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What will it take to lower the cost of insulin in the United States?
Mayo Clinic hematologist S. Vincent Rajkumar, MD, argues in a new commentary.
The High Cost of Insulin in the United States: An Urgent Call to Action was published in the January 2020 issue of the Mayo Clinic Proceedings by Dr. Rajkumar, professor of medicine at the Mayo Clinic, Rochester, Minn., who specializes in treating myeloma and, more recently, has become an expert in drug pricing.
He also presented the information in a YouTube video.
As has been widely reported and examined by Congress in the past few years, the cost of insulin in the United States has risen at a far higher rate than inflation. For example, the list price of a single vial of Humalog jumped from $21 in 1999 to $275 in 2019, a far higher price than anywhere else in the world.
Stories of one in four patients having to ration their insulin use because of cost, and of some dying, have fueled protests, leading to legislative efforts and to a few initiatives by some of the manufacturers to address the cost problem.
Collective advocacy
Much of the blame has been placed on the manufacturers for charging such high prices and on the pharmacy benefit managers (PBMs) – also known as “middlemen” – for incentivizing higher-priced products on formularies through rebates. Those are major factors, Dr. Rajkumar argues, but they are not the only ones.
“There is no one reason why this is happening, and no one solution. It’s very complicated. It’s multiple factors all playing together. The only way to tackle it is to really understand it 360,” he said in an interview.
This is true of drug prices overall in the United States, but insulin is a special case. The current analog formulations have not changed in more than 20 years, yet only in the past 5 years have a handful of biosimilar and generic versions started to appear from the same manufacturers as the branded products.
“Insulin is a window into what’s wrong with the pharma industry. ... It’s the best example of how the system is broken,” Dr. Rajkumar stressed.
Physicians can help ease the problem, he said, by becoming educated about drug prices, taking cost into account when prescribing, and routinely discussing prescription drug affordability with patients.
Resources such as www.goodrx.com and www.blinkhealth.com provide information about drug prices and pharmacies that offer drugs at the lowest prices.
“Doctors need to not be suspicious of biosimilars and generics,” he emphasized.
Physicians can also advocate for policies that will lower insulin prices, and their institutions can establish preferences for lower-cost biosimilars in formularies.
“Our individual and collective advocacy gives voice to the needs of our patients,” Dr. Rajkumar emphasized.
‘Everyone in the supply chain benefits’
In his commentary, Dr. Rajkumar lists six major reasons for the high cost of insulin:
1. People with type 1 diabetes are a “vulnerable population” who will die without insulin and are therefore willing to pay a high price to stay alive.
2. Just three manufacturers – Eli Lilly, Novo Nordisk, and Sanofi-Aventis – control nearly the entire insulin market in the United States, with no regulations to cap or control the prices they can charge.
3. The manufacturers continually file new patents for existing insulin products – 70 in the case of Lantus, for example – that provide additional years of monopoly protection from competition.
4. Although the Food and Drug Administration has been receptive to approving insulin biosimilars, it still requires manufacturers to go through a long and cumbersome process to obtain licensure, sometimes taking as long as 10 years.
5.PBMs, paid by insurance companies to negotiate prices with retail pharmacies and pharmaceutical companies (through rebates), stand to benefit from higher, not lower, list prices.
6. Pharmaceutical companies have vast lobbying power.
In regard to the fifth point, about PBMs, Dr. Rajkumar said, “It’s not just the PBMs – it’s the whole supply chain. It’s hard to put a finger on the source of the problem. There’s no transparency in any of the arrangements for you to know why only certain drugs are on a given formulary of an insurance company or PBM. But we do know that, in general, the whole supply chain benefits from the higher list price. Everyone.”
‘Authorized generic’ insulins
That is why Dr. Rajkumar is not convinced that Eli Lilly’s recent launch of half-priced “authorized generic” insulins – first the Lispro injection in March 2019, and then two combination pen products in January 2020 – or Novo Nordisk’s My$99Insulin program and “follow-on” authorized generic versions of Novolog and NovoLog Mix, launched Jan. 2, 2020, will have a huge impact.
“It’s common sense. If Apple made the same iPhone for two different prices, who would pay the full price? It gives you a window into asking what is wrong with the system that allows that? To pay for the higher-priced product, somebody is being paid,” he said.
Indeed, in December 2019, the offices of Sen. Elizabeth Warren (D-MA) and Sen. Richard Blumenthal (D-CT) issued a report from a survey of 400 pharmacies nationwide that found that 83% of the less expensive authorized generic Insulin Lispro was not in stock.
More than two-thirds of pharmacies reported they could not order the product.
“Eli Lilly has failed to take consequential steps – such as simply lowering the list price of Humalog, as it has in foreign markets – to provide lower-cost access to this important diabetes drug,” according to the senators’ report, which concludes by urging Eli Lilly to lower the list price of its insulin and calling for Congress to take steps to enact systemic change to reduce drug prices nationwide.
Asked for comment, Dani Barnhizer, Eli Lilly’s manager of global diabetes communications, said, “Like Senators Warren and Blumenthal, Lilly would like to see even broader use of Insulin Lispro injection because it’s a real solution that can lower copays for people living with diabetes.”
“But the Senators’ paper failed to identify the system challenges that have inhibited access to this lower list price product,” Ms. Barnhizer said. “Payers determine an individual’s premiums and copays, which are subsidized by rebates that pharmaceutical companies pay. And many payers prioritize these rebates to lower premiums instead of offering low copays for chronic medications such as insulin.
“It’s why only one in four people using Medicare Part D, and one in five with commercial plans, have coverage for Insulin Lispro injection. That will not change until payers prioritize providing consistent, affordable insulin copays,” she added.
However, Ms. Barnhizer also noted, “It is not unusual for pharmacies to not stock a medicine. Any pharmacy can place an order for Insulin Lispro injection, with delivery in 1-2 days. All major U.S. wholesalers are now distributing Insulin Lispro injection.”
She also said that people who earn 400% or less of the federal poverty level may be eligible for free insulin, and that Lilly can provide free insulin to anyone in emergency situations. (Novo Nordisk offers that as well.)
Asked why Lilly does not simply lower the price of all their insulins, Ms. Barnhizer responded: “Cutting the list prices would significantly disrupt access to branded insulins, which thousands of insured patients depend on. Launching lower-priced insulin options is a less disruptive approach to help reduce the amount people pay at the pharmacy for people who need the help.”
Government role needed
In addition to the recommendations for physicians and their institutions, Dr. Rajkumar listed several potential policy-level solutions:
1. At the state and federal level, regulations should protect against excessive drug launch prices through the same type of value-based pricing approaches used in other developed countries. “Capping the maximum price increases to the rate of inflation is needed and can happen only through state and/or federal legislation,” he wrote.
Although some may see this as antithetical to “free market” economics, Dr. Rajkumar points out that, in the case of many prescription drugs, including insulin, “we not only have an unregulated monopoly, but it’s a prolonged unregulated monopoly for a lifesaving product, not a luxury item.”
“When you grant monopoly protection and put a barrier on competition, that’s not a free market. People have always had regulations on monopolies. Unregulated monopoly is a recipe for high prices. You have to have some regulation that protects citizens from exploitation.”
And here, he believes, the United States could adopt price negotiations as practiced in Europe and other parts of the world, but which are currently forbidden in the United States.
“Other countries negotiate the price in exchange for monopoly protection. You don’t have to reinvent the wheel,” he said.
2. Reform of the regulatory and legal processes to ease the path for approval of generics and biosimilars to enter the market. This could include reciprocal approval so that biosimilars approved in Canada or the European Union could automatically be granted FDA approval in the United States.
3. Reform of the patent system to prevent overpatenting and patent abuse, by capping patent life to 7-10 years and forbidding use of additional patents as a way of prolonging market exclusivity.
To this point, Barnhizer pointed out that “none of the Lilly insulins are patent protected. Our most commonly used insulin, Humalog U-100, lost patent protection in 2014.”
4. A nongovernmental agency should oversee pricing and make recommendations to Medicare and insurers on the maximum price of new and existing drugs, including insulin. One body poised to do that work is the Institute for Clinical and Economic Review, which receives 77% of its funding from nonprofit foundations. “I have worked with them and they are the best there is,” Dr. Rajkumar said.
5. Any rebates paid by manufacturers to PBMs should be transparent to all stakeholders, including patients.
6. Nonprofit generic manufacturing should be established. The Mayo Clinic has recently partnered with Intermountain Healthcare and several other organizations in creating Civica Rx, a nonprofit generic company.
7. Measures and laws that provide access to insulin in emergency situations are needed, particularly for people with type 1 diabetes.
Recent proposed and enacted legislation has been aimed at some of these goals.
The Insulin Price Reduction Act, introduced in October 2019 and just endorsed by the American Diabetes Association, would reduce insulin costs by providing incentives for manufacturers to revert to the 2006 list price of all insulins.
The Affordable Insulin Approvals Now Act, introduced in July 2019, aims to speed up approvals of generic and biosimilar insulins.
And in May 2019, the state of Colorado passed a bill to cap patient copays for insulin at $100 a month, and similar legislation has been introduced in several other states.
Dr. Rajkumar says that an overall fix will require changes at the federal level.
But, he said, they do not need to happen all at once.
“There are a number of changes that need to happen, but we can do one legislation at a time. ... I’m optimistic that something will happen. This is a national conversation. Both sides of the aisle want to do something about it. People are indeed feeling the pinch, so maybe something will get done,” he said.
Dr. Rajkumar has reported no relevant financial relationships.
This article first appeared on Medscape.com.
Mayo Clinic hematologist S. Vincent Rajkumar, MD, argues in a new commentary.
The High Cost of Insulin in the United States: An Urgent Call to Action was published in the January 2020 issue of the Mayo Clinic Proceedings by Dr. Rajkumar, professor of medicine at the Mayo Clinic, Rochester, Minn., who specializes in treating myeloma and, more recently, has become an expert in drug pricing.
He also presented the information in a YouTube video.
As has been widely reported and examined by Congress in the past few years, the cost of insulin in the United States has risen at a far higher rate than inflation. For example, the list price of a single vial of Humalog jumped from $21 in 1999 to $275 in 2019, a far higher price than anywhere else in the world.
Stories of one in four patients having to ration their insulin use because of cost, and of some dying, have fueled protests, leading to legislative efforts and to a few initiatives by some of the manufacturers to address the cost problem.
Collective advocacy
Much of the blame has been placed on the manufacturers for charging such high prices and on the pharmacy benefit managers (PBMs) – also known as “middlemen” – for incentivizing higher-priced products on formularies through rebates. Those are major factors, Dr. Rajkumar argues, but they are not the only ones.
“There is no one reason why this is happening, and no one solution. It’s very complicated. It’s multiple factors all playing together. The only way to tackle it is to really understand it 360,” he said in an interview.
This is true of drug prices overall in the United States, but insulin is a special case. The current analog formulations have not changed in more than 20 years, yet only in the past 5 years have a handful of biosimilar and generic versions started to appear from the same manufacturers as the branded products.
“Insulin is a window into what’s wrong with the pharma industry. ... It’s the best example of how the system is broken,” Dr. Rajkumar stressed.
Physicians can help ease the problem, he said, by becoming educated about drug prices, taking cost into account when prescribing, and routinely discussing prescription drug affordability with patients.
Resources such as www.goodrx.com and www.blinkhealth.com provide information about drug prices and pharmacies that offer drugs at the lowest prices.
“Doctors need to not be suspicious of biosimilars and generics,” he emphasized.
Physicians can also advocate for policies that will lower insulin prices, and their institutions can establish preferences for lower-cost biosimilars in formularies.
“Our individual and collective advocacy gives voice to the needs of our patients,” Dr. Rajkumar emphasized.
‘Everyone in the supply chain benefits’
In his commentary, Dr. Rajkumar lists six major reasons for the high cost of insulin:
1. People with type 1 diabetes are a “vulnerable population” who will die without insulin and are therefore willing to pay a high price to stay alive.
2. Just three manufacturers – Eli Lilly, Novo Nordisk, and Sanofi-Aventis – control nearly the entire insulin market in the United States, with no regulations to cap or control the prices they can charge.
3. The manufacturers continually file new patents for existing insulin products – 70 in the case of Lantus, for example – that provide additional years of monopoly protection from competition.
4. Although the Food and Drug Administration has been receptive to approving insulin biosimilars, it still requires manufacturers to go through a long and cumbersome process to obtain licensure, sometimes taking as long as 10 years.
5.PBMs, paid by insurance companies to negotiate prices with retail pharmacies and pharmaceutical companies (through rebates), stand to benefit from higher, not lower, list prices.
6. Pharmaceutical companies have vast lobbying power.
In regard to the fifth point, about PBMs, Dr. Rajkumar said, “It’s not just the PBMs – it’s the whole supply chain. It’s hard to put a finger on the source of the problem. There’s no transparency in any of the arrangements for you to know why only certain drugs are on a given formulary of an insurance company or PBM. But we do know that, in general, the whole supply chain benefits from the higher list price. Everyone.”
‘Authorized generic’ insulins
That is why Dr. Rajkumar is not convinced that Eli Lilly’s recent launch of half-priced “authorized generic” insulins – first the Lispro injection in March 2019, and then two combination pen products in January 2020 – or Novo Nordisk’s My$99Insulin program and “follow-on” authorized generic versions of Novolog and NovoLog Mix, launched Jan. 2, 2020, will have a huge impact.
“It’s common sense. If Apple made the same iPhone for two different prices, who would pay the full price? It gives you a window into asking what is wrong with the system that allows that? To pay for the higher-priced product, somebody is being paid,” he said.
Indeed, in December 2019, the offices of Sen. Elizabeth Warren (D-MA) and Sen. Richard Blumenthal (D-CT) issued a report from a survey of 400 pharmacies nationwide that found that 83% of the less expensive authorized generic Insulin Lispro was not in stock.
More than two-thirds of pharmacies reported they could not order the product.
“Eli Lilly has failed to take consequential steps – such as simply lowering the list price of Humalog, as it has in foreign markets – to provide lower-cost access to this important diabetes drug,” according to the senators’ report, which concludes by urging Eli Lilly to lower the list price of its insulin and calling for Congress to take steps to enact systemic change to reduce drug prices nationwide.
Asked for comment, Dani Barnhizer, Eli Lilly’s manager of global diabetes communications, said, “Like Senators Warren and Blumenthal, Lilly would like to see even broader use of Insulin Lispro injection because it’s a real solution that can lower copays for people living with diabetes.”
“But the Senators’ paper failed to identify the system challenges that have inhibited access to this lower list price product,” Ms. Barnhizer said. “Payers determine an individual’s premiums and copays, which are subsidized by rebates that pharmaceutical companies pay. And many payers prioritize these rebates to lower premiums instead of offering low copays for chronic medications such as insulin.
“It’s why only one in four people using Medicare Part D, and one in five with commercial plans, have coverage for Insulin Lispro injection. That will not change until payers prioritize providing consistent, affordable insulin copays,” she added.
However, Ms. Barnhizer also noted, “It is not unusual for pharmacies to not stock a medicine. Any pharmacy can place an order for Insulin Lispro injection, with delivery in 1-2 days. All major U.S. wholesalers are now distributing Insulin Lispro injection.”
She also said that people who earn 400% or less of the federal poverty level may be eligible for free insulin, and that Lilly can provide free insulin to anyone in emergency situations. (Novo Nordisk offers that as well.)
Asked why Lilly does not simply lower the price of all their insulins, Ms. Barnhizer responded: “Cutting the list prices would significantly disrupt access to branded insulins, which thousands of insured patients depend on. Launching lower-priced insulin options is a less disruptive approach to help reduce the amount people pay at the pharmacy for people who need the help.”
Government role needed
In addition to the recommendations for physicians and their institutions, Dr. Rajkumar listed several potential policy-level solutions:
1. At the state and federal level, regulations should protect against excessive drug launch prices through the same type of value-based pricing approaches used in other developed countries. “Capping the maximum price increases to the rate of inflation is needed and can happen only through state and/or federal legislation,” he wrote.
Although some may see this as antithetical to “free market” economics, Dr. Rajkumar points out that, in the case of many prescription drugs, including insulin, “we not only have an unregulated monopoly, but it’s a prolonged unregulated monopoly for a lifesaving product, not a luxury item.”
“When you grant monopoly protection and put a barrier on competition, that’s not a free market. People have always had regulations on monopolies. Unregulated monopoly is a recipe for high prices. You have to have some regulation that protects citizens from exploitation.”
And here, he believes, the United States could adopt price negotiations as practiced in Europe and other parts of the world, but which are currently forbidden in the United States.
“Other countries negotiate the price in exchange for monopoly protection. You don’t have to reinvent the wheel,” he said.
2. Reform of the regulatory and legal processes to ease the path for approval of generics and biosimilars to enter the market. This could include reciprocal approval so that biosimilars approved in Canada or the European Union could automatically be granted FDA approval in the United States.
3. Reform of the patent system to prevent overpatenting and patent abuse, by capping patent life to 7-10 years and forbidding use of additional patents as a way of prolonging market exclusivity.
To this point, Barnhizer pointed out that “none of the Lilly insulins are patent protected. Our most commonly used insulin, Humalog U-100, lost patent protection in 2014.”
4. A nongovernmental agency should oversee pricing and make recommendations to Medicare and insurers on the maximum price of new and existing drugs, including insulin. One body poised to do that work is the Institute for Clinical and Economic Review, which receives 77% of its funding from nonprofit foundations. “I have worked with them and they are the best there is,” Dr. Rajkumar said.
5. Any rebates paid by manufacturers to PBMs should be transparent to all stakeholders, including patients.
6. Nonprofit generic manufacturing should be established. The Mayo Clinic has recently partnered with Intermountain Healthcare and several other organizations in creating Civica Rx, a nonprofit generic company.
7. Measures and laws that provide access to insulin in emergency situations are needed, particularly for people with type 1 diabetes.
Recent proposed and enacted legislation has been aimed at some of these goals.
The Insulin Price Reduction Act, introduced in October 2019 and just endorsed by the American Diabetes Association, would reduce insulin costs by providing incentives for manufacturers to revert to the 2006 list price of all insulins.
The Affordable Insulin Approvals Now Act, introduced in July 2019, aims to speed up approvals of generic and biosimilar insulins.
And in May 2019, the state of Colorado passed a bill to cap patient copays for insulin at $100 a month, and similar legislation has been introduced in several other states.
Dr. Rajkumar says that an overall fix will require changes at the federal level.
But, he said, they do not need to happen all at once.
“There are a number of changes that need to happen, but we can do one legislation at a time. ... I’m optimistic that something will happen. This is a national conversation. Both sides of the aisle want to do something about it. People are indeed feeling the pinch, so maybe something will get done,” he said.
Dr. Rajkumar has reported no relevant financial relationships.
This article first appeared on Medscape.com.
Mayo Clinic hematologist S. Vincent Rajkumar, MD, argues in a new commentary.
The High Cost of Insulin in the United States: An Urgent Call to Action was published in the January 2020 issue of the Mayo Clinic Proceedings by Dr. Rajkumar, professor of medicine at the Mayo Clinic, Rochester, Minn., who specializes in treating myeloma and, more recently, has become an expert in drug pricing.
He also presented the information in a YouTube video.
As has been widely reported and examined by Congress in the past few years, the cost of insulin in the United States has risen at a far higher rate than inflation. For example, the list price of a single vial of Humalog jumped from $21 in 1999 to $275 in 2019, a far higher price than anywhere else in the world.
Stories of one in four patients having to ration their insulin use because of cost, and of some dying, have fueled protests, leading to legislative efforts and to a few initiatives by some of the manufacturers to address the cost problem.
Collective advocacy
Much of the blame has been placed on the manufacturers for charging such high prices and on the pharmacy benefit managers (PBMs) – also known as “middlemen” – for incentivizing higher-priced products on formularies through rebates. Those are major factors, Dr. Rajkumar argues, but they are not the only ones.
“There is no one reason why this is happening, and no one solution. It’s very complicated. It’s multiple factors all playing together. The only way to tackle it is to really understand it 360,” he said in an interview.
This is true of drug prices overall in the United States, but insulin is a special case. The current analog formulations have not changed in more than 20 years, yet only in the past 5 years have a handful of biosimilar and generic versions started to appear from the same manufacturers as the branded products.
“Insulin is a window into what’s wrong with the pharma industry. ... It’s the best example of how the system is broken,” Dr. Rajkumar stressed.
Physicians can help ease the problem, he said, by becoming educated about drug prices, taking cost into account when prescribing, and routinely discussing prescription drug affordability with patients.
Resources such as www.goodrx.com and www.blinkhealth.com provide information about drug prices and pharmacies that offer drugs at the lowest prices.
“Doctors need to not be suspicious of biosimilars and generics,” he emphasized.
Physicians can also advocate for policies that will lower insulin prices, and their institutions can establish preferences for lower-cost biosimilars in formularies.
“Our individual and collective advocacy gives voice to the needs of our patients,” Dr. Rajkumar emphasized.
‘Everyone in the supply chain benefits’
In his commentary, Dr. Rajkumar lists six major reasons for the high cost of insulin:
1. People with type 1 diabetes are a “vulnerable population” who will die without insulin and are therefore willing to pay a high price to stay alive.
2. Just three manufacturers – Eli Lilly, Novo Nordisk, and Sanofi-Aventis – control nearly the entire insulin market in the United States, with no regulations to cap or control the prices they can charge.
3. The manufacturers continually file new patents for existing insulin products – 70 in the case of Lantus, for example – that provide additional years of monopoly protection from competition.
4. Although the Food and Drug Administration has been receptive to approving insulin biosimilars, it still requires manufacturers to go through a long and cumbersome process to obtain licensure, sometimes taking as long as 10 years.
5.PBMs, paid by insurance companies to negotiate prices with retail pharmacies and pharmaceutical companies (through rebates), stand to benefit from higher, not lower, list prices.
6. Pharmaceutical companies have vast lobbying power.
In regard to the fifth point, about PBMs, Dr. Rajkumar said, “It’s not just the PBMs – it’s the whole supply chain. It’s hard to put a finger on the source of the problem. There’s no transparency in any of the arrangements for you to know why only certain drugs are on a given formulary of an insurance company or PBM. But we do know that, in general, the whole supply chain benefits from the higher list price. Everyone.”
‘Authorized generic’ insulins
That is why Dr. Rajkumar is not convinced that Eli Lilly’s recent launch of half-priced “authorized generic” insulins – first the Lispro injection in March 2019, and then two combination pen products in January 2020 – or Novo Nordisk’s My$99Insulin program and “follow-on” authorized generic versions of Novolog and NovoLog Mix, launched Jan. 2, 2020, will have a huge impact.
“It’s common sense. If Apple made the same iPhone for two different prices, who would pay the full price? It gives you a window into asking what is wrong with the system that allows that? To pay for the higher-priced product, somebody is being paid,” he said.
Indeed, in December 2019, the offices of Sen. Elizabeth Warren (D-MA) and Sen. Richard Blumenthal (D-CT) issued a report from a survey of 400 pharmacies nationwide that found that 83% of the less expensive authorized generic Insulin Lispro was not in stock.
More than two-thirds of pharmacies reported they could not order the product.
“Eli Lilly has failed to take consequential steps – such as simply lowering the list price of Humalog, as it has in foreign markets – to provide lower-cost access to this important diabetes drug,” according to the senators’ report, which concludes by urging Eli Lilly to lower the list price of its insulin and calling for Congress to take steps to enact systemic change to reduce drug prices nationwide.
Asked for comment, Dani Barnhizer, Eli Lilly’s manager of global diabetes communications, said, “Like Senators Warren and Blumenthal, Lilly would like to see even broader use of Insulin Lispro injection because it’s a real solution that can lower copays for people living with diabetes.”
“But the Senators’ paper failed to identify the system challenges that have inhibited access to this lower list price product,” Ms. Barnhizer said. “Payers determine an individual’s premiums and copays, which are subsidized by rebates that pharmaceutical companies pay. And many payers prioritize these rebates to lower premiums instead of offering low copays for chronic medications such as insulin.
“It’s why only one in four people using Medicare Part D, and one in five with commercial plans, have coverage for Insulin Lispro injection. That will not change until payers prioritize providing consistent, affordable insulin copays,” she added.
However, Ms. Barnhizer also noted, “It is not unusual for pharmacies to not stock a medicine. Any pharmacy can place an order for Insulin Lispro injection, with delivery in 1-2 days. All major U.S. wholesalers are now distributing Insulin Lispro injection.”
She also said that people who earn 400% or less of the federal poverty level may be eligible for free insulin, and that Lilly can provide free insulin to anyone in emergency situations. (Novo Nordisk offers that as well.)
Asked why Lilly does not simply lower the price of all their insulins, Ms. Barnhizer responded: “Cutting the list prices would significantly disrupt access to branded insulins, which thousands of insured patients depend on. Launching lower-priced insulin options is a less disruptive approach to help reduce the amount people pay at the pharmacy for people who need the help.”
Government role needed
In addition to the recommendations for physicians and their institutions, Dr. Rajkumar listed several potential policy-level solutions:
1. At the state and federal level, regulations should protect against excessive drug launch prices through the same type of value-based pricing approaches used in other developed countries. “Capping the maximum price increases to the rate of inflation is needed and can happen only through state and/or federal legislation,” he wrote.
Although some may see this as antithetical to “free market” economics, Dr. Rajkumar points out that, in the case of many prescription drugs, including insulin, “we not only have an unregulated monopoly, but it’s a prolonged unregulated monopoly for a lifesaving product, not a luxury item.”
“When you grant monopoly protection and put a barrier on competition, that’s not a free market. People have always had regulations on monopolies. Unregulated monopoly is a recipe for high prices. You have to have some regulation that protects citizens from exploitation.”
And here, he believes, the United States could adopt price negotiations as practiced in Europe and other parts of the world, but which are currently forbidden in the United States.
“Other countries negotiate the price in exchange for monopoly protection. You don’t have to reinvent the wheel,” he said.
2. Reform of the regulatory and legal processes to ease the path for approval of generics and biosimilars to enter the market. This could include reciprocal approval so that biosimilars approved in Canada or the European Union could automatically be granted FDA approval in the United States.
3. Reform of the patent system to prevent overpatenting and patent abuse, by capping patent life to 7-10 years and forbidding use of additional patents as a way of prolonging market exclusivity.
To this point, Barnhizer pointed out that “none of the Lilly insulins are patent protected. Our most commonly used insulin, Humalog U-100, lost patent protection in 2014.”
4. A nongovernmental agency should oversee pricing and make recommendations to Medicare and insurers on the maximum price of new and existing drugs, including insulin. One body poised to do that work is the Institute for Clinical and Economic Review, which receives 77% of its funding from nonprofit foundations. “I have worked with them and they are the best there is,” Dr. Rajkumar said.
5. Any rebates paid by manufacturers to PBMs should be transparent to all stakeholders, including patients.
6. Nonprofit generic manufacturing should be established. The Mayo Clinic has recently partnered with Intermountain Healthcare and several other organizations in creating Civica Rx, a nonprofit generic company.
7. Measures and laws that provide access to insulin in emergency situations are needed, particularly for people with type 1 diabetes.
Recent proposed and enacted legislation has been aimed at some of these goals.
The Insulin Price Reduction Act, introduced in October 2019 and just endorsed by the American Diabetes Association, would reduce insulin costs by providing incentives for manufacturers to revert to the 2006 list price of all insulins.
The Affordable Insulin Approvals Now Act, introduced in July 2019, aims to speed up approvals of generic and biosimilar insulins.
And in May 2019, the state of Colorado passed a bill to cap patient copays for insulin at $100 a month, and similar legislation has been introduced in several other states.
Dr. Rajkumar says that an overall fix will require changes at the federal level.
But, he said, they do not need to happen all at once.
“There are a number of changes that need to happen, but we can do one legislation at a time. ... I’m optimistic that something will happen. This is a national conversation. Both sides of the aisle want to do something about it. People are indeed feeling the pinch, so maybe something will get done,” he said.
Dr. Rajkumar has reported no relevant financial relationships.
This article first appeared on Medscape.com.
FDA approves CV disease benefit for once-weekly semaglutide
(Ozempic, Novo Nordisk) in the treatment of type 2 diabetes and has added new trial data information to the label of the oral version (Rybelsus, Novo Nordisk) pertaining to CV safety.
The agency expanded the once-weekly injectable semaglutide’s label to include an indication for reducing the risk for major adverse cardiovascular events (MACE), including CV death, nonfatal myocardial infarction (MI), or nonfatal stroke, in adults with type 2 diabetes who have established CV disease.
Initially approved for the treatment of type 2 diabetes in adults in December 2017, once-weekly subcutaneously injectable semaglutide comes in 0.5-mg and 1.0-mg doses in a dedicated prefilled pen device.
The approval for the new indication was based on data from the 2-year randomized Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN 6), in which injectable semaglutide or placebo was added to standard of care in 3,297 adults with type 2 diabetes and established CV disease.
As reported by Medscape Medical News in September 2016, patients who underwent treatment with one of the two doses of semaglutide had a significant 26% lower risk for the primary composite outcome of first occurrence of CV death, nonfatal MI, or nonfatal stroke, compared with those who received placebo.
The reduced CV risk was driven primarily by significant reductions in nonfatal stroke and nonfatal MI (39% and 26%, respectively). There was no difference in CV death between drug and placebo groups. Gastrointestinal adverse events were more frequent with semaglutide than placebo, with the majority occurring during the first 30 weeks.
The oral semaglutide formulation, taken daily in 7-mg or 14-mg doses, was approved for the treatment of type 2 diabetes in September 2019, the first orally available GLP-1 agonist.
Now, the FDA has updated the prescribing information in the clinical studies section (section 14) to include results from the randomized, placebo-controlled, 3,183-subject Trial Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects With Type 2 Diabetes (PIONEER 6), reported in June 2019, which found a nonsignificant 21% reduction in three-component MACE with oral semaglutide. The addition to the label for Rybelsus is with regard to CV safety, not benefit.
SOUL: Large ongoing CV outcomes trial for oral semaglutide
In June 2019, Novo Nordisk initiated a larger CV outcomes trial of oral semaglutide, A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes (SOUL). The trial, which includes 9,642 adults with type 2 diabetes and established CV disease, is further investigating the drug’s effects on the incidence of MACE. The estimated completion date is July 2024.
Semaglutide joins a growing list of drugs approved for treating type 2 diabetes that have been granted additional label indications for benefits beyond the lowering of glucose.
These include Novo Nordisk’s other injectable GLP-1 agonist, liraglutide (Victoza), additionally approved for reducing CV events in high-risk patients with type 2 diabetes, and the sodium-glucose transport 2 inhibitors empagliflozin (Jardiance, Boehringer Ingelheim/Lilly), for reducing CV death; canagliflozin (Invokana, Janssen), for reducing major adverse CV events,; kidney disease, CV death, and heart failure hospitalization; and dapagliflozin (Farxiga, AstraZeneca), for reducing heart failure hospitalization.
Recently, in an exclusive Medscape Medical News article, some experts questioned the design of these CV outcomes trials, suggesting that imbalances in glycemic control, blood pressure, and diuretic use between treatment and placebo arms could have biased the CV and renal outcomes of the trials in favor of the study drugs
A version of this story originally appeared on Medscape.com.
(Ozempic, Novo Nordisk) in the treatment of type 2 diabetes and has added new trial data information to the label of the oral version (Rybelsus, Novo Nordisk) pertaining to CV safety.
The agency expanded the once-weekly injectable semaglutide’s label to include an indication for reducing the risk for major adverse cardiovascular events (MACE), including CV death, nonfatal myocardial infarction (MI), or nonfatal stroke, in adults with type 2 diabetes who have established CV disease.
Initially approved for the treatment of type 2 diabetes in adults in December 2017, once-weekly subcutaneously injectable semaglutide comes in 0.5-mg and 1.0-mg doses in a dedicated prefilled pen device.
The approval for the new indication was based on data from the 2-year randomized Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN 6), in which injectable semaglutide or placebo was added to standard of care in 3,297 adults with type 2 diabetes and established CV disease.
As reported by Medscape Medical News in September 2016, patients who underwent treatment with one of the two doses of semaglutide had a significant 26% lower risk for the primary composite outcome of first occurrence of CV death, nonfatal MI, or nonfatal stroke, compared with those who received placebo.
The reduced CV risk was driven primarily by significant reductions in nonfatal stroke and nonfatal MI (39% and 26%, respectively). There was no difference in CV death between drug and placebo groups. Gastrointestinal adverse events were more frequent with semaglutide than placebo, with the majority occurring during the first 30 weeks.
The oral semaglutide formulation, taken daily in 7-mg or 14-mg doses, was approved for the treatment of type 2 diabetes in September 2019, the first orally available GLP-1 agonist.
Now, the FDA has updated the prescribing information in the clinical studies section (section 14) to include results from the randomized, placebo-controlled, 3,183-subject Trial Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects With Type 2 Diabetes (PIONEER 6), reported in June 2019, which found a nonsignificant 21% reduction in three-component MACE with oral semaglutide. The addition to the label for Rybelsus is with regard to CV safety, not benefit.
SOUL: Large ongoing CV outcomes trial for oral semaglutide
In June 2019, Novo Nordisk initiated a larger CV outcomes trial of oral semaglutide, A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes (SOUL). The trial, which includes 9,642 adults with type 2 diabetes and established CV disease, is further investigating the drug’s effects on the incidence of MACE. The estimated completion date is July 2024.
Semaglutide joins a growing list of drugs approved for treating type 2 diabetes that have been granted additional label indications for benefits beyond the lowering of glucose.
These include Novo Nordisk’s other injectable GLP-1 agonist, liraglutide (Victoza), additionally approved for reducing CV events in high-risk patients with type 2 diabetes, and the sodium-glucose transport 2 inhibitors empagliflozin (Jardiance, Boehringer Ingelheim/Lilly), for reducing CV death; canagliflozin (Invokana, Janssen), for reducing major adverse CV events,; kidney disease, CV death, and heart failure hospitalization; and dapagliflozin (Farxiga, AstraZeneca), for reducing heart failure hospitalization.
Recently, in an exclusive Medscape Medical News article, some experts questioned the design of these CV outcomes trials, suggesting that imbalances in glycemic control, blood pressure, and diuretic use between treatment and placebo arms could have biased the CV and renal outcomes of the trials in favor of the study drugs
A version of this story originally appeared on Medscape.com.
(Ozempic, Novo Nordisk) in the treatment of type 2 diabetes and has added new trial data information to the label of the oral version (Rybelsus, Novo Nordisk) pertaining to CV safety.
The agency expanded the once-weekly injectable semaglutide’s label to include an indication for reducing the risk for major adverse cardiovascular events (MACE), including CV death, nonfatal myocardial infarction (MI), or nonfatal stroke, in adults with type 2 diabetes who have established CV disease.
Initially approved for the treatment of type 2 diabetes in adults in December 2017, once-weekly subcutaneously injectable semaglutide comes in 0.5-mg and 1.0-mg doses in a dedicated prefilled pen device.
The approval for the new indication was based on data from the 2-year randomized Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN 6), in which injectable semaglutide or placebo was added to standard of care in 3,297 adults with type 2 diabetes and established CV disease.
As reported by Medscape Medical News in September 2016, patients who underwent treatment with one of the two doses of semaglutide had a significant 26% lower risk for the primary composite outcome of first occurrence of CV death, nonfatal MI, or nonfatal stroke, compared with those who received placebo.
The reduced CV risk was driven primarily by significant reductions in nonfatal stroke and nonfatal MI (39% and 26%, respectively). There was no difference in CV death between drug and placebo groups. Gastrointestinal adverse events were more frequent with semaglutide than placebo, with the majority occurring during the first 30 weeks.
The oral semaglutide formulation, taken daily in 7-mg or 14-mg doses, was approved for the treatment of type 2 diabetes in September 2019, the first orally available GLP-1 agonist.
Now, the FDA has updated the prescribing information in the clinical studies section (section 14) to include results from the randomized, placebo-controlled, 3,183-subject Trial Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects With Type 2 Diabetes (PIONEER 6), reported in June 2019, which found a nonsignificant 21% reduction in three-component MACE with oral semaglutide. The addition to the label for Rybelsus is with regard to CV safety, not benefit.
SOUL: Large ongoing CV outcomes trial for oral semaglutide
In June 2019, Novo Nordisk initiated a larger CV outcomes trial of oral semaglutide, A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes (SOUL). The trial, which includes 9,642 adults with type 2 diabetes and established CV disease, is further investigating the drug’s effects on the incidence of MACE. The estimated completion date is July 2024.
Semaglutide joins a growing list of drugs approved for treating type 2 diabetes that have been granted additional label indications for benefits beyond the lowering of glucose.
These include Novo Nordisk’s other injectable GLP-1 agonist, liraglutide (Victoza), additionally approved for reducing CV events in high-risk patients with type 2 diabetes, and the sodium-glucose transport 2 inhibitors empagliflozin (Jardiance, Boehringer Ingelheim/Lilly), for reducing CV death; canagliflozin (Invokana, Janssen), for reducing major adverse CV events,; kidney disease, CV death, and heart failure hospitalization; and dapagliflozin (Farxiga, AstraZeneca), for reducing heart failure hospitalization.
Recently, in an exclusive Medscape Medical News article, some experts questioned the design of these CV outcomes trials, suggesting that imbalances in glycemic control, blood pressure, and diuretic use between treatment and placebo arms could have biased the CV and renal outcomes of the trials in favor of the study drugs
A version of this story originally appeared on Medscape.com.
Sarcopenia associated with increased cardiometabolic risk
LOS ANGELES –
“Loss of lean body mass and function with aging decreases the amount of metabolically active tissue, which can lead to insulin resistance,” Elena Volpi, MD, said at the World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease. “Insulin resistance reduces muscle protein anabolism and accelerates sarcopenia, perpetuating a vicious cycle.”
Sarcopenia, the involuntary loss of muscle mass and function that occurs with aging, is an ICD-10 codable condition that can be diagnosed by measuring muscle strength and quality, said Dr. Volpi, director of the Sealy Center on Aging at the University of Texas Medical Branch at Galveston. In the Health, Aging and Body Composition Study (Health ABC), researchers followed 2,292 relatively healthy adults aged 70-79 years for an average of 4.9 years (J Gerontol A Biol Sci Med. 2006;61[1]:72-7). The researchers used isokinetic dynamometry to measure knee extension strength, isometric dynamometry to measure grip strength, CT scan to measure thigh muscle area, and dual X-ray absorptiometry to determine leg and arm lean soft-tissue mass. “Those individuals who started with the highest levels of muscle strength had the greatest survival, while those who had the lowest levels of muscle strength died earlier,” said Dr. Volpi, who was not affiliated with the study. “That was true for both men and women.”
More recently, researchers conducted a pooled analysis of nine cohort studies involving 34,485 community-dwelling older individuals who were tested with gait speed and followed for 6-21 years (JAMA. 2011;305[1]:50-8). They found that a higher gait speed was associated with higher survival at 5 and 10 years (P less than .001). “Muscle mass also appears to be associated in part with mortality and survival, although the association is not as strong as measures of strength and gait speed,” Dr. Volpi said.
Data from the 2009 Korea National Health and Nutrition Examination Survey of 1,537 participants, aged 65 years and older, found that sarcopenia is independently associated with cardiovascular disease (PLoS One. 2013 Mar 22. doi: 10.1371/journal.pone.0060119). Most of the risk factors for cardiovascular disease – such as age, waist circumference, body mass index, fasting plasma glucose, and total cholesterol – showed significant negative correlations with the ratio between appendicular skeletal muscle mass and body weight. Multiple logistic regression analysis demonstrated that sarcopenia was associated with cardiovascular disease, independent of other well-documented risk factors, renal function, and medications (odds ratio, 1.77; P = .025).
In addition, data from the British Regional Heart Study, which followed 4,252 older men for a mean of 11.3 years, found an association of sarcopenia and adiposity with cardiovascular mortality and all-cause mortality (J Am Geriatr Soc. 2014;62[2]:253-60). Specifically, all-cause mortality risk was significantly greater in men in the sarcopenic and obese groups (HRs, 1.41 and 1.21, respectively), compared with those in the optimal reference group, with the highest risk in sarcopenic obese individuals (HR, 1.72) after adjustment for lifestyle characteristics.
“Diabetes also accelerates loss of lean body mass in older adults,” added Dr. Volpi. “Data from the Health ABC study showed that individuals who did not have diabetes at the beginning of the 6-year observation period ... lost the least amount of muscle, compared with those who had undiagnosed or already diagnosed diabetes.”
The precise way in which sarcopenia is linked to metabolic disease remains elusive, she continued, but current evidence suggests that sarcopenia is characterized by a reduction in the protein synthetic response to metabolic stimulation by amino acids, exercise, and insulin in skeletal muscle. “This reduction in the anabolic response to protein synthesis is called anabolic resistance of aging, and it is mediated by reduced acute activation of mTORC1 [mTOR complex 1] signaling,” Dr. Volpi said. “There’s another step upstream of the mTORC1, in which the amino acids and insulin have to cross the blood-muscle barrier. Amino acids need to be transported into the muscle actively, like glucose. That is an important unexplored area that may contribute to sarcopenia.”
Dr. Volpi went on to note that endothelial dysfunction underlies muscle anabolic resistance and cardiovascular risk and is likely to be a fundamental cause of both problems. Recent studies have shown that increased levels of physical activity improve endothelial function, enhance insulin sensitivity and anabolic sensitivity to nutrients, and reduce cardiovascular risk.
For example, in a cohort of 45 nonfrail older adults with a mean age of 72 years, Dr. Volpi and colleagues carried out a phase 1, double-blind, placebo-controlled, randomized clinical trial to determine if chronic essential amino acid supplementation, aerobic exercise training, or a combination of the two interventions could improve muscle mass and function by stimulating muscle protein synthesis over the course of 24 weeks (J Gerontol A Biol Sci Med Sci. 2019;74[10]:1598-604). “We found that exercise supervised three times per week on a treadmill for 6 months improved physical function in both groups randomized to exercise,” Dr. Volpi said. “Disappointingly, there was no change in total lean mass with any of the interventions. There was a decrease in fat mass with exercise alone, and no change with exercise and amino acids. [Of note is that] the individuals who were randomized to the amino acids plus exercise group had a significant increase in leg strength, whereas the others did not.”
Preliminary findings from ongoing work by Dr. Volpi and colleagues suggest that, in diabetes, muscle protein synthesis and blood flow really “are not different in response to insulin in healthy older adults and diabetic older adults because they don’t change at all. However, we did find alterations in amino acid trafficking in diabetes. We found that older individuals with type 2 diabetes had a reduction of amino acid transport and a higher intracellular amino acid concentration, compared with age-matched, healthier individuals. The intracellular amino acid clearance improved in the healthy, nondiabetic older adults with hyperinsulinemia, whereas it did not change in diabetic older adults. As a result, the net muscle protein balance improved a little in the nondiabetic patients, but did not change in the diabetic patients.”
The researchers are evaluating older patients with type 2 diabetes to see whether there are alterations in vascular reactivity and protein synthesis and whether those can be overcome by resistance-exercise training. “Preliminary results show that flow-mediated dilation can actually increase in an older diabetic patient with resistance exercise training three times a week for 3 months,” she said. “Exercise can improve both endothelial dysfunction and sarcopenia and therefore improve physical function and reduce cardiovascular risk.”
Dr. Volpi reported having no relevant disclosures.
LOS ANGELES –
“Loss of lean body mass and function with aging decreases the amount of metabolically active tissue, which can lead to insulin resistance,” Elena Volpi, MD, said at the World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease. “Insulin resistance reduces muscle protein anabolism and accelerates sarcopenia, perpetuating a vicious cycle.”
Sarcopenia, the involuntary loss of muscle mass and function that occurs with aging, is an ICD-10 codable condition that can be diagnosed by measuring muscle strength and quality, said Dr. Volpi, director of the Sealy Center on Aging at the University of Texas Medical Branch at Galveston. In the Health, Aging and Body Composition Study (Health ABC), researchers followed 2,292 relatively healthy adults aged 70-79 years for an average of 4.9 years (J Gerontol A Biol Sci Med. 2006;61[1]:72-7). The researchers used isokinetic dynamometry to measure knee extension strength, isometric dynamometry to measure grip strength, CT scan to measure thigh muscle area, and dual X-ray absorptiometry to determine leg and arm lean soft-tissue mass. “Those individuals who started with the highest levels of muscle strength had the greatest survival, while those who had the lowest levels of muscle strength died earlier,” said Dr. Volpi, who was not affiliated with the study. “That was true for both men and women.”
More recently, researchers conducted a pooled analysis of nine cohort studies involving 34,485 community-dwelling older individuals who were tested with gait speed and followed for 6-21 years (JAMA. 2011;305[1]:50-8). They found that a higher gait speed was associated with higher survival at 5 and 10 years (P less than .001). “Muscle mass also appears to be associated in part with mortality and survival, although the association is not as strong as measures of strength and gait speed,” Dr. Volpi said.
Data from the 2009 Korea National Health and Nutrition Examination Survey of 1,537 participants, aged 65 years and older, found that sarcopenia is independently associated with cardiovascular disease (PLoS One. 2013 Mar 22. doi: 10.1371/journal.pone.0060119). Most of the risk factors for cardiovascular disease – such as age, waist circumference, body mass index, fasting plasma glucose, and total cholesterol – showed significant negative correlations with the ratio between appendicular skeletal muscle mass and body weight. Multiple logistic regression analysis demonstrated that sarcopenia was associated with cardiovascular disease, independent of other well-documented risk factors, renal function, and medications (odds ratio, 1.77; P = .025).
In addition, data from the British Regional Heart Study, which followed 4,252 older men for a mean of 11.3 years, found an association of sarcopenia and adiposity with cardiovascular mortality and all-cause mortality (J Am Geriatr Soc. 2014;62[2]:253-60). Specifically, all-cause mortality risk was significantly greater in men in the sarcopenic and obese groups (HRs, 1.41 and 1.21, respectively), compared with those in the optimal reference group, with the highest risk in sarcopenic obese individuals (HR, 1.72) after adjustment for lifestyle characteristics.
“Diabetes also accelerates loss of lean body mass in older adults,” added Dr. Volpi. “Data from the Health ABC study showed that individuals who did not have diabetes at the beginning of the 6-year observation period ... lost the least amount of muscle, compared with those who had undiagnosed or already diagnosed diabetes.”
The precise way in which sarcopenia is linked to metabolic disease remains elusive, she continued, but current evidence suggests that sarcopenia is characterized by a reduction in the protein synthetic response to metabolic stimulation by amino acids, exercise, and insulin in skeletal muscle. “This reduction in the anabolic response to protein synthesis is called anabolic resistance of aging, and it is mediated by reduced acute activation of mTORC1 [mTOR complex 1] signaling,” Dr. Volpi said. “There’s another step upstream of the mTORC1, in which the amino acids and insulin have to cross the blood-muscle barrier. Amino acids need to be transported into the muscle actively, like glucose. That is an important unexplored area that may contribute to sarcopenia.”
Dr. Volpi went on to note that endothelial dysfunction underlies muscle anabolic resistance and cardiovascular risk and is likely to be a fundamental cause of both problems. Recent studies have shown that increased levels of physical activity improve endothelial function, enhance insulin sensitivity and anabolic sensitivity to nutrients, and reduce cardiovascular risk.
For example, in a cohort of 45 nonfrail older adults with a mean age of 72 years, Dr. Volpi and colleagues carried out a phase 1, double-blind, placebo-controlled, randomized clinical trial to determine if chronic essential amino acid supplementation, aerobic exercise training, or a combination of the two interventions could improve muscle mass and function by stimulating muscle protein synthesis over the course of 24 weeks (J Gerontol A Biol Sci Med Sci. 2019;74[10]:1598-604). “We found that exercise supervised three times per week on a treadmill for 6 months improved physical function in both groups randomized to exercise,” Dr. Volpi said. “Disappointingly, there was no change in total lean mass with any of the interventions. There was a decrease in fat mass with exercise alone, and no change with exercise and amino acids. [Of note is that] the individuals who were randomized to the amino acids plus exercise group had a significant increase in leg strength, whereas the others did not.”
Preliminary findings from ongoing work by Dr. Volpi and colleagues suggest that, in diabetes, muscle protein synthesis and blood flow really “are not different in response to insulin in healthy older adults and diabetic older adults because they don’t change at all. However, we did find alterations in amino acid trafficking in diabetes. We found that older individuals with type 2 diabetes had a reduction of amino acid transport and a higher intracellular amino acid concentration, compared with age-matched, healthier individuals. The intracellular amino acid clearance improved in the healthy, nondiabetic older adults with hyperinsulinemia, whereas it did not change in diabetic older adults. As a result, the net muscle protein balance improved a little in the nondiabetic patients, but did not change in the diabetic patients.”
The researchers are evaluating older patients with type 2 diabetes to see whether there are alterations in vascular reactivity and protein synthesis and whether those can be overcome by resistance-exercise training. “Preliminary results show that flow-mediated dilation can actually increase in an older diabetic patient with resistance exercise training three times a week for 3 months,” she said. “Exercise can improve both endothelial dysfunction and sarcopenia and therefore improve physical function and reduce cardiovascular risk.”
Dr. Volpi reported having no relevant disclosures.
LOS ANGELES –
“Loss of lean body mass and function with aging decreases the amount of metabolically active tissue, which can lead to insulin resistance,” Elena Volpi, MD, said at the World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease. “Insulin resistance reduces muscle protein anabolism and accelerates sarcopenia, perpetuating a vicious cycle.”
Sarcopenia, the involuntary loss of muscle mass and function that occurs with aging, is an ICD-10 codable condition that can be diagnosed by measuring muscle strength and quality, said Dr. Volpi, director of the Sealy Center on Aging at the University of Texas Medical Branch at Galveston. In the Health, Aging and Body Composition Study (Health ABC), researchers followed 2,292 relatively healthy adults aged 70-79 years for an average of 4.9 years (J Gerontol A Biol Sci Med. 2006;61[1]:72-7). The researchers used isokinetic dynamometry to measure knee extension strength, isometric dynamometry to measure grip strength, CT scan to measure thigh muscle area, and dual X-ray absorptiometry to determine leg and arm lean soft-tissue mass. “Those individuals who started with the highest levels of muscle strength had the greatest survival, while those who had the lowest levels of muscle strength died earlier,” said Dr. Volpi, who was not affiliated with the study. “That was true for both men and women.”
More recently, researchers conducted a pooled analysis of nine cohort studies involving 34,485 community-dwelling older individuals who were tested with gait speed and followed for 6-21 years (JAMA. 2011;305[1]:50-8). They found that a higher gait speed was associated with higher survival at 5 and 10 years (P less than .001). “Muscle mass also appears to be associated in part with mortality and survival, although the association is not as strong as measures of strength and gait speed,” Dr. Volpi said.
Data from the 2009 Korea National Health and Nutrition Examination Survey of 1,537 participants, aged 65 years and older, found that sarcopenia is independently associated with cardiovascular disease (PLoS One. 2013 Mar 22. doi: 10.1371/journal.pone.0060119). Most of the risk factors for cardiovascular disease – such as age, waist circumference, body mass index, fasting plasma glucose, and total cholesterol – showed significant negative correlations with the ratio between appendicular skeletal muscle mass and body weight. Multiple logistic regression analysis demonstrated that sarcopenia was associated with cardiovascular disease, independent of other well-documented risk factors, renal function, and medications (odds ratio, 1.77; P = .025).
In addition, data from the British Regional Heart Study, which followed 4,252 older men for a mean of 11.3 years, found an association of sarcopenia and adiposity with cardiovascular mortality and all-cause mortality (J Am Geriatr Soc. 2014;62[2]:253-60). Specifically, all-cause mortality risk was significantly greater in men in the sarcopenic and obese groups (HRs, 1.41 and 1.21, respectively), compared with those in the optimal reference group, with the highest risk in sarcopenic obese individuals (HR, 1.72) after adjustment for lifestyle characteristics.
“Diabetes also accelerates loss of lean body mass in older adults,” added Dr. Volpi. “Data from the Health ABC study showed that individuals who did not have diabetes at the beginning of the 6-year observation period ... lost the least amount of muscle, compared with those who had undiagnosed or already diagnosed diabetes.”
The precise way in which sarcopenia is linked to metabolic disease remains elusive, she continued, but current evidence suggests that sarcopenia is characterized by a reduction in the protein synthetic response to metabolic stimulation by amino acids, exercise, and insulin in skeletal muscle. “This reduction in the anabolic response to protein synthesis is called anabolic resistance of aging, and it is mediated by reduced acute activation of mTORC1 [mTOR complex 1] signaling,” Dr. Volpi said. “There’s another step upstream of the mTORC1, in which the amino acids and insulin have to cross the blood-muscle barrier. Amino acids need to be transported into the muscle actively, like glucose. That is an important unexplored area that may contribute to sarcopenia.”
Dr. Volpi went on to note that endothelial dysfunction underlies muscle anabolic resistance and cardiovascular risk and is likely to be a fundamental cause of both problems. Recent studies have shown that increased levels of physical activity improve endothelial function, enhance insulin sensitivity and anabolic sensitivity to nutrients, and reduce cardiovascular risk.
For example, in a cohort of 45 nonfrail older adults with a mean age of 72 years, Dr. Volpi and colleagues carried out a phase 1, double-blind, placebo-controlled, randomized clinical trial to determine if chronic essential amino acid supplementation, aerobic exercise training, or a combination of the two interventions could improve muscle mass and function by stimulating muscle protein synthesis over the course of 24 weeks (J Gerontol A Biol Sci Med Sci. 2019;74[10]:1598-604). “We found that exercise supervised three times per week on a treadmill for 6 months improved physical function in both groups randomized to exercise,” Dr. Volpi said. “Disappointingly, there was no change in total lean mass with any of the interventions. There was a decrease in fat mass with exercise alone, and no change with exercise and amino acids. [Of note is that] the individuals who were randomized to the amino acids plus exercise group had a significant increase in leg strength, whereas the others did not.”
Preliminary findings from ongoing work by Dr. Volpi and colleagues suggest that, in diabetes, muscle protein synthesis and blood flow really “are not different in response to insulin in healthy older adults and diabetic older adults because they don’t change at all. However, we did find alterations in amino acid trafficking in diabetes. We found that older individuals with type 2 diabetes had a reduction of amino acid transport and a higher intracellular amino acid concentration, compared with age-matched, healthier individuals. The intracellular amino acid clearance improved in the healthy, nondiabetic older adults with hyperinsulinemia, whereas it did not change in diabetic older adults. As a result, the net muscle protein balance improved a little in the nondiabetic patients, but did not change in the diabetic patients.”
The researchers are evaluating older patients with type 2 diabetes to see whether there are alterations in vascular reactivity and protein synthesis and whether those can be overcome by resistance-exercise training. “Preliminary results show that flow-mediated dilation can actually increase in an older diabetic patient with resistance exercise training three times a week for 3 months,” she said. “Exercise can improve both endothelial dysfunction and sarcopenia and therefore improve physical function and reduce cardiovascular risk.”
Dr. Volpi reported having no relevant disclosures.
EXPERT ANALYSIS FROM WCIRDC 2019
Bariatric surgery is most effective early in the diabetes trajectory
LOS ANGELES – In the clinical experience of Kurt GMM Alberti, DPhil, FRCP, FRCPath, The problem is, far fewer people with diabetes are being referred for the surgery than would benefit from it.
At the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease, Dr. Alberti said that only about 1% of eligible patients in the United States undergo bariatric surgery, compared with just 0.22% of eligible patients in the United Kingdom.
“Obesity is an increasing problem,” said Dr. Alberti, a senior research investigator in the section of diabetes, endocrinology, and metabolism at Imperial College, London. “The United States is leading the field [in obesity], and it doesn’t seem to be going away. This is in parallel with diabetes. According to the 2019 International Diabetes Federation’s Diabetes Atlas, the diabetes prevalence worldwide is now 463 million. It’s projected to reach 578 million by 2030 and 700 million by 2045. We have a major problem.”
Lifestyle modification with diet and exercise have been the cornerstone of diabetes therapy for more than 100 years, with only modest success. “A range of oral agents have been added [and they] certainly improve glycemic control, but few achieve lasting success, and few achieve remission,” Dr. Alberti said. Findings from DiRECT (Lancet. 2018;391:541-51) and the Look AHEAD (Action for Health in Diabetes) study (N Engl J Med. 2013;369:145-54) have shown dramatic improvements in glycemia, but only in the minority of patients who achieved weight loss of 10 kg or more. “In this group, 80% achieved remission after 2 years in DiRECT,” he said. “It is uncertain whether this can be sustained long term in real life, and how many people will respond. Major community prevention programs are under way in the U.S. and [United Kingdom], but many target individuals with prediabetes. Currently, it is unknown how successful these programs will be.”
The 2018 American Diabetes Association/European Association for the Study of Diabetes clinical guidelines state that bariatric surgery is a recommended treatment option for adults with type 2 diabetes and a body mass index of either 40.0 kg/m2 or higher (or 37.5 kg/m2 or higher in people of Asian ancestry) or 35.0-39.9 kg/m2 (32.5-37.4 kg/m2 in people of Asian ancestry) and who do not achieve durable weight loss and improvement in comorbidities with reasonable nonsurgical methods. According to Dr. Alberti, surgery should be an accepted option in people who have type 2 diabetes and a body mass index of 30 kg/m2 or higher, and priority should be given to adolescents, young adults, and those with a shorter duration of diabetes.
The main suggestive evidence in favor of bariatric surgery having an impact on diabetes comes from the Swedish Obese Subjects Study, which had a median follow-up of 10 years (J Intern Med. 2013;273[3]:219-34). In patients with diabetes at baseline, 30% were still in remission at 15 years after surgery. After 18 years, cumulative microvascular disease had fallen from 42 to 21 per 1,000 person-years, and macrovascular complications had fallen by 25%. “This was not a randomized, controlled trial, however,” Dr. Alberti said. Several of these studies have now been performed, including the STAMPEDE trial (N Engl J Med. 2017;376:641-51) and recent studies led by Geltrude Mingrone, MD, PhD, which show major glycemic benefit (Lancet. 2015;386[9997]:P964-73) with bariatric surgery.
According to Dr. Alberti, laparoscopic adjustable gastric lap band is the easiest bariatric surgery to perform but it has fallen out of favor because of lower diabetes remission rates, compared with the other procedures. Roux-en-Y gastric bypass, sleeve gastrectomy, and biliary pancreatic diversion are all in use. Slightly higher remission rates have been shown with biliary pancreatic diversion. “There have also been consistent improvements in quality of life and cardiovascular risk factors,” he said. “Long-term follow-up is still [needed], but, in general, it seems that diabetic complications are lower than in medically treated control groups, and mortality may also be lower. The real question is, what is the impact on complications? There we have a problem, because we do not have any good randomized, controlled trials covering a 10- to 20-year period, which would give us clear evidence. There is reasonable evidence from cohort studies, though.”
Added benefits of bariatric surgery include improved quality of life, decreased blood pressure, less sleep apnea, improved cardiovascular risk factors, and better musculoskeletal function. For now, though, an unmet need persists. “The problem is that far fewer people are referred for bariatric surgery than would benefit,” Dr. Alberti said. “There are several barriers to greater use of bariatric surgery in those with diabetes. These include physician attitudes, inadequate referrals, patient perceptions, lack of awareness among patients, inadequate insurance coverage, and particularly health system capacity. There is also a lack of sympathy for overweight people in some places.”
Dr. Alberti reported having no financial disclosures.
LOS ANGELES – In the clinical experience of Kurt GMM Alberti, DPhil, FRCP, FRCPath, The problem is, far fewer people with diabetes are being referred for the surgery than would benefit from it.
At the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease, Dr. Alberti said that only about 1% of eligible patients in the United States undergo bariatric surgery, compared with just 0.22% of eligible patients in the United Kingdom.
“Obesity is an increasing problem,” said Dr. Alberti, a senior research investigator in the section of diabetes, endocrinology, and metabolism at Imperial College, London. “The United States is leading the field [in obesity], and it doesn’t seem to be going away. This is in parallel with diabetes. According to the 2019 International Diabetes Federation’s Diabetes Atlas, the diabetes prevalence worldwide is now 463 million. It’s projected to reach 578 million by 2030 and 700 million by 2045. We have a major problem.”
Lifestyle modification with diet and exercise have been the cornerstone of diabetes therapy for more than 100 years, with only modest success. “A range of oral agents have been added [and they] certainly improve glycemic control, but few achieve lasting success, and few achieve remission,” Dr. Alberti said. Findings from DiRECT (Lancet. 2018;391:541-51) and the Look AHEAD (Action for Health in Diabetes) study (N Engl J Med. 2013;369:145-54) have shown dramatic improvements in glycemia, but only in the minority of patients who achieved weight loss of 10 kg or more. “In this group, 80% achieved remission after 2 years in DiRECT,” he said. “It is uncertain whether this can be sustained long term in real life, and how many people will respond. Major community prevention programs are under way in the U.S. and [United Kingdom], but many target individuals with prediabetes. Currently, it is unknown how successful these programs will be.”
The 2018 American Diabetes Association/European Association for the Study of Diabetes clinical guidelines state that bariatric surgery is a recommended treatment option for adults with type 2 diabetes and a body mass index of either 40.0 kg/m2 or higher (or 37.5 kg/m2 or higher in people of Asian ancestry) or 35.0-39.9 kg/m2 (32.5-37.4 kg/m2 in people of Asian ancestry) and who do not achieve durable weight loss and improvement in comorbidities with reasonable nonsurgical methods. According to Dr. Alberti, surgery should be an accepted option in people who have type 2 diabetes and a body mass index of 30 kg/m2 or higher, and priority should be given to adolescents, young adults, and those with a shorter duration of diabetes.
The main suggestive evidence in favor of bariatric surgery having an impact on diabetes comes from the Swedish Obese Subjects Study, which had a median follow-up of 10 years (J Intern Med. 2013;273[3]:219-34). In patients with diabetes at baseline, 30% were still in remission at 15 years after surgery. After 18 years, cumulative microvascular disease had fallen from 42 to 21 per 1,000 person-years, and macrovascular complications had fallen by 25%. “This was not a randomized, controlled trial, however,” Dr. Alberti said. Several of these studies have now been performed, including the STAMPEDE trial (N Engl J Med. 2017;376:641-51) and recent studies led by Geltrude Mingrone, MD, PhD, which show major glycemic benefit (Lancet. 2015;386[9997]:P964-73) with bariatric surgery.
According to Dr. Alberti, laparoscopic adjustable gastric lap band is the easiest bariatric surgery to perform but it has fallen out of favor because of lower diabetes remission rates, compared with the other procedures. Roux-en-Y gastric bypass, sleeve gastrectomy, and biliary pancreatic diversion are all in use. Slightly higher remission rates have been shown with biliary pancreatic diversion. “There have also been consistent improvements in quality of life and cardiovascular risk factors,” he said. “Long-term follow-up is still [needed], but, in general, it seems that diabetic complications are lower than in medically treated control groups, and mortality may also be lower. The real question is, what is the impact on complications? There we have a problem, because we do not have any good randomized, controlled trials covering a 10- to 20-year period, which would give us clear evidence. There is reasonable evidence from cohort studies, though.”
Added benefits of bariatric surgery include improved quality of life, decreased blood pressure, less sleep apnea, improved cardiovascular risk factors, and better musculoskeletal function. For now, though, an unmet need persists. “The problem is that far fewer people are referred for bariatric surgery than would benefit,” Dr. Alberti said. “There are several barriers to greater use of bariatric surgery in those with diabetes. These include physician attitudes, inadequate referrals, patient perceptions, lack of awareness among patients, inadequate insurance coverage, and particularly health system capacity. There is also a lack of sympathy for overweight people in some places.”
Dr. Alberti reported having no financial disclosures.
LOS ANGELES – In the clinical experience of Kurt GMM Alberti, DPhil, FRCP, FRCPath, The problem is, far fewer people with diabetes are being referred for the surgery than would benefit from it.
At the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease, Dr. Alberti said that only about 1% of eligible patients in the United States undergo bariatric surgery, compared with just 0.22% of eligible patients in the United Kingdom.
“Obesity is an increasing problem,” said Dr. Alberti, a senior research investigator in the section of diabetes, endocrinology, and metabolism at Imperial College, London. “The United States is leading the field [in obesity], and it doesn’t seem to be going away. This is in parallel with diabetes. According to the 2019 International Diabetes Federation’s Diabetes Atlas, the diabetes prevalence worldwide is now 463 million. It’s projected to reach 578 million by 2030 and 700 million by 2045. We have a major problem.”
Lifestyle modification with diet and exercise have been the cornerstone of diabetes therapy for more than 100 years, with only modest success. “A range of oral agents have been added [and they] certainly improve glycemic control, but few achieve lasting success, and few achieve remission,” Dr. Alberti said. Findings from DiRECT (Lancet. 2018;391:541-51) and the Look AHEAD (Action for Health in Diabetes) study (N Engl J Med. 2013;369:145-54) have shown dramatic improvements in glycemia, but only in the minority of patients who achieved weight loss of 10 kg or more. “In this group, 80% achieved remission after 2 years in DiRECT,” he said. “It is uncertain whether this can be sustained long term in real life, and how many people will respond. Major community prevention programs are under way in the U.S. and [United Kingdom], but many target individuals with prediabetes. Currently, it is unknown how successful these programs will be.”
The 2018 American Diabetes Association/European Association for the Study of Diabetes clinical guidelines state that bariatric surgery is a recommended treatment option for adults with type 2 diabetes and a body mass index of either 40.0 kg/m2 or higher (or 37.5 kg/m2 or higher in people of Asian ancestry) or 35.0-39.9 kg/m2 (32.5-37.4 kg/m2 in people of Asian ancestry) and who do not achieve durable weight loss and improvement in comorbidities with reasonable nonsurgical methods. According to Dr. Alberti, surgery should be an accepted option in people who have type 2 diabetes and a body mass index of 30 kg/m2 or higher, and priority should be given to adolescents, young adults, and those with a shorter duration of diabetes.
The main suggestive evidence in favor of bariatric surgery having an impact on diabetes comes from the Swedish Obese Subjects Study, which had a median follow-up of 10 years (J Intern Med. 2013;273[3]:219-34). In patients with diabetes at baseline, 30% were still in remission at 15 years after surgery. After 18 years, cumulative microvascular disease had fallen from 42 to 21 per 1,000 person-years, and macrovascular complications had fallen by 25%. “This was not a randomized, controlled trial, however,” Dr. Alberti said. Several of these studies have now been performed, including the STAMPEDE trial (N Engl J Med. 2017;376:641-51) and recent studies led by Geltrude Mingrone, MD, PhD, which show major glycemic benefit (Lancet. 2015;386[9997]:P964-73) with bariatric surgery.
According to Dr. Alberti, laparoscopic adjustable gastric lap band is the easiest bariatric surgery to perform but it has fallen out of favor because of lower diabetes remission rates, compared with the other procedures. Roux-en-Y gastric bypass, sleeve gastrectomy, and biliary pancreatic diversion are all in use. Slightly higher remission rates have been shown with biliary pancreatic diversion. “There have also been consistent improvements in quality of life and cardiovascular risk factors,” he said. “Long-term follow-up is still [needed], but, in general, it seems that diabetic complications are lower than in medically treated control groups, and mortality may also be lower. The real question is, what is the impact on complications? There we have a problem, because we do not have any good randomized, controlled trials covering a 10- to 20-year period, which would give us clear evidence. There is reasonable evidence from cohort studies, though.”
Added benefits of bariatric surgery include improved quality of life, decreased blood pressure, less sleep apnea, improved cardiovascular risk factors, and better musculoskeletal function. For now, though, an unmet need persists. “The problem is that far fewer people are referred for bariatric surgery than would benefit,” Dr. Alberti said. “There are several barriers to greater use of bariatric surgery in those with diabetes. These include physician attitudes, inadequate referrals, patient perceptions, lack of awareness among patients, inadequate insurance coverage, and particularly health system capacity. There is also a lack of sympathy for overweight people in some places.”
Dr. Alberti reported having no financial disclosures.
EXPERT ANALYSIS FROM WCIRDC 2019
FDA warns of possible cancer risk with lorcaserin
after results from a clinical trial assessing the drug’s safety showed a possible increased risk of cancer.
“At this time, the cause of the cancer is uncertain, and we cannot conclude that lorcaserin contributes to the cancer risk. However, we wanted to make the public aware of this potential risk,” the agency said in a press release.
The agency advised that health care providers consider whether the benefits of taking lorcaserin outweighed the potential cancer risk, and that patients currently taking the medication should talk to their providers about the risks.
“We are continuing to evaluate the clinical trial results and will communicate our final conclusions and recommendations when we have completed our review,” the FDA noted in the statement.
Lorcaserin, a serotonin 2C receptor agonist, was approved by the FDA in 2012 at a dosage of 20 mg once daily for use with a reduced-calorie diet and increased physical activity as a means to improve weight loss in adults who are obese or overweight and have at least one weight-related medical problem, such as such as hypertension, type 2 diabetes, or dyslipidemia. In July 2016, the agency approved a New Drug Application for an extended-release, once-daily formulation.
Headache, dizziness, fatigue, nausea, dry mouth, and constipation are the more common adverse effects in patients without diabetes, whereas hypoglycemia, headache, back pain, cough, and fatigue are more common in patients with diabetes. The treatment is contraindicated for pregnancy.
Lorcaserin is distributed by Eisai.*
*Correction, 1/15/2020: An earlier version of this story misstated the manufacturer of lorcaserin.
after results from a clinical trial assessing the drug’s safety showed a possible increased risk of cancer.
“At this time, the cause of the cancer is uncertain, and we cannot conclude that lorcaserin contributes to the cancer risk. However, we wanted to make the public aware of this potential risk,” the agency said in a press release.
The agency advised that health care providers consider whether the benefits of taking lorcaserin outweighed the potential cancer risk, and that patients currently taking the medication should talk to their providers about the risks.
“We are continuing to evaluate the clinical trial results and will communicate our final conclusions and recommendations when we have completed our review,” the FDA noted in the statement.
Lorcaserin, a serotonin 2C receptor agonist, was approved by the FDA in 2012 at a dosage of 20 mg once daily for use with a reduced-calorie diet and increased physical activity as a means to improve weight loss in adults who are obese or overweight and have at least one weight-related medical problem, such as such as hypertension, type 2 diabetes, or dyslipidemia. In July 2016, the agency approved a New Drug Application for an extended-release, once-daily formulation.
Headache, dizziness, fatigue, nausea, dry mouth, and constipation are the more common adverse effects in patients without diabetes, whereas hypoglycemia, headache, back pain, cough, and fatigue are more common in patients with diabetes. The treatment is contraindicated for pregnancy.
Lorcaserin is distributed by Eisai.*
*Correction, 1/15/2020: An earlier version of this story misstated the manufacturer of lorcaserin.
after results from a clinical trial assessing the drug’s safety showed a possible increased risk of cancer.
“At this time, the cause of the cancer is uncertain, and we cannot conclude that lorcaserin contributes to the cancer risk. However, we wanted to make the public aware of this potential risk,” the agency said in a press release.
The agency advised that health care providers consider whether the benefits of taking lorcaserin outweighed the potential cancer risk, and that patients currently taking the medication should talk to their providers about the risks.
“We are continuing to evaluate the clinical trial results and will communicate our final conclusions and recommendations when we have completed our review,” the FDA noted in the statement.
Lorcaserin, a serotonin 2C receptor agonist, was approved by the FDA in 2012 at a dosage of 20 mg once daily for use with a reduced-calorie diet and increased physical activity as a means to improve weight loss in adults who are obese or overweight and have at least one weight-related medical problem, such as such as hypertension, type 2 diabetes, or dyslipidemia. In July 2016, the agency approved a New Drug Application for an extended-release, once-daily formulation.
Headache, dizziness, fatigue, nausea, dry mouth, and constipation are the more common adverse effects in patients without diabetes, whereas hypoglycemia, headache, back pain, cough, and fatigue are more common in patients with diabetes. The treatment is contraindicated for pregnancy.
Lorcaserin is distributed by Eisai.*
*Correction, 1/15/2020: An earlier version of this story misstated the manufacturer of lorcaserin.
Gout rates reduced with SGLT2 inhibitors
The incidence of gout was approximately 40% lower in diabetes patients who were prescribed sodium-glucose cotransporter 2 inhibitors (SGLT2) than it was in those who were prescribed glucagonlike peptide–1 receptor (GLP-1) agonists in a population-based new-user cohort study.
Hyperuricemia is a known cause of gout and common in type 2 diabetes patients. SGLT2 inhibitors may reduce the risk of gout by preventing the reabsorption of glucose and lowering serum uric acid levels; however, the impact on gout risk remains uncertain, wrote Michael Fralick, MD, of Brigham and Women’s Hospital, Boston, and colleagues.
In a study published in the Annals of Internal Medicine, the researchers compared SGLT2 inhibitors and GLP-1 agonists in patients with type 2 diabetes to assess protection against gout.
The study population included adults with type 2 diabetes mellitus who had a new prescription for an SGTL2 inhibitor or GLP-1 agonist. The average age of the patients was 54 years; approximately half were women. Baseline characteristics were similar between the groups.
Overall, the researchers found a relative risk reduction of approximately 40% and an absolute risk reduction of approximately three fewer cases per 1,000 person-years in patients who received SGLT2 inhibitors, compared with those who received GLP-1 agonists. The incidence rate for gout in the SGLT2 and GLP-1 groups were 4.9 per 1,000 person-years and 7.8 per 1,000 person-years, respectively.
The study findings were limited by the investigators’ inability to measure potential confounding variables such as body mass index, alcohol use, and high purine diet; incomplete lab data on creatinine and hemoglobin A; and a low baseline risk for gout in the study population, the researchers noted. However, the results persisted across sensitivity analysis and, if replicated, suggest that “SGLT2 inhibitors might be an effective class of medication for the prevention of gout for patients with diabetes or metabolic disorders,” they wrote.
The study was supported in part by Brigham and Women’s Hospital; lead author Dr. Fralick disclosed funding from the Eliot Phillipson Clinician-Scientist Training Program at the University of Toronto and the Canadian Institutes of Health Research.
SOURCE: Fralick M et al. Ann Intern Med. 2020 Jan 14. doi: 10.7326/M19-2610.
The incidence of gout was approximately 40% lower in diabetes patients who were prescribed sodium-glucose cotransporter 2 inhibitors (SGLT2) than it was in those who were prescribed glucagonlike peptide–1 receptor (GLP-1) agonists in a population-based new-user cohort study.
Hyperuricemia is a known cause of gout and common in type 2 diabetes patients. SGLT2 inhibitors may reduce the risk of gout by preventing the reabsorption of glucose and lowering serum uric acid levels; however, the impact on gout risk remains uncertain, wrote Michael Fralick, MD, of Brigham and Women’s Hospital, Boston, and colleagues.
In a study published in the Annals of Internal Medicine, the researchers compared SGLT2 inhibitors and GLP-1 agonists in patients with type 2 diabetes to assess protection against gout.
The study population included adults with type 2 diabetes mellitus who had a new prescription for an SGTL2 inhibitor or GLP-1 agonist. The average age of the patients was 54 years; approximately half were women. Baseline characteristics were similar between the groups.
Overall, the researchers found a relative risk reduction of approximately 40% and an absolute risk reduction of approximately three fewer cases per 1,000 person-years in patients who received SGLT2 inhibitors, compared with those who received GLP-1 agonists. The incidence rate for gout in the SGLT2 and GLP-1 groups were 4.9 per 1,000 person-years and 7.8 per 1,000 person-years, respectively.
The study findings were limited by the investigators’ inability to measure potential confounding variables such as body mass index, alcohol use, and high purine diet; incomplete lab data on creatinine and hemoglobin A; and a low baseline risk for gout in the study population, the researchers noted. However, the results persisted across sensitivity analysis and, if replicated, suggest that “SGLT2 inhibitors might be an effective class of medication for the prevention of gout for patients with diabetes or metabolic disorders,” they wrote.
The study was supported in part by Brigham and Women’s Hospital; lead author Dr. Fralick disclosed funding from the Eliot Phillipson Clinician-Scientist Training Program at the University of Toronto and the Canadian Institutes of Health Research.
SOURCE: Fralick M et al. Ann Intern Med. 2020 Jan 14. doi: 10.7326/M19-2610.
The incidence of gout was approximately 40% lower in diabetes patients who were prescribed sodium-glucose cotransporter 2 inhibitors (SGLT2) than it was in those who were prescribed glucagonlike peptide–1 receptor (GLP-1) agonists in a population-based new-user cohort study.
Hyperuricemia is a known cause of gout and common in type 2 diabetes patients. SGLT2 inhibitors may reduce the risk of gout by preventing the reabsorption of glucose and lowering serum uric acid levels; however, the impact on gout risk remains uncertain, wrote Michael Fralick, MD, of Brigham and Women’s Hospital, Boston, and colleagues.
In a study published in the Annals of Internal Medicine, the researchers compared SGLT2 inhibitors and GLP-1 agonists in patients with type 2 diabetes to assess protection against gout.
The study population included adults with type 2 diabetes mellitus who had a new prescription for an SGTL2 inhibitor or GLP-1 agonist. The average age of the patients was 54 years; approximately half were women. Baseline characteristics were similar between the groups.
Overall, the researchers found a relative risk reduction of approximately 40% and an absolute risk reduction of approximately three fewer cases per 1,000 person-years in patients who received SGLT2 inhibitors, compared with those who received GLP-1 agonists. The incidence rate for gout in the SGLT2 and GLP-1 groups were 4.9 per 1,000 person-years and 7.8 per 1,000 person-years, respectively.
The study findings were limited by the investigators’ inability to measure potential confounding variables such as body mass index, alcohol use, and high purine diet; incomplete lab data on creatinine and hemoglobin A; and a low baseline risk for gout in the study population, the researchers noted. However, the results persisted across sensitivity analysis and, if replicated, suggest that “SGLT2 inhibitors might be an effective class of medication for the prevention of gout for patients with diabetes or metabolic disorders,” they wrote.
The study was supported in part by Brigham and Women’s Hospital; lead author Dr. Fralick disclosed funding from the Eliot Phillipson Clinician-Scientist Training Program at the University of Toronto and the Canadian Institutes of Health Research.
SOURCE: Fralick M et al. Ann Intern Med. 2020 Jan 14. doi: 10.7326/M19-2610.
FROM ANNALS OF INTERNAL MEDICINE
Key clinical point: Sodium-glucose cotransporter 2 (SGLT2) inhibitor use was associated with lower rates of gout in type 2 diabetes patients compared with glucagonlike peptide–1 (GLP-1) agonist use.
Major finding: The incidence of gout was 4.9 per 1,000 person-years in patients on SGLT2 inhibitors and 7.8 per 1,000 person-years in patients on GLP1 agonists.
Study details: The data come from a population-based cohort study of 295,907 adults with type 2 diabetes.
Disclosures: The study was supported in part by Brigham and Women’s Hospital; lead author Dr. Fralick disclosed funding from the Eliot Phillipson Clinician-Scientist Training Program at the University of Toronto and the Canadian Institutes of Health Research.
Source: Fralick M et al. Ann Intern Med. 2020 Jan 14. doi: 10.7326/M19-2610.
Treatment of heart failure with preserved ejection fraction is a work in progress
LOS ANGELES – When it comes to the optimal treatment of patients with heart failure with preserved ejection fraction and diabetes, cardiologists like Mark T. Kearney, MB ChB, MD, remain stumped.
“Over the years, the diagnosis of heart failure with preserved ejection fraction has been notoriously difficult [to treat], controversial, and ultimately involves aggressive catheterization of the heart to assess diastolic dysfunction, complex echocardiography, and invasive tests,” Dr. Kearney said at the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease. “These patients have an ejection fraction of over 50% and classic signs and symptoms of heart failure. Studies of beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers have been unsuccessful in this group of patients. We’re at the beginning of a journey in understanding this disorder, and it’s important, because more and more patients present to us with signs and symptoms of heart failure with an ejection fraction greater than 50%.”
In a recent analysis of 1,797 patients with chronic heart failure, Dr. Kearney, British Heart Foundation Professor of Cardiovascular and Diabetes Research at the Leeds (England) Institute of Cardiovascular and Metabolic Medicine, and colleagues examined whether beta-blockers and ACE inhibitors were associated with differential effects on mortality in patients with and without diabetes (Diabetes Care. 2018;41:136-42). Mean follow-up was 4 years.
For the ACE inhibitor component of the trial, the researchers correlated the dose of ramipril to outcomes and found that each milligram increase of ramipril reduced the risk of death by about 3%. “In the nondiabetic patients who did not receive an ACE inhibitor, mortality was about 60% – worse than most cancers,” Dr. Kearney said. “In patients with diabetes, there was a similar pattern. If you didn’t get an ACE inhibitor, mortality was 70%. So, if you get patients on an optimal dose of an ACE inhibitor, you improve their mortality substantially, whether they have diabetes or not.”
The beta-blocker component of the trial yielded similar results. “Among patients who did not receive a beta-blocker, the mortality was about 70% at 5 years – really terrible,” he said. “Every milligram of bisoprolol was associated with a reduction in mortality of about 9%. So, if a patient gets on an optimal dose of a beta-blocker and they have diabetes, it’s associated with prolongation of life over a year.”
Dr. Kearney said that patients often do not want to take an increased dose of a beta-blocker because of concerns about side effects, such as tiredness. “They ask me what the side effects of an increased dose would be. My answer is: ‘It will make you live longer.’ Usually, they’ll respond by agreeing to have a little bit more of the beta-blocker. The message here is, if you have a patient with ejection fraction heart failure and diabetes, get them on the optimal dose of a beta-blocker, even at the expense of an ACE inhibitor.”
In 2016, the European Society of Cardiology introduced guidelines for physicians to make a diagnosis of heart failure with preserved ejection fraction. The guidelines mandate that a diagnosis requires signs and symptoms of heart failure, elevated levels of natriuretic peptide, and echocardiographic abnormalities of cardiac structure and/or function in the presence of a left ventricular ejection fraction of 50% or more (Eur J Heart Fail. 2016;18[8]:891-975).
“Signs and symptoms of heart failure, elevated BNP [brain natriuretic peptide], and echocardiography allow us to make a diagnosis of heart failure with preserved ejection fraction,” Dr. Kearney, who is also dean of the Leeds University School of Medicine. “But we don’t know the outcome of these patients, we don’t know how to treat them, and we don’t know the impact on hospitalizations.”
In a large, unpublished cohort study conducted at Leeds, Dr. Kearney and colleagues evaluated how many patients met criteria for heart failure with reduced ejection fraction or heart failure with preserved ejection fraction after undergoing a BNP measurement. Ultimately, 959 patients met criteria. After assessment, 23% had no heart failure, 44% had heart failure with preserved ejection fraction, and 33% had heart failure with reduced ejection fraction. They found that patients with preserved ejection fraction were older (mean age, 84 years); were more likely to be female; and had less ischemia, less diabetes, and more hypertension. In addition, patients with preserved ejection fraction had significantly better survival than patients with reduced ejection fraction over 5 years follow-up.
“What was really interesting were the findings related to hospitalization,” he said. “All 959 patients accounted for 20,517 days in the hospital over 5 years, which is the equivalent of 1 patient occupying a hospital bed for 56 years. This disorder [heart failure with preserved ejection fraction], despite having a lower mortality than heart failure with reduced ejection fraction, leads to a significant burden on health care systems.”
Among patients with preserved ejection fraction, 82% were hospitalized for a noncardiovascular cause, 6.9% because of heart failure, and 11% were caused by other cardiovascular causes. Most of the hospital admissions were because of chest infections, falls, and other frailty-linked causes. “This link between systemic frailty and heart failure with preserved ejection fraction warrants further investigation,” Dr. Kearney said. “This is a major burden on patient hospital care.”
When the researchers examined outcomes in patients with and without diabetes, those with diabetes were younger, more likely to be male, and have a higher body mass index. They found that, in the presence of diabetes, mortality was increased in heart failure with preserved and reduced ejection fraction. “So, even at the age of 81 or 82, diabetes changes the pathophysiology of mortality in what was previously believed to be a benign disease,” he said.
In a subset analysis of patients with and without diabetes who were not taking a beta-blocker, there did not seem to be increased sympathetic activation in the patients with diabetes and heart failure with preserved ejection fraction, nor a difference in heart rate between the nondiabetic patients and patients with diabetes. However, among patients with heart failure with reduced ejection fraction, those with diabetes had an increased heart rate.
“Is heart failure with preserved ejection fraction in diabetes benign? I think the answer is no,” Dr. Kearney said. “It increases hospitalization and is a major burden on health care systems. What should we do? We deal with comorbidity and fall risk. It’s good old-fashioned doctoring, really. We address frailty and respiratory tract infections, but the key thing here is that we need more research.”
Dr. Kearney reported having no relevant financial disclosures.
LOS ANGELES – When it comes to the optimal treatment of patients with heart failure with preserved ejection fraction and diabetes, cardiologists like Mark T. Kearney, MB ChB, MD, remain stumped.
“Over the years, the diagnosis of heart failure with preserved ejection fraction has been notoriously difficult [to treat], controversial, and ultimately involves aggressive catheterization of the heart to assess diastolic dysfunction, complex echocardiography, and invasive tests,” Dr. Kearney said at the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease. “These patients have an ejection fraction of over 50% and classic signs and symptoms of heart failure. Studies of beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers have been unsuccessful in this group of patients. We’re at the beginning of a journey in understanding this disorder, and it’s important, because more and more patients present to us with signs and symptoms of heart failure with an ejection fraction greater than 50%.”
In a recent analysis of 1,797 patients with chronic heart failure, Dr. Kearney, British Heart Foundation Professor of Cardiovascular and Diabetes Research at the Leeds (England) Institute of Cardiovascular and Metabolic Medicine, and colleagues examined whether beta-blockers and ACE inhibitors were associated with differential effects on mortality in patients with and without diabetes (Diabetes Care. 2018;41:136-42). Mean follow-up was 4 years.
For the ACE inhibitor component of the trial, the researchers correlated the dose of ramipril to outcomes and found that each milligram increase of ramipril reduced the risk of death by about 3%. “In the nondiabetic patients who did not receive an ACE inhibitor, mortality was about 60% – worse than most cancers,” Dr. Kearney said. “In patients with diabetes, there was a similar pattern. If you didn’t get an ACE inhibitor, mortality was 70%. So, if you get patients on an optimal dose of an ACE inhibitor, you improve their mortality substantially, whether they have diabetes or not.”
The beta-blocker component of the trial yielded similar results. “Among patients who did not receive a beta-blocker, the mortality was about 70% at 5 years – really terrible,” he said. “Every milligram of bisoprolol was associated with a reduction in mortality of about 9%. So, if a patient gets on an optimal dose of a beta-blocker and they have diabetes, it’s associated with prolongation of life over a year.”
Dr. Kearney said that patients often do not want to take an increased dose of a beta-blocker because of concerns about side effects, such as tiredness. “They ask me what the side effects of an increased dose would be. My answer is: ‘It will make you live longer.’ Usually, they’ll respond by agreeing to have a little bit more of the beta-blocker. The message here is, if you have a patient with ejection fraction heart failure and diabetes, get them on the optimal dose of a beta-blocker, even at the expense of an ACE inhibitor.”
In 2016, the European Society of Cardiology introduced guidelines for physicians to make a diagnosis of heart failure with preserved ejection fraction. The guidelines mandate that a diagnosis requires signs and symptoms of heart failure, elevated levels of natriuretic peptide, and echocardiographic abnormalities of cardiac structure and/or function in the presence of a left ventricular ejection fraction of 50% or more (Eur J Heart Fail. 2016;18[8]:891-975).
“Signs and symptoms of heart failure, elevated BNP [brain natriuretic peptide], and echocardiography allow us to make a diagnosis of heart failure with preserved ejection fraction,” Dr. Kearney, who is also dean of the Leeds University School of Medicine. “But we don’t know the outcome of these patients, we don’t know how to treat them, and we don’t know the impact on hospitalizations.”
In a large, unpublished cohort study conducted at Leeds, Dr. Kearney and colleagues evaluated how many patients met criteria for heart failure with reduced ejection fraction or heart failure with preserved ejection fraction after undergoing a BNP measurement. Ultimately, 959 patients met criteria. After assessment, 23% had no heart failure, 44% had heart failure with preserved ejection fraction, and 33% had heart failure with reduced ejection fraction. They found that patients with preserved ejection fraction were older (mean age, 84 years); were more likely to be female; and had less ischemia, less diabetes, and more hypertension. In addition, patients with preserved ejection fraction had significantly better survival than patients with reduced ejection fraction over 5 years follow-up.
“What was really interesting were the findings related to hospitalization,” he said. “All 959 patients accounted for 20,517 days in the hospital over 5 years, which is the equivalent of 1 patient occupying a hospital bed for 56 years. This disorder [heart failure with preserved ejection fraction], despite having a lower mortality than heart failure with reduced ejection fraction, leads to a significant burden on health care systems.”
Among patients with preserved ejection fraction, 82% were hospitalized for a noncardiovascular cause, 6.9% because of heart failure, and 11% were caused by other cardiovascular causes. Most of the hospital admissions were because of chest infections, falls, and other frailty-linked causes. “This link between systemic frailty and heart failure with preserved ejection fraction warrants further investigation,” Dr. Kearney said. “This is a major burden on patient hospital care.”
When the researchers examined outcomes in patients with and without diabetes, those with diabetes were younger, more likely to be male, and have a higher body mass index. They found that, in the presence of diabetes, mortality was increased in heart failure with preserved and reduced ejection fraction. “So, even at the age of 81 or 82, diabetes changes the pathophysiology of mortality in what was previously believed to be a benign disease,” he said.
In a subset analysis of patients with and without diabetes who were not taking a beta-blocker, there did not seem to be increased sympathetic activation in the patients with diabetes and heart failure with preserved ejection fraction, nor a difference in heart rate between the nondiabetic patients and patients with diabetes. However, among patients with heart failure with reduced ejection fraction, those with diabetes had an increased heart rate.
“Is heart failure with preserved ejection fraction in diabetes benign? I think the answer is no,” Dr. Kearney said. “It increases hospitalization and is a major burden on health care systems. What should we do? We deal with comorbidity and fall risk. It’s good old-fashioned doctoring, really. We address frailty and respiratory tract infections, but the key thing here is that we need more research.”
Dr. Kearney reported having no relevant financial disclosures.
LOS ANGELES – When it comes to the optimal treatment of patients with heart failure with preserved ejection fraction and diabetes, cardiologists like Mark T. Kearney, MB ChB, MD, remain stumped.
“Over the years, the diagnosis of heart failure with preserved ejection fraction has been notoriously difficult [to treat], controversial, and ultimately involves aggressive catheterization of the heart to assess diastolic dysfunction, complex echocardiography, and invasive tests,” Dr. Kearney said at the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease. “These patients have an ejection fraction of over 50% and classic signs and symptoms of heart failure. Studies of beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers have been unsuccessful in this group of patients. We’re at the beginning of a journey in understanding this disorder, and it’s important, because more and more patients present to us with signs and symptoms of heart failure with an ejection fraction greater than 50%.”
In a recent analysis of 1,797 patients with chronic heart failure, Dr. Kearney, British Heart Foundation Professor of Cardiovascular and Diabetes Research at the Leeds (England) Institute of Cardiovascular and Metabolic Medicine, and colleagues examined whether beta-blockers and ACE inhibitors were associated with differential effects on mortality in patients with and without diabetes (Diabetes Care. 2018;41:136-42). Mean follow-up was 4 years.
For the ACE inhibitor component of the trial, the researchers correlated the dose of ramipril to outcomes and found that each milligram increase of ramipril reduced the risk of death by about 3%. “In the nondiabetic patients who did not receive an ACE inhibitor, mortality was about 60% – worse than most cancers,” Dr. Kearney said. “In patients with diabetes, there was a similar pattern. If you didn’t get an ACE inhibitor, mortality was 70%. So, if you get patients on an optimal dose of an ACE inhibitor, you improve their mortality substantially, whether they have diabetes or not.”
The beta-blocker component of the trial yielded similar results. “Among patients who did not receive a beta-blocker, the mortality was about 70% at 5 years – really terrible,” he said. “Every milligram of bisoprolol was associated with a reduction in mortality of about 9%. So, if a patient gets on an optimal dose of a beta-blocker and they have diabetes, it’s associated with prolongation of life over a year.”
Dr. Kearney said that patients often do not want to take an increased dose of a beta-blocker because of concerns about side effects, such as tiredness. “They ask me what the side effects of an increased dose would be. My answer is: ‘It will make you live longer.’ Usually, they’ll respond by agreeing to have a little bit more of the beta-blocker. The message here is, if you have a patient with ejection fraction heart failure and diabetes, get them on the optimal dose of a beta-blocker, even at the expense of an ACE inhibitor.”
In 2016, the European Society of Cardiology introduced guidelines for physicians to make a diagnosis of heart failure with preserved ejection fraction. The guidelines mandate that a diagnosis requires signs and symptoms of heart failure, elevated levels of natriuretic peptide, and echocardiographic abnormalities of cardiac structure and/or function in the presence of a left ventricular ejection fraction of 50% or more (Eur J Heart Fail. 2016;18[8]:891-975).
“Signs and symptoms of heart failure, elevated BNP [brain natriuretic peptide], and echocardiography allow us to make a diagnosis of heart failure with preserved ejection fraction,” Dr. Kearney, who is also dean of the Leeds University School of Medicine. “But we don’t know the outcome of these patients, we don’t know how to treat them, and we don’t know the impact on hospitalizations.”
In a large, unpublished cohort study conducted at Leeds, Dr. Kearney and colleagues evaluated how many patients met criteria for heart failure with reduced ejection fraction or heart failure with preserved ejection fraction after undergoing a BNP measurement. Ultimately, 959 patients met criteria. After assessment, 23% had no heart failure, 44% had heart failure with preserved ejection fraction, and 33% had heart failure with reduced ejection fraction. They found that patients with preserved ejection fraction were older (mean age, 84 years); were more likely to be female; and had less ischemia, less diabetes, and more hypertension. In addition, patients with preserved ejection fraction had significantly better survival than patients with reduced ejection fraction over 5 years follow-up.
“What was really interesting were the findings related to hospitalization,” he said. “All 959 patients accounted for 20,517 days in the hospital over 5 years, which is the equivalent of 1 patient occupying a hospital bed for 56 years. This disorder [heart failure with preserved ejection fraction], despite having a lower mortality than heart failure with reduced ejection fraction, leads to a significant burden on health care systems.”
Among patients with preserved ejection fraction, 82% were hospitalized for a noncardiovascular cause, 6.9% because of heart failure, and 11% were caused by other cardiovascular causes. Most of the hospital admissions were because of chest infections, falls, and other frailty-linked causes. “This link between systemic frailty and heart failure with preserved ejection fraction warrants further investigation,” Dr. Kearney said. “This is a major burden on patient hospital care.”
When the researchers examined outcomes in patients with and without diabetes, those with diabetes were younger, more likely to be male, and have a higher body mass index. They found that, in the presence of diabetes, mortality was increased in heart failure with preserved and reduced ejection fraction. “So, even at the age of 81 or 82, diabetes changes the pathophysiology of mortality in what was previously believed to be a benign disease,” he said.
In a subset analysis of patients with and without diabetes who were not taking a beta-blocker, there did not seem to be increased sympathetic activation in the patients with diabetes and heart failure with preserved ejection fraction, nor a difference in heart rate between the nondiabetic patients and patients with diabetes. However, among patients with heart failure with reduced ejection fraction, those with diabetes had an increased heart rate.
“Is heart failure with preserved ejection fraction in diabetes benign? I think the answer is no,” Dr. Kearney said. “It increases hospitalization and is a major burden on health care systems. What should we do? We deal with comorbidity and fall risk. It’s good old-fashioned doctoring, really. We address frailty and respiratory tract infections, but the key thing here is that we need more research.”
Dr. Kearney reported having no relevant financial disclosures.
EXPERT ANALYSIS FROM WCIRDC 2019
Diabetes boosts bariatric surgery complications
LAS VEGAS – compared with patients without diabetes, in an analysis of more than 550,000 patients who underwent this surgery.
The analysis also showed that among patients with diabetes undergoing bariatric surgery, those with insulin-dependent diabetes had significantly higher rates of these and other complications, compared with patients with diabetes but no insulin dependence, Andrew A. Wheeler, MD, said at a meeting presented by The Obesity Society and the American Society for Metabolic and Bariatric Surgery.
The specific factors driving these observations remain unknown, but may relate at least in part to the efficacy of glycemic control in patients during the months and weeks before surgery, said Dr. Wheeler, chief of metabolic and bariatric surgery at the University of Missouri in Columbia.
“Perioperative blood glucose control reflected in hemoglobin A1c may help us understand if certain patients with diabetes are at increased risk of surgical complications,” Dr. Wheeler said during his talk. “We need to see whether preoperative hemoglobin A1c tracks with the rate of complications,” he added in an interview. “Some surgeons will defer surgery until the level goes down, but right now, everyone uses a different level.”
The study by Dr. Wheeler and associates used data collected from essentially all the bariatric surgeries done at the roughly 840 U.S. centers accredited to do the surgery during 2015-2017 – a total of 555,239 patients – in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program run by the American College of Surgeons and the American Society for Metabolic and Bariatric Surgery. The cohort included 413,239 patients without diabetes and 136,010 with diabetes, with the remainder having an unknown status. Nearly all patients underwent either sleeve gastrectomy or gastric bypass, with significantly more patients, 74%, having sleeve gastrectomy in the group without diabetes, and 62% of those with diabetes undergoing sleeve gastrectomy.
Patients with diabetes uniformly had significantly higher rates of complications as measured by several parameters, and among those with diabetes, the complication rates were highest in those with insulin dependence. The researchers ran a multivariate analysis that controlled for many demographic and clinical variables, and found that despite these corrections, patients with diabetes, and especially those with insulin dependence, had higher relative rates of many complications that were statistically significant. In addition to the increased rates of deep surgical-site infections and 30-day ICU admissions, patients with diabetes had a 54% relatively increased rate of wound disruption, and a 29% increased relative rate of superficial surgical-site infections, compared with those without diabetes. And among patients with diabetes, those with insulin dependence had a 40% increased rate of surgical-site infections, a 74% increase in progressive renal failure, and a 39% increased rate of hospital readmission relative to patients with diabetes that was not insulin dependent, Dr. Wheeler reported.
The absolute complication rates were, in general, low. For example, the total rate of superficial plus deep surgical-site infections was less than 1% both in patients with diabetes and those without, although the rate rose above 1% in patients with insulin-dependent diabetes. The most common complication reported by Dr. Wheeler was 30-day hospital readmission, which was 4.0% in patients without diabetes, 4.8% in those with diabetes, and 6.4% in patients with insulin-dependent diabetes. The data also showed that gastric bypass led to more complications than did sleeve gastrectomy, but complications with both types of surgeries increased in patients with diabetes, compared with those without diabetes.
Dr. Wheeler had no disclosures.
SOURCE: Wheeler AA et al. Obesity Week 2019, Abstract A133.
Most bariatric surgeons believe that patients with diabetes who undergo this surgery will have more complications than will patients without diabetes, based on their anecdotal experience and findings from previous, smaller studies. But in Dr. Wheeler’s report, we see this demonstrated in an incredibly large number of patients. This is one of the first studies to use 3 years of data from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program, which included more than half a million patients.
A randomized study involving more than 18,000 cases showed that putting bariatric surgery patients on an “enhanced recovery program” before surgery and including measures that minimized insulin resistance and catabolism perioperatively led to a substantial reduction in extended length of stay (Surg Obes Relat Dis. 2019 Nov;15[11]:1977-89). In routine care, bariatric surgeons are now often routinely using “prehabilitation” to prepare patients for surgery.
Corrigan McBride, MD , is professor of surgery and director of bariatric surgery at the University of Nebraska Medical Center in Omaha. She had no disclosures. She made these comments in an interview.
Most bariatric surgeons believe that patients with diabetes who undergo this surgery will have more complications than will patients without diabetes, based on their anecdotal experience and findings from previous, smaller studies. But in Dr. Wheeler’s report, we see this demonstrated in an incredibly large number of patients. This is one of the first studies to use 3 years of data from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program, which included more than half a million patients.
A randomized study involving more than 18,000 cases showed that putting bariatric surgery patients on an “enhanced recovery program” before surgery and including measures that minimized insulin resistance and catabolism perioperatively led to a substantial reduction in extended length of stay (Surg Obes Relat Dis. 2019 Nov;15[11]:1977-89). In routine care, bariatric surgeons are now often routinely using “prehabilitation” to prepare patients for surgery.
Corrigan McBride, MD , is professor of surgery and director of bariatric surgery at the University of Nebraska Medical Center in Omaha. She had no disclosures. She made these comments in an interview.
Most bariatric surgeons believe that patients with diabetes who undergo this surgery will have more complications than will patients without diabetes, based on their anecdotal experience and findings from previous, smaller studies. But in Dr. Wheeler’s report, we see this demonstrated in an incredibly large number of patients. This is one of the first studies to use 3 years of data from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program, which included more than half a million patients.
A randomized study involving more than 18,000 cases showed that putting bariatric surgery patients on an “enhanced recovery program” before surgery and including measures that minimized insulin resistance and catabolism perioperatively led to a substantial reduction in extended length of stay (Surg Obes Relat Dis. 2019 Nov;15[11]:1977-89). In routine care, bariatric surgeons are now often routinely using “prehabilitation” to prepare patients for surgery.
Corrigan McBride, MD , is professor of surgery and director of bariatric surgery at the University of Nebraska Medical Center in Omaha. She had no disclosures. She made these comments in an interview.
LAS VEGAS – compared with patients without diabetes, in an analysis of more than 550,000 patients who underwent this surgery.
The analysis also showed that among patients with diabetes undergoing bariatric surgery, those with insulin-dependent diabetes had significantly higher rates of these and other complications, compared with patients with diabetes but no insulin dependence, Andrew A. Wheeler, MD, said at a meeting presented by The Obesity Society and the American Society for Metabolic and Bariatric Surgery.
The specific factors driving these observations remain unknown, but may relate at least in part to the efficacy of glycemic control in patients during the months and weeks before surgery, said Dr. Wheeler, chief of metabolic and bariatric surgery at the University of Missouri in Columbia.
“Perioperative blood glucose control reflected in hemoglobin A1c may help us understand if certain patients with diabetes are at increased risk of surgical complications,” Dr. Wheeler said during his talk. “We need to see whether preoperative hemoglobin A1c tracks with the rate of complications,” he added in an interview. “Some surgeons will defer surgery until the level goes down, but right now, everyone uses a different level.”
The study by Dr. Wheeler and associates used data collected from essentially all the bariatric surgeries done at the roughly 840 U.S. centers accredited to do the surgery during 2015-2017 – a total of 555,239 patients – in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program run by the American College of Surgeons and the American Society for Metabolic and Bariatric Surgery. The cohort included 413,239 patients without diabetes and 136,010 with diabetes, with the remainder having an unknown status. Nearly all patients underwent either sleeve gastrectomy or gastric bypass, with significantly more patients, 74%, having sleeve gastrectomy in the group without diabetes, and 62% of those with diabetes undergoing sleeve gastrectomy.
Patients with diabetes uniformly had significantly higher rates of complications as measured by several parameters, and among those with diabetes, the complication rates were highest in those with insulin dependence. The researchers ran a multivariate analysis that controlled for many demographic and clinical variables, and found that despite these corrections, patients with diabetes, and especially those with insulin dependence, had higher relative rates of many complications that were statistically significant. In addition to the increased rates of deep surgical-site infections and 30-day ICU admissions, patients with diabetes had a 54% relatively increased rate of wound disruption, and a 29% increased relative rate of superficial surgical-site infections, compared with those without diabetes. And among patients with diabetes, those with insulin dependence had a 40% increased rate of surgical-site infections, a 74% increase in progressive renal failure, and a 39% increased rate of hospital readmission relative to patients with diabetes that was not insulin dependent, Dr. Wheeler reported.
The absolute complication rates were, in general, low. For example, the total rate of superficial plus deep surgical-site infections was less than 1% both in patients with diabetes and those without, although the rate rose above 1% in patients with insulin-dependent diabetes. The most common complication reported by Dr. Wheeler was 30-day hospital readmission, which was 4.0% in patients without diabetes, 4.8% in those with diabetes, and 6.4% in patients with insulin-dependent diabetes. The data also showed that gastric bypass led to more complications than did sleeve gastrectomy, but complications with both types of surgeries increased in patients with diabetes, compared with those without diabetes.
Dr. Wheeler had no disclosures.
SOURCE: Wheeler AA et al. Obesity Week 2019, Abstract A133.
LAS VEGAS – compared with patients without diabetes, in an analysis of more than 550,000 patients who underwent this surgery.
The analysis also showed that among patients with diabetes undergoing bariatric surgery, those with insulin-dependent diabetes had significantly higher rates of these and other complications, compared with patients with diabetes but no insulin dependence, Andrew A. Wheeler, MD, said at a meeting presented by The Obesity Society and the American Society for Metabolic and Bariatric Surgery.
The specific factors driving these observations remain unknown, but may relate at least in part to the efficacy of glycemic control in patients during the months and weeks before surgery, said Dr. Wheeler, chief of metabolic and bariatric surgery at the University of Missouri in Columbia.
“Perioperative blood glucose control reflected in hemoglobin A1c may help us understand if certain patients with diabetes are at increased risk of surgical complications,” Dr. Wheeler said during his talk. “We need to see whether preoperative hemoglobin A1c tracks with the rate of complications,” he added in an interview. “Some surgeons will defer surgery until the level goes down, but right now, everyone uses a different level.”
The study by Dr. Wheeler and associates used data collected from essentially all the bariatric surgeries done at the roughly 840 U.S. centers accredited to do the surgery during 2015-2017 – a total of 555,239 patients – in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program run by the American College of Surgeons and the American Society for Metabolic and Bariatric Surgery. The cohort included 413,239 patients without diabetes and 136,010 with diabetes, with the remainder having an unknown status. Nearly all patients underwent either sleeve gastrectomy or gastric bypass, with significantly more patients, 74%, having sleeve gastrectomy in the group without diabetes, and 62% of those with diabetes undergoing sleeve gastrectomy.
Patients with diabetes uniformly had significantly higher rates of complications as measured by several parameters, and among those with diabetes, the complication rates were highest in those with insulin dependence. The researchers ran a multivariate analysis that controlled for many demographic and clinical variables, and found that despite these corrections, patients with diabetes, and especially those with insulin dependence, had higher relative rates of many complications that were statistically significant. In addition to the increased rates of deep surgical-site infections and 30-day ICU admissions, patients with diabetes had a 54% relatively increased rate of wound disruption, and a 29% increased relative rate of superficial surgical-site infections, compared with those without diabetes. And among patients with diabetes, those with insulin dependence had a 40% increased rate of surgical-site infections, a 74% increase in progressive renal failure, and a 39% increased rate of hospital readmission relative to patients with diabetes that was not insulin dependent, Dr. Wheeler reported.
The absolute complication rates were, in general, low. For example, the total rate of superficial plus deep surgical-site infections was less than 1% both in patients with diabetes and those without, although the rate rose above 1% in patients with insulin-dependent diabetes. The most common complication reported by Dr. Wheeler was 30-day hospital readmission, which was 4.0% in patients without diabetes, 4.8% in those with diabetes, and 6.4% in patients with insulin-dependent diabetes. The data also showed that gastric bypass led to more complications than did sleeve gastrectomy, but complications with both types of surgeries increased in patients with diabetes, compared with those without diabetes.
Dr. Wheeler had no disclosures.
SOURCE: Wheeler AA et al. Obesity Week 2019, Abstract A133.
REPORTING FROM OBESITY WEEK 2019
Carbohydrate restriction a viable choice for reversal of type 2 diabetes, expert says
LOS ANGELES – according to Sarah Hallberg, DO.
“Nutritional ketosis supports diabetes reversal by reducing insulin resistance while providing an alternative fuel to glucose with favorable signaling properties,” she said at the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease.
Low-carbohydrate nutritional patterns including ketosis have extensive clinical trial evidence for improvement of type 2 diabetes, including preliminary results from a 5-year study of 465 patients enrolled in the Indiana Type 2 Diabetes Reversal Trial that Dr. Hallberg is overseeing in her role as medical director and founder of the medically supervised weight-loss program at Indiana University Health Arnett, Lafayette.
“The ketogenic diet is not a fad diet, it’s what we used to treat people with before the advent of insulin,” said Dr. Hallberg, who has been recommending and counseling patients with type 2 diabetes to follow a ketogenic diet for nearly 10 years. “Of course, insulin has been wonderful. It’s saved so many people with type 1 diabetes. But we also misused it in type 2 diabetes. Instead of counseling people the way we used to about the food that they’re taking in to control their blood sugar, we’ve just been putting [them] on medication, including insulin.”
The American Diabetes Association and other organizations have updated their guidelines to include low-carbohydrate eating patterns for type 2 diabetes treatment, she continued. Veterans Affairs/Department of Defense recommend carbohydrate levels as low as 14%.
Dr. Hallberg, who is also medical director for Virta Health, defined a very-low-carbohydrate or ketogenic diet as less than 50 g of carbohydrates per day, or fewer than 10% of calories consumed. A low-carbohydrate diet is 51-130 g of carbohydrates per day, or 25% or fewer calories consumed, whereas anything above 25% calories consumed is a not a low-carbohydrate diet. A well-formulated ketogenic diet, she continued, consists of 5%-10% carbohydrates (or less than 50 g), 15%-20% protein, and 70%-80% fat. The carbohydrates include 5-10 g per day of protein-based food, 10-15 g of vegetables, 5-10 g of nuts/seeds, 5-10 g of fruits, and 5-10 g of miscellaneous nutrients. “When we’re talking about a total carbohydrate intake per day of under 50 g, you can get a lot of vegetables and nuts in,” she said. “I like to tell my patients they’re not eating GPS: no grains, no potatoes, and no sugar.”
Recently, Dr. Hallberg and colleagues published a review in which they sought to evaluate the appropriateness of sources cited in the ADA’s guidelines on eating patterns for the management of type 2 diabetes, identify additional relevant sources, and evaluate the evidence (Diabetes Obes Metab. 2019;21[8]:1769-79). “We looked at how much evidence there is for the low-carb diet, the Mediterranean diet, the DASH [Dietary Approaches to Stop Hypertension] diet, and a plant-based diet,” she said. “We found a wide variation in the evidence for each eating pattern, but the low-carb eating pattern for diabetes has so much more evidence than any of the other eating patterns.”
In an earlier study, researchers followed 10 inpatients with diabetes in a metabolic ward for 3 weeks. Their mean age was 51 years, and their mean body mass index was 40.3 kg/m2. The patients were fed a standard diet for 7 days, then a low-carbohydrate diet (21 g per day) for 14 days (Ann Intern Med 2005; 142[6]:403-11). After 2 weeks of the low-carbohydrate diet, their mean fasting blood glucose dropped from 7.5 to 6.3 mmol/L, and their mean hemoglobin A1c (HbA1c) fell from 7.3% to 6.8%. “The levels came down very fast,” said Dr. Hallberg, who was not involved with the study. “This is an important part of the intervention, because when you get a patient who’s tried everything, who’s injecting hundreds of units of insulin every day, you can make a huge difference in the first couple of weeks. It is not unusual for us to pull patients off of 200-plus units of insulin. This is as motivating as all get out. It also affects their pocketbook right away. This is one of the reasons our patients are able to sustain a ketogenic diet along with support: early motivation and satisfaction.”
In a longer-term trial, researchers evaluated the impact of a ketogenic diet in 64 obese patients with diabetes over the course of 56 weeks (Moll Cell Biochem. 2007;302[1-2]:249-56). The body weight, body mass index, and levels of blood glucose, total cholesterol, LDL cholesterol, triglycerides, and urea showed a significant decrease from week 1 to week 56 (P less than .0001), while the level of HDL cholesterol increased significantly (P less than .0001).
A separate trial conducted in Israel evaluated the effects of a low-carbohydrate diet, compared with a Mediterranean or low-fat diet in 322 moderately obese patients over the course of 2 years (N Engl J Med. 2008;359:229-41). The rate of adherence to a study diet was 85% at 2 years. The mean weight change was greatest for those on the low-carbohydrate diet, followed by the Mediterranean and low-fat diets. Fasting glucose was best for those on the Mediterranean diet at the end of 2 years, whereas change in HbA1c was best among those on the low-carbohydrate diet.
Another study randomized patients to a low-carbohydrate ketogenic diet (less than 20 g per day with no calorie restriction) or to a low–glycemic index diet (55% carbohydrate restriction of 500 kcal from baseline) over the course of 24 weeks (Nutr Metab [Lond]. 2008 Dec 19. doi:10.1186/1743-7075-5-36). Between baseline and week 24, the mean HbA1c fell from 8.8% to 7.3% in the very-low-carbohydrate diet group, and from 8.3% to 7.8% in the low–glycemic diet group, for a between-group comparison P value of .03. In addition, 95% of patients in the low-carbohydrate diet group were able to reduce or eliminate the number of medications they were taking, compared with 62% of patients in the low–glycemic diet group (P less than .01).
Dr. Hallberg and colleagues are currently in year 4 of the 5-year Indiana Type 2 Diabetes Reversal Study, a prospective, nonrandomized, controlled trial of carbohydrate restriction in 465 patients, making it the largest and longest study of its kind. Of the 465 patients, 387 are in the continuous-care arm, which consists of a diet from Virta Health based on principles of nutritional ketosis, and 87 patients in a usual care arm who are followed for 2 years. The trial includes patients who have been prescribed insulin and who have been diagnosed with diabetes for an average of 8 years.
At the meeting, Dr. Hallberg presented preliminary results based on 2 years of data collection. The retention rate was 83% at 1 year and 74% at 2 years. In the treatment arm, the researchers observed that the level of beta hydroxybutyrate, or evidence of ketogenesis, was the same at 2 years as it had been at 1 year. “So, people were still following the diet, as well as being engaged,” she said.
At the end of 2 years, the mean HbA1c reduction was 0.9, the mean reduction for the Homeostatic Model Assessment of Insulin Resistance was 32%, and 55% of completers experienced reversal of their diabetes. Overall, 91% of insulin users reduced or eliminated their use of insulin, and the average weight loss was 10% of baseline weight. “Medication reduction was across the board,” she added. “This is huge from a cost-savings and a patient-satisfaction standpoint. We were improving A1c levels in patients who have had diabetes for an average of over 8 years while we were getting [them] off medication, including insulin. Low carb is now the standard of care.”
Even patients who did not experience a reversal of their diabetes were conferred a benefit. They had an average reduction of 1.2 in HbA1c level, to 7%; their average weight loss was 9.8%; 45% of patients eliminated their diabetes prescriptions; 81% reduced or eliminated their use of insulin; there was an average reduction of 27% in triglyceride levels; and they had a 17% reduction in their 10-year risk score for atherosclerotic cardiovascular disease.
In the overall cohort, the 10-year Atherosclerotic Cardiovascular Disease risk score improved by 12%; almost all markers for cardiovascular disease improved at 1 year. “We were giving these patients appropriate support, which I think is key,” Dr. Hallberg said. “No matter what you do, you have to have a high-touch intervention, and supply that through technology. We do better than medication adherence. Putting patients on a carbohydrate-restricted diet with the appropriate support works for sustainability.”
Dr. Hallberg disclosed that she is an employee of Virta Health and that she is an adviser for Simply Good Foods.
LOS ANGELES – according to Sarah Hallberg, DO.
“Nutritional ketosis supports diabetes reversal by reducing insulin resistance while providing an alternative fuel to glucose with favorable signaling properties,” she said at the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease.
Low-carbohydrate nutritional patterns including ketosis have extensive clinical trial evidence for improvement of type 2 diabetes, including preliminary results from a 5-year study of 465 patients enrolled in the Indiana Type 2 Diabetes Reversal Trial that Dr. Hallberg is overseeing in her role as medical director and founder of the medically supervised weight-loss program at Indiana University Health Arnett, Lafayette.
“The ketogenic diet is not a fad diet, it’s what we used to treat people with before the advent of insulin,” said Dr. Hallberg, who has been recommending and counseling patients with type 2 diabetes to follow a ketogenic diet for nearly 10 years. “Of course, insulin has been wonderful. It’s saved so many people with type 1 diabetes. But we also misused it in type 2 diabetes. Instead of counseling people the way we used to about the food that they’re taking in to control their blood sugar, we’ve just been putting [them] on medication, including insulin.”
The American Diabetes Association and other organizations have updated their guidelines to include low-carbohydrate eating patterns for type 2 diabetes treatment, she continued. Veterans Affairs/Department of Defense recommend carbohydrate levels as low as 14%.
Dr. Hallberg, who is also medical director for Virta Health, defined a very-low-carbohydrate or ketogenic diet as less than 50 g of carbohydrates per day, or fewer than 10% of calories consumed. A low-carbohydrate diet is 51-130 g of carbohydrates per day, or 25% or fewer calories consumed, whereas anything above 25% calories consumed is a not a low-carbohydrate diet. A well-formulated ketogenic diet, she continued, consists of 5%-10% carbohydrates (or less than 50 g), 15%-20% protein, and 70%-80% fat. The carbohydrates include 5-10 g per day of protein-based food, 10-15 g of vegetables, 5-10 g of nuts/seeds, 5-10 g of fruits, and 5-10 g of miscellaneous nutrients. “When we’re talking about a total carbohydrate intake per day of under 50 g, you can get a lot of vegetables and nuts in,” she said. “I like to tell my patients they’re not eating GPS: no grains, no potatoes, and no sugar.”
Recently, Dr. Hallberg and colleagues published a review in which they sought to evaluate the appropriateness of sources cited in the ADA’s guidelines on eating patterns for the management of type 2 diabetes, identify additional relevant sources, and evaluate the evidence (Diabetes Obes Metab. 2019;21[8]:1769-79). “We looked at how much evidence there is for the low-carb diet, the Mediterranean diet, the DASH [Dietary Approaches to Stop Hypertension] diet, and a plant-based diet,” she said. “We found a wide variation in the evidence for each eating pattern, but the low-carb eating pattern for diabetes has so much more evidence than any of the other eating patterns.”
In an earlier study, researchers followed 10 inpatients with diabetes in a metabolic ward for 3 weeks. Their mean age was 51 years, and their mean body mass index was 40.3 kg/m2. The patients were fed a standard diet for 7 days, then a low-carbohydrate diet (21 g per day) for 14 days (Ann Intern Med 2005; 142[6]:403-11). After 2 weeks of the low-carbohydrate diet, their mean fasting blood glucose dropped from 7.5 to 6.3 mmol/L, and their mean hemoglobin A1c (HbA1c) fell from 7.3% to 6.8%. “The levels came down very fast,” said Dr. Hallberg, who was not involved with the study. “This is an important part of the intervention, because when you get a patient who’s tried everything, who’s injecting hundreds of units of insulin every day, you can make a huge difference in the first couple of weeks. It is not unusual for us to pull patients off of 200-plus units of insulin. This is as motivating as all get out. It also affects their pocketbook right away. This is one of the reasons our patients are able to sustain a ketogenic diet along with support: early motivation and satisfaction.”
In a longer-term trial, researchers evaluated the impact of a ketogenic diet in 64 obese patients with diabetes over the course of 56 weeks (Moll Cell Biochem. 2007;302[1-2]:249-56). The body weight, body mass index, and levels of blood glucose, total cholesterol, LDL cholesterol, triglycerides, and urea showed a significant decrease from week 1 to week 56 (P less than .0001), while the level of HDL cholesterol increased significantly (P less than .0001).
A separate trial conducted in Israel evaluated the effects of a low-carbohydrate diet, compared with a Mediterranean or low-fat diet in 322 moderately obese patients over the course of 2 years (N Engl J Med. 2008;359:229-41). The rate of adherence to a study diet was 85% at 2 years. The mean weight change was greatest for those on the low-carbohydrate diet, followed by the Mediterranean and low-fat diets. Fasting glucose was best for those on the Mediterranean diet at the end of 2 years, whereas change in HbA1c was best among those on the low-carbohydrate diet.
Another study randomized patients to a low-carbohydrate ketogenic diet (less than 20 g per day with no calorie restriction) or to a low–glycemic index diet (55% carbohydrate restriction of 500 kcal from baseline) over the course of 24 weeks (Nutr Metab [Lond]. 2008 Dec 19. doi:10.1186/1743-7075-5-36). Between baseline and week 24, the mean HbA1c fell from 8.8% to 7.3% in the very-low-carbohydrate diet group, and from 8.3% to 7.8% in the low–glycemic diet group, for a between-group comparison P value of .03. In addition, 95% of patients in the low-carbohydrate diet group were able to reduce or eliminate the number of medications they were taking, compared with 62% of patients in the low–glycemic diet group (P less than .01).
Dr. Hallberg and colleagues are currently in year 4 of the 5-year Indiana Type 2 Diabetes Reversal Study, a prospective, nonrandomized, controlled trial of carbohydrate restriction in 465 patients, making it the largest and longest study of its kind. Of the 465 patients, 387 are in the continuous-care arm, which consists of a diet from Virta Health based on principles of nutritional ketosis, and 87 patients in a usual care arm who are followed for 2 years. The trial includes patients who have been prescribed insulin and who have been diagnosed with diabetes for an average of 8 years.
At the meeting, Dr. Hallberg presented preliminary results based on 2 years of data collection. The retention rate was 83% at 1 year and 74% at 2 years. In the treatment arm, the researchers observed that the level of beta hydroxybutyrate, or evidence of ketogenesis, was the same at 2 years as it had been at 1 year. “So, people were still following the diet, as well as being engaged,” she said.
At the end of 2 years, the mean HbA1c reduction was 0.9, the mean reduction for the Homeostatic Model Assessment of Insulin Resistance was 32%, and 55% of completers experienced reversal of their diabetes. Overall, 91% of insulin users reduced or eliminated their use of insulin, and the average weight loss was 10% of baseline weight. “Medication reduction was across the board,” she added. “This is huge from a cost-savings and a patient-satisfaction standpoint. We were improving A1c levels in patients who have had diabetes for an average of over 8 years while we were getting [them] off medication, including insulin. Low carb is now the standard of care.”
Even patients who did not experience a reversal of their diabetes were conferred a benefit. They had an average reduction of 1.2 in HbA1c level, to 7%; their average weight loss was 9.8%; 45% of patients eliminated their diabetes prescriptions; 81% reduced or eliminated their use of insulin; there was an average reduction of 27% in triglyceride levels; and they had a 17% reduction in their 10-year risk score for atherosclerotic cardiovascular disease.
In the overall cohort, the 10-year Atherosclerotic Cardiovascular Disease risk score improved by 12%; almost all markers for cardiovascular disease improved at 1 year. “We were giving these patients appropriate support, which I think is key,” Dr. Hallberg said. “No matter what you do, you have to have a high-touch intervention, and supply that through technology. We do better than medication adherence. Putting patients on a carbohydrate-restricted diet with the appropriate support works for sustainability.”
Dr. Hallberg disclosed that she is an employee of Virta Health and that she is an adviser for Simply Good Foods.
LOS ANGELES – according to Sarah Hallberg, DO.
“Nutritional ketosis supports diabetes reversal by reducing insulin resistance while providing an alternative fuel to glucose with favorable signaling properties,” she said at the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease.
Low-carbohydrate nutritional patterns including ketosis have extensive clinical trial evidence for improvement of type 2 diabetes, including preliminary results from a 5-year study of 465 patients enrolled in the Indiana Type 2 Diabetes Reversal Trial that Dr. Hallberg is overseeing in her role as medical director and founder of the medically supervised weight-loss program at Indiana University Health Arnett, Lafayette.
“The ketogenic diet is not a fad diet, it’s what we used to treat people with before the advent of insulin,” said Dr. Hallberg, who has been recommending and counseling patients with type 2 diabetes to follow a ketogenic diet for nearly 10 years. “Of course, insulin has been wonderful. It’s saved so many people with type 1 diabetes. But we also misused it in type 2 diabetes. Instead of counseling people the way we used to about the food that they’re taking in to control their blood sugar, we’ve just been putting [them] on medication, including insulin.”
The American Diabetes Association and other organizations have updated their guidelines to include low-carbohydrate eating patterns for type 2 diabetes treatment, she continued. Veterans Affairs/Department of Defense recommend carbohydrate levels as low as 14%.
Dr. Hallberg, who is also medical director for Virta Health, defined a very-low-carbohydrate or ketogenic diet as less than 50 g of carbohydrates per day, or fewer than 10% of calories consumed. A low-carbohydrate diet is 51-130 g of carbohydrates per day, or 25% or fewer calories consumed, whereas anything above 25% calories consumed is a not a low-carbohydrate diet. A well-formulated ketogenic diet, she continued, consists of 5%-10% carbohydrates (or less than 50 g), 15%-20% protein, and 70%-80% fat. The carbohydrates include 5-10 g per day of protein-based food, 10-15 g of vegetables, 5-10 g of nuts/seeds, 5-10 g of fruits, and 5-10 g of miscellaneous nutrients. “When we’re talking about a total carbohydrate intake per day of under 50 g, you can get a lot of vegetables and nuts in,” she said. “I like to tell my patients they’re not eating GPS: no grains, no potatoes, and no sugar.”
Recently, Dr. Hallberg and colleagues published a review in which they sought to evaluate the appropriateness of sources cited in the ADA’s guidelines on eating patterns for the management of type 2 diabetes, identify additional relevant sources, and evaluate the evidence (Diabetes Obes Metab. 2019;21[8]:1769-79). “We looked at how much evidence there is for the low-carb diet, the Mediterranean diet, the DASH [Dietary Approaches to Stop Hypertension] diet, and a plant-based diet,” she said. “We found a wide variation in the evidence for each eating pattern, but the low-carb eating pattern for diabetes has so much more evidence than any of the other eating patterns.”
In an earlier study, researchers followed 10 inpatients with diabetes in a metabolic ward for 3 weeks. Their mean age was 51 years, and their mean body mass index was 40.3 kg/m2. The patients were fed a standard diet for 7 days, then a low-carbohydrate diet (21 g per day) for 14 days (Ann Intern Med 2005; 142[6]:403-11). After 2 weeks of the low-carbohydrate diet, their mean fasting blood glucose dropped from 7.5 to 6.3 mmol/L, and their mean hemoglobin A1c (HbA1c) fell from 7.3% to 6.8%. “The levels came down very fast,” said Dr. Hallberg, who was not involved with the study. “This is an important part of the intervention, because when you get a patient who’s tried everything, who’s injecting hundreds of units of insulin every day, you can make a huge difference in the first couple of weeks. It is not unusual for us to pull patients off of 200-plus units of insulin. This is as motivating as all get out. It also affects their pocketbook right away. This is one of the reasons our patients are able to sustain a ketogenic diet along with support: early motivation and satisfaction.”
In a longer-term trial, researchers evaluated the impact of a ketogenic diet in 64 obese patients with diabetes over the course of 56 weeks (Moll Cell Biochem. 2007;302[1-2]:249-56). The body weight, body mass index, and levels of blood glucose, total cholesterol, LDL cholesterol, triglycerides, and urea showed a significant decrease from week 1 to week 56 (P less than .0001), while the level of HDL cholesterol increased significantly (P less than .0001).
A separate trial conducted in Israel evaluated the effects of a low-carbohydrate diet, compared with a Mediterranean or low-fat diet in 322 moderately obese patients over the course of 2 years (N Engl J Med. 2008;359:229-41). The rate of adherence to a study diet was 85% at 2 years. The mean weight change was greatest for those on the low-carbohydrate diet, followed by the Mediterranean and low-fat diets. Fasting glucose was best for those on the Mediterranean diet at the end of 2 years, whereas change in HbA1c was best among those on the low-carbohydrate diet.
Another study randomized patients to a low-carbohydrate ketogenic diet (less than 20 g per day with no calorie restriction) or to a low–glycemic index diet (55% carbohydrate restriction of 500 kcal from baseline) over the course of 24 weeks (Nutr Metab [Lond]. 2008 Dec 19. doi:10.1186/1743-7075-5-36). Between baseline and week 24, the mean HbA1c fell from 8.8% to 7.3% in the very-low-carbohydrate diet group, and from 8.3% to 7.8% in the low–glycemic diet group, for a between-group comparison P value of .03. In addition, 95% of patients in the low-carbohydrate diet group were able to reduce or eliminate the number of medications they were taking, compared with 62% of patients in the low–glycemic diet group (P less than .01).
Dr. Hallberg and colleagues are currently in year 4 of the 5-year Indiana Type 2 Diabetes Reversal Study, a prospective, nonrandomized, controlled trial of carbohydrate restriction in 465 patients, making it the largest and longest study of its kind. Of the 465 patients, 387 are in the continuous-care arm, which consists of a diet from Virta Health based on principles of nutritional ketosis, and 87 patients in a usual care arm who are followed for 2 years. The trial includes patients who have been prescribed insulin and who have been diagnosed with diabetes for an average of 8 years.
At the meeting, Dr. Hallberg presented preliminary results based on 2 years of data collection. The retention rate was 83% at 1 year and 74% at 2 years. In the treatment arm, the researchers observed that the level of beta hydroxybutyrate, or evidence of ketogenesis, was the same at 2 years as it had been at 1 year. “So, people were still following the diet, as well as being engaged,” she said.
At the end of 2 years, the mean HbA1c reduction was 0.9, the mean reduction for the Homeostatic Model Assessment of Insulin Resistance was 32%, and 55% of completers experienced reversal of their diabetes. Overall, 91% of insulin users reduced or eliminated their use of insulin, and the average weight loss was 10% of baseline weight. “Medication reduction was across the board,” she added. “This is huge from a cost-savings and a patient-satisfaction standpoint. We were improving A1c levels in patients who have had diabetes for an average of over 8 years while we were getting [them] off medication, including insulin. Low carb is now the standard of care.”
Even patients who did not experience a reversal of their diabetes were conferred a benefit. They had an average reduction of 1.2 in HbA1c level, to 7%; their average weight loss was 9.8%; 45% of patients eliminated their diabetes prescriptions; 81% reduced or eliminated their use of insulin; there was an average reduction of 27% in triglyceride levels; and they had a 17% reduction in their 10-year risk score for atherosclerotic cardiovascular disease.
In the overall cohort, the 10-year Atherosclerotic Cardiovascular Disease risk score improved by 12%; almost all markers for cardiovascular disease improved at 1 year. “We were giving these patients appropriate support, which I think is key,” Dr. Hallberg said. “No matter what you do, you have to have a high-touch intervention, and supply that through technology. We do better than medication adherence. Putting patients on a carbohydrate-restricted diet with the appropriate support works for sustainability.”
Dr. Hallberg disclosed that she is an employee of Virta Health and that she is an adviser for Simply Good Foods.
EXPERT ANALYSIS FROM WCIRDC 2019
Score predicts bariatric surgery’s benefits for obesity, type 2 diabetes
LAS VEGAS –
The Individualized Diabetes Complications risk score “can provide personalized, evidence-based risk information for patients with type 2 diabetes and obesity about their future cardiovascular disease outcomes and mortality with and without metabolic surgery,” Ali Aminian, MD, said at a meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.
Although the calculator needs validation in a prospective, randomized study to document its impact on practice, it is now available on two separate websites and as a downloadable app, said Dr. Aminian, a surgeon at the Cleveland Clinic.
The calculator inputs data for 26 distinct, “readily available” demographic and clinical entries, and based on that, estimates the patient’s 10-year risk for all-cause death, diabetic kidney disease, cerebrovascular disease, heart failure, and coronary artery disease if no surgery occurs or after some type of metabolic or bariatric surgery. The calculator does not currently have the ability to individualize predicted risks based on the specific type of metabolic surgery performed, but that is planned as a future refinement of the score.
“We validated the model in the nonsurgical patients, which showed it was very accurate. The next step is to run a randomized trial to see how useful the calculator is” for assisting in patients’ decision making, Dr. Aminian said.
The data for deriving the risk calculator, and for a preliminary validation of it, came from 13,722 patients with obesity (body mass index, 30 kg/m2 or greater) and type 2 diabetes, who were managed at the Cleveland Clinic during 1998-2017, drawn from more than 287,000 such patients in the clinic’s database. The study focused on 2,287 patients who underwent metabolic (bariatric) surgery and 11,435 patients from the same database who did not have surgery and matched by propensity scoring on a 5:1 basis with those who had surgery. The two cohorts this created matched well for age (about 54 years), sex (about two-thirds women), body mass index (about 44 kg/m2), and the prevalence of various comorbidities at baseline.
Dr. Aminian and associates then analyzed the incidence of all-cause mortality and various cardiovascular disease endpoints, as well as nephropathy during follow-up, through December 2018. Patients who had undergone metabolic surgery showed statistically significant reductions in the incidence of each of those events, compared with patients who did not have surgery (JAMA. 2019;322[13]:1271-82).
The investigators used these findings to create their model for calculating a patient’s risk score. For example, to calculate an estimate for the 10-year risk from all-cause mortality, the results showed that the most powerful risk factors were age; baseline body mass index, heart failure, and need for insulin; and smoking status. For the endpoint of nephropathy, the most important factors were estimated glomerular filtration rate at baseline and age. Identified risk factors could account for about 80% of the 10-year risk for all-cause death and for about 75% of the risk for developing nephropathy during 10 years, based on the area-under-the-curve values the model produced.
The risk score may help patients better understand the potential role that metabolic surgery can have in reducing their future event risk, thereby helping them better appreciate the benefit they stand to gain from undergoing surgery, Dr. Aminian said.
The calculator is available at a website maintained by the Cleveland Clinic, at a site of the American Society for Metabolic and Bariatric Surgery, and in app stores, he said.
The work was partially funded by Medtronic. Dr. Aminian has received grants from Medtronic.
SOURCE: Aminian A et al. Obesity Week 2019, Abstract A101.
LAS VEGAS –
The Individualized Diabetes Complications risk score “can provide personalized, evidence-based risk information for patients with type 2 diabetes and obesity about their future cardiovascular disease outcomes and mortality with and without metabolic surgery,” Ali Aminian, MD, said at a meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.
Although the calculator needs validation in a prospective, randomized study to document its impact on practice, it is now available on two separate websites and as a downloadable app, said Dr. Aminian, a surgeon at the Cleveland Clinic.
The calculator inputs data for 26 distinct, “readily available” demographic and clinical entries, and based on that, estimates the patient’s 10-year risk for all-cause death, diabetic kidney disease, cerebrovascular disease, heart failure, and coronary artery disease if no surgery occurs or after some type of metabolic or bariatric surgery. The calculator does not currently have the ability to individualize predicted risks based on the specific type of metabolic surgery performed, but that is planned as a future refinement of the score.
“We validated the model in the nonsurgical patients, which showed it was very accurate. The next step is to run a randomized trial to see how useful the calculator is” for assisting in patients’ decision making, Dr. Aminian said.
The data for deriving the risk calculator, and for a preliminary validation of it, came from 13,722 patients with obesity (body mass index, 30 kg/m2 or greater) and type 2 diabetes, who were managed at the Cleveland Clinic during 1998-2017, drawn from more than 287,000 such patients in the clinic’s database. The study focused on 2,287 patients who underwent metabolic (bariatric) surgery and 11,435 patients from the same database who did not have surgery and matched by propensity scoring on a 5:1 basis with those who had surgery. The two cohorts this created matched well for age (about 54 years), sex (about two-thirds women), body mass index (about 44 kg/m2), and the prevalence of various comorbidities at baseline.
Dr. Aminian and associates then analyzed the incidence of all-cause mortality and various cardiovascular disease endpoints, as well as nephropathy during follow-up, through December 2018. Patients who had undergone metabolic surgery showed statistically significant reductions in the incidence of each of those events, compared with patients who did not have surgery (JAMA. 2019;322[13]:1271-82).
The investigators used these findings to create their model for calculating a patient’s risk score. For example, to calculate an estimate for the 10-year risk from all-cause mortality, the results showed that the most powerful risk factors were age; baseline body mass index, heart failure, and need for insulin; and smoking status. For the endpoint of nephropathy, the most important factors were estimated glomerular filtration rate at baseline and age. Identified risk factors could account for about 80% of the 10-year risk for all-cause death and for about 75% of the risk for developing nephropathy during 10 years, based on the area-under-the-curve values the model produced.
The risk score may help patients better understand the potential role that metabolic surgery can have in reducing their future event risk, thereby helping them better appreciate the benefit they stand to gain from undergoing surgery, Dr. Aminian said.
The calculator is available at a website maintained by the Cleveland Clinic, at a site of the American Society for Metabolic and Bariatric Surgery, and in app stores, he said.
The work was partially funded by Medtronic. Dr. Aminian has received grants from Medtronic.
SOURCE: Aminian A et al. Obesity Week 2019, Abstract A101.
LAS VEGAS –
The Individualized Diabetes Complications risk score “can provide personalized, evidence-based risk information for patients with type 2 diabetes and obesity about their future cardiovascular disease outcomes and mortality with and without metabolic surgery,” Ali Aminian, MD, said at a meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.
Although the calculator needs validation in a prospective, randomized study to document its impact on practice, it is now available on two separate websites and as a downloadable app, said Dr. Aminian, a surgeon at the Cleveland Clinic.
The calculator inputs data for 26 distinct, “readily available” demographic and clinical entries, and based on that, estimates the patient’s 10-year risk for all-cause death, diabetic kidney disease, cerebrovascular disease, heart failure, and coronary artery disease if no surgery occurs or after some type of metabolic or bariatric surgery. The calculator does not currently have the ability to individualize predicted risks based on the specific type of metabolic surgery performed, but that is planned as a future refinement of the score.
“We validated the model in the nonsurgical patients, which showed it was very accurate. The next step is to run a randomized trial to see how useful the calculator is” for assisting in patients’ decision making, Dr. Aminian said.
The data for deriving the risk calculator, and for a preliminary validation of it, came from 13,722 patients with obesity (body mass index, 30 kg/m2 or greater) and type 2 diabetes, who were managed at the Cleveland Clinic during 1998-2017, drawn from more than 287,000 such patients in the clinic’s database. The study focused on 2,287 patients who underwent metabolic (bariatric) surgery and 11,435 patients from the same database who did not have surgery and matched by propensity scoring on a 5:1 basis with those who had surgery. The two cohorts this created matched well for age (about 54 years), sex (about two-thirds women), body mass index (about 44 kg/m2), and the prevalence of various comorbidities at baseline.
Dr. Aminian and associates then analyzed the incidence of all-cause mortality and various cardiovascular disease endpoints, as well as nephropathy during follow-up, through December 2018. Patients who had undergone metabolic surgery showed statistically significant reductions in the incidence of each of those events, compared with patients who did not have surgery (JAMA. 2019;322[13]:1271-82).
The investigators used these findings to create their model for calculating a patient’s risk score. For example, to calculate an estimate for the 10-year risk from all-cause mortality, the results showed that the most powerful risk factors were age; baseline body mass index, heart failure, and need for insulin; and smoking status. For the endpoint of nephropathy, the most important factors were estimated glomerular filtration rate at baseline and age. Identified risk factors could account for about 80% of the 10-year risk for all-cause death and for about 75% of the risk for developing nephropathy during 10 years, based on the area-under-the-curve values the model produced.
The risk score may help patients better understand the potential role that metabolic surgery can have in reducing their future event risk, thereby helping them better appreciate the benefit they stand to gain from undergoing surgery, Dr. Aminian said.
The calculator is available at a website maintained by the Cleveland Clinic, at a site of the American Society for Metabolic and Bariatric Surgery, and in app stores, he said.
The work was partially funded by Medtronic. Dr. Aminian has received grants from Medtronic.
SOURCE: Aminian A et al. Obesity Week 2019, Abstract A101.
REPORTING FROM OBESITY WEEK 2019