In back-to-back appearances on Capitol Hill Wednesday, Health and Human Services Secretary Tom Price sparred with Democrats over the Trump administration’s budget cuts for his department and the coming troubles in the individual health insurance market.

“President Trump’s budget does not confuse government spending with government success,” Price said, defending a spending plan that calls for substantial funding reductions to Medicaid, the Centers for Disease Control and Prevention, the National Institutes of Health, and other HHS agencies.

The problem with many federal programs “is not that they are too expensive or too underfunded. The real problem is that they do not work – they fail the very people they are meant to help,” Price said in testimony before the Senate Finance Committee and the House Ways and Means Committee.

He cited Medicaid, the federal-state insurance program for low-income people, as an example of an area in which rising costs require reforms. The administration’s budget would reduce federal Medicaid funds to states by $610 billion over a decade. Under its proposal, states would gain latitude over how to spend those funds, which Price said would lead to innovations and efficiencies.

Sen. Sherrod Brown (D-Ohio) questioned whether HHS is budgeting enough money under Medicaid to fight the opioid-abuse epidemic. Of the $939 million that Ohio spent on opioid treatment in 2016, 70% came from federal Medicaid dollars, he said.

“You would never propose we fight cancer with a $50 million increase to a grant program,” Brown said. “How does this possibly work if you’re going to cut the biggest revenue stream to treat people?”

Price pushed back, pointing out that more than 52,000 Americans died of overdose deaths in 2015.

“We continue to tolerate a system that allows for overdose deaths, and I simply won’t allow it,” Price said.

Trump’s budget has come under heavy attack in Congress since its release last month and is expected to undergo much rewriting. The budget would take effect for the fiscal year starting Oct. 1.

Democratic senators and representatives on the committees repeatedly challenged Price on his testimony and the administration’s health care policies, sometimes using strong words and loud voices.

“It’s mean-spirited. It’s not good for America. We can do much better,” thundered Rep. John Lewis (D-Ga.).

With insurers facing looming deadlines to decide whether to participate in the Affordable Care Act’s online marketplaces next year, lawmakers also pressed Price on whether the Trump administration will pay insurers about $7 billion in “cost-sharing subsidies” for 2018. The White House has sent mixed signals, but many insurers’ decisions about next year’s premiums and where they will offer health plans hinge on the verdict.

Sen. Debbie Stabenow (D-Mich.) repeatedly asked Price if he would commit to making subsidy payments, but Price refused to answer beyond reiterating that the budget includes payments through 2018. Price said he could not elaborate because he is the defendant in a lawsuit regarding these subsidies – a still-pending case brought by the Republican-led House of Representatives during the Obama administration.

Democrats accused Price of doing little to stabilize the individual insurance marketplace as insurers have announced withdrawal plans. But, Sen. Pat Roberts (R-Kan.) said the market was failing and it wasn’t Price’s fault.

“We are in the Obama car and it’s like being in the same car as Thelma and Louise going into the canyon,” he said. “We need to get out of the car.”

Price was also asked about a draft rule from HHS that would scale back the ACA’s mandate requiring nearly all employers to offer health insurance covering birth control. The HHS proposal would allow more types of employers to claim moral or religious exemptions to the mandate. “I think that, for women who desire birth control, it should be available,” Price said.

When Sen. Maria Cantwell (D-Wash.) pressed him to answer whether birth control should be available to women through their employers, Price reiterated that it should be available to women who want it.

“This is a very big problem,” she said. ”Women cannot be discriminated against by their employers who want to cherry-pick women’s health.”

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

In back-to-back appearances on Capitol Hill Wednesday, Health and Human Services Secretary Tom Price sparred with Democrats over the Trump administration’s budget cuts for his department and the coming troubles in the individual health insurance market.

“President Trump’s budget does not confuse government spending with government success,” Price said, defending a spending plan that calls for substantial funding reductions to Medicaid, the Centers for Disease Control and Prevention, the National Institutes of Health, and other HHS agencies.

The problem with many federal programs “is not that they are too expensive or too underfunded. The real problem is that they do not work – they fail the very people they are meant to help,” Price said in testimony before the Senate Finance Committee and the House Ways and Means Committee.

He cited Medicaid, the federal-state insurance program for low-income people, as an example of an area in which rising costs require reforms. The administration’s budget would reduce federal Medicaid funds to states by $610 billion over a decade. Under its proposal, states would gain latitude over how to spend those funds, which Price said would lead to innovations and efficiencies.

Sen. Sherrod Brown (D-Ohio) questioned whether HHS is budgeting enough money under Medicaid to fight the opioid-abuse epidemic. Of the $939 million that Ohio spent on opioid treatment in 2016, 70% came from federal Medicaid dollars, he said.

“You would never propose we fight cancer with a $50 million increase to a grant program,” Brown said. “How does this possibly work if you’re going to cut the biggest revenue stream to treat people?”

Price pushed back, pointing out that more than 52,000 Americans died of overdose deaths in 2015.

“We continue to tolerate a system that allows for overdose deaths, and I simply won’t allow it,” Price said.

Trump’s budget has come under heavy attack in Congress since its release last month and is expected to undergo much rewriting. The budget would take effect for the fiscal year starting Oct. 1.

Democratic senators and representatives on the committees repeatedly challenged Price on his testimony and the administration’s health care policies, sometimes using strong words and loud voices.

“It’s mean-spirited. It’s not good for America. We can do much better,” thundered Rep. John Lewis (D-Ga.).

With insurers facing looming deadlines to decide whether to participate in the Affordable Care Act’s online marketplaces next year, lawmakers also pressed Price on whether the Trump administration will pay insurers about $7 billion in “cost-sharing subsidies” for 2018. The White House has sent mixed signals, but many insurers’ decisions about next year’s premiums and where they will offer health plans hinge on the verdict.

Sen. Debbie Stabenow (D-Mich.) repeatedly asked Price if he would commit to making subsidy payments, but Price refused to answer beyond reiterating that the budget includes payments through 2018. Price said he could not elaborate because he is the defendant in a lawsuit regarding these subsidies – a still-pending case brought by the Republican-led House of Representatives during the Obama administration.

Democrats accused Price of doing little to stabilize the individual insurance marketplace as insurers have announced withdrawal plans. But, Sen. Pat Roberts (R-Kan.) said the market was failing and it wasn’t Price’s fault.

“We are in the Obama car and it’s like being in the same car as Thelma and Louise going into the canyon,” he said. “We need to get out of the car.”

Price was also asked about a draft rule from HHS that would scale back the ACA’s mandate requiring nearly all employers to offer health insurance covering birth control. The HHS proposal would allow more types of employers to claim moral or religious exemptions to the mandate. “I think that, for women who desire birth control, it should be available,” Price said.

When Sen. Maria Cantwell (D-Wash.) pressed him to answer whether birth control should be available to women through their employers, Price reiterated that it should be available to women who want it.

“This is a very big problem,” she said. ”Women cannot be discriminated against by their employers who want to cherry-pick women’s health.”

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

In back-to-back appearances on Capitol Hill Wednesday, Health and Human Services Secretary Tom Price sparred with Democrats over the Trump administration’s budget cuts for his department and the coming troubles in the individual health insurance market.

“President Trump’s budget does not confuse government spending with government success,” Price said, defending a spending plan that calls for substantial funding reductions to Medicaid, the Centers for Disease Control and Prevention, the National Institutes of Health, and other HHS agencies.

The problem with many federal programs “is not that they are too expensive or too underfunded. The real problem is that they do not work – they fail the very people they are meant to help,” Price said in testimony before the Senate Finance Committee and the House Ways and Means Committee.

He cited Medicaid, the federal-state insurance program for low-income people, as an example of an area in which rising costs require reforms. The administration’s budget would reduce federal Medicaid funds to states by $610 billion over a decade. Under its proposal, states would gain latitude over how to spend those funds, which Price said would lead to innovations and efficiencies.

Sen. Sherrod Brown (D-Ohio) questioned whether HHS is budgeting enough money under Medicaid to fight the opioid-abuse epidemic. Of the $939 million that Ohio spent on opioid treatment in 2016, 70% came from federal Medicaid dollars, he said.

“You would never propose we fight cancer with a $50 million increase to a grant program,” Brown said. “How does this possibly work if you’re going to cut the biggest revenue stream to treat people?”

Price pushed back, pointing out that more than 52,000 Americans died of overdose deaths in 2015.

“We continue to tolerate a system that allows for overdose deaths, and I simply won’t allow it,” Price said.

Trump’s budget has come under heavy attack in Congress since its release last month and is expected to undergo much rewriting. The budget would take effect for the fiscal year starting Oct. 1.

Democratic senators and representatives on the committees repeatedly challenged Price on his testimony and the administration’s health care policies, sometimes using strong words and loud voices.

“It’s mean-spirited. It’s not good for America. We can do much better,” thundered Rep. John Lewis (D-Ga.).

With insurers facing looming deadlines to decide whether to participate in the Affordable Care Act’s online marketplaces next year, lawmakers also pressed Price on whether the Trump administration will pay insurers about $7 billion in “cost-sharing subsidies” for 2018. The White House has sent mixed signals, but many insurers’ decisions about next year’s premiums and where they will offer health plans hinge on the verdict.

Sen. Debbie Stabenow (D-Mich.) repeatedly asked Price if he would commit to making subsidy payments, but Price refused to answer beyond reiterating that the budget includes payments through 2018. Price said he could not elaborate because he is the defendant in a lawsuit regarding these subsidies – a still-pending case brought by the Republican-led House of Representatives during the Obama administration.

Democrats accused Price of doing little to stabilize the individual insurance marketplace as insurers have announced withdrawal plans. But, Sen. Pat Roberts (R-Kan.) said the market was failing and it wasn’t Price’s fault.

“We are in the Obama car and it’s like being in the same car as Thelma and Louise going into the canyon,” he said. “We need to get out of the car.”

Price was also asked about a draft rule from HHS that would scale back the ACA’s mandate requiring nearly all employers to offer health insurance covering birth control. The HHS proposal would allow more types of employers to claim moral or religious exemptions to the mandate. “I think that, for women who desire birth control, it should be available,” Price said.

When Sen. Maria Cantwell (D-Wash.) pressed him to answer whether birth control should be available to women through their employers, Price reiterated that it should be available to women who want it.

“This is a very big problem,” she said. ”Women cannot be discriminated against by their employers who want to cherry-pick women’s health.”

Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

BOSTON – Women who were prepregnancy, frequent, and loud snorers during pregnancy had a significantly higher risk of preterm or early term delivery, in a study presented at the annual meeting of the Associated Professional Sleep Societies.

“The fact that there is an association between snoring and time to delivery in a cohort which is not hypertensive is alarming, and I think that treatment for snoring earlier on in pregnancy may alleviate some of these outcomes,” reported Galit Levi Dunietz, PhD, MPH, of the University of Michigan in a session at the meeting.

BOSTON – Women who were prepregnancy, frequent, and loud snorers during pregnancy had a significantly higher risk of preterm or early term delivery, in a study presented at the annual meeting of the Associated Professional Sleep Societies.

“The fact that there is an association between snoring and time to delivery in a cohort which is not hypertensive is alarming, and I think that treatment for snoring earlier on in pregnancy may alleviate some of these outcomes,” reported Galit Levi Dunietz, PhD, MPH, of the University of Michigan in a session at the meeting.

BOSTON – Women who were prepregnancy, frequent, and loud snorers during pregnancy had a significantly higher risk of preterm or early term delivery, in a study presented at the annual meeting of the Associated Professional Sleep Societies.

“The fact that there is an association between snoring and time to delivery in a cohort which is not hypertensive is alarming, and I think that treatment for snoring earlier on in pregnancy may alleviate some of these outcomes,” reported Galit Levi Dunietz, PhD, MPH, of the University of Michigan in a session at the meeting.

SAN DIEGO – Findings from the landmark 3-year REMOVAL trial find that metformin could hold potential as a tool to reduce cardiovascular disease (CVD) risk in patients with type 1 diabetes. But – in a challenge to current British and American guidelines – findings from the study suggest that the drug doesn’t meaningfully improve glycemic control.

“The CVD benefit is suggestive, but it’s by no means conclusive,” Naveed Sattar, MD, PhD, of the University of Glasgow said in a presentation at the scientific meetings of the American Diabetic Association. As for glycemic control, “you should not prescribe metformin if you want a clinical change in hemoglobin A1c,” he said.

The findings don’t examine CVD outcomes, and researchers bemoaned their inability to launch such a project because of limitations in funding. Still, the study, funded by the Juvenile Diabetes Research Foundation, is the largest to examine metformin in type 1 diabetes.

The Food and Drug Administration has not approved metformin for type 1 diabetes. However, the American Diabetes Association’s 2017 Standard of Care guidelines note that “adding metformin to insulin therapy may reduce insulin requirements and improve metabolic control in overweight/obese patients with poorly controlled type 1 diabetes” (Diabetes Care. 2017 Jan;40[Suppl 1]).

“Metformin has known efficacy for reducing HbA1c, and, at the time we did this, it was one of few diabetes drugs with indications of an effect on cardiovascular disease risk,” study coauthor Helen M. Colhoun, MD, of the University of Edinburgh said during the discussion following the presentation.

The REMOVAL (cardiovascular and metabolic effects of metformin in patients with type 1 diabetes) trial took place from 2011 to 2014. Involved researchers at 23 hospital diabetes clinics around the world randomly assigned 428 patients to metformin (n = 219) and placebo (n = 209) arms.

The patients were all 40 years or older, with a mean age of 55 years. All patients had been diagnosed with type 1 diabetes at least five years prior to the study and met at least 3 of 10 criteria for high risk of cardiovascular disease. Men accounted for 59% of the patients, about 98% were white, and about 79% were obese or overweight. Patients had high levels of use of statins (73%), blood pressure medications (73%), and antiplatelet drugs (39%).

Participants took oral metformin 1,000 mg twice daily or placebo. The results were reported at the ADA meeting and simultaneously online on June 11, 2017 in Lancet Diabetes Endocrinology (2017 Jun 11. doi: 10.1016/S2213-8587[17]30194-8).

In regard to CVD indicators, the researchers did not find significant reduction in the progression of average common carotid artery intima-media thickness (cIMT) (–0.005 mm per year; 95% confidence interval, –0.012-0.002; P = .1664) in metformin, vs. placebo.

There was, however, a significant reduction in maximal cIMT (–0.013 mm per year; 95% CI, –0.024 to –0.003; P = .0093). The study describes this as a surrogate measure for atherosclerosis progression, although it’s a tertiary rather than primary outcome.

Researchers saw a slight decline in HbA1c in the metformin group (–0.13%; 95% CI, –0.22 to –0.037; P = .0060), but researchers say this occurred early and was not sustained.

In the metformin group, compared with placebo, researchers also found reductions in body weight (–1.17 kg; 95% CI,–1.66 to –0.69; p less than .0001) and LDL cholesterol (–0.13 mmol/L; 95% CI, –0.24 to –0.03; P = .0117) on average.

Researchers didn’t find a significant average reduction in insulin use in the metformin group, compared with placebo (–0.005 units per kg; 95% CI, –0.022-0.012, P = .545), although they did notice “a small but sustained reduction in patients allocated to metformin (estimated in post-hoc analyses as –0.023 units per kg; 95% CI, –0.045 to –0.0005; P = .045).”

Rates of gastrointestinal problems were higher in the metformin group, and 27% of these patients discontinued treatment, compared with 12% of placebo patients (P = .0002). Five of the metformin patients died (as did two of the placebo patients), but researchers didn’t link the deaths to medication.

The findings were clearly disappointing. “We’re certainly not claiming that this is a positive trial,” said study coauthor Dr. Colhoun.

A member of the audience at the AAD meeting asked another coauthor, Irene Hramiak, MD, of the University of Western Ontario, London, whether she would prescribe metformin to a patient with type 1 diabetes and a high risk of CVD. “Probably not,” she said, but she added that it may have value in adolescents with weight issues. In those cases, she said, there may be a benefit to improving weight control and lowering insulin doses.

In light of the study findings, the authors recommend revising guidelines that suggest the use of metformin in type 1 diabetes: “We identified a transient improvement in glycemia that reverted to baseline with insulin dose reduction and identified no suggestion of greater benefit in overweight or obese patients.”

The study adds, “Rather than a role in glycemic control, our findings suggest that long-term use of metformin in type 1 diabetes might reduce the long-term risk of cardiovascular disease via small but sustained reductions in bodyweight and LDL cholesterol.”

The Juvenile Diabetes Research Foundation funded the study. Merck Germany KGaA provided medication and shipping for free. Itamar Medical donated equipment and services. Dr. Sataar reported consulting fees and/or research support from Amgen, Boehringer Ingelheim, Eli Lilly, Janssen, and Novo Nordisk. Dr. Colhoun and Dr. Hramiak reported multiple disclosures, including advisory panel, research support, and speaker’s bureau and stock/shareholder relationships.

This article was updated June 19, 2017.

SAN DIEGO – Findings from the landmark 3-year REMOVAL trial find that metformin could hold potential as a tool to reduce cardiovascular disease (CVD) risk in patients with type 1 diabetes. But – in a challenge to current British and American guidelines – findings from the study suggest that the drug doesn’t meaningfully improve glycemic control.

“The CVD benefit is suggestive, but it’s by no means conclusive,” Naveed Sattar, MD, PhD, of the University of Glasgow said in a presentation at the scientific meetings of the American Diabetic Association. As for glycemic control, “you should not prescribe metformin if you want a clinical change in hemoglobin A1c,” he said.

The findings don’t examine CVD outcomes, and researchers bemoaned their inability to launch such a project because of limitations in funding. Still, the study, funded by the Juvenile Diabetes Research Foundation, is the largest to examine metformin in type 1 diabetes.

The Food and Drug Administration has not approved metformin for type 1 diabetes. However, the American Diabetes Association’s 2017 Standard of Care guidelines note that “adding metformin to insulin therapy may reduce insulin requirements and improve metabolic control in overweight/obese patients with poorly controlled type 1 diabetes” (Diabetes Care. 2017 Jan;40[Suppl 1]).

“Metformin has known efficacy for reducing HbA1c, and, at the time we did this, it was one of few diabetes drugs with indications of an effect on cardiovascular disease risk,” study coauthor Helen M. Colhoun, MD, of the University of Edinburgh said during the discussion following the presentation.

The REMOVAL (cardiovascular and metabolic effects of metformin in patients with type 1 diabetes) trial took place from 2011 to 2014. Involved researchers at 23 hospital diabetes clinics around the world randomly assigned 428 patients to metformin (n = 219) and placebo (n = 209) arms.

The patients were all 40 years or older, with a mean age of 55 years. All patients had been diagnosed with type 1 diabetes at least five years prior to the study and met at least 3 of 10 criteria for high risk of cardiovascular disease. Men accounted for 59% of the patients, about 98% were white, and about 79% were obese or overweight. Patients had high levels of use of statins (73%), blood pressure medications (73%), and antiplatelet drugs (39%).

Participants took oral metformin 1,000 mg twice daily or placebo. The results were reported at the ADA meeting and simultaneously online on June 11, 2017 in Lancet Diabetes Endocrinology (2017 Jun 11. doi: 10.1016/S2213-8587[17]30194-8).

In regard to CVD indicators, the researchers did not find significant reduction in the progression of average common carotid artery intima-media thickness (cIMT) (–0.005 mm per year; 95% confidence interval, –0.012-0.002; P = .1664) in metformin, vs. placebo.

There was, however, a significant reduction in maximal cIMT (–0.013 mm per year; 95% CI, –0.024 to –0.003; P = .0093). The study describes this as a surrogate measure for atherosclerosis progression, although it’s a tertiary rather than primary outcome.

Researchers saw a slight decline in HbA1c in the metformin group (–0.13%; 95% CI, –0.22 to –0.037; P = .0060), but researchers say this occurred early and was not sustained.

In the metformin group, compared with placebo, researchers also found reductions in body weight (–1.17 kg; 95% CI,–1.66 to –0.69; p less than .0001) and LDL cholesterol (–0.13 mmol/L; 95% CI, –0.24 to –0.03; P = .0117) on average.

Researchers didn’t find a significant average reduction in insulin use in the metformin group, compared with placebo (–0.005 units per kg; 95% CI, –0.022-0.012, P = .545), although they did notice “a small but sustained reduction in patients allocated to metformin (estimated in post-hoc analyses as –0.023 units per kg; 95% CI, –0.045 to –0.0005; P = .045).”

Rates of gastrointestinal problems were higher in the metformin group, and 27% of these patients discontinued treatment, compared with 12% of placebo patients (P = .0002). Five of the metformin patients died (as did two of the placebo patients), but researchers didn’t link the deaths to medication.

The findings were clearly disappointing. “We’re certainly not claiming that this is a positive trial,” said study coauthor Dr. Colhoun.

A member of the audience at the AAD meeting asked another coauthor, Irene Hramiak, MD, of the University of Western Ontario, London, whether she would prescribe metformin to a patient with type 1 diabetes and a high risk of CVD. “Probably not,” she said, but she added that it may have value in adolescents with weight issues. In those cases, she said, there may be a benefit to improving weight control and lowering insulin doses.

In light of the study findings, the authors recommend revising guidelines that suggest the use of metformin in type 1 diabetes: “We identified a transient improvement in glycemia that reverted to baseline with insulin dose reduction and identified no suggestion of greater benefit in overweight or obese patients.”

The study adds, “Rather than a role in glycemic control, our findings suggest that long-term use of metformin in type 1 diabetes might reduce the long-term risk of cardiovascular disease via small but sustained reductions in bodyweight and LDL cholesterol.”

The Juvenile Diabetes Research Foundation funded the study. Merck Germany KGaA provided medication and shipping for free. Itamar Medical donated equipment and services. Dr. Sataar reported consulting fees and/or research support from Amgen, Boehringer Ingelheim, Eli Lilly, Janssen, and Novo Nordisk. Dr. Colhoun and Dr. Hramiak reported multiple disclosures, including advisory panel, research support, and speaker’s bureau and stock/shareholder relationships.

This article was updated June 19, 2017.

SAN DIEGO – Findings from the landmark 3-year REMOVAL trial find that metformin could hold potential as a tool to reduce cardiovascular disease (CVD) risk in patients with type 1 diabetes. But – in a challenge to current British and American guidelines – findings from the study suggest that the drug doesn’t meaningfully improve glycemic control.

“The CVD benefit is suggestive, but it’s by no means conclusive,” Naveed Sattar, MD, PhD, of the University of Glasgow said in a presentation at the scientific meetings of the American Diabetic Association. As for glycemic control, “you should not prescribe metformin if you want a clinical change in hemoglobin A1c,” he said.

The findings don’t examine CVD outcomes, and researchers bemoaned their inability to launch such a project because of limitations in funding. Still, the study, funded by the Juvenile Diabetes Research Foundation, is the largest to examine metformin in type 1 diabetes.

The Food and Drug Administration has not approved metformin for type 1 diabetes. However, the American Diabetes Association’s 2017 Standard of Care guidelines note that “adding metformin to insulin therapy may reduce insulin requirements and improve metabolic control in overweight/obese patients with poorly controlled type 1 diabetes” (Diabetes Care. 2017 Jan;40[Suppl 1]).

“Metformin has known efficacy for reducing HbA1c, and, at the time we did this, it was one of few diabetes drugs with indications of an effect on cardiovascular disease risk,” study coauthor Helen M. Colhoun, MD, of the University of Edinburgh said during the discussion following the presentation.

The REMOVAL (cardiovascular and metabolic effects of metformin in patients with type 1 diabetes) trial took place from 2011 to 2014. Involved researchers at 23 hospital diabetes clinics around the world randomly assigned 428 patients to metformin (n = 219) and placebo (n = 209) arms.

The patients were all 40 years or older, with a mean age of 55 years. All patients had been diagnosed with type 1 diabetes at least five years prior to the study and met at least 3 of 10 criteria for high risk of cardiovascular disease. Men accounted for 59% of the patients, about 98% were white, and about 79% were obese or overweight. Patients had high levels of use of statins (73%), blood pressure medications (73%), and antiplatelet drugs (39%).

Participants took oral metformin 1,000 mg twice daily or placebo. The results were reported at the ADA meeting and simultaneously online on June 11, 2017 in Lancet Diabetes Endocrinology (2017 Jun 11. doi: 10.1016/S2213-8587[17]30194-8).

In regard to CVD indicators, the researchers did not find significant reduction in the progression of average common carotid artery intima-media thickness (cIMT) (–0.005 mm per year; 95% confidence interval, –0.012-0.002; P = .1664) in metformin, vs. placebo.

There was, however, a significant reduction in maximal cIMT (–0.013 mm per year; 95% CI, –0.024 to –0.003; P = .0093). The study describes this as a surrogate measure for atherosclerosis progression, although it’s a tertiary rather than primary outcome.

Researchers saw a slight decline in HbA1c in the metformin group (–0.13%; 95% CI, –0.22 to –0.037; P = .0060), but researchers say this occurred early and was not sustained.

In the metformin group, compared with placebo, researchers also found reductions in body weight (–1.17 kg; 95% CI,–1.66 to –0.69; p less than .0001) and LDL cholesterol (–0.13 mmol/L; 95% CI, –0.24 to –0.03; P = .0117) on average.

Researchers didn’t find a significant average reduction in insulin use in the metformin group, compared with placebo (–0.005 units per kg; 95% CI, –0.022-0.012, P = .545), although they did notice “a small but sustained reduction in patients allocated to metformin (estimated in post-hoc analyses as –0.023 units per kg; 95% CI, –0.045 to –0.0005; P = .045).”

Rates of gastrointestinal problems were higher in the metformin group, and 27% of these patients discontinued treatment, compared with 12% of placebo patients (P = .0002). Five of the metformin patients died (as did two of the placebo patients), but researchers didn’t link the deaths to medication.

The findings were clearly disappointing. “We’re certainly not claiming that this is a positive trial,” said study coauthor Dr. Colhoun.

A member of the audience at the AAD meeting asked another coauthor, Irene Hramiak, MD, of the University of Western Ontario, London, whether she would prescribe metformin to a patient with type 1 diabetes and a high risk of CVD. “Probably not,” she said, but she added that it may have value in adolescents with weight issues. In those cases, she said, there may be a benefit to improving weight control and lowering insulin doses.

In light of the study findings, the authors recommend revising guidelines that suggest the use of metformin in type 1 diabetes: “We identified a transient improvement in glycemia that reverted to baseline with insulin dose reduction and identified no suggestion of greater benefit in overweight or obese patients.”

The study adds, “Rather than a role in glycemic control, our findings suggest that long-term use of metformin in type 1 diabetes might reduce the long-term risk of cardiovascular disease via small but sustained reductions in bodyweight and LDL cholesterol.”

The Juvenile Diabetes Research Foundation funded the study. Merck Germany KGaA provided medication and shipping for free. Itamar Medical donated equipment and services. Dr. Sataar reported consulting fees and/or research support from Amgen, Boehringer Ingelheim, Eli Lilly, Janssen, and Novo Nordisk. Dr. Colhoun and Dr. Hramiak reported multiple disclosures, including advisory panel, research support, and speaker’s bureau and stock/shareholder relationships.

This article was updated June 19, 2017.

CHICAGO – A substantial number of adenomas may be missed by pathologists, but changes in the standard methodology can significantly decrease that amount, according to findings presented at Digestive Disease Week^®.

A nondiagnostic result is common in histologic specimens obtained from the colon and occurs in about 9% of biopsies. However, a protocol known as “exhaustive leveling of histologically nondiagnostic specimens” can significantly increase the detection of adenomas.

“In our study, we were answering the question, Are pathologists missing adenomas?” said Lauren Suzanne Cole, MD, of the University of Arizona, Phoenix.

During a standard pathology analysis, 50% of the polyp isn’t analyzed at all, and the remaining half is cut into three different levels that are approximately 2 microns each. “Ultimately, less than 1% is actually reviewed by the pathologist,” she said.

GI physicians may perceive that the pathology review is definitive, Dr. Cole explained. “They believe that the section is viewed in its entirety, when, in reality, 50% of the tissue block is cut and less than 1% is viewed to come up with a diagnosis.”

The term nondiagnostic biopsy generally indicates that a specific diagnosis cannot be made. In their literature review, Dr. Cole and her team looked at eight published studies and found that a nondiagnostic biopsy was a very common result, ranging from 9% to 16%. In addition, the literature also showed that there was a significant conversion rate in nondiagnostic biopsies, from 4% to 20%, when additional leveling was performed.

In the current study, they investigated whether the detection of adenomas is improved when pathologists examine representative levels taken from the entire tissue block of specimens that have been diagnosed as nondiagnostic.

They conducted a retrospective review of pathology results that had been performed by a large GI practice (from November 2012 to November 2016) after implementing a so-called “polyp protocol,” which included an analysis of tissue sections from the entire tissue block (exhaustive leveling) of polyps initially deemed histologically nondiagnostic.

A total of 120,115 polyps had been removed during the study period, and, of this group, 10,768 (9%) were initially found to be nondiagnostic and were selected for exhaustive leveling. After exhaustive leveling, more than one-third (37%; n = 3,964) of the diagnoses converted to adenoma.

When the detection rate for adenomas for exhaustive leveling was compared with that for standard leveling, there was a statistically significant 3.3% increase (P less than .0001) from baseline.

“Our conclusion is that adenomas are missed,” said Dr. Cole. “This is partially because pathologists are not typically evaluating an entire specimen.”

These results support the need for implementing standardized protocols for exhaustive leveling as a means of increasing the adenoma detection rate, she noted. “Our research emphasizes the need for further studies assessing pathology specimen processing and analysis.”

Digestive Disease Week^® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).

Dr. Cole declared no relevant disclosures.

CHICAGO – A substantial number of adenomas may be missed by pathologists, but changes in the standard methodology can significantly decrease that amount, according to findings presented at Digestive Disease Week^®.

A nondiagnostic result is common in histologic specimens obtained from the colon and occurs in about 9% of biopsies. However, a protocol known as “exhaustive leveling of histologically nondiagnostic specimens” can significantly increase the detection of adenomas.

“In our study, we were answering the question, Are pathologists missing adenomas?” said Lauren Suzanne Cole, MD, of the University of Arizona, Phoenix.

During a standard pathology analysis, 50% of the polyp isn’t analyzed at all, and the remaining half is cut into three different levels that are approximately 2 microns each. “Ultimately, less than 1% is actually reviewed by the pathologist,” she said.

GI physicians may perceive that the pathology review is definitive, Dr. Cole explained. “They believe that the section is viewed in its entirety, when, in reality, 50% of the tissue block is cut and less than 1% is viewed to come up with a diagnosis.”

The term nondiagnostic biopsy generally indicates that a specific diagnosis cannot be made. In their literature review, Dr. Cole and her team looked at eight published studies and found that a nondiagnostic biopsy was a very common result, ranging from 9% to 16%. In addition, the literature also showed that there was a significant conversion rate in nondiagnostic biopsies, from 4% to 20%, when additional leveling was performed.

In the current study, they investigated whether the detection of adenomas is improved when pathologists examine representative levels taken from the entire tissue block of specimens that have been diagnosed as nondiagnostic.

They conducted a retrospective review of pathology results that had been performed by a large GI practice (from November 2012 to November 2016) after implementing a so-called “polyp protocol,” which included an analysis of tissue sections from the entire tissue block (exhaustive leveling) of polyps initially deemed histologically nondiagnostic.

A total of 120,115 polyps had been removed during the study period, and, of this group, 10,768 (9%) were initially found to be nondiagnostic and were selected for exhaustive leveling. After exhaustive leveling, more than one-third (37%; n = 3,964) of the diagnoses converted to adenoma.

When the detection rate for adenomas for exhaustive leveling was compared with that for standard leveling, there was a statistically significant 3.3% increase (P less than .0001) from baseline.

“Our conclusion is that adenomas are missed,” said Dr. Cole. “This is partially because pathologists are not typically evaluating an entire specimen.”

These results support the need for implementing standardized protocols for exhaustive leveling as a means of increasing the adenoma detection rate, she noted. “Our research emphasizes the need for further studies assessing pathology specimen processing and analysis.”

Digestive Disease Week^® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).

Dr. Cole declared no relevant disclosures.

CHICAGO – A substantial number of adenomas may be missed by pathologists, but changes in the standard methodology can significantly decrease that amount, according to findings presented at Digestive Disease Week^®.

A nondiagnostic result is common in histologic specimens obtained from the colon and occurs in about 9% of biopsies. However, a protocol known as “exhaustive leveling of histologically nondiagnostic specimens” can significantly increase the detection of adenomas.

“In our study, we were answering the question, Are pathologists missing adenomas?” said Lauren Suzanne Cole, MD, of the University of Arizona, Phoenix.

During a standard pathology analysis, 50% of the polyp isn’t analyzed at all, and the remaining half is cut into three different levels that are approximately 2 microns each. “Ultimately, less than 1% is actually reviewed by the pathologist,” she said.

GI physicians may perceive that the pathology review is definitive, Dr. Cole explained. “They believe that the section is viewed in its entirety, when, in reality, 50% of the tissue block is cut and less than 1% is viewed to come up with a diagnosis.”

The term nondiagnostic biopsy generally indicates that a specific diagnosis cannot be made. In their literature review, Dr. Cole and her team looked at eight published studies and found that a nondiagnostic biopsy was a very common result, ranging from 9% to 16%. In addition, the literature also showed that there was a significant conversion rate in nondiagnostic biopsies, from 4% to 20%, when additional leveling was performed.

In the current study, they investigated whether the detection of adenomas is improved when pathologists examine representative levels taken from the entire tissue block of specimens that have been diagnosed as nondiagnostic.

They conducted a retrospective review of pathology results that had been performed by a large GI practice (from November 2012 to November 2016) after implementing a so-called “polyp protocol,” which included an analysis of tissue sections from the entire tissue block (exhaustive leveling) of polyps initially deemed histologically nondiagnostic.

A total of 120,115 polyps had been removed during the study period, and, of this group, 10,768 (9%) were initially found to be nondiagnostic and were selected for exhaustive leveling. After exhaustive leveling, more than one-third (37%; n = 3,964) of the diagnoses converted to adenoma.

When the detection rate for adenomas for exhaustive leveling was compared with that for standard leveling, there was a statistically significant 3.3% increase (P less than .0001) from baseline.

“Our conclusion is that adenomas are missed,” said Dr. Cole. “This is partially because pathologists are not typically evaluating an entire specimen.”

These results support the need for implementing standardized protocols for exhaustive leveling as a means of increasing the adenoma detection rate, she noted. “Our research emphasizes the need for further studies assessing pathology specimen processing and analysis.”

Digestive Disease Week^® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).

Dr. Cole declared no relevant disclosures.

CHICAGO – Immune therapy shows promise for use in the treatment of melanoma brain metastases, especially for treatment-naive patients, judging from the findings of a new phase II randomized study.

For patients with asymptomatic brain metastases from melanoma who had not had prior treatment, nivolumab combined with ipilimumab produced a 50% intracranial response rate after at least 12 weeks of therapy. When nivolumab alone was given to untreated patients, the intracranial response rate was 21%, Georgina Long MD, PhD, co–medical director of the Melanoma Institute Australia , said during a video interview at the annual meeting of the American Society of Clinical Oncology.

“If you look at progression-free survival by response, none of our complete responders have progressed,” said Dr. Long. “And this is with a median follow-up of 16.4 months.” The partial responders have also done well, with little progression, she said. “Remember, these patients usually survive only a few weeks.”

The Anti-PD1 Brain Collaboration study, a phase II clinical trial, enrolled patients with melanoma brain metastases at least 5 mm but less than 40 mm in diameter who had not received previous anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed cell death protein 1 (anti-PD-1), or anti-programmed death-ligand 1 (anti-PD-L1) therapies. Patients were permitted to have had previous BRAF and MEK inhibitor therapies. Asymptomatic patients who had no previous local brain therapy (i.e., radiation treatment or surgery) were randomized 1:1 to receive nivolumab alone, or nivolumab plus ipilimumab.

The nivolumab arm received 3 mg/kg by intravenous infusion every 2 weeks. The combination arm began with nivolumab 1 mg/kg and ipilimumab 3 mg/kg every 3 weeks for four doses. After this, they also received nivolumab 3 mg/kg monotherapy every 2 weeks.

The third cohort – a small group of 15 patients who received nivolumab alone – either had symptomatic brain metastases or leptomeningeal disease and could have had previous brain surgery or radiotherapy. Unlike the first two cohorts, they were also permitted to be on up to 10 mg/day of prednisone; these patients received nivolumab alone at 3 mg/kg every 2 weeks.

For all patients, immune therapy was given until the disease progressed, consent was withdrawn, or patients experienced unacceptable toxicity or they died.

“We were most interested in the randomized cohorts,” said Dr. Long. Interestingly, she said, ipilimumab became available in Australia when 27 patients were enrolled in the nivolumab arm and 26 to the combination arm. “So we stopped the monotherapy arm, and the rest of the 60 patients to be recruited all went into the combination arm,” she said. A total of 76 patients were recruited, 33 into the combination arm, 27 to the asymptomatic nivolumab monotherapy arm, and 16 to the symptomatic and/or previously treated arm.

Data analysis from the point of the data cut included 67 patients who were followed for a period ranging from 5 to 34 months. Intracranial disease was evaluated by gadolinium-enhanced MRI and modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

“The results of the trial were very interesting,” said Dr. Long. The nivolumab plus ipilimumab combo resulted in an overall 42% intracranial response rate, while nivolumab alone produced an overall intracranial response rate of 21%. However, patients in either arm who had prior BRAF or MEK inhibitor exposure “didn’t do too well on immunotherapy,” said Dr. Long, noting that the response rate was just 16% for these patients. These were, she said, “small numbers, but still, an interesting signal there.”

When comparing the secondary endpoint of extracranial response to intracranial response on a per-patient basis, Dr. Long and her collaborators could see that “the intracranial and extracranial results were mostly concordant.”

Analysis of the additional secondary endpoints of progression-free survival (PFS) and overall survival (OS) also showed an interesting pattern, said Dr. Long. After an initial drop-off period of about 5 months, the curves for patients in all arms have stabilized, so that patients who were responders are maintaining that response. The overall 6-month PFS rate for the combination cohort was 47%, with a durable response: “If you look at the curve, it’s flattened out since that stage, and we haven’t had any progression since that time,” said Dr. Long. The PFS rate was 29% for the cohort receiving nivolumab alone. “Activity is highest when nivolumab and ipilimumab are given upfront,” said Dr. Long.

For asymptomatic patients pretreated with BRAF or MEK inhibitors, “activity is low,” said Dr. Long, with an intracranial response rate of 16% in both cohorts.

Symptomatic patients who were more heavily pretreated fared even worse: “The activity of nivolumab monotherapy is low after multiple modality therapy or in leptomeningeal melanoma,” said Dr. Long. The intracranial response rate in the third cohort was just 6%.

The combination therapy cohort had the most treatment-related adverse events, with 96% of patients experiencing some adverse event. About half (12/26, 46%) had grade 3 or 4 events, and the same number had a serious adverse event. Seven patients (27%) discontinued therapy because of treatment-related adverse events in the combination study arm. However, said Dr. Long, this side effect profile is in keeping with what has been seen in other studies of combination therapy with nivolumab and ipilimumab. “There were not unexpected adverse events,” she said.

Dr. Long reported relationships with Bristol-Myers Squibb, Merck, and Roche.

[email protected]

On Twitter @karioakes

CHICAGO – Immune therapy shows promise for use in the treatment of melanoma brain metastases, especially for treatment-naive patients, judging from the findings of a new phase II randomized study.

For patients with asymptomatic brain metastases from melanoma who had not had prior treatment, nivolumab combined with ipilimumab produced a 50% intracranial response rate after at least 12 weeks of therapy. When nivolumab alone was given to untreated patients, the intracranial response rate was 21%, Georgina Long MD, PhD, co–medical director of the Melanoma Institute Australia , said during a video interview at the annual meeting of the American Society of Clinical Oncology.

“If you look at progression-free survival by response, none of our complete responders have progressed,” said Dr. Long. “And this is with a median follow-up of 16.4 months.” The partial responders have also done well, with little progression, she said. “Remember, these patients usually survive only a few weeks.”

The Anti-PD1 Brain Collaboration study, a phase II clinical trial, enrolled patients with melanoma brain metastases at least 5 mm but less than 40 mm in diameter who had not received previous anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed cell death protein 1 (anti-PD-1), or anti-programmed death-ligand 1 (anti-PD-L1) therapies. Patients were permitted to have had previous BRAF and MEK inhibitor therapies. Asymptomatic patients who had no previous local brain therapy (i.e., radiation treatment or surgery) were randomized 1:1 to receive nivolumab alone, or nivolumab plus ipilimumab.

The nivolumab arm received 3 mg/kg by intravenous infusion every 2 weeks. The combination arm began with nivolumab 1 mg/kg and ipilimumab 3 mg/kg every 3 weeks for four doses. After this, they also received nivolumab 3 mg/kg monotherapy every 2 weeks.

The third cohort – a small group of 15 patients who received nivolumab alone – either had symptomatic brain metastases or leptomeningeal disease and could have had previous brain surgery or radiotherapy. Unlike the first two cohorts, they were also permitted to be on up to 10 mg/day of prednisone; these patients received nivolumab alone at 3 mg/kg every 2 weeks.

For all patients, immune therapy was given until the disease progressed, consent was withdrawn, or patients experienced unacceptable toxicity or they died.

“We were most interested in the randomized cohorts,” said Dr. Long. Interestingly, she said, ipilimumab became available in Australia when 27 patients were enrolled in the nivolumab arm and 26 to the combination arm. “So we stopped the monotherapy arm, and the rest of the 60 patients to be recruited all went into the combination arm,” she said. A total of 76 patients were recruited, 33 into the combination arm, 27 to the asymptomatic nivolumab monotherapy arm, and 16 to the symptomatic and/or previously treated arm.

Data analysis from the point of the data cut included 67 patients who were followed for a period ranging from 5 to 34 months. Intracranial disease was evaluated by gadolinium-enhanced MRI and modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

“The results of the trial were very interesting,” said Dr. Long. The nivolumab plus ipilimumab combo resulted in an overall 42% intracranial response rate, while nivolumab alone produced an overall intracranial response rate of 21%. However, patients in either arm who had prior BRAF or MEK inhibitor exposure “didn’t do too well on immunotherapy,” said Dr. Long, noting that the response rate was just 16% for these patients. These were, she said, “small numbers, but still, an interesting signal there.”

When comparing the secondary endpoint of extracranial response to intracranial response on a per-patient basis, Dr. Long and her collaborators could see that “the intracranial and extracranial results were mostly concordant.”

Analysis of the additional secondary endpoints of progression-free survival (PFS) and overall survival (OS) also showed an interesting pattern, said Dr. Long. After an initial drop-off period of about 5 months, the curves for patients in all arms have stabilized, so that patients who were responders are maintaining that response. The overall 6-month PFS rate for the combination cohort was 47%, with a durable response: “If you look at the curve, it’s flattened out since that stage, and we haven’t had any progression since that time,” said Dr. Long. The PFS rate was 29% for the cohort receiving nivolumab alone. “Activity is highest when nivolumab and ipilimumab are given upfront,” said Dr. Long.

For asymptomatic patients pretreated with BRAF or MEK inhibitors, “activity is low,” said Dr. Long, with an intracranial response rate of 16% in both cohorts.

Symptomatic patients who were more heavily pretreated fared even worse: “The activity of nivolumab monotherapy is low after multiple modality therapy or in leptomeningeal melanoma,” said Dr. Long. The intracranial response rate in the third cohort was just 6%.

The combination therapy cohort had the most treatment-related adverse events, with 96% of patients experiencing some adverse event. About half (12/26, 46%) had grade 3 or 4 events, and the same number had a serious adverse event. Seven patients (27%) discontinued therapy because of treatment-related adverse events in the combination study arm. However, said Dr. Long, this side effect profile is in keeping with what has been seen in other studies of combination therapy with nivolumab and ipilimumab. “There were not unexpected adverse events,” she said.

Dr. Long reported relationships with Bristol-Myers Squibb, Merck, and Roche.

[email protected]

On Twitter @karioakes

CHICAGO – Immune therapy shows promise for use in the treatment of melanoma brain metastases, especially for treatment-naive patients, judging from the findings of a new phase II randomized study.

For patients with asymptomatic brain metastases from melanoma who had not had prior treatment, nivolumab combined with ipilimumab produced a 50% intracranial response rate after at least 12 weeks of therapy. When nivolumab alone was given to untreated patients, the intracranial response rate was 21%, Georgina Long MD, PhD, co–medical director of the Melanoma Institute Australia , said during a video interview at the annual meeting of the American Society of Clinical Oncology.

“If you look at progression-free survival by response, none of our complete responders have progressed,” said Dr. Long. “And this is with a median follow-up of 16.4 months.” The partial responders have also done well, with little progression, she said. “Remember, these patients usually survive only a few weeks.”

The Anti-PD1 Brain Collaboration study, a phase II clinical trial, enrolled patients with melanoma brain metastases at least 5 mm but less than 40 mm in diameter who had not received previous anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed cell death protein 1 (anti-PD-1), or anti-programmed death-ligand 1 (anti-PD-L1) therapies. Patients were permitted to have had previous BRAF and MEK inhibitor therapies. Asymptomatic patients who had no previous local brain therapy (i.e., radiation treatment or surgery) were randomized 1:1 to receive nivolumab alone, or nivolumab plus ipilimumab.

The nivolumab arm received 3 mg/kg by intravenous infusion every 2 weeks. The combination arm began with nivolumab 1 mg/kg and ipilimumab 3 mg/kg every 3 weeks for four doses. After this, they also received nivolumab 3 mg/kg monotherapy every 2 weeks.

The third cohort – a small group of 15 patients who received nivolumab alone – either had symptomatic brain metastases or leptomeningeal disease and could have had previous brain surgery or radiotherapy. Unlike the first two cohorts, they were also permitted to be on up to 10 mg/day of prednisone; these patients received nivolumab alone at 3 mg/kg every 2 weeks.

For all patients, immune therapy was given until the disease progressed, consent was withdrawn, or patients experienced unacceptable toxicity or they died.

“We were most interested in the randomized cohorts,” said Dr. Long. Interestingly, she said, ipilimumab became available in Australia when 27 patients were enrolled in the nivolumab arm and 26 to the combination arm. “So we stopped the monotherapy arm, and the rest of the 60 patients to be recruited all went into the combination arm,” she said. A total of 76 patients were recruited, 33 into the combination arm, 27 to the asymptomatic nivolumab monotherapy arm, and 16 to the symptomatic and/or previously treated arm.

Data analysis from the point of the data cut included 67 patients who were followed for a period ranging from 5 to 34 months. Intracranial disease was evaluated by gadolinium-enhanced MRI and modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

“The results of the trial were very interesting,” said Dr. Long. The nivolumab plus ipilimumab combo resulted in an overall 42% intracranial response rate, while nivolumab alone produced an overall intracranial response rate of 21%. However, patients in either arm who had prior BRAF or MEK inhibitor exposure “didn’t do too well on immunotherapy,” said Dr. Long, noting that the response rate was just 16% for these patients. These were, she said, “small numbers, but still, an interesting signal there.”

When comparing the secondary endpoint of extracranial response to intracranial response on a per-patient basis, Dr. Long and her collaborators could see that “the intracranial and extracranial results were mostly concordant.”

Analysis of the additional secondary endpoints of progression-free survival (PFS) and overall survival (OS) also showed an interesting pattern, said Dr. Long. After an initial drop-off period of about 5 months, the curves for patients in all arms have stabilized, so that patients who were responders are maintaining that response. The overall 6-month PFS rate for the combination cohort was 47%, with a durable response: “If you look at the curve, it’s flattened out since that stage, and we haven’t had any progression since that time,” said Dr. Long. The PFS rate was 29% for the cohort receiving nivolumab alone. “Activity is highest when nivolumab and ipilimumab are given upfront,” said Dr. Long.

For asymptomatic patients pretreated with BRAF or MEK inhibitors, “activity is low,” said Dr. Long, with an intracranial response rate of 16% in both cohorts.

Symptomatic patients who were more heavily pretreated fared even worse: “The activity of nivolumab monotherapy is low after multiple modality therapy or in leptomeningeal melanoma,” said Dr. Long. The intracranial response rate in the third cohort was just 6%.

The combination therapy cohort had the most treatment-related adverse events, with 96% of patients experiencing some adverse event. About half (12/26, 46%) had grade 3 or 4 events, and the same number had a serious adverse event. Seven patients (27%) discontinued therapy because of treatment-related adverse events in the combination study arm. However, said Dr. Long, this side effect profile is in keeping with what has been seen in other studies of combination therapy with nivolumab and ipilimumab. “There were not unexpected adverse events,” she said.

Dr. Long reported relationships with Bristol-Myers Squibb, Merck, and Roche.

[email protected]

On Twitter @karioakes

The rising cost of care has been a major concern in the U.S. health care system. In 1990, about $714 million was spent on health care. In 2010, the cost had risen exponentially to about $2.6 trillion.¹ An estimated $750 billion dollars is attributed to health care waste.²

Health care waste includes spending on laboratory testing, diagnostic imaging, procedures or other treatments. Below is a list of the various sources that contribute to health care spending waste:²

1. Unnecessary Services ($210 billion)

2. Excessive Administrative Costs (190 billion)

3. Inefficient Service Delivery ($130 billion)

4. Overpricing ($105 billion)

5. Fraud ($75 billion)

6. Treatment for services that could have been prevented ($55 billion)

Reducing the cost of care

The predominant fee-for-service method of reimbursement does not encourage hospitals or providers to try to control areas of waste. One strategy that puts pressure on the providers of health care to control these areas of waste is the bundled payment system. Bundled payment systems deter unnecessary testing and procedures and encourage care coordination between care providers to promote efficiency.

As hospitalists, we play a key role in the bundled payment arena. Hospitalists are strategically placed to ensure that each episode of care is provided in the most cost-efficient way possible without sacrificing quality.

Training about the evidence supporting bundled payments can be incorporated into medical school and the residency curriculum. Hospitalists can serve as educators for trainees regarding the benefits of bundled payments. This will help drive sustainability by making sure new doctors entering the health field are already equipped with knowledge about bundled payments and their advantages.

Hospitalists can also help spur innovation by engaging with hospital leadership to develop new bundled systems. Payment incentives to organizations that participate will help to drive hospitalist engagement. Hospitalists can also advocate for the development of a risk adjustment system to ensure that each patient’s severity is reflected in the payment. This will allow for more buy-in by hospitals and providers.
 

Improving the quality of care

The Institute of Medicine published a report that made recommendations for improving the quality of the U.S. health care system by identifying six dimensions that need to be addressed:

1. Safety

2. Effectiveness

3. Patient-centeredness

4. Timeliness

5. Efficiency

6. Equity

The Value Based Purchasing program aims to address these dimensions. The fee-for-service system does not provide an incentive to provide quality care, similar to the way it does not drive cost-conscious care. By linking reimbursement to quality care, hospitals and providers have a significant incentive to ensure that their patients receive high quality care. The passage of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) is another step in the direction of rewarding providers for quality of care rendered, not just quantity.
 

Role of hospitalists

Again, hospitalists should serve as educators about the importance of value based purchasing on quality outcomes,\ and its potential for cost savings through rendering appropriate and effective care.

Hospitalists should advocate for expanding value based purchasing across all payers. This will encourage providers to treat all their patients the same, with the expectation of improving quality of care for all patients and not just a limited insurance pool.

Hospitalists can also advocate for the utilization of the same measure for determining quality across all payers. This will allow for more efficient administrative efforts by eliminating the time used to report different measures to different insurance companies.

Unfortunately, the digital era has not made the same advances in the field of medicine as it has in other areas of life. As hospitalists, our clinical perspective puts us in a position of leadership in the area of informatics. We are uniquely qualified to exploit the power of the hospital’s information technology service and push it to its full potential.

Dr. Arole is chief hospitalist, Griffin Faculty Physicians, at Griffin Hospital in Derby, Conn.

References

1. The Healthcare Imperative: Lowering Costs and Improving Outcomes – Workshop Series Summary. 2011 Feb 24. The Institute of Medicine.

2. Health Affairs Policy Brief; Reducing Waste in Health Care. http://www.healthaffairs.org/healthpolicybriefs/brief.

The rising cost of care has been a major concern in the U.S. health care system. In 1990, about $714 million was spent on health care. In 2010, the cost had risen exponentially to about $2.6 trillion.¹ An estimated $750 billion dollars is attributed to health care waste.²

Health care waste includes spending on laboratory testing, diagnostic imaging, procedures or other treatments. Below is a list of the various sources that contribute to health care spending waste:²

1. Unnecessary Services ($210 billion)

2. Excessive Administrative Costs (190 billion)

3. Inefficient Service Delivery ($130 billion)

4. Overpricing ($105 billion)

5. Fraud ($75 billion)

6. Treatment for services that could have been prevented ($55 billion)

Reducing the cost of care

The predominant fee-for-service method of reimbursement does not encourage hospitals or providers to try to control areas of waste. One strategy that puts pressure on the providers of health care to control these areas of waste is the bundled payment system. Bundled payment systems deter unnecessary testing and procedures and encourage care coordination between care providers to promote efficiency.

As hospitalists, we play a key role in the bundled payment arena. Hospitalists are strategically placed to ensure that each episode of care is provided in the most cost-efficient way possible without sacrificing quality.

Training about the evidence supporting bundled payments can be incorporated into medical school and the residency curriculum. Hospitalists can serve as educators for trainees regarding the benefits of bundled payments. This will help drive sustainability by making sure new doctors entering the health field are already equipped with knowledge about bundled payments and their advantages.

Hospitalists can also help spur innovation by engaging with hospital leadership to develop new bundled systems. Payment incentives to organizations that participate will help to drive hospitalist engagement. Hospitalists can also advocate for the development of a risk adjustment system to ensure that each patient’s severity is reflected in the payment. This will allow for more buy-in by hospitals and providers.
 

Improving the quality of care

The Institute of Medicine published a report that made recommendations for improving the quality of the U.S. health care system by identifying six dimensions that need to be addressed:

1. Safety

2. Effectiveness

3. Patient-centeredness

4. Timeliness

5. Efficiency

6. Equity

The Value Based Purchasing program aims to address these dimensions. The fee-for-service system does not provide an incentive to provide quality care, similar to the way it does not drive cost-conscious care. By linking reimbursement to quality care, hospitals and providers have a significant incentive to ensure that their patients receive high quality care. The passage of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) is another step in the direction of rewarding providers for quality of care rendered, not just quantity.
 

Role of hospitalists

Again, hospitalists should serve as educators about the importance of value based purchasing on quality outcomes,\ and its potential for cost savings through rendering appropriate and effective care.

Hospitalists should advocate for expanding value based purchasing across all payers. This will encourage providers to treat all their patients the same, with the expectation of improving quality of care for all patients and not just a limited insurance pool.

Hospitalists can also advocate for the utilization of the same measure for determining quality across all payers. This will allow for more efficient administrative efforts by eliminating the time used to report different measures to different insurance companies.

Unfortunately, the digital era has not made the same advances in the field of medicine as it has in other areas of life. As hospitalists, our clinical perspective puts us in a position of leadership in the area of informatics. We are uniquely qualified to exploit the power of the hospital’s information technology service and push it to its full potential.

Dr. Arole is chief hospitalist, Griffin Faculty Physicians, at Griffin Hospital in Derby, Conn.

References

1. The Healthcare Imperative: Lowering Costs and Improving Outcomes – Workshop Series Summary. 2011 Feb 24. The Institute of Medicine.

2. Health Affairs Policy Brief; Reducing Waste in Health Care. http://www.healthaffairs.org/healthpolicybriefs/brief.

The rising cost of care has been a major concern in the U.S. health care system. In 1990, about $714 million was spent on health care. In 2010, the cost had risen exponentially to about $2.6 trillion.¹ An estimated $750 billion dollars is attributed to health care waste.²

Health care waste includes spending on laboratory testing, diagnostic imaging, procedures or other treatments. Below is a list of the various sources that contribute to health care spending waste:²

1. Unnecessary Services ($210 billion)

2. Excessive Administrative Costs (190 billion)

3. Inefficient Service Delivery ($130 billion)

4. Overpricing ($105 billion)

5. Fraud ($75 billion)

6. Treatment for services that could have been prevented ($55 billion)

Reducing the cost of care

The predominant fee-for-service method of reimbursement does not encourage hospitals or providers to try to control areas of waste. One strategy that puts pressure on the providers of health care to control these areas of waste is the bundled payment system. Bundled payment systems deter unnecessary testing and procedures and encourage care coordination between care providers to promote efficiency.

As hospitalists, we play a key role in the bundled payment arena. Hospitalists are strategically placed to ensure that each episode of care is provided in the most cost-efficient way possible without sacrificing quality.

Training about the evidence supporting bundled payments can be incorporated into medical school and the residency curriculum. Hospitalists can serve as educators for trainees regarding the benefits of bundled payments. This will help drive sustainability by making sure new doctors entering the health field are already equipped with knowledge about bundled payments and their advantages.

Hospitalists can also help spur innovation by engaging with hospital leadership to develop new bundled systems. Payment incentives to organizations that participate will help to drive hospitalist engagement. Hospitalists can also advocate for the development of a risk adjustment system to ensure that each patient’s severity is reflected in the payment. This will allow for more buy-in by hospitals and providers.
 

Improving the quality of care

The Institute of Medicine published a report that made recommendations for improving the quality of the U.S. health care system by identifying six dimensions that need to be addressed:

1. Safety

2. Effectiveness

3. Patient-centeredness

4. Timeliness

5. Efficiency

6. Equity

The Value Based Purchasing program aims to address these dimensions. The fee-for-service system does not provide an incentive to provide quality care, similar to the way it does not drive cost-conscious care. By linking reimbursement to quality care, hospitals and providers have a significant incentive to ensure that their patients receive high quality care. The passage of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) is another step in the direction of rewarding providers for quality of care rendered, not just quantity.
 

Role of hospitalists

Again, hospitalists should serve as educators about the importance of value based purchasing on quality outcomes,\ and its potential for cost savings through rendering appropriate and effective care.

Hospitalists should advocate for expanding value based purchasing across all payers. This will encourage providers to treat all their patients the same, with the expectation of improving quality of care for all patients and not just a limited insurance pool.

Hospitalists can also advocate for the utilization of the same measure for determining quality across all payers. This will allow for more efficient administrative efforts by eliminating the time used to report different measures to different insurance companies.

Unfortunately, the digital era has not made the same advances in the field of medicine as it has in other areas of life. As hospitalists, our clinical perspective puts us in a position of leadership in the area of informatics. We are uniquely qualified to exploit the power of the hospital’s information technology service and push it to its full potential.

Dr. Arole is chief hospitalist, Griffin Faculty Physicians, at Griffin Hospital in Derby, Conn.

References

1. The Healthcare Imperative: Lowering Costs and Improving Outcomes – Workshop Series Summary. 2011 Feb 24. The Institute of Medicine.

2. Health Affairs Policy Brief; Reducing Waste in Health Care. http://www.healthaffairs.org/healthpolicybriefs/brief.

SAN DIEGO – The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide significantly lessened glucose tolerance, glycemic control, and other cardiometabolic risk factors in overweight or obese prediabetic patients receiving clozapine or olanzapine for schizophrenia, according to the findings of a randomized, double-blind, placebo-controlled trial.

Liraglutide was generally well tolerated and conferred cardiometabolic benefits similar to those in past studies of patients who were not on antipsychotic therapy, said Louise Vedtofte, PhD, of the University of Copenhagen. After 16 weeks of treatment, a 75-gram oral glucose tolerance test showed that 2-hour plasma glucose levels were 23% lower with liraglutide compared with placebo (P less than .001), she said at the annual scientific sessions of the American Diabetes Association.

Liraglutide patients also lost an average of 5.2 kg more body weight, cut 4.1 cm more from their waist circumference, and were significantly more likely to normalize their fasting plasma glucose and hemoglobin A_1c levels compared with the placebo group (P less than .001 for each comparison), she said. The report by Dr. Vedtofte and her associates was published in JAMA Psychiatry simultaneously with the presentation at the meeting (2017 June 10. doi: 10.1001/jamapsychiatry.2017.1220).

Antipsychotics are core therapies in schizophrenia spectrum disorders but also cause increased appetite, weight gain, and cardiometabolic disturbances, noted Dr. Vedtofte. About a third of patients with schizophrenia who receive antipsychotics develop metabolic syndrome, and some 15% go on to develop diabetes. Clozapine and olanzapine cause more weight gain than do other antipsychotics, but swapping either medication for a more weight-neutral alternative can threaten the well-being of patients with schizophrenia, she emphasized. “Olanzapine and clozapine are good for the patients’ mental health, but are detrimental for their somatic health.”

As a GLP-1 receptor agonist, liraglutide inhibits appetite and food intake, and the Food and Drug Administration has approved treatment at doses of 1.8 mg for type 2 diabetes and 3 mg once daily for obesity. To explore how liraglutide affects patients on antipsychotics, Dr. Vedtofte and her associates randomly assigned 103 adults with schizophrenia spectrum disorders from two clinical sites in Denmark to receive placebo or 0.6 mg liraglutide subcutaneously once daily, up-titrated by 0.6 mg weekly to a maximum dose of 1.8 mg. At baseline, all patients were receiving stable treatment with clozapine, olanzapine, or both; had a body mass index of at least 27 kg/m²; and were prediabetic, with fasting plasma glucose levels of 110 to 125 mg/dL, HbA_1c levels of 6.1%-6.4%, or 2-hour plasma glucose levels of 140 mg/dL or higher during the 75-gram oral glucose tolerance test.[[{"fid":"198022","view_mode":"medstat_image_flush_right","attributes":{"alt":"Louise Vedtofte, PhD, of the University of Copenhagen","height":"220","width":"147","class":"media-element file-medstat-image-flush-right","data-delta":"1"},"fields":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Dr. Louise Vedtofte","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"1":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Dr. Louise Vedtofte","field_file_image_credit[und][0][value]":""}},"link_text":false}]]

Fully 93% of patients completed the study. At week 16, glucose tolerance improved significantly in the liraglutide group (P less than .001) but not in the placebo group (P less than .001 for difference between groups) after the researchers controlled for age, sex, illness duration, BMI, Clinical Global Impressions Scale severity score, and antipsychotic treatment. Glucose tolerance normalized in 30 patients who received liraglutide (64%) compared with 8 in the placebo group (16%; P less than .001), Dr. Vedtofte said.

Besides its benefits to waist circumference and weight loss, liraglutide was associated with reductions in systolic blood pressure (average, 5 mm Hg; visceral fat, 0.25 kg; and low-density lipoprotein levels, 15 mg/dL). These changes occurred even though liraglutide did not significantly alter C-peptide or glucagon secretion in the multivariate analysis of glucose tolerance test results, Dr. Vedtofte said. “The rate of nausea was 62% in liraglutide patients and 32% with placebo, but nausea was transient and did not explain the weight loss in subgroup analyses,” she added.

Liraglutide did not alter clinical liver function, but treated patients experienced a small (1.3 U/L), statistically significant rise in amylase levels. Rates of other adverse events were similar between groups except that patients were more likely to experience orthostatic hypotension on liraglutide (8.2%) than on placebo (0%; P = .04). Treatment with liraglutide did not significantly increase the likelihood of serious somatic or psychiatric adverse events, but one patient died while on therapy. “This patient was a man in his 60s with longstanding schizophrenia who was admitted to the hospital with vomiting and diarrhea, and died 3 days later,” Dr. Vedtofte said. Autopsy did not reveal the cause of death, but the patients showed no change in mental status or other signs of adverse therapeutic effects, she added.

Novo Nordisk funded the study and provided liraglutide and placebo injections. Additional support came from Capital Region Psychiatry Research Group, the foundation of King Christian X of Denmark, and the Lundbeck Foundation. Dr. Vedtofte had no disclosures.

SAN DIEGO – The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide significantly lessened glucose tolerance, glycemic control, and other cardiometabolic risk factors in overweight or obese prediabetic patients receiving clozapine or olanzapine for schizophrenia, according to the findings of a randomized, double-blind, placebo-controlled trial.

Liraglutide was generally well tolerated and conferred cardiometabolic benefits similar to those in past studies of patients who were not on antipsychotic therapy, said Louise Vedtofte, PhD, of the University of Copenhagen. After 16 weeks of treatment, a 75-gram oral glucose tolerance test showed that 2-hour plasma glucose levels were 23% lower with liraglutide compared with placebo (P less than .001), she said at the annual scientific sessions of the American Diabetes Association.

Liraglutide patients also lost an average of 5.2 kg more body weight, cut 4.1 cm more from their waist circumference, and were significantly more likely to normalize their fasting plasma glucose and hemoglobin A_1c levels compared with the placebo group (P less than .001 for each comparison), she said. The report by Dr. Vedtofte and her associates was published in JAMA Psychiatry simultaneously with the presentation at the meeting (2017 June 10. doi: 10.1001/jamapsychiatry.2017.1220).

Antipsychotics are core therapies in schizophrenia spectrum disorders but also cause increased appetite, weight gain, and cardiometabolic disturbances, noted Dr. Vedtofte. About a third of patients with schizophrenia who receive antipsychotics develop metabolic syndrome, and some 15% go on to develop diabetes. Clozapine and olanzapine cause more weight gain than do other antipsychotics, but swapping either medication for a more weight-neutral alternative can threaten the well-being of patients with schizophrenia, she emphasized. “Olanzapine and clozapine are good for the patients’ mental health, but are detrimental for their somatic health.”

As a GLP-1 receptor agonist, liraglutide inhibits appetite and food intake, and the Food and Drug Administration has approved treatment at doses of 1.8 mg for type 2 diabetes and 3 mg once daily for obesity. To explore how liraglutide affects patients on antipsychotics, Dr. Vedtofte and her associates randomly assigned 103 adults with schizophrenia spectrum disorders from two clinical sites in Denmark to receive placebo or 0.6 mg liraglutide subcutaneously once daily, up-titrated by 0.6 mg weekly to a maximum dose of 1.8 mg. At baseline, all patients were receiving stable treatment with clozapine, olanzapine, or both; had a body mass index of at least 27 kg/m²; and were prediabetic, with fasting plasma glucose levels of 110 to 125 mg/dL, HbA_1c levels of 6.1%-6.4%, or 2-hour plasma glucose levels of 140 mg/dL or higher during the 75-gram oral glucose tolerance test.[[{"fid":"198022","view_mode":"medstat_image_flush_right","attributes":{"alt":"Louise Vedtofte, PhD, of the University of Copenhagen","height":"220","width":"147","class":"media-element file-medstat-image-flush-right","data-delta":"1"},"fields":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Dr. Louise Vedtofte","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"1":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Dr. Louise Vedtofte","field_file_image_credit[und][0][value]":""}},"link_text":false}]]

Fully 93% of patients completed the study. At week 16, glucose tolerance improved significantly in the liraglutide group (P less than .001) but not in the placebo group (P less than .001 for difference between groups) after the researchers controlled for age, sex, illness duration, BMI, Clinical Global Impressions Scale severity score, and antipsychotic treatment. Glucose tolerance normalized in 30 patients who received liraglutide (64%) compared with 8 in the placebo group (16%; P less than .001), Dr. Vedtofte said.

Besides its benefits to waist circumference and weight loss, liraglutide was associated with reductions in systolic blood pressure (average, 5 mm Hg; visceral fat, 0.25 kg; and low-density lipoprotein levels, 15 mg/dL). These changes occurred even though liraglutide did not significantly alter C-peptide or glucagon secretion in the multivariate analysis of glucose tolerance test results, Dr. Vedtofte said. “The rate of nausea was 62% in liraglutide patients and 32% with placebo, but nausea was transient and did not explain the weight loss in subgroup analyses,” she added.

Liraglutide did not alter clinical liver function, but treated patients experienced a small (1.3 U/L), statistically significant rise in amylase levels. Rates of other adverse events were similar between groups except that patients were more likely to experience orthostatic hypotension on liraglutide (8.2%) than on placebo (0%; P = .04). Treatment with liraglutide did not significantly increase the likelihood of serious somatic or psychiatric adverse events, but one patient died while on therapy. “This patient was a man in his 60s with longstanding schizophrenia who was admitted to the hospital with vomiting and diarrhea, and died 3 days later,” Dr. Vedtofte said. Autopsy did not reveal the cause of death, but the patients showed no change in mental status or other signs of adverse therapeutic effects, she added.

Novo Nordisk funded the study and provided liraglutide and placebo injections. Additional support came from Capital Region Psychiatry Research Group, the foundation of King Christian X of Denmark, and the Lundbeck Foundation. Dr. Vedtofte had no disclosures.

SAN DIEGO – The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide significantly lessened glucose tolerance, glycemic control, and other cardiometabolic risk factors in overweight or obese prediabetic patients receiving clozapine or olanzapine for schizophrenia, according to the findings of a randomized, double-blind, placebo-controlled trial.

Liraglutide was generally well tolerated and conferred cardiometabolic benefits similar to those in past studies of patients who were not on antipsychotic therapy, said Louise Vedtofte, PhD, of the University of Copenhagen. After 16 weeks of treatment, a 75-gram oral glucose tolerance test showed that 2-hour plasma glucose levels were 23% lower with liraglutide compared with placebo (P less than .001), she said at the annual scientific sessions of the American Diabetes Association.

Liraglutide patients also lost an average of 5.2 kg more body weight, cut 4.1 cm more from their waist circumference, and were significantly more likely to normalize their fasting plasma glucose and hemoglobin A_1c levels compared with the placebo group (P less than .001 for each comparison), she said. The report by Dr. Vedtofte and her associates was published in JAMA Psychiatry simultaneously with the presentation at the meeting (2017 June 10. doi: 10.1001/jamapsychiatry.2017.1220).

Antipsychotics are core therapies in schizophrenia spectrum disorders but also cause increased appetite, weight gain, and cardiometabolic disturbances, noted Dr. Vedtofte. About a third of patients with schizophrenia who receive antipsychotics develop metabolic syndrome, and some 15% go on to develop diabetes. Clozapine and olanzapine cause more weight gain than do other antipsychotics, but swapping either medication for a more weight-neutral alternative can threaten the well-being of patients with schizophrenia, she emphasized. “Olanzapine and clozapine are good for the patients’ mental health, but are detrimental for their somatic health.”

As a GLP-1 receptor agonist, liraglutide inhibits appetite and food intake, and the Food and Drug Administration has approved treatment at doses of 1.8 mg for type 2 diabetes and 3 mg once daily for obesity. To explore how liraglutide affects patients on antipsychotics, Dr. Vedtofte and her associates randomly assigned 103 adults with schizophrenia spectrum disorders from two clinical sites in Denmark to receive placebo or 0.6 mg liraglutide subcutaneously once daily, up-titrated by 0.6 mg weekly to a maximum dose of 1.8 mg. At baseline, all patients were receiving stable treatment with clozapine, olanzapine, or both; had a body mass index of at least 27 kg/m²; and were prediabetic, with fasting plasma glucose levels of 110 to 125 mg/dL, HbA_1c levels of 6.1%-6.4%, or 2-hour plasma glucose levels of 140 mg/dL or higher during the 75-gram oral glucose tolerance test.[[{"fid":"198022","view_mode":"medstat_image_flush_right","attributes":{"alt":"Louise Vedtofte, PhD, of the University of Copenhagen","height":"220","width":"147","class":"media-element file-medstat-image-flush-right","data-delta":"1"},"fields":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Dr. Louise Vedtofte","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"1":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Dr. Louise Vedtofte","field_file_image_credit[und][0][value]":""}},"link_text":false}]]

Fully 93% of patients completed the study. At week 16, glucose tolerance improved significantly in the liraglutide group (P less than .001) but not in the placebo group (P less than .001 for difference between groups) after the researchers controlled for age, sex, illness duration, BMI, Clinical Global Impressions Scale severity score, and antipsychotic treatment. Glucose tolerance normalized in 30 patients who received liraglutide (64%) compared with 8 in the placebo group (16%; P less than .001), Dr. Vedtofte said.

Besides its benefits to waist circumference and weight loss, liraglutide was associated with reductions in systolic blood pressure (average, 5 mm Hg; visceral fat, 0.25 kg; and low-density lipoprotein levels, 15 mg/dL). These changes occurred even though liraglutide did not significantly alter C-peptide or glucagon secretion in the multivariate analysis of glucose tolerance test results, Dr. Vedtofte said. “The rate of nausea was 62% in liraglutide patients and 32% with placebo, but nausea was transient and did not explain the weight loss in subgroup analyses,” she added.

Liraglutide did not alter clinical liver function, but treated patients experienced a small (1.3 U/L), statistically significant rise in amylase levels. Rates of other adverse events were similar between groups except that patients were more likely to experience orthostatic hypotension on liraglutide (8.2%) than on placebo (0%; P = .04). Treatment with liraglutide did not significantly increase the likelihood of serious somatic or psychiatric adverse events, but one patient died while on therapy. “This patient was a man in his 60s with longstanding schizophrenia who was admitted to the hospital with vomiting and diarrhea, and died 3 days later,” Dr. Vedtofte said. Autopsy did not reveal the cause of death, but the patients showed no change in mental status or other signs of adverse therapeutic effects, she added.

Novo Nordisk funded the study and provided liraglutide and placebo injections. Additional support came from Capital Region Psychiatry Research Group, the foundation of King Christian X of Denmark, and the Lundbeck Foundation. Dr. Vedtofte had no disclosures.

SAN FRANCISCO – Using telemedicine for a follow-up appointment 1 week after discharge of medically complex infants reduced extra visits or calls to a clinic or emergency department, a recent study found.

The telemedicine visits also helped providers identify ways to improve the neonatal ICU (NICU) discharge process while assessing infants’ home care and answering parents’ questions.

SAN FRANCISCO – Using telemedicine for a follow-up appointment 1 week after discharge of medically complex infants reduced extra visits or calls to a clinic or emergency department, a recent study found.

The telemedicine visits also helped providers identify ways to improve the neonatal ICU (NICU) discharge process while assessing infants’ home care and answering parents’ questions.

SAN FRANCISCO – Using telemedicine for a follow-up appointment 1 week after discharge of medically complex infants reduced extra visits or calls to a clinic or emergency department, a recent study found.

The telemedicine visits also helped providers identify ways to improve the neonatal ICU (NICU) discharge process while assessing infants’ home care and answering parents’ questions.

Photo © ASCO/Danny Morton 2017

CHICAGO—Next generation sequencing (NGS) has shown that the FLT3 inhibitor gilteritinib can produce deep molecular responses in a subset of patients with acute myeloid leukemia (AML), according to new research.

Gilteritinib is a highly selective FLT3/AXL inhibitor that is active against FLT3-ITD and FLT3-D835 mutations, but minimal residual disease (MRD) had not systematically been assessed previously in AML patients treated with potent FLT3 inhibitors.

Investigators believed that MRD evaluation in these patients could serve as a useful marker of FLT3 inhibitor efficacy. They therefore conducted an exploratory analysis of a subset of AML patients treated with gilteritinib on the Chrysalis study.

Jessica K. Altman, MD, of the Robert H. Lurie Cancer Center of Northwestern University in Chicago, Illinois, presented the findings at the ASCO 2017 Annual Meeting (abstract 7003).

Chrysalis study: Efficacy and survival

The phase 1/2 Chrysalis study examined the tolerability and antileukemic activity of once daily gilteritinib in a FLT3-ITD-enriched relapsed/refractory AML population of approximately 250 patients.

Overall, gilteritinib was well tolerated and had consistency and potent FLT3 inhibition at doses of >80 mg/day.

The maximum tolerated dose was 300 mg/day. Dose-limiting toxicities were diarrhea and liver function abnormalities.

The greatest overall response rate was 52% and the longest median overall survival (OS) duration was 31 weeks, observed in patients at doses >80 mg/day.

The composite complete remission (CR) rate, comprised of CR, CR with incomplete count recovery (Cri), and CR with incomplete platelet recovery (CRp), was 41%.

The median OS was 31 weeks, and median duration of response 20 weeks.

“Survival probabilities demonstrated that the overall survival for patients who received 80 mg of gilteritinib was higher than those who received less than 80 mg,” Dr Altman said.

Molecular response assessment

Dr Altman then presented the molecular response assessment.

The investigators included all FLT3-ITD mutated patients enrolled in the gilteritinib 120 and 200 mg/day dose cohorts and had bone marrow aspirates available at baseline and at 1 or more additional time points.

“The group I’m reporting on,” Dr Altman explained, “comprises 51% of all FLT3-ITD mutated patients treated at these 2 dose levels.”

FLT3-ITD and total FLT3 alleles were quantified by a novel NGS assay using an Illumina® sequencing platform. Read depth of at least 100,000 reads per sample were implemented.

“Evaluation of MRD was exploratory and it was not prespecified in the study,” Dr Altman noted.

Hence, the investigators defined a molecular response as an ITD signal ratio—FLT3-ITD : FLT3 total—of <10^-2.

They defined major molecular response (MMR) as an ITD signal ratio of <10^-3, and negative MRD status as <10^-4.

Patient characteristics

Baseline characteristics of the 80 patients in the MRD analysis group were similar to those of the entire Chrysalis study population.

Median age was 61 years (range, 23 – 86) and the patients were heavily pretreated: 35% had 3 or more prior lines of AML therapy, and 28% had received a prior FLT3 inhibitor. About a third had prior allogeneic hematopoietic stem cell transplant.

Molecular response

Median OS in this cohort was 32.6 weeks, very similar to the entire study population.

Twenty patients (25%) achieved a molecular response, 18 (23%) an MMR, and 13 (16%) were MRD negative.

The median time to achieve a minimum ITD signal ratio was 8.2 weeks (range, 3.7 – 64).

And molecular response correlated with improved OS.

“The 20 patients who achieved a molecular response had a median overall survival of 59.6 weeks,” Dr Altman said, “which is statistically significantly different and I think clinically different than those who did not attain a molecular response.”

Patients who did not achieve a molecular response had a median overall survival of 28.4 weeks.

“As you could predict,” she added, “the molecular response was greater in those who attained a complete remission than those who had a CRp or Cri.”

Investigators observed similar results in patients who achieved an MMR, using the the cutoff point of 10^-3.

“When we stratified by MRD negative status,” she said, “which was an ITD signal ratio of 10^-4 or better, there’s clear separation of the Kaplan Meier curves for OS in this cohort again.”

Dr Altman pointed out that this was the first clinical trial to demonstrate that patients with AML treated with a FLT3 inhibitor can attain a molecular response.

“Also, and importantly, there is now a sensitive and specific assay for the detection of minimal residual disease in FLT3-ITD mutated patients and it has the potential to be widely adopted across trials and in clinical practice.”

MRD is prospectively being evaluated in 2 gilteritinib phase 3 maintenance studies.

The trial was sponsored by Astellas Pharma Global Development, Inc. 

Photo © ASCO/Danny Morton 2017

CHICAGO—Next generation sequencing (NGS) has shown that the FLT3 inhibitor gilteritinib can produce deep molecular responses in a subset of patients with acute myeloid leukemia (AML), according to new research.

Gilteritinib is a highly selective FLT3/AXL inhibitor that is active against FLT3-ITD and FLT3-D835 mutations, but minimal residual disease (MRD) had not systematically been assessed previously in AML patients treated with potent FLT3 inhibitors.

Investigators believed that MRD evaluation in these patients could serve as a useful marker of FLT3 inhibitor efficacy. They therefore conducted an exploratory analysis of a subset of AML patients treated with gilteritinib on the Chrysalis study.

Jessica K. Altman, MD, of the Robert H. Lurie Cancer Center of Northwestern University in Chicago, Illinois, presented the findings at the ASCO 2017 Annual Meeting (abstract 7003).

Chrysalis study: Efficacy and survival

The phase 1/2 Chrysalis study examined the tolerability and antileukemic activity of once daily gilteritinib in a FLT3-ITD-enriched relapsed/refractory AML population of approximately 250 patients.

Overall, gilteritinib was well tolerated and had consistency and potent FLT3 inhibition at doses of >80 mg/day.

The maximum tolerated dose was 300 mg/day. Dose-limiting toxicities were diarrhea and liver function abnormalities.

The greatest overall response rate was 52% and the longest median overall survival (OS) duration was 31 weeks, observed in patients at doses >80 mg/day.

The composite complete remission (CR) rate, comprised of CR, CR with incomplete count recovery (Cri), and CR with incomplete platelet recovery (CRp), was 41%.

The median OS was 31 weeks, and median duration of response 20 weeks.

“Survival probabilities demonstrated that the overall survival for patients who received 80 mg of gilteritinib was higher than those who received less than 80 mg,” Dr Altman said.

Molecular response assessment

Dr Altman then presented the molecular response assessment.

The investigators included all FLT3-ITD mutated patients enrolled in the gilteritinib 120 and 200 mg/day dose cohorts and had bone marrow aspirates available at baseline and at 1 or more additional time points.

“The group I’m reporting on,” Dr Altman explained, “comprises 51% of all FLT3-ITD mutated patients treated at these 2 dose levels.”

FLT3-ITD and total FLT3 alleles were quantified by a novel NGS assay using an Illumina® sequencing platform. Read depth of at least 100,000 reads per sample were implemented.

“Evaluation of MRD was exploratory and it was not prespecified in the study,” Dr Altman noted.

Hence, the investigators defined a molecular response as an ITD signal ratio—FLT3-ITD : FLT3 total—of <10^-2.

They defined major molecular response (MMR) as an ITD signal ratio of <10^-3, and negative MRD status as <10^-4.

Patient characteristics

Baseline characteristics of the 80 patients in the MRD analysis group were similar to those of the entire Chrysalis study population.

Median age was 61 years (range, 23 – 86) and the patients were heavily pretreated: 35% had 3 or more prior lines of AML therapy, and 28% had received a prior FLT3 inhibitor. About a third had prior allogeneic hematopoietic stem cell transplant.

Molecular response

Median OS in this cohort was 32.6 weeks, very similar to the entire study population.

Twenty patients (25%) achieved a molecular response, 18 (23%) an MMR, and 13 (16%) were MRD negative.

The median time to achieve a minimum ITD signal ratio was 8.2 weeks (range, 3.7 – 64).

And molecular response correlated with improved OS.

“The 20 patients who achieved a molecular response had a median overall survival of 59.6 weeks,” Dr Altman said, “which is statistically significantly different and I think clinically different than those who did not attain a molecular response.”

Patients who did not achieve a molecular response had a median overall survival of 28.4 weeks.

“As you could predict,” she added, “the molecular response was greater in those who attained a complete remission than those who had a CRp or Cri.”

Investigators observed similar results in patients who achieved an MMR, using the the cutoff point of 10^-3.

“When we stratified by MRD negative status,” she said, “which was an ITD signal ratio of 10^-4 or better, there’s clear separation of the Kaplan Meier curves for OS in this cohort again.”

Dr Altman pointed out that this was the first clinical trial to demonstrate that patients with AML treated with a FLT3 inhibitor can attain a molecular response.

“Also, and importantly, there is now a sensitive and specific assay for the detection of minimal residual disease in FLT3-ITD mutated patients and it has the potential to be widely adopted across trials and in clinical practice.”

MRD is prospectively being evaluated in 2 gilteritinib phase 3 maintenance studies.

The trial was sponsored by Astellas Pharma Global Development, Inc. 

Photo © ASCO/Danny Morton 2017

CHICAGO—Next generation sequencing (NGS) has shown that the FLT3 inhibitor gilteritinib can produce deep molecular responses in a subset of patients with acute myeloid leukemia (AML), according to new research.

Gilteritinib is a highly selective FLT3/AXL inhibitor that is active against FLT3-ITD and FLT3-D835 mutations, but minimal residual disease (MRD) had not systematically been assessed previously in AML patients treated with potent FLT3 inhibitors.

Investigators believed that MRD evaluation in these patients could serve as a useful marker of FLT3 inhibitor efficacy. They therefore conducted an exploratory analysis of a subset of AML patients treated with gilteritinib on the Chrysalis study.

Jessica K. Altman, MD, of the Robert H. Lurie Cancer Center of Northwestern University in Chicago, Illinois, presented the findings at the ASCO 2017 Annual Meeting (abstract 7003).

Chrysalis study: Efficacy and survival

The phase 1/2 Chrysalis study examined the tolerability and antileukemic activity of once daily gilteritinib in a FLT3-ITD-enriched relapsed/refractory AML population of approximately 250 patients.

Overall, gilteritinib was well tolerated and had consistency and potent FLT3 inhibition at doses of >80 mg/day.

The maximum tolerated dose was 300 mg/day. Dose-limiting toxicities were diarrhea and liver function abnormalities.

The greatest overall response rate was 52% and the longest median overall survival (OS) duration was 31 weeks, observed in patients at doses >80 mg/day.

The composite complete remission (CR) rate, comprised of CR, CR with incomplete count recovery (Cri), and CR with incomplete platelet recovery (CRp), was 41%.

The median OS was 31 weeks, and median duration of response 20 weeks.

“Survival probabilities demonstrated that the overall survival for patients who received 80 mg of gilteritinib was higher than those who received less than 80 mg,” Dr Altman said.

Molecular response assessment

Dr Altman then presented the molecular response assessment.

The investigators included all FLT3-ITD mutated patients enrolled in the gilteritinib 120 and 200 mg/day dose cohorts and had bone marrow aspirates available at baseline and at 1 or more additional time points.

“The group I’m reporting on,” Dr Altman explained, “comprises 51% of all FLT3-ITD mutated patients treated at these 2 dose levels.”

FLT3-ITD and total FLT3 alleles were quantified by a novel NGS assay using an Illumina® sequencing platform. Read depth of at least 100,000 reads per sample were implemented.

“Evaluation of MRD was exploratory and it was not prespecified in the study,” Dr Altman noted.

Hence, the investigators defined a molecular response as an ITD signal ratio—FLT3-ITD : FLT3 total—of <10^-2.

They defined major molecular response (MMR) as an ITD signal ratio of <10^-3, and negative MRD status as <10^-4.

Patient characteristics

Baseline characteristics of the 80 patients in the MRD analysis group were similar to those of the entire Chrysalis study population.

Median age was 61 years (range, 23 – 86) and the patients were heavily pretreated: 35% had 3 or more prior lines of AML therapy, and 28% had received a prior FLT3 inhibitor. About a third had prior allogeneic hematopoietic stem cell transplant.

Molecular response

Median OS in this cohort was 32.6 weeks, very similar to the entire study population.

Twenty patients (25%) achieved a molecular response, 18 (23%) an MMR, and 13 (16%) were MRD negative.

The median time to achieve a minimum ITD signal ratio was 8.2 weeks (range, 3.7 – 64).

And molecular response correlated with improved OS.

“The 20 patients who achieved a molecular response had a median overall survival of 59.6 weeks,” Dr Altman said, “which is statistically significantly different and I think clinically different than those who did not attain a molecular response.”

Patients who did not achieve a molecular response had a median overall survival of 28.4 weeks.

“As you could predict,” she added, “the molecular response was greater in those who attained a complete remission than those who had a CRp or Cri.”

Investigators observed similar results in patients who achieved an MMR, using the the cutoff point of 10^-3.

“When we stratified by MRD negative status,” she said, “which was an ITD signal ratio of 10^-4 or better, there’s clear separation of the Kaplan Meier curves for OS in this cohort again.”

Dr Altman pointed out that this was the first clinical trial to demonstrate that patients with AML treated with a FLT3 inhibitor can attain a molecular response.

“Also, and importantly, there is now a sensitive and specific assay for the detection of minimal residual disease in FLT3-ITD mutated patients and it has the potential to be widely adopted across trials and in clinical practice.”

MRD is prospectively being evaluated in 2 gilteritinib phase 3 maintenance studies.

The trial was sponsored by Astellas Pharma Global Development, Inc.