Miriam E. Tucker

The Endocrine Society will now hold its annual meeting online in June.

ENDO 2020, originally scheduled for March 27-31 in San Francisco, was canceled March 9 because of the COVID-19 pandemic. Virtual press briefings were held on March 30 and 31.

Now, ENDO Online 2020, scheduled for June 8-22, will include both on-demand and live programming. Registration will be complimentary for health care providers who treat endocrine conditions and researchers in the field.

“The Endocrine Society will host its largest-ever online meeting in June to ensure endocrine researchers and clinicians continue to have access to the latest scientific information, despite the COVID-19 pandemic,” the society said in an announcement.

Content will include on-demand clinical sessions, continuing medical education sessions, programming for early career endocrinologists, and a digital exhibit hall.

The exact content mix is still being worked out, Endocrine Society spokeswoman Jenni Gingery told Medscape Medical News.

Society President E. Dale Abel, MD, PhD, said: “We recognize that many of the members of our field have been mobilized and are actively responding to the COVID-19 pandemic, and we also acknowledge that many have had to close their offices and labs.”

However, Abel, of the University of Iowa, Carver College of Medicine, Iowa City, noted, “We have received feedback that many endocrine investigators, clinicians, and trainees have indicated their desire to continue to advance their clinical knowledge and to be exposed to emerging science. We are proud to support them by virtually delivering the content they need during this challenging period.”

About 9,500 attendees were expected to attend ENDO 2020 in San Francisco.

This is only the third annual meeting cancellation in the Society’s 104-year history. The other two were both during World War II.

This article first appeared on Medscape.com.

The Endocrine Society will now hold its annual meeting online in June.

ENDO 2020, originally scheduled for March 27-31 in San Francisco, was canceled March 9 because of the COVID-19 pandemic. Virtual press briefings were held on March 30 and 31.

Now, ENDO Online 2020, scheduled for June 8-22, will include both on-demand and live programming. Registration will be complimentary for health care providers who treat endocrine conditions and researchers in the field.

“The Endocrine Society will host its largest-ever online meeting in June to ensure endocrine researchers and clinicians continue to have access to the latest scientific information, despite the COVID-19 pandemic,” the society said in an announcement.

Content will include on-demand clinical sessions, continuing medical education sessions, programming for early career endocrinologists, and a digital exhibit hall.

The exact content mix is still being worked out, Endocrine Society spokeswoman Jenni Gingery told Medscape Medical News.

Society President E. Dale Abel, MD, PhD, said: “We recognize that many of the members of our field have been mobilized and are actively responding to the COVID-19 pandemic, and we also acknowledge that many have had to close their offices and labs.”

However, Abel, of the University of Iowa, Carver College of Medicine, Iowa City, noted, “We have received feedback that many endocrine investigators, clinicians, and trainees have indicated their desire to continue to advance their clinical knowledge and to be exposed to emerging science. We are proud to support them by virtually delivering the content they need during this challenging period.”

About 9,500 attendees were expected to attend ENDO 2020 in San Francisco.

This is only the third annual meeting cancellation in the Society’s 104-year history. The other two were both during World War II.

This article first appeared on Medscape.com.

The Endocrine Society will now hold its annual meeting online in June.

ENDO 2020, originally scheduled for March 27-31 in San Francisco, was canceled March 9 because of the COVID-19 pandemic. Virtual press briefings were held on March 30 and 31.

Now, ENDO Online 2020, scheduled for June 8-22, will include both on-demand and live programming. Registration will be complimentary for health care providers who treat endocrine conditions and researchers in the field.

“The Endocrine Society will host its largest-ever online meeting in June to ensure endocrine researchers and clinicians continue to have access to the latest scientific information, despite the COVID-19 pandemic,” the society said in an announcement.

Content will include on-demand clinical sessions, continuing medical education sessions, programming for early career endocrinologists, and a digital exhibit hall.

The exact content mix is still being worked out, Endocrine Society spokeswoman Jenni Gingery told Medscape Medical News.

Society President E. Dale Abel, MD, PhD, said: “We recognize that many of the members of our field have been mobilized and are actively responding to the COVID-19 pandemic, and we also acknowledge that many have had to close their offices and labs.”

However, Abel, of the University of Iowa, Carver College of Medicine, Iowa City, noted, “We have received feedback that many endocrine investigators, clinicians, and trainees have indicated their desire to continue to advance their clinical knowledge and to be exposed to emerging science. We are proud to support them by virtually delivering the content they need during this challenging period.”

About 9,500 attendees were expected to attend ENDO 2020 in San Francisco.

This is only the third annual meeting cancellation in the Society’s 104-year history. The other two were both during World War II.

This article first appeared on Medscape.com.

Two histologically distinct “endotypes” of type 1 diabetes, T1DE1 and T1DE2, have been identified in children based on their age at diagnosis

The findings were published online March 15 in Diabetologia by Pia Leete, PhD, of the Institute of Biomedical and Clinical Science, University of Exeter Medical School, UK, and colleagues.

The results suggest that the immune attack is far more aggressive and the islets more inflamed in the younger-onset group (T1DE1) and less intense in the older-onset group (T1DE2), the authors explain.

“We’re extremely excited to find evidence that type 1 diabetes is two separate conditions: T1DE1 and T1DE2. The significance of this could be enormous in helping us to understand what causes the illness and in unlocking avenues to prevent future generations of children from getting type 1 diabetes,” said senior author Noel G. Morgan, PhD, also of the University of Exeter, in a statement.

Morgan added that the discovery “might also lead to new treatments if we can find ways to reactivate dormant insulin-producing cells in the older age group. This would be a significant step towards the holy grail to find a cure for some people.”

Endotypes can inform immune interventions

The study involved an immunohistological analysis of proinsulin and insulin distribution in the islets of pancreas samples recovered from 19 youth who died soon after (<2 years) onset of type 1 diabetes and from 13 with onset more than 5 years prior to harvesting. Those results were compared with C-peptide and proinsulin measurements in 171 living individuals with type 1 diabetes of longer than 5 years duration.

The Exeter team has previously reported that the immune cell profiles in the inflamed islets of children younger than 7 years of age soon after the diagnosis of type 1 diabetes seem to be distinctly different for those in children aged 13 and older at diagnosis. The younger group at diagnosis (termed “T1DE1”) retained a lower proportion of insulin-containing islets than did the older-onset group (“T1DE2”).

Those aged 7-12 at diagnosis could belong to either group, but there was no continuum. Rather, they appeared to align distinctly with one or the other “endotype,” Leete and colleagues say.

In the new analysis, proinsulin processing was aberrant to a much greater degree among children diagnosed with type 1 diabetes prior to age 7 years than among those diagnosed after age 12 years, with the profiles of proinsulin processing correlating with the previously defined immune cell profiles.

For those aged 7-12, the proinsulin distribution in islets directly correlated with their immune phenotypes, either T1DE1 or T1DE2.

And among the living patients, circulating proinsulin:C-peptide ratios were elevated in the <7-year onset group compared with the ≥13-year group, even 5 years after diagnosis.

“Together, these data imply that, when considered alongside age at diagnosis, measurement of the ratio of proinsulin to C-peptide may represent a convenient biomarker to distinguish the endotypes defined here,” Leete and colleagues say.

The two-endotype proposal isn’t meant to suggest that “a simple dichotomy will ultimately be sufficient to account for the entire heterogeneity seen in people developing type 1 diabetes,” the authors stress. Rather, additional endotypes will likely be defined as more variables are considered.

They write, “Recognition of such differences should inform the design of future immunotherapeutic interventions designed to arrest disease progression.”

The research was sponsored by Diabetes UK and JDRF.

This article first appeared on Medscape.com.

Two histologically distinct “endotypes” of type 1 diabetes, T1DE1 and T1DE2, have been identified in children based on their age at diagnosis

The findings were published online March 15 in Diabetologia by Pia Leete, PhD, of the Institute of Biomedical and Clinical Science, University of Exeter Medical School, UK, and colleagues.

The results suggest that the immune attack is far more aggressive and the islets more inflamed in the younger-onset group (T1DE1) and less intense in the older-onset group (T1DE2), the authors explain.

“We’re extremely excited to find evidence that type 1 diabetes is two separate conditions: T1DE1 and T1DE2. The significance of this could be enormous in helping us to understand what causes the illness and in unlocking avenues to prevent future generations of children from getting type 1 diabetes,” said senior author Noel G. Morgan, PhD, also of the University of Exeter, in a statement.

Morgan added that the discovery “might also lead to new treatments if we can find ways to reactivate dormant insulin-producing cells in the older age group. This would be a significant step towards the holy grail to find a cure for some people.”

Endotypes can inform immune interventions

The study involved an immunohistological analysis of proinsulin and insulin distribution in the islets of pancreas samples recovered from 19 youth who died soon after (<2 years) onset of type 1 diabetes and from 13 with onset more than 5 years prior to harvesting. Those results were compared with C-peptide and proinsulin measurements in 171 living individuals with type 1 diabetes of longer than 5 years duration.

The Exeter team has previously reported that the immune cell profiles in the inflamed islets of children younger than 7 years of age soon after the diagnosis of type 1 diabetes seem to be distinctly different for those in children aged 13 and older at diagnosis. The younger group at diagnosis (termed “T1DE1”) retained a lower proportion of insulin-containing islets than did the older-onset group (“T1DE2”).

Those aged 7-12 at diagnosis could belong to either group, but there was no continuum. Rather, they appeared to align distinctly with one or the other “endotype,” Leete and colleagues say.

In the new analysis, proinsulin processing was aberrant to a much greater degree among children diagnosed with type 1 diabetes prior to age 7 years than among those diagnosed after age 12 years, with the profiles of proinsulin processing correlating with the previously defined immune cell profiles.

For those aged 7-12, the proinsulin distribution in islets directly correlated with their immune phenotypes, either T1DE1 or T1DE2.

And among the living patients, circulating proinsulin:C-peptide ratios were elevated in the <7-year onset group compared with the ≥13-year group, even 5 years after diagnosis.

“Together, these data imply that, when considered alongside age at diagnosis, measurement of the ratio of proinsulin to C-peptide may represent a convenient biomarker to distinguish the endotypes defined here,” Leete and colleagues say.

The two-endotype proposal isn’t meant to suggest that “a simple dichotomy will ultimately be sufficient to account for the entire heterogeneity seen in people developing type 1 diabetes,” the authors stress. Rather, additional endotypes will likely be defined as more variables are considered.

They write, “Recognition of such differences should inform the design of future immunotherapeutic interventions designed to arrest disease progression.”

The research was sponsored by Diabetes UK and JDRF.

This article first appeared on Medscape.com.

Two histologically distinct “endotypes” of type 1 diabetes, T1DE1 and T1DE2, have been identified in children based on their age at diagnosis

The findings were published online March 15 in Diabetologia by Pia Leete, PhD, of the Institute of Biomedical and Clinical Science, University of Exeter Medical School, UK, and colleagues.

The results suggest that the immune attack is far more aggressive and the islets more inflamed in the younger-onset group (T1DE1) and less intense in the older-onset group (T1DE2), the authors explain.

“We’re extremely excited to find evidence that type 1 diabetes is two separate conditions: T1DE1 and T1DE2. The significance of this could be enormous in helping us to understand what causes the illness and in unlocking avenues to prevent future generations of children from getting type 1 diabetes,” said senior author Noel G. Morgan, PhD, also of the University of Exeter, in a statement.

Morgan added that the discovery “might also lead to new treatments if we can find ways to reactivate dormant insulin-producing cells in the older age group. This would be a significant step towards the holy grail to find a cure for some people.”

Endotypes can inform immune interventions

The study involved an immunohistological analysis of proinsulin and insulin distribution in the islets of pancreas samples recovered from 19 youth who died soon after (<2 years) onset of type 1 diabetes and from 13 with onset more than 5 years prior to harvesting. Those results were compared with C-peptide and proinsulin measurements in 171 living individuals with type 1 diabetes of longer than 5 years duration.

The Exeter team has previously reported that the immune cell profiles in the inflamed islets of children younger than 7 years of age soon after the diagnosis of type 1 diabetes seem to be distinctly different for those in children aged 13 and older at diagnosis. The younger group at diagnosis (termed “T1DE1”) retained a lower proportion of insulin-containing islets than did the older-onset group (“T1DE2”).

Those aged 7-12 at diagnosis could belong to either group, but there was no continuum. Rather, they appeared to align distinctly with one or the other “endotype,” Leete and colleagues say.

In the new analysis, proinsulin processing was aberrant to a much greater degree among children diagnosed with type 1 diabetes prior to age 7 years than among those diagnosed after age 12 years, with the profiles of proinsulin processing correlating with the previously defined immune cell profiles.

For those aged 7-12, the proinsulin distribution in islets directly correlated with their immune phenotypes, either T1DE1 or T1DE2.

And among the living patients, circulating proinsulin:C-peptide ratios were elevated in the <7-year onset group compared with the ≥13-year group, even 5 years after diagnosis.

“Together, these data imply that, when considered alongside age at diagnosis, measurement of the ratio of proinsulin to C-peptide may represent a convenient biomarker to distinguish the endotypes defined here,” Leete and colleagues say.

The two-endotype proposal isn’t meant to suggest that “a simple dichotomy will ultimately be sufficient to account for the entire heterogeneity seen in people developing type 1 diabetes,” the authors stress. Rather, additional endotypes will likely be defined as more variables are considered.

They write, “Recognition of such differences should inform the design of future immunotherapeutic interventions designed to arrest disease progression.”

The research was sponsored by Diabetes UK and JDRF.

This article first appeared on Medscape.com.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.

The European Society of Cardiology (ESC) has issued a statement urging physicians and patients to continue treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), in light of a newly described theory that those agents could increase the risk of developing COVID-19 and/or worsen its severity.

The concern arises from the observation that the new coronavirus SARS-CoV-2 causing COVID-19 binds to angiotensin-converting enzyme 2 (ACE2) to infect cells, and both ACE inhibitors and ARBs increase ACE2 levels.

This mechanism has been theorized as a possible risk factor for facilitating the acquisition of COVID-19 infection and worsening its severity. However, paradoxically, it has also been hypothesized to protect against acute lung injury from the disease.

Meanwhile, a Lancet Respiratory Medicine article was published March 11 entitled, “Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?”

“We ... hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” said the authors.

This prompted some media coverage in the United Kingdom and “social media-related amplification,” leading to concern and, in some cases, discontinuation of the drugs by patients.

But on March 13, the ESC Council on Hypertension dismissed the concerns as entirely speculative, in a statement posted to the ESC website.

It said that the council “strongly recommend that physicians and patients should continue treatment with their usual antihypertensive therapy because there is no clinical or scientific evidence to suggest that treatment with ACE inhibitors or ARBs should be discontinued because of the COVID-19 infection.”

The statement, signed by Council Chair Professor Giovanni de Simone, MD, on behalf of the nucleus members, also says that in regard to the theorized protective effect against serious lung complications in individuals with COVID-19, the data come only from animal, and not human, studies.

“Speculation about the safety of ACE-inhibitor or ARB treatment in relation to COVID-19 does not have a sound scientific basis or evidence to support it,” the ESC panel concludes.

This article first appeared on Medscape.com.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.

The European Society of Cardiology (ESC) has issued a statement urging physicians and patients to continue treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), in light of a newly described theory that those agents could increase the risk of developing COVID-19 and/or worsen its severity.

The concern arises from the observation that the new coronavirus SARS-CoV-2 causing COVID-19 binds to angiotensin-converting enzyme 2 (ACE2) to infect cells, and both ACE inhibitors and ARBs increase ACE2 levels.

This mechanism has been theorized as a possible risk factor for facilitating the acquisition of COVID-19 infection and worsening its severity. However, paradoxically, it has also been hypothesized to protect against acute lung injury from the disease.

Meanwhile, a Lancet Respiratory Medicine article was published March 11 entitled, “Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?”

“We ... hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” said the authors.

This prompted some media coverage in the United Kingdom and “social media-related amplification,” leading to concern and, in some cases, discontinuation of the drugs by patients.

But on March 13, the ESC Council on Hypertension dismissed the concerns as entirely speculative, in a statement posted to the ESC website.

It said that the council “strongly recommend that physicians and patients should continue treatment with their usual antihypertensive therapy because there is no clinical or scientific evidence to suggest that treatment with ACE inhibitors or ARBs should be discontinued because of the COVID-19 infection.”

The statement, signed by Council Chair Professor Giovanni de Simone, MD, on behalf of the nucleus members, also says that in regard to the theorized protective effect against serious lung complications in individuals with COVID-19, the data come only from animal, and not human, studies.

“Speculation about the safety of ACE-inhibitor or ARB treatment in relation to COVID-19 does not have a sound scientific basis or evidence to support it,” the ESC panel concludes.

This article first appeared on Medscape.com.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.

The European Society of Cardiology (ESC) has issued a statement urging physicians and patients to continue treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), in light of a newly described theory that those agents could increase the risk of developing COVID-19 and/or worsen its severity.

The concern arises from the observation that the new coronavirus SARS-CoV-2 causing COVID-19 binds to angiotensin-converting enzyme 2 (ACE2) to infect cells, and both ACE inhibitors and ARBs increase ACE2 levels.

This mechanism has been theorized as a possible risk factor for facilitating the acquisition of COVID-19 infection and worsening its severity. However, paradoxically, it has also been hypothesized to protect against acute lung injury from the disease.

Meanwhile, a Lancet Respiratory Medicine article was published March 11 entitled, “Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?”

“We ... hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” said the authors.

This prompted some media coverage in the United Kingdom and “social media-related amplification,” leading to concern and, in some cases, discontinuation of the drugs by patients.

But on March 13, the ESC Council on Hypertension dismissed the concerns as entirely speculative, in a statement posted to the ESC website.

It said that the council “strongly recommend that physicians and patients should continue treatment with their usual antihypertensive therapy because there is no clinical or scientific evidence to suggest that treatment with ACE inhibitors or ARBs should be discontinued because of the COVID-19 infection.”

The statement, signed by Council Chair Professor Giovanni de Simone, MD, on behalf of the nucleus members, also says that in regard to the theorized protective effect against serious lung complications in individuals with COVID-19, the data come only from animal, and not human, studies.

“Speculation about the safety of ACE-inhibitor or ARB treatment in relation to COVID-19 does not have a sound scientific basis or evidence to support it,” the ESC panel concludes.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has issued new draft guidance for industry on evaluating the safety of new drugs for type 2 diabetes and removed the “outdated” 12-year-old requirement for standardized cardiovascular outcomes trials (CVOTs).

The new draft guidance, “Type 2 Diabetes Mellitus: Evaluating the Safety of New Drugs for Improving Glycemic Control,” will replace the December 2008 requirement that manufacturers conduct CVOTs to rule out unacceptable cardiovascular safety risk. That move followed concerns raised at the time about the thiazolidinedione class of glucose-lowering drugs.

Since then, “FDA has reviewed the results of several [CVOTs] conducted to meet the December 2008 guidance recommendations. None of the CVOTs to date have identified an increased risk of ischemic cardiovascular events; some of the CVOTs have instead demonstrated a reduced risk for cardiovascular events,” according to the federal register announcement.

In October 2018, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee narrowly voted (10 to 9) to continue requiring CVOTs, but most panel members also recommended some changes to them, including requirements for safety data beyond cardiovascular events.

Based on the CVOT results over the years and the panel’s recommendations, “FDA is revisiting the recommendations of the December 2008 guidance and is now proposing an updated approach to evaluating the safety of new drugs and biologics to improve glycemic control.”

“The new draft guidance does not contain the recommendation that sponsors of all new therapies for type 2 diabetes uniformly rule out a specific degree of risk for ischemic cardiovascular adverse outcomes,” the FDA said.

Instead, the draft calls for at least 4000 patient-years of exposure to the new drug in phase 3 trials and inclusion of study participants with comorbid conditions and/or diabetes complications, including at least 500 with stage 3-4 chronic kidney disease, 600 with established cardiovascular disease, and at least 600 over the age of 65 years.

The FDA is soliciting stakeholder input on these and other issues, including study duration, subject demographics, specific safety concerns, and event adjudication.

In a statement, Lisa Yanoff, MD, acting director of the Division for Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research, said: “By following previous FDA recommendations, sponsors have shown that new type 2 diabetes drugs do not have excess ischemic cardiovascular risk, which has provided reassuring cardiovascular safety information for millions of diabetes patients. Now, with this proposed approach, we will have broader, valuable safety information for these medications.”

The draft is open for comments for 90 days after March 9, 2020. It is available online, along with a link for submitting comments.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has issued new draft guidance for industry on evaluating the safety of new drugs for type 2 diabetes and removed the “outdated” 12-year-old requirement for standardized cardiovascular outcomes trials (CVOTs).

The new draft guidance, “Type 2 Diabetes Mellitus: Evaluating the Safety of New Drugs for Improving Glycemic Control,” will replace the December 2008 requirement that manufacturers conduct CVOTs to rule out unacceptable cardiovascular safety risk. That move followed concerns raised at the time about the thiazolidinedione class of glucose-lowering drugs.

Since then, “FDA has reviewed the results of several [CVOTs] conducted to meet the December 2008 guidance recommendations. None of the CVOTs to date have identified an increased risk of ischemic cardiovascular events; some of the CVOTs have instead demonstrated a reduced risk for cardiovascular events,” according to the federal register announcement.

In October 2018, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee narrowly voted (10 to 9) to continue requiring CVOTs, but most panel members also recommended some changes to them, including requirements for safety data beyond cardiovascular events.

Based on the CVOT results over the years and the panel’s recommendations, “FDA is revisiting the recommendations of the December 2008 guidance and is now proposing an updated approach to evaluating the safety of new drugs and biologics to improve glycemic control.”

“The new draft guidance does not contain the recommendation that sponsors of all new therapies for type 2 diabetes uniformly rule out a specific degree of risk for ischemic cardiovascular adverse outcomes,” the FDA said.

Instead, the draft calls for at least 4000 patient-years of exposure to the new drug in phase 3 trials and inclusion of study participants with comorbid conditions and/or diabetes complications, including at least 500 with stage 3-4 chronic kidney disease, 600 with established cardiovascular disease, and at least 600 over the age of 65 years.

The FDA is soliciting stakeholder input on these and other issues, including study duration, subject demographics, specific safety concerns, and event adjudication.

In a statement, Lisa Yanoff, MD, acting director of the Division for Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research, said: “By following previous FDA recommendations, sponsors have shown that new type 2 diabetes drugs do not have excess ischemic cardiovascular risk, which has provided reassuring cardiovascular safety information for millions of diabetes patients. Now, with this proposed approach, we will have broader, valuable safety information for these medications.”

The draft is open for comments for 90 days after March 9, 2020. It is available online, along with a link for submitting comments.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has issued new draft guidance for industry on evaluating the safety of new drugs for type 2 diabetes and removed the “outdated” 12-year-old requirement for standardized cardiovascular outcomes trials (CVOTs).

The new draft guidance, “Type 2 Diabetes Mellitus: Evaluating the Safety of New Drugs for Improving Glycemic Control,” will replace the December 2008 requirement that manufacturers conduct CVOTs to rule out unacceptable cardiovascular safety risk. That move followed concerns raised at the time about the thiazolidinedione class of glucose-lowering drugs.

Since then, “FDA has reviewed the results of several [CVOTs] conducted to meet the December 2008 guidance recommendations. None of the CVOTs to date have identified an increased risk of ischemic cardiovascular events; some of the CVOTs have instead demonstrated a reduced risk for cardiovascular events,” according to the federal register announcement.

In October 2018, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee narrowly voted (10 to 9) to continue requiring CVOTs, but most panel members also recommended some changes to them, including requirements for safety data beyond cardiovascular events.

Based on the CVOT results over the years and the panel’s recommendations, “FDA is revisiting the recommendations of the December 2008 guidance and is now proposing an updated approach to evaluating the safety of new drugs and biologics to improve glycemic control.”

“The new draft guidance does not contain the recommendation that sponsors of all new therapies for type 2 diabetes uniformly rule out a specific degree of risk for ischemic cardiovascular adverse outcomes,” the FDA said.

Instead, the draft calls for at least 4000 patient-years of exposure to the new drug in phase 3 trials and inclusion of study participants with comorbid conditions and/or diabetes complications, including at least 500 with stage 3-4 chronic kidney disease, 600 with established cardiovascular disease, and at least 600 over the age of 65 years.

The FDA is soliciting stakeholder input on these and other issues, including study duration, subject demographics, specific safety concerns, and event adjudication.

In a statement, Lisa Yanoff, MD, acting director of the Division for Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research, said: “By following previous FDA recommendations, sponsors have shown that new type 2 diabetes drugs do not have excess ischemic cardiovascular risk, which has provided reassuring cardiovascular safety information for millions of diabetes patients. Now, with this proposed approach, we will have broader, valuable safety information for these medications.”

The draft is open for comments for 90 days after March 9, 2020. It is available online, along with a link for submitting comments.

This article first appeared on Medscape.com.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s  Coronavirus Resource Center.

The Endocrine Society has canceled its annual scientific meeting because of concerns about the novel coronavirus.

The conference was scheduled to take place March 28-31 in San Francisco. The announcement comes the same day as the American College of Cardiology/World Congress of Cardiology joint conference, scheduled for March 27-30 in Chicago, was also canceled.

“This is an unprecedented public health emergency that is clearly impacting not only the city of San Francisco, but many nations around the world. As such, it is with a very heavy heart that I am reporting to you that out of an abundance of caution, the board of directors has decided to cancel ENDO 2020,” Endocrine Society president E. Dale Abel, MD, PhD, said in a news release.

The Endocrine Society has canceled its annual meeting only twice before in its 104-year history, both during World War II. This year, more than 9,000 people were expected to attend the meeting. “Like you, ENDO is one of the highlights of my professional life each year, and I am sure that you are just as disappointed as I am to hear this news,” Dr. Abel said.

As recently as last week, the society’s board of directors had still hoped that the meeting could take place, but over the weekend it consulted with the San Francisco Department of Public Health, which has recommended canceling or postponing all nonessential gatherings.

The society also has been following reports from the U.S. Centers for Disease Control and Prevention and the World Health Organization.

Moreover, Dr. Abel said, “To add to our concerns, institutions across the world are restricting travel, making it impossible for many who have registered for ENDO 2020 to attend and enjoy the meeting.”

The concerns extend even further, as attendance could take health care providers away from where they’re needed most during the emergency.

“By holding the meeting, we might not only put attendees at risk, but we may also displace health care workers during a public health crisis. This could occur because of the need to self-quarantine upon your return home or, in a worse scenario, contribute to spreading the virus to our attendees’ hometowns,” he said.

Meeting registrants will be contacted soon with refund information. Dr. Abel gave a “special thank you” to the annual meeting steering committee and staff, “who have poured so much into this meeting.”

The society is currently “exploring ways in which we might be able to deliver to our registrants content from ENDO 2020 in various venues in the coming year.”

This article first appeared on Medscape.com.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s  Coronavirus Resource Center.

The Endocrine Society has canceled its annual scientific meeting because of concerns about the novel coronavirus.

The conference was scheduled to take place March 28-31 in San Francisco. The announcement comes the same day as the American College of Cardiology/World Congress of Cardiology joint conference, scheduled for March 27-30 in Chicago, was also canceled.

“This is an unprecedented public health emergency that is clearly impacting not only the city of San Francisco, but many nations around the world. As such, it is with a very heavy heart that I am reporting to you that out of an abundance of caution, the board of directors has decided to cancel ENDO 2020,” Endocrine Society president E. Dale Abel, MD, PhD, said in a news release.

The Endocrine Society has canceled its annual meeting only twice before in its 104-year history, both during World War II. This year, more than 9,000 people were expected to attend the meeting. “Like you, ENDO is one of the highlights of my professional life each year, and I am sure that you are just as disappointed as I am to hear this news,” Dr. Abel said.

As recently as last week, the society’s board of directors had still hoped that the meeting could take place, but over the weekend it consulted with the San Francisco Department of Public Health, which has recommended canceling or postponing all nonessential gatherings.

The society also has been following reports from the U.S. Centers for Disease Control and Prevention and the World Health Organization.

Moreover, Dr. Abel said, “To add to our concerns, institutions across the world are restricting travel, making it impossible for many who have registered for ENDO 2020 to attend and enjoy the meeting.”

The concerns extend even further, as attendance could take health care providers away from where they’re needed most during the emergency.

“By holding the meeting, we might not only put attendees at risk, but we may also displace health care workers during a public health crisis. This could occur because of the need to self-quarantine upon your return home or, in a worse scenario, contribute to spreading the virus to our attendees’ hometowns,” he said.

Meeting registrants will be contacted soon with refund information. Dr. Abel gave a “special thank you” to the annual meeting steering committee and staff, “who have poured so much into this meeting.”

The society is currently “exploring ways in which we might be able to deliver to our registrants content from ENDO 2020 in various venues in the coming year.”

This article first appeared on Medscape.com.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s  Coronavirus Resource Center.

The Endocrine Society has canceled its annual scientific meeting because of concerns about the novel coronavirus.

The conference was scheduled to take place March 28-31 in San Francisco. The announcement comes the same day as the American College of Cardiology/World Congress of Cardiology joint conference, scheduled for March 27-30 in Chicago, was also canceled.

“This is an unprecedented public health emergency that is clearly impacting not only the city of San Francisco, but many nations around the world. As such, it is with a very heavy heart that I am reporting to you that out of an abundance of caution, the board of directors has decided to cancel ENDO 2020,” Endocrine Society president E. Dale Abel, MD, PhD, said in a news release.

The Endocrine Society has canceled its annual meeting only twice before in its 104-year history, both during World War II. This year, more than 9,000 people were expected to attend the meeting. “Like you, ENDO is one of the highlights of my professional life each year, and I am sure that you are just as disappointed as I am to hear this news,” Dr. Abel said.

As recently as last week, the society’s board of directors had still hoped that the meeting could take place, but over the weekend it consulted with the San Francisco Department of Public Health, which has recommended canceling or postponing all nonessential gatherings.

The society also has been following reports from the U.S. Centers for Disease Control and Prevention and the World Health Organization.

Moreover, Dr. Abel said, “To add to our concerns, institutions across the world are restricting travel, making it impossible for many who have registered for ENDO 2020 to attend and enjoy the meeting.”

The concerns extend even further, as attendance could take health care providers away from where they’re needed most during the emergency.

“By holding the meeting, we might not only put attendees at risk, but we may also displace health care workers during a public health crisis. This could occur because of the need to self-quarantine upon your return home or, in a worse scenario, contribute to spreading the virus to our attendees’ hometowns,” he said.

Meeting registrants will be contacted soon with refund information. Dr. Abel gave a “special thank you” to the annual meeting steering committee and staff, “who have poured so much into this meeting.”

The society is currently “exploring ways in which we might be able to deliver to our registrants content from ENDO 2020 in various venues in the coming year.”

This article first appeared on Medscape.com.

Oral hygiene may be a key factor in diabetes risk, new data from a Korean national health database suggest.

“Frequent tooth brushing may be an attenuating factor for the risk of new-onset diabetes, and the presence of periodontal disease and increased number of missing teeth may be augmenting factors,” wrote Yoonkyung Chang, MD, of the Department of Neurology, Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, South Korea, and colleagues.

“Improving oral hygiene may be associated with a decreased risk of occurrence of new-onset diabetes,” they continued in an article published online in Diabetologia.

Periodontal disease involves inflammatory reactions that affect the surrounding tissues of the teeth. Inflammation, in turn, is an important cause of diabetes because it increases insulin resistance and endothelial dysfunction, Dr. Chang and colleagues explained.

They analyzed data gathered during 2003-2006 from 188,013 individuals from the Korean National Health Insurance System – Health Screening Cohort who had complete data and did not have diabetes at baseline. Oral hygiene behaviors, including frequency of tooth brushing, and dental visits or cleanings, were collected by self-report.

Over a median follow-up of 10 years, there were 31,545 new cases of diabetes, with an estimated overall 10-year event rate of 16.1%. The rate was 17.2% for those with periodontal disease at baseline, compared with 15.8% for those without, which was a significant difference even after adjustments for multiple confounders (hazard ratio, 1.09; P less than .001).

Compared with patients who had no missing teeth, the event rate for new-onset diabetes rose from 15.4% for patients with 1 missing tooth (HR, 1.08; P less than .001) to 21.4% for those with 15 or more missing teeth (HR, 1.21; P less than .001).

Professional dental cleaning did not have a significant effect after multivariate analysis. However, the number of daily tooth brushings by the individual did. Compared with brushing 0-1 times/day, those who brushed 3 or more times/day had a significantly lower risk for new-onset diabetes (HR, 0.92; P less than .001).

In subgroup analyses, periodontal disease was more strongly associated with new-onset diabetes in adults aged 51 years and younger (HR, 1.14), compared with those who were 52 years or older (HR, 1.06).

The study was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education. The authors reported no relevant financial relationships.
 

This article first appeared on Medscape.com.

Oral hygiene may be a key factor in diabetes risk, new data from a Korean national health database suggest.

“Frequent tooth brushing may be an attenuating factor for the risk of new-onset diabetes, and the presence of periodontal disease and increased number of missing teeth may be augmenting factors,” wrote Yoonkyung Chang, MD, of the Department of Neurology, Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, South Korea, and colleagues.

“Improving oral hygiene may be associated with a decreased risk of occurrence of new-onset diabetes,” they continued in an article published online in Diabetologia.

Periodontal disease involves inflammatory reactions that affect the surrounding tissues of the teeth. Inflammation, in turn, is an important cause of diabetes because it increases insulin resistance and endothelial dysfunction, Dr. Chang and colleagues explained.

They analyzed data gathered during 2003-2006 from 188,013 individuals from the Korean National Health Insurance System – Health Screening Cohort who had complete data and did not have diabetes at baseline. Oral hygiene behaviors, including frequency of tooth brushing, and dental visits or cleanings, were collected by self-report.

Over a median follow-up of 10 years, there were 31,545 new cases of diabetes, with an estimated overall 10-year event rate of 16.1%. The rate was 17.2% for those with periodontal disease at baseline, compared with 15.8% for those without, which was a significant difference even after adjustments for multiple confounders (hazard ratio, 1.09; P less than .001).

Compared with patients who had no missing teeth, the event rate for new-onset diabetes rose from 15.4% for patients with 1 missing tooth (HR, 1.08; P less than .001) to 21.4% for those with 15 or more missing teeth (HR, 1.21; P less than .001).

Professional dental cleaning did not have a significant effect after multivariate analysis. However, the number of daily tooth brushings by the individual did. Compared with brushing 0-1 times/day, those who brushed 3 or more times/day had a significantly lower risk for new-onset diabetes (HR, 0.92; P less than .001).

In subgroup analyses, periodontal disease was more strongly associated with new-onset diabetes in adults aged 51 years and younger (HR, 1.14), compared with those who were 52 years or older (HR, 1.06).

The study was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education. The authors reported no relevant financial relationships.
 

This article first appeared on Medscape.com.

Oral hygiene may be a key factor in diabetes risk, new data from a Korean national health database suggest.

“Frequent tooth brushing may be an attenuating factor for the risk of new-onset diabetes, and the presence of periodontal disease and increased number of missing teeth may be augmenting factors,” wrote Yoonkyung Chang, MD, of the Department of Neurology, Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, South Korea, and colleagues.

“Improving oral hygiene may be associated with a decreased risk of occurrence of new-onset diabetes,” they continued in an article published online in Diabetologia.

Periodontal disease involves inflammatory reactions that affect the surrounding tissues of the teeth. Inflammation, in turn, is an important cause of diabetes because it increases insulin resistance and endothelial dysfunction, Dr. Chang and colleagues explained.

They analyzed data gathered during 2003-2006 from 188,013 individuals from the Korean National Health Insurance System – Health Screening Cohort who had complete data and did not have diabetes at baseline. Oral hygiene behaviors, including frequency of tooth brushing, and dental visits or cleanings, were collected by self-report.

Over a median follow-up of 10 years, there were 31,545 new cases of diabetes, with an estimated overall 10-year event rate of 16.1%. The rate was 17.2% for those with periodontal disease at baseline, compared with 15.8% for those without, which was a significant difference even after adjustments for multiple confounders (hazard ratio, 1.09; P less than .001).

Compared with patients who had no missing teeth, the event rate for new-onset diabetes rose from 15.4% for patients with 1 missing tooth (HR, 1.08; P less than .001) to 21.4% for those with 15 or more missing teeth (HR, 1.21; P less than .001).

Professional dental cleaning did not have a significant effect after multivariate analysis. However, the number of daily tooth brushings by the individual did. Compared with brushing 0-1 times/day, those who brushed 3 or more times/day had a significantly lower risk for new-onset diabetes (HR, 0.92; P less than .001).

In subgroup analyses, periodontal disease was more strongly associated with new-onset diabetes in adults aged 51 years and younger (HR, 1.14), compared with those who were 52 years or older (HR, 1.06).

The study was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education. The authors reported no relevant financial relationships.
 

This article first appeared on Medscape.com.

Empagliflozin and dulaglutide became the most-prescribed drugs in their respective classes for treating type 2 diabetes in the United States from July 2013 to June 2018, new research shows.

The findings, from U.S.-based administrative claims data, were published online in Diabetes Care by Chintan V. Dave, PharmD, PhD, and colleagues.

Among patients initiating oral sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) over the 5-year period, empagliflozin (Jardiance, Boehringer Ingelheim/Lilly) became the most commonly prescribed glucose-lowering drug, primarily driven by an increasing proportion of patients with diabetes who had a diagnosis of myocardial infarction, stroke, or heart failure (collectively called cardiovascular disease-heart failure [CVD-HF]).

And within the subcutaneous injectable glucagonlike peptide–1 receptor (GLP-1) agonist class, initiations of dulaglutide (Trulicity, Lilly) surpassed liraglutide in 2013-2018, although patients starting liraglutide (Victoza, Novo Nordisk) were more likely to have a CVD-HF diagnosis.

“This study shows that by preferring empagliflozin, prescribers have largely reacted in accordance with the available evidence and drug labels, while other factors such as lower price, frequency of administration [dulaglutide is given weekly and liraglutide is given daily], or prior authorizations may have led prescribers to select dulaglutide over liraglutide,” Dr. Dave, of the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, and colleagues wrote.

Internists and endocrinologists were the most frequent prescribers of both drug classes, but cardiologists rarely prescribed them, even for patients with established CVD-HF. “As patients with co-occurring diabetes and CVD are likely to see their cardiologist, these encounters may provide an additional opportunity to optimize their treatment,” the authors emphasized.

SGLT2 inhibitors and label changes

Over the study period, the proportion of patients who had CVD-HF and who received SGLT2 inhibitors rose by 3.4 percentage points, from 8.8% to 12.2% (P trend < .001).

The proportion of overall prescriptions for SGLT2 inhibitors written by endocrinologists dropped by 12.0%, although the absolute number of SGLT2-inhibitor prescriptions written by endocrinologists increased (P < .001).

The proportion written by internists did not change (P = .58), whereas it increased slightly among cardiologists but still barely exceeded 1% (P < .001). The findings were similar for the subgroup of patients with CVD-HF who initiated SGLT2 inhibitors.

By individual agents, canagliflozin (Invokana, Janssen) prescriptions dropped by 75.1 percentage points over the study period, from 100% in 2013 to just 24.9% by 2018 (P < .001), whereas empagliflozin initiation rose by 51.7 percentage points, from 13.9% to 65.6% of all SGLT2 inhibitor initiations (P < .001).

Among those initiating empagliflozin, the proportion with CVD-HF rose by 5.3 percentage points, from 8.8% to 14.1% (P < .001), mostly after the additional indication for reducing CV events and death was added to the U.S. label in December 2016.

In contrast, there were no significant changes in the proportions of those with CVD-HF who initiated canagliflozin (P = 065), dapagliflozin (P = .87), or other medications (P = .060).

“Changes in the drug label for canagliflozin (boxed warning for amputation) and empagliflozin (for reduction in CV events and death) in 2016 likely contributed to a rapid change in prescribing preference for empagliflozin,” Dr. Dave and colleagues wrote.
 

GLP-1 agonists and frequency

Among the patients starting GLP-1 agonists, the proportion with CVD-HF increased by 3.9 percentage points, from 10.5% to 14.4% (P < .001) during the study period.

Prescriptions by endocrinologists declined as a proportion, but rose in absolute numbers (P < .001), and remained consistent for internists (> 55%; P = .12).

Prescribing of GLP-1 agonists by cardiologists remained low (< 0.5%) and was not higher for individuals with CVD-HF.

By individual GLP-1 agonist, liraglutide initiation declined by 32.1 percentage points, from 72.4% to 40.3% of GLP-1 agonist initiations (P < .001), whereas dulaglutide initiation rose by 43.8 percentage points, from 5.0% to 48.8% (P < .001). Again, these trends were similar in the subgroup of patients with CVD-HF.

The proportion of patients with CVD-HF in liraglutide initiators increased by 5.1 percentage points, from 10.5% to 15.6% (P = .018), and in exenatide initiators by 2.1 percentage points, from 10.3% to 13.8% (P = .77).

“Due to the reduced frequency of administration and possible formulary preferences, dulaglutide initiations surpassed liraglutide, the only GLP-1 agonist with evidence of CV benefit at the time,” Dr. Dave and colleagues noted.

Dulaglutide has just been granted an additional approval by the Food and Drug Administration for reducing the risk of major adverse cardiovascular events in adults with type 2 diabetes with and without established CVD or multiple CV risk factors. That makes it the first and only type 2 diabetes medicine approved to reduce the risk of CV events for both primary and secondary prevention populations.

The study was funded by the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston. Dr. Dave has reported receiving support from the New Jersey Alliance for Clinical and Translational Science.
 

This article first appeared on Medscape.com.

Empagliflozin and dulaglutide became the most-prescribed drugs in their respective classes for treating type 2 diabetes in the United States from July 2013 to June 2018, new research shows.

The findings, from U.S.-based administrative claims data, were published online in Diabetes Care by Chintan V. Dave, PharmD, PhD, and colleagues.

Among patients initiating oral sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) over the 5-year period, empagliflozin (Jardiance, Boehringer Ingelheim/Lilly) became the most commonly prescribed glucose-lowering drug, primarily driven by an increasing proportion of patients with diabetes who had a diagnosis of myocardial infarction, stroke, or heart failure (collectively called cardiovascular disease-heart failure [CVD-HF]).

And within the subcutaneous injectable glucagonlike peptide–1 receptor (GLP-1) agonist class, initiations of dulaglutide (Trulicity, Lilly) surpassed liraglutide in 2013-2018, although patients starting liraglutide (Victoza, Novo Nordisk) were more likely to have a CVD-HF diagnosis.

“This study shows that by preferring empagliflozin, prescribers have largely reacted in accordance with the available evidence and drug labels, while other factors such as lower price, frequency of administration [dulaglutide is given weekly and liraglutide is given daily], or prior authorizations may have led prescribers to select dulaglutide over liraglutide,” Dr. Dave, of the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, and colleagues wrote.

Internists and endocrinologists were the most frequent prescribers of both drug classes, but cardiologists rarely prescribed them, even for patients with established CVD-HF. “As patients with co-occurring diabetes and CVD are likely to see their cardiologist, these encounters may provide an additional opportunity to optimize their treatment,” the authors emphasized.

SGLT2 inhibitors and label changes

Over the study period, the proportion of patients who had CVD-HF and who received SGLT2 inhibitors rose by 3.4 percentage points, from 8.8% to 12.2% (P trend < .001).

The proportion of overall prescriptions for SGLT2 inhibitors written by endocrinologists dropped by 12.0%, although the absolute number of SGLT2-inhibitor prescriptions written by endocrinologists increased (P < .001).

The proportion written by internists did not change (P = .58), whereas it increased slightly among cardiologists but still barely exceeded 1% (P < .001). The findings were similar for the subgroup of patients with CVD-HF who initiated SGLT2 inhibitors.

By individual agents, canagliflozin (Invokana, Janssen) prescriptions dropped by 75.1 percentage points over the study period, from 100% in 2013 to just 24.9% by 2018 (P < .001), whereas empagliflozin initiation rose by 51.7 percentage points, from 13.9% to 65.6% of all SGLT2 inhibitor initiations (P < .001).

Among those initiating empagliflozin, the proportion with CVD-HF rose by 5.3 percentage points, from 8.8% to 14.1% (P < .001), mostly after the additional indication for reducing CV events and death was added to the U.S. label in December 2016.

In contrast, there were no significant changes in the proportions of those with CVD-HF who initiated canagliflozin (P = 065), dapagliflozin (P = .87), or other medications (P = .060).

“Changes in the drug label for canagliflozin (boxed warning for amputation) and empagliflozin (for reduction in CV events and death) in 2016 likely contributed to a rapid change in prescribing preference for empagliflozin,” Dr. Dave and colleagues wrote.
 

GLP-1 agonists and frequency

Among the patients starting GLP-1 agonists, the proportion with CVD-HF increased by 3.9 percentage points, from 10.5% to 14.4% (P < .001) during the study period.

Prescriptions by endocrinologists declined as a proportion, but rose in absolute numbers (P < .001), and remained consistent for internists (> 55%; P = .12).

Prescribing of GLP-1 agonists by cardiologists remained low (< 0.5%) and was not higher for individuals with CVD-HF.

By individual GLP-1 agonist, liraglutide initiation declined by 32.1 percentage points, from 72.4% to 40.3% of GLP-1 agonist initiations (P < .001), whereas dulaglutide initiation rose by 43.8 percentage points, from 5.0% to 48.8% (P < .001). Again, these trends were similar in the subgroup of patients with CVD-HF.

The proportion of patients with CVD-HF in liraglutide initiators increased by 5.1 percentage points, from 10.5% to 15.6% (P = .018), and in exenatide initiators by 2.1 percentage points, from 10.3% to 13.8% (P = .77).

“Due to the reduced frequency of administration and possible formulary preferences, dulaglutide initiations surpassed liraglutide, the only GLP-1 agonist with evidence of CV benefit at the time,” Dr. Dave and colleagues noted.

Dulaglutide has just been granted an additional approval by the Food and Drug Administration for reducing the risk of major adverse cardiovascular events in adults with type 2 diabetes with and without established CVD or multiple CV risk factors. That makes it the first and only type 2 diabetes medicine approved to reduce the risk of CV events for both primary and secondary prevention populations.

The study was funded by the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston. Dr. Dave has reported receiving support from the New Jersey Alliance for Clinical and Translational Science.
 

This article first appeared on Medscape.com.

Empagliflozin and dulaglutide became the most-prescribed drugs in their respective classes for treating type 2 diabetes in the United States from July 2013 to June 2018, new research shows.

The findings, from U.S.-based administrative claims data, were published online in Diabetes Care by Chintan V. Dave, PharmD, PhD, and colleagues.

Among patients initiating oral sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) over the 5-year period, empagliflozin (Jardiance, Boehringer Ingelheim/Lilly) became the most commonly prescribed glucose-lowering drug, primarily driven by an increasing proportion of patients with diabetes who had a diagnosis of myocardial infarction, stroke, or heart failure (collectively called cardiovascular disease-heart failure [CVD-HF]).

And within the subcutaneous injectable glucagonlike peptide–1 receptor (GLP-1) agonist class, initiations of dulaglutide (Trulicity, Lilly) surpassed liraglutide in 2013-2018, although patients starting liraglutide (Victoza, Novo Nordisk) were more likely to have a CVD-HF diagnosis.

“This study shows that by preferring empagliflozin, prescribers have largely reacted in accordance with the available evidence and drug labels, while other factors such as lower price, frequency of administration [dulaglutide is given weekly and liraglutide is given daily], or prior authorizations may have led prescribers to select dulaglutide over liraglutide,” Dr. Dave, of the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, and colleagues wrote.

Internists and endocrinologists were the most frequent prescribers of both drug classes, but cardiologists rarely prescribed them, even for patients with established CVD-HF. “As patients with co-occurring diabetes and CVD are likely to see their cardiologist, these encounters may provide an additional opportunity to optimize their treatment,” the authors emphasized.

SGLT2 inhibitors and label changes

Over the study period, the proportion of patients who had CVD-HF and who received SGLT2 inhibitors rose by 3.4 percentage points, from 8.8% to 12.2% (P trend < .001).

The proportion of overall prescriptions for SGLT2 inhibitors written by endocrinologists dropped by 12.0%, although the absolute number of SGLT2-inhibitor prescriptions written by endocrinologists increased (P < .001).

The proportion written by internists did not change (P = .58), whereas it increased slightly among cardiologists but still barely exceeded 1% (P < .001). The findings were similar for the subgroup of patients with CVD-HF who initiated SGLT2 inhibitors.

By individual agents, canagliflozin (Invokana, Janssen) prescriptions dropped by 75.1 percentage points over the study period, from 100% in 2013 to just 24.9% by 2018 (P < .001), whereas empagliflozin initiation rose by 51.7 percentage points, from 13.9% to 65.6% of all SGLT2 inhibitor initiations (P < .001).

Among those initiating empagliflozin, the proportion with CVD-HF rose by 5.3 percentage points, from 8.8% to 14.1% (P < .001), mostly after the additional indication for reducing CV events and death was added to the U.S. label in December 2016.

In contrast, there were no significant changes in the proportions of those with CVD-HF who initiated canagliflozin (P = 065), dapagliflozin (P = .87), or other medications (P = .060).

“Changes in the drug label for canagliflozin (boxed warning for amputation) and empagliflozin (for reduction in CV events and death) in 2016 likely contributed to a rapid change in prescribing preference for empagliflozin,” Dr. Dave and colleagues wrote.
 

GLP-1 agonists and frequency

Among the patients starting GLP-1 agonists, the proportion with CVD-HF increased by 3.9 percentage points, from 10.5% to 14.4% (P < .001) during the study period.

Prescriptions by endocrinologists declined as a proportion, but rose in absolute numbers (P < .001), and remained consistent for internists (> 55%; P = .12).

Prescribing of GLP-1 agonists by cardiologists remained low (< 0.5%) and was not higher for individuals with CVD-HF.

By individual GLP-1 agonist, liraglutide initiation declined by 32.1 percentage points, from 72.4% to 40.3% of GLP-1 agonist initiations (P < .001), whereas dulaglutide initiation rose by 43.8 percentage points, from 5.0% to 48.8% (P < .001). Again, these trends were similar in the subgroup of patients with CVD-HF.

The proportion of patients with CVD-HF in liraglutide initiators increased by 5.1 percentage points, from 10.5% to 15.6% (P = .018), and in exenatide initiators by 2.1 percentage points, from 10.3% to 13.8% (P = .77).

“Due to the reduced frequency of administration and possible formulary preferences, dulaglutide initiations surpassed liraglutide, the only GLP-1 agonist with evidence of CV benefit at the time,” Dr. Dave and colleagues noted.

Dulaglutide has just been granted an additional approval by the Food and Drug Administration for reducing the risk of major adverse cardiovascular events in adults with type 2 diabetes with and without established CVD or multiple CV risk factors. That makes it the first and only type 2 diabetes medicine approved to reduce the risk of CV events for both primary and secondary prevention populations.

The study was funded by the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston. Dr. Dave has reported receiving support from the New Jersey Alliance for Clinical and Translational Science.
 

This article first appeared on Medscape.com.

Reducing the cost of insulin – and other high-priced medications – in the United States will require a concerted effort involving multiple changes to the current convoluted drug pricing system, 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.

Reducing the cost of insulin – and other high-priced medications – in the United States will require a concerted effort involving multiple changes to the current convoluted drug pricing system, 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.

Reducing the cost of insulin – and other high-priced medications – in the United States will require a concerted effort involving multiple changes to the current convoluted drug pricing system, 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.

The Food and Drug Administration has approved an additional indication – reduction of cardiovascular (CV) disease risk – for the injectable formulation of the GLP-1 agonist 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.

The Food and Drug Administration has approved an additional indication – reduction of cardiovascular (CV) disease risk – for the injectable formulation of the GLP-1 agonist 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.

The Food and Drug Administration has approved an additional indication – reduction of cardiovascular (CV) disease risk – for the injectable formulation of the GLP-1 agonist 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.

BUSAN, SOUTH KOREA – Sodium-glucose transporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes seem to be as safe and effective in people aged 65 years and older as they are in younger individuals, new research suggests.

Findings from a real-world observational study of 50 older adults with type 2 diabetes were recently presented at the International Diabetes Federation congress by Carlos Trescoli-Serrano, MD, of Hospital Universitario de la Ribera, Valencia, Spain.

“The results are quite similar to those of younger people. … In a selected population they are safe. It doesn’t matter if patients are older or younger. You have to review the patients for complications,” Dr. Trescoli-Serrano said in an interview.

Asked to comment, session moderator Samuel Dagogo-Jack, MD, said: “We need more and more studies in older people for reassurance. The elderly have impaired kidneys, and these drugs depend on kidney filtration. It’s good to have data on elderly patients in the real world.”
 

Most had comorbidities

The 50 adults were a mean age of 67 years, and the oldest was 81 years. They had a mean diabetes duration of 12.5 years, and 40% were women. They had all been taking SGLT2 inhibitors for more than 3 years (mean 43.9 months) during 2015-2019.

At baseline, most (75%) were also taking metformin, 45% also took sulfonylureas, 37% dipeptidyl peptidase-4 (DPP-4) inhibitors, and 36% insulin.

Most (81%) also had hypertension, half (51%) had hypercholesterolemia, a third (33%) had obesity, and 32% had a previous cardiovascular event.

With SGLT2-inhibitor treatment, the average hemoglobin A_1c level dropped from 8.5% to 7.3% (P less than .01), body weight was reduced from 91.0 kg to 84.7 kg (P less than .01), systolic blood pressure from 134.5 mm Hg to 130.4 mm Hg (P = .02), and diastolic blood pressure from 76.2 mm Hg to 73.3 mm Hg (P = .04).

This effect on blood pressure “should be considered” because it means that “antihypertensive treatment might need to be reviewed,” Dr. Trescoli-Serrano commented.

There were no significant changes in estimated glomerular filtration rate (eGFR), microalbuminuria, lipid profile, hematocrit, or heart rate, although there were positive trends in both renal function and lipid profiles.

No patient had a fall, volume depletion symptoms, or diabetic ketoacidosis. However, 38% of patients were treated for urinary-genital infections, and 8% had to stop taking the SGLT2 inhibitor because of such infections.

That percentage seemed unusually high and was “an outlier, not the general experience,” commented Dr. Dagogo-Jack, chief of the Division of Endocrinology, Diabetes and Metabolism at the University of Tennessee Health Science Center, Memphis. He noted that infections with SGLT2 inhibitors are more often genital fungal than urinary tract infections, but the latter are more common in people with diabetes overall, and the study wasn’t randomized, so this might explain the finding.

New nonfatal cardiovascular events occurred in 22% of the patients, mainly cerebrovascular disease during the treatment period. Of those, 66% had had a previous cardiovascular event prior to starting on SGLT2 inhibitors.

Severe hypoglycemia was recorded in one patient, who was also taking insulin. Overall 10% died, mainly because of neoplastic causes.

“Long-term treatment with SGLT2 inhibitors are safe and effective when added to not-well-controlled elderly type 2 diabetes patients in a real-world experience,” Dr. Trescoli-Serrano concluded.

Dr. Dagogo-Jack is a consultant for Merck, Janssen, and Sanofi and owns stock in Dance Pharma and Jana Care.



A version of this story originally appeared on Medscape.com.

BUSAN, SOUTH KOREA – Sodium-glucose transporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes seem to be as safe and effective in people aged 65 years and older as they are in younger individuals, new research suggests.

Findings from a real-world observational study of 50 older adults with type 2 diabetes were recently presented at the International Diabetes Federation congress by Carlos Trescoli-Serrano, MD, of Hospital Universitario de la Ribera, Valencia, Spain.

“The results are quite similar to those of younger people. … In a selected population they are safe. It doesn’t matter if patients are older or younger. You have to review the patients for complications,” Dr. Trescoli-Serrano said in an interview.

Asked to comment, session moderator Samuel Dagogo-Jack, MD, said: “We need more and more studies in older people for reassurance. The elderly have impaired kidneys, and these drugs depend on kidney filtration. It’s good to have data on elderly patients in the real world.”
 

Most had comorbidities

The 50 adults were a mean age of 67 years, and the oldest was 81 years. They had a mean diabetes duration of 12.5 years, and 40% were women. They had all been taking SGLT2 inhibitors for more than 3 years (mean 43.9 months) during 2015-2019.

At baseline, most (75%) were also taking metformin, 45% also took sulfonylureas, 37% dipeptidyl peptidase-4 (DPP-4) inhibitors, and 36% insulin.

Most (81%) also had hypertension, half (51%) had hypercholesterolemia, a third (33%) had obesity, and 32% had a previous cardiovascular event.

With SGLT2-inhibitor treatment, the average hemoglobin A_1c level dropped from 8.5% to 7.3% (P less than .01), body weight was reduced from 91.0 kg to 84.7 kg (P less than .01), systolic blood pressure from 134.5 mm Hg to 130.4 mm Hg (P = .02), and diastolic blood pressure from 76.2 mm Hg to 73.3 mm Hg (P = .04).

This effect on blood pressure “should be considered” because it means that “antihypertensive treatment might need to be reviewed,” Dr. Trescoli-Serrano commented.

There were no significant changes in estimated glomerular filtration rate (eGFR), microalbuminuria, lipid profile, hematocrit, or heart rate, although there were positive trends in both renal function and lipid profiles.

No patient had a fall, volume depletion symptoms, or diabetic ketoacidosis. However, 38% of patients were treated for urinary-genital infections, and 8% had to stop taking the SGLT2 inhibitor because of such infections.

That percentage seemed unusually high and was “an outlier, not the general experience,” commented Dr. Dagogo-Jack, chief of the Division of Endocrinology, Diabetes and Metabolism at the University of Tennessee Health Science Center, Memphis. He noted that infections with SGLT2 inhibitors are more often genital fungal than urinary tract infections, but the latter are more common in people with diabetes overall, and the study wasn’t randomized, so this might explain the finding.

New nonfatal cardiovascular events occurred in 22% of the patients, mainly cerebrovascular disease during the treatment period. Of those, 66% had had a previous cardiovascular event prior to starting on SGLT2 inhibitors.

Severe hypoglycemia was recorded in one patient, who was also taking insulin. Overall 10% died, mainly because of neoplastic causes.

“Long-term treatment with SGLT2 inhibitors are safe and effective when added to not-well-controlled elderly type 2 diabetes patients in a real-world experience,” Dr. Trescoli-Serrano concluded.

Dr. Dagogo-Jack is a consultant for Merck, Janssen, and Sanofi and owns stock in Dance Pharma and Jana Care.



A version of this story originally appeared on Medscape.com.

BUSAN, SOUTH KOREA – Sodium-glucose transporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes seem to be as safe and effective in people aged 65 years and older as they are in younger individuals, new research suggests.

Findings from a real-world observational study of 50 older adults with type 2 diabetes were recently presented at the International Diabetes Federation congress by Carlos Trescoli-Serrano, MD, of Hospital Universitario de la Ribera, Valencia, Spain.

“The results are quite similar to those of younger people. … In a selected population they are safe. It doesn’t matter if patients are older or younger. You have to review the patients for complications,” Dr. Trescoli-Serrano said in an interview.

Asked to comment, session moderator Samuel Dagogo-Jack, MD, said: “We need more and more studies in older people for reassurance. The elderly have impaired kidneys, and these drugs depend on kidney filtration. It’s good to have data on elderly patients in the real world.”
 

Most had comorbidities

The 50 adults were a mean age of 67 years, and the oldest was 81 years. They had a mean diabetes duration of 12.5 years, and 40% were women. They had all been taking SGLT2 inhibitors for more than 3 years (mean 43.9 months) during 2015-2019.

At baseline, most (75%) were also taking metformin, 45% also took sulfonylureas, 37% dipeptidyl peptidase-4 (DPP-4) inhibitors, and 36% insulin.

Most (81%) also had hypertension, half (51%) had hypercholesterolemia, a third (33%) had obesity, and 32% had a previous cardiovascular event.

With SGLT2-inhibitor treatment, the average hemoglobin A_1c level dropped from 8.5% to 7.3% (P less than .01), body weight was reduced from 91.0 kg to 84.7 kg (P less than .01), systolic blood pressure from 134.5 mm Hg to 130.4 mm Hg (P = .02), and diastolic blood pressure from 76.2 mm Hg to 73.3 mm Hg (P = .04).

This effect on blood pressure “should be considered” because it means that “antihypertensive treatment might need to be reviewed,” Dr. Trescoli-Serrano commented.

There were no significant changes in estimated glomerular filtration rate (eGFR), microalbuminuria, lipid profile, hematocrit, or heart rate, although there were positive trends in both renal function and lipid profiles.

No patient had a fall, volume depletion symptoms, or diabetic ketoacidosis. However, 38% of patients were treated for urinary-genital infections, and 8% had to stop taking the SGLT2 inhibitor because of such infections.

That percentage seemed unusually high and was “an outlier, not the general experience,” commented Dr. Dagogo-Jack, chief of the Division of Endocrinology, Diabetes and Metabolism at the University of Tennessee Health Science Center, Memphis. He noted that infections with SGLT2 inhibitors are more often genital fungal than urinary tract infections, but the latter are more common in people with diabetes overall, and the study wasn’t randomized, so this might explain the finding.

New nonfatal cardiovascular events occurred in 22% of the patients, mainly cerebrovascular disease during the treatment period. Of those, 66% had had a previous cardiovascular event prior to starting on SGLT2 inhibitors.

Severe hypoglycemia was recorded in one patient, who was also taking insulin. Overall 10% died, mainly because of neoplastic causes.

“Long-term treatment with SGLT2 inhibitors are safe and effective when added to not-well-controlled elderly type 2 diabetes patients in a real-world experience,” Dr. Trescoli-Serrano concluded.

Dr. Dagogo-Jack is a consultant for Merck, Janssen, and Sanofi and owns stock in Dance Pharma and Jana Care.



A version of this story originally appeared on Medscape.com.