highlights the consideration for further screening to those with weight loss at the time of diabetes diagnosis, which is very sensible given how unusual weight loss is as a presenting symptom at the time of diagnosis of typical type 2 diabetes,” Dr. Jellinger added. “The combination of weight loss and no family history of diabetes at the time of diagnosis should be an even stronger signal for pancreatic cancer screening and potential detection at a much earlier stage.”
The authors acknowledged their study’s limitations, including some patients with pancreatic cancer not returning their questionnaires and the timing of the questionnaires meaning that patients could’ve developed diabetes after returning it. In addition, they recognized that the participants were “predominantly White health professionals” and recommended a study of “additional patient populations” in the future.
The authors noted numerous potential conflicts of interest, including receiving grants and personal fees from various initiatives, organizations, and pharmaceutical companies.
SOURCE: Yuan C et al. JAMA Oncol. 2020 Aug 13. doi: 10.1001/jamaoncol.2020.2948.
FROM JAMA ONCOLOGY
