Clinical Topics & News

The investigational drug momelotinib has shown benefits in myelofibrosis in a new phase 3 trial, which could now lead to a Food and Drug Administration approval.

This drug had previously shown mixed results in a phase 3 trial funded by Gilead, which stopped development of the product; it was acquired by Sierra Oncology, which conducted the latest positive phase 3 trial and now plans to use it to apply for FDA approval.

Momelotinib, an oral Janus kinase 1 and JAK2 inhibitor, significantly outperformed danazol on symptoms, spleen size, and anemia in adults with anemic myelofibrosis in the randomized trial of 195 patients from 21 countries presented at the annual meeting of the American Society of Clinical Oncology.

“The current state for the treatment of myelofibrosis relies on JAK2,” said Ruben Mesa, MD, of the Mays Cancer Center at the UT Health San Antonio MD Anderson Cancer Center.

“Momelotinib is a JAK1 and JAK2 inhibitor.” However, in the early days of studying momelotinib,“it became clear that there was also potentially an improvement in anemia,” which may be related to the additional inhibition of ACVR1, he explained.

Data suggest that the ability to curb anemia in anemic myelofibrosis patients prolongs their lives for up to 8 years, Dr. Mesa added.

Previous studies, notably the phase 3 SIMPLIFY study, showed that momelotinib was associated with comparable effects on spleen volume, transfusion, and total symptom scores from baseline that were similar to ruxolitinib.

In the current study, known as MOMENTUM, a daily dose of momelotinib was compared to danazol for treatment of symptomatic and anemic myelofibrosis (MF) patients who had previously received standard JAK-inhibitor therapy.

In the study, the researchers randomized 130 patients to momelotinib and 65 to danazol. After 24 weeks, those in the danazol group were allowed to cross over to momelotinib. The primary endpoint of the study was total symptom score (TSS) response after 24 weeks. Secondary endpoints included transfusion independence and splenic response at 24 weeks. The median age of the patients in the momelotinib group was 71 years, 60.8% were male, and 82% were white. The baseline demographics were not significantly different in the danazol group.

Overall, 24.6% of momelotinib patients responded with improved total symptom scores at 24 weeks vs. 9.2% of the danazol group. Spleen response also was significantly higher in the momelotinib group; 40% of patients showed a 25% reduction and 23% showed a 35% reduction, compared with 6.2% and 3.1%, respectively, of patients in the danazol group. Transfusion independence at week 24 also was higher for momelotinib patients, compared with danazol patients (31% vs. 20%, respectively, P = 0064).

Adverse events of grade 3 or higher occurred in 53.8% of momelotinib patients and 64.6% of danazol patients, and serious adverse events occurred in 34.6% and 40.0%, respectively. Nearly all patients had anemia, but only 27.7% and 26.2% of the momelotinib and danazol groups, respectively, had thrombocytopenia of grade 3 or higher. The most common nonhematologic adverse events were diarrhea, nausea, and increased blood creatinine. A total of 27.7% of the patients in the momelotinib group discontinued treatment; 16 of whom did so because of an adverse event.

Also, at 24 weeks, patients in the momelotinib group showed a trend towards increased overall survival, compared with danazol (HR, 0.506, P = 0.719).

With momelotinib, there is a consistent thrombocytopenic profile across subgroups, the data on which were presented separately at ASCO (poster 7061), Dr. Mesa added.

“We feel that these findings support the future use of momelotinib as an effective treatment in MF patients, especially those with anemia,” he concluded.
 

Cytopenia data are exciting

The key finding in the current study is that “momelotinib leads to important endpoints including significant improvement in symptoms and spleen reduction,” said Dr. Gabriela Hobbs of Harvard Medical School, Boston, who served as the discussant for the study.

“I think a novel finding of momelotinib that is definitely exciting from the treatment perspective is that momelotinib can also lead to improvement in cytopenias,” she said. “We often have to decide between treating the symptoms of the spleen at the expense of blood counts,” in MF patients, she noted.

The study was sponsored by Sierra Oncology. Dr. Mesa disclosed relationships with companies including Constellation Pharmaceutical, La Jolla Pharma, and study sponsor Sierra Oncology, as well as funding from AbbVie, Celgene, Constellation Pharmaceuticals, CTI, Genentech, Incyte, Mays Cancer Center, NCI, Promedior, and Samus. Dr. Hobbs had no financial conflicts to disclose.

This article was updated 06/14/2022.

The investigational drug momelotinib has shown benefits in myelofibrosis in a new phase 3 trial, which could now lead to a Food and Drug Administration approval.

This drug had previously shown mixed results in a phase 3 trial funded by Gilead, which stopped development of the product; it was acquired by Sierra Oncology, which conducted the latest positive phase 3 trial and now plans to use it to apply for FDA approval.

Momelotinib, an oral Janus kinase 1 and JAK2 inhibitor, significantly outperformed danazol on symptoms, spleen size, and anemia in adults with anemic myelofibrosis in the randomized trial of 195 patients from 21 countries presented at the annual meeting of the American Society of Clinical Oncology.

“The current state for the treatment of myelofibrosis relies on JAK2,” said Ruben Mesa, MD, of the Mays Cancer Center at the UT Health San Antonio MD Anderson Cancer Center.

“Momelotinib is a JAK1 and JAK2 inhibitor.” However, in the early days of studying momelotinib,“it became clear that there was also potentially an improvement in anemia,” which may be related to the additional inhibition of ACVR1, he explained.

Data suggest that the ability to curb anemia in anemic myelofibrosis patients prolongs their lives for up to 8 years, Dr. Mesa added.

Previous studies, notably the phase 3 SIMPLIFY study, showed that momelotinib was associated with comparable effects on spleen volume, transfusion, and total symptom scores from baseline that were similar to ruxolitinib.

In the current study, known as MOMENTUM, a daily dose of momelotinib was compared to danazol for treatment of symptomatic and anemic myelofibrosis (MF) patients who had previously received standard JAK-inhibitor therapy.

In the study, the researchers randomized 130 patients to momelotinib and 65 to danazol. After 24 weeks, those in the danazol group were allowed to cross over to momelotinib. The primary endpoint of the study was total symptom score (TSS) response after 24 weeks. Secondary endpoints included transfusion independence and splenic response at 24 weeks. The median age of the patients in the momelotinib group was 71 years, 60.8% were male, and 82% were white. The baseline demographics were not significantly different in the danazol group.

Overall, 24.6% of momelotinib patients responded with improved total symptom scores at 24 weeks vs. 9.2% of the danazol group. Spleen response also was significantly higher in the momelotinib group; 40% of patients showed a 25% reduction and 23% showed a 35% reduction, compared with 6.2% and 3.1%, respectively, of patients in the danazol group. Transfusion independence at week 24 also was higher for momelotinib patients, compared with danazol patients (31% vs. 20%, respectively, P = 0064).

Adverse events of grade 3 or higher occurred in 53.8% of momelotinib patients and 64.6% of danazol patients, and serious adverse events occurred in 34.6% and 40.0%, respectively. Nearly all patients had anemia, but only 27.7% and 26.2% of the momelotinib and danazol groups, respectively, had thrombocytopenia of grade 3 or higher. The most common nonhematologic adverse events were diarrhea, nausea, and increased blood creatinine. A total of 27.7% of the patients in the momelotinib group discontinued treatment; 16 of whom did so because of an adverse event.

Also, at 24 weeks, patients in the momelotinib group showed a trend towards increased overall survival, compared with danazol (HR, 0.506, P = 0.719).

With momelotinib, there is a consistent thrombocytopenic profile across subgroups, the data on which were presented separately at ASCO (poster 7061), Dr. Mesa added.

“We feel that these findings support the future use of momelotinib as an effective treatment in MF patients, especially those with anemia,” he concluded.
 

Cytopenia data are exciting

The key finding in the current study is that “momelotinib leads to important endpoints including significant improvement in symptoms and spleen reduction,” said Dr. Gabriela Hobbs of Harvard Medical School, Boston, who served as the discussant for the study.

“I think a novel finding of momelotinib that is definitely exciting from the treatment perspective is that momelotinib can also lead to improvement in cytopenias,” she said. “We often have to decide between treating the symptoms of the spleen at the expense of blood counts,” in MF patients, she noted.

The study was sponsored by Sierra Oncology. Dr. Mesa disclosed relationships with companies including Constellation Pharmaceutical, La Jolla Pharma, and study sponsor Sierra Oncology, as well as funding from AbbVie, Celgene, Constellation Pharmaceuticals, CTI, Genentech, Incyte, Mays Cancer Center, NCI, Promedior, and Samus. Dr. Hobbs had no financial conflicts to disclose.

This article was updated 06/14/2022.

The investigational drug momelotinib has shown benefits in myelofibrosis in a new phase 3 trial, which could now lead to a Food and Drug Administration approval.

This drug had previously shown mixed results in a phase 3 trial funded by Gilead, which stopped development of the product; it was acquired by Sierra Oncology, which conducted the latest positive phase 3 trial and now plans to use it to apply for FDA approval.

Momelotinib, an oral Janus kinase 1 and JAK2 inhibitor, significantly outperformed danazol on symptoms, spleen size, and anemia in adults with anemic myelofibrosis in the randomized trial of 195 patients from 21 countries presented at the annual meeting of the American Society of Clinical Oncology.

“The current state for the treatment of myelofibrosis relies on JAK2,” said Ruben Mesa, MD, of the Mays Cancer Center at the UT Health San Antonio MD Anderson Cancer Center.

“Momelotinib is a JAK1 and JAK2 inhibitor.” However, in the early days of studying momelotinib,“it became clear that there was also potentially an improvement in anemia,” which may be related to the additional inhibition of ACVR1, he explained.

Data suggest that the ability to curb anemia in anemic myelofibrosis patients prolongs their lives for up to 8 years, Dr. Mesa added.

Previous studies, notably the phase 3 SIMPLIFY study, showed that momelotinib was associated with comparable effects on spleen volume, transfusion, and total symptom scores from baseline that were similar to ruxolitinib.

In the current study, known as MOMENTUM, a daily dose of momelotinib was compared to danazol for treatment of symptomatic and anemic myelofibrosis (MF) patients who had previously received standard JAK-inhibitor therapy.

In the study, the researchers randomized 130 patients to momelotinib and 65 to danazol. After 24 weeks, those in the danazol group were allowed to cross over to momelotinib. The primary endpoint of the study was total symptom score (TSS) response after 24 weeks. Secondary endpoints included transfusion independence and splenic response at 24 weeks. The median age of the patients in the momelotinib group was 71 years, 60.8% were male, and 82% were white. The baseline demographics were not significantly different in the danazol group.

Overall, 24.6% of momelotinib patients responded with improved total symptom scores at 24 weeks vs. 9.2% of the danazol group. Spleen response also was significantly higher in the momelotinib group; 40% of patients showed a 25% reduction and 23% showed a 35% reduction, compared with 6.2% and 3.1%, respectively, of patients in the danazol group. Transfusion independence at week 24 also was higher for momelotinib patients, compared with danazol patients (31% vs. 20%, respectively, P = 0064).

Adverse events of grade 3 or higher occurred in 53.8% of momelotinib patients and 64.6% of danazol patients, and serious adverse events occurred in 34.6% and 40.0%, respectively. Nearly all patients had anemia, but only 27.7% and 26.2% of the momelotinib and danazol groups, respectively, had thrombocytopenia of grade 3 or higher. The most common nonhematologic adverse events were diarrhea, nausea, and increased blood creatinine. A total of 27.7% of the patients in the momelotinib group discontinued treatment; 16 of whom did so because of an adverse event.

Also, at 24 weeks, patients in the momelotinib group showed a trend towards increased overall survival, compared with danazol (HR, 0.506, P = 0.719).

With momelotinib, there is a consistent thrombocytopenic profile across subgroups, the data on which were presented separately at ASCO (poster 7061), Dr. Mesa added.

“We feel that these findings support the future use of momelotinib as an effective treatment in MF patients, especially those with anemia,” he concluded.
 

Cytopenia data are exciting

The key finding in the current study is that “momelotinib leads to important endpoints including significant improvement in symptoms and spleen reduction,” said Dr. Gabriela Hobbs of Harvard Medical School, Boston, who served as the discussant for the study.

“I think a novel finding of momelotinib that is definitely exciting from the treatment perspective is that momelotinib can also lead to improvement in cytopenias,” she said. “We often have to decide between treating the symptoms of the spleen at the expense of blood counts,” in MF patients, she noted.

The study was sponsored by Sierra Oncology. Dr. Mesa disclosed relationships with companies including Constellation Pharmaceutical, La Jolla Pharma, and study sponsor Sierra Oncology, as well as funding from AbbVie, Celgene, Constellation Pharmaceuticals, CTI, Genentech, Incyte, Mays Cancer Center, NCI, Promedior, and Samus. Dr. Hobbs had no financial conflicts to disclose.

This article was updated 06/14/2022.

NEW ORLEANS – The case continues to grow for prioritizing a sodium-glucose transporter 2 (SGLT2) inhibitor in patients with type 2 diabetes, as real-world evidence of benefit and safety accumulates on top of the data from randomized trials that first established this class as a management pillar.

Another important effect of these agents gaining increasing currency, on top of their well-established benefits in patients with type 2 diabetes for preventing acute heart failure exacerbations and slowing progression of diabetic kidney disease, is that they cut the incidence of new-onset atrial fibrillation (AFib). That effect was confirmed in an analysis of data from about 300,000 U.S. patients included in recent Medicare records, Elisabetta Patorno, MD, reported at the annual scientific sessions of the American Diabetes Association.

Mitchel L. Zoler/MDedge News

But despite documentation like this, real-world evidence also continues to show limited uptake of SGLT2 inhibitors in U.S. patients with type 2 diabetes. Records from more than 1.3 million patients with type 2 diabetes managed in the Veterans Affairs Healthcare System during 2019 or 2022 documented that just 10% of these patients received an agent from this class, even though all were eligible to receive it, according to findings in a separate report at the meeting.

The AFib analysis analyzed two sets of propensity score–matched Medicare patients during 2013-2018 aged 65 years or older with type 2 diabetes and no history of AFib. One analysis focused on 80,475 matched patients who started on treatment with either an SGLT2 inhibitor or a glucagonlike peptide–1 (GLP-1) receptor agonist, and a second on 74,868 matched patients who began either an SGTL2 inhibitor or a dipeptidyl peptidase–4 (DPP4) inhibitor. In both analyses, matching involved more than 130 variables. In both pair sets, patients at baseline averaged about 72 years old, nearly two-thirds were women, about 8%-9% had heart failure, 77%-80% were on metformin, and 20%-25% were using insulin.

The study’s primary endpoint was the incidence of hospitalization for AFib, which occurred a significant 18% less often in the patients who started on an SGLT2, compared with those who started a DPP4 inhibitor during median follow-up of 6.7 months, and a significant 10% less often, compared with those starting a GLP-1 receptor agonist during a median follow-up of 6.0 months, Elisabetta Patorno, MD, DrPH, reported at the meeting. This worked out to 3.7 fewer hospitalizations for AFib per 1,000 patient-years of follow-up among the people who received an SGLT2 inhibitor, compared with a DPP4 inhibitor, and a decrease of 1.8 hospitalizations/1,000 patient-years when compared against patients in a GLP-1 receptor agonist.

Two secondary outcomes showed significantly fewer episodes of newly diagnosed AFib, and significantly fewer patients initiating AFib treatment among those who received an SGLT2 inhibitor relative to the comparator groups. In addition, these associations were consistent across subgroup analyses that divided patients by their age, sex, history of heart failure, and history of atherosclerotic cardiovascular disease.
 

AFib effects add to benefits

The findings “suggest that initiation of an SGLT2 inhibitor may be beneficial in older adults with type 2 diabetes who are at risk for AFib,” said Dr. Patorno, a researcher in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, Boston. “These new findings on AFib may be helpful when weighing the potential risks and benefits of various glucose-lowering drugs in older patients with type 2 diabetes.”

This new evidence follows several prior reports from other research groups of data supporting an AFib benefit from SGLT2 inhibitors. The earlier reports include a post hoc analysis of more than 17,000 patients enrolled in the DECLARE-TIMI 58 cardiovascular outcome trial of dapagliflozin (Farxiga), which showed a 19% relative decrease in the rate of incident AFib or atrial flutter events during a median 4.2 year follow-up.

Other prior reports that found a reduced incidence of AFib events linked with SGLT2 inhibitor treatment include a 2020 meta-analysis based on data from more than 38,000 patients with type 2 diabetes enrolled in any of 16 randomized, controlled trials, which found a 24% relative risk reduction. And an as-yet unpublished report from researchers at the University of Rochester (N.Y.) and their associates presented in November 2021 at the annual scientific sessions of the American Heart Association that documented a significant 24% relative risk reduction in incident AFib events linked to SGLT2 inhibitor treatment in a prospective study of 13,890 patients at several hospitals in Israel or the United States.
 

Evidence ‘convincing’ in totality

The accumulated evidence for a reduced incidence of AFib when patients were on treatment with an SGLT2 inhibitor are “convincing because it’s real world data that complements what we know from clinical trials,” commented Silvio E. Inzucchi, MD, professor of medicine at Yale University and director of the Yale Medicine Diabetes Center in New Haven, Conn., who was not involved with the study.

“If these drugs reduce heart failure, they may also reduce AFib. Heart failure patients easily slip into AFib,” he noted in an interview, but added that “I don’t think this explains all cases” of the reduced AFib incidence.

Dr. Patorno offered a few other possible mechanisms for the observed effect. The class may work by reducing blood pressure, weight, inflammation, and oxidative stress, mitochondrial dysfunction, atrial remodeling, and AFib susceptibility. These agents are also known to cause natriuresis and diuresis, which could reduce atrial dilation, a mechanism that again relates the AFib effect to the better documented reduction in acute heart failure exacerbations.

“With the diuretic effect, we’d expect less overload at the atrium and less dilation, and the same mechanism would reduce heart failure,” she said in an interview.

“If you reduce preload and afterload you may reduce stress on the ventricle and reduce atrial stretch, and that might have a significant effect on atrial arrhythmia,” agreed Dr. Inzucchi.
 

EMPRISE produces more real-world evidence

A pair of additional reports at the meeting that Dr. Patorno coauthored provided real-world evidence supporting the dramatic heart failure benefit of the SGLT2 inhibitor empagliflozin (Jardiance) in U.S. patients with type 2 diabetes, compared with alternative drug classes. The EMPRISE study used data from the Medicare, Optum Clinformatics, and MarketScan databases during the period from August 2014, when empagliflozin became available, to September 2019. The study used more than 140 variables to match patients treated with either empagliflozin or a comparator agent.

The results showed that, in an analysis of more than 130,000 matched pairs, treatment with empagliflozin was linked to a significant 30% reduction in the incidence of hospitalization for heart failure, compared with patients treated with a GLP-1 receptor agonist. Analysis of more than 116,000 matched pairs of patients showed that treatment with empagliflozin linked with a significant 29%-50% reduced rate of hospitalization for heart failure, compared with matched patients treated with a DPP4 inhibitor.

These findings “add to the pool of information” on the efficacy of agents from the SGLT2 inhibitor class, Dr. Patorno said in an interview. “We wanted to look at the full range of patients with type 2 diabetes who we see in practice,” rather than the more selected group of patients enrolled in randomized trials.

SGLT2 inhibitor use lags even when cost isn’t an issue

Despite all the accumulated evidence for efficacy and safety of the class, usage remains low, Julio A. Lamprea-Montealegre, MD, PhD, a cardiologist at the University of California, San Francisco, reported in a separate talk at the meeting. The study he presented examined records for 1,319,500 adults with type 2 diabetes managed in the VA Healthcare System during 2019 and 2020. Despite being in a system that “removes the influence of cost,” just 10% of these patients received treatment with an SGLT2 inhibitor, and 7% received treatment with a GLP-1 receptor agonist.

Notably, his analysis further showed that treatment with an SGLT2 inhibitor was especially depressed among patients with an estimated glomerular filtration rate (eGFR) of 30-44 mL/min per 1.73m². In this subgroup, usage of a drug from this class was at two-thirds of the rate, compared with patients with an eGFR of at least 90 mL/min per 1.73m2. His findings also documented lower rates of use in patients with higher risk for atherosclerotic cardiovascular disease. Dr. Lamprea-Montealegre called this a “treatment paradox,” in which patients likely to get the most benefit from an SGLT2 inhibitor were also less likely to actually receive it.

While his findings from the VA System suggest that drug cost is not the only factor driving underuse, the high price set for the SGLT2 inhibitor drugs that all currently remain on U.S. patents is widely considered an important factor.

“There is a big problem of affordability,” said Dr. Patorno.

“SGLT2 inhibitors should probably be first-line therapy” for many patients with type 2 diabetes, said Dr. Inzucchi. “The only thing holding it back is cost,” a situation that he hopes will dramatically shift once agents from this class become generic and have substantially lower price tags.

The EMPRISE study received funding from Boehringer Ingelheim, the company that markets empagliflozin (Jardiance). Dr. Patorno had no relevant commercial disclosures. Dr. Inzucchi is an adviser to Abbott Diagnostics, Esperion Therapeutics, and vTv Therapeutics, a consultant to Merck and Pfizer, and has other relationships with AstraZeneca, Boehringer Ingelheim, Lexicon, and Novo Nordisk. Dr. Lamprea-Montealegre had received research funding from Bayer.

NEW ORLEANS – The case continues to grow for prioritizing a sodium-glucose transporter 2 (SGLT2) inhibitor in patients with type 2 diabetes, as real-world evidence of benefit and safety accumulates on top of the data from randomized trials that first established this class as a management pillar.

Another important effect of these agents gaining increasing currency, on top of their well-established benefits in patients with type 2 diabetes for preventing acute heart failure exacerbations and slowing progression of diabetic kidney disease, is that they cut the incidence of new-onset atrial fibrillation (AFib). That effect was confirmed in an analysis of data from about 300,000 U.S. patients included in recent Medicare records, Elisabetta Patorno, MD, reported at the annual scientific sessions of the American Diabetes Association.

Mitchel L. Zoler/MDedge News

But despite documentation like this, real-world evidence also continues to show limited uptake of SGLT2 inhibitors in U.S. patients with type 2 diabetes. Records from more than 1.3 million patients with type 2 diabetes managed in the Veterans Affairs Healthcare System during 2019 or 2022 documented that just 10% of these patients received an agent from this class, even though all were eligible to receive it, according to findings in a separate report at the meeting.

The AFib analysis analyzed two sets of propensity score–matched Medicare patients during 2013-2018 aged 65 years or older with type 2 diabetes and no history of AFib. One analysis focused on 80,475 matched patients who started on treatment with either an SGLT2 inhibitor or a glucagonlike peptide–1 (GLP-1) receptor agonist, and a second on 74,868 matched patients who began either an SGTL2 inhibitor or a dipeptidyl peptidase–4 (DPP4) inhibitor. In both analyses, matching involved more than 130 variables. In both pair sets, patients at baseline averaged about 72 years old, nearly two-thirds were women, about 8%-9% had heart failure, 77%-80% were on metformin, and 20%-25% were using insulin.

The study’s primary endpoint was the incidence of hospitalization for AFib, which occurred a significant 18% less often in the patients who started on an SGLT2, compared with those who started a DPP4 inhibitor during median follow-up of 6.7 months, and a significant 10% less often, compared with those starting a GLP-1 receptor agonist during a median follow-up of 6.0 months, Elisabetta Patorno, MD, DrPH, reported at the meeting. This worked out to 3.7 fewer hospitalizations for AFib per 1,000 patient-years of follow-up among the people who received an SGLT2 inhibitor, compared with a DPP4 inhibitor, and a decrease of 1.8 hospitalizations/1,000 patient-years when compared against patients in a GLP-1 receptor agonist.

Two secondary outcomes showed significantly fewer episodes of newly diagnosed AFib, and significantly fewer patients initiating AFib treatment among those who received an SGLT2 inhibitor relative to the comparator groups. In addition, these associations were consistent across subgroup analyses that divided patients by their age, sex, history of heart failure, and history of atherosclerotic cardiovascular disease.
 

AFib effects add to benefits

The findings “suggest that initiation of an SGLT2 inhibitor may be beneficial in older adults with type 2 diabetes who are at risk for AFib,” said Dr. Patorno, a researcher in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, Boston. “These new findings on AFib may be helpful when weighing the potential risks and benefits of various glucose-lowering drugs in older patients with type 2 diabetes.”

This new evidence follows several prior reports from other research groups of data supporting an AFib benefit from SGLT2 inhibitors. The earlier reports include a post hoc analysis of more than 17,000 patients enrolled in the DECLARE-TIMI 58 cardiovascular outcome trial of dapagliflozin (Farxiga), which showed a 19% relative decrease in the rate of incident AFib or atrial flutter events during a median 4.2 year follow-up.

Other prior reports that found a reduced incidence of AFib events linked with SGLT2 inhibitor treatment include a 2020 meta-analysis based on data from more than 38,000 patients with type 2 diabetes enrolled in any of 16 randomized, controlled trials, which found a 24% relative risk reduction. And an as-yet unpublished report from researchers at the University of Rochester (N.Y.) and their associates presented in November 2021 at the annual scientific sessions of the American Heart Association that documented a significant 24% relative risk reduction in incident AFib events linked to SGLT2 inhibitor treatment in a prospective study of 13,890 patients at several hospitals in Israel or the United States.
 

Evidence ‘convincing’ in totality

The accumulated evidence for a reduced incidence of AFib when patients were on treatment with an SGLT2 inhibitor are “convincing because it’s real world data that complements what we know from clinical trials,” commented Silvio E. Inzucchi, MD, professor of medicine at Yale University and director of the Yale Medicine Diabetes Center in New Haven, Conn., who was not involved with the study.

“If these drugs reduce heart failure, they may also reduce AFib. Heart failure patients easily slip into AFib,” he noted in an interview, but added that “I don’t think this explains all cases” of the reduced AFib incidence.

Dr. Patorno offered a few other possible mechanisms for the observed effect. The class may work by reducing blood pressure, weight, inflammation, and oxidative stress, mitochondrial dysfunction, atrial remodeling, and AFib susceptibility. These agents are also known to cause natriuresis and diuresis, which could reduce atrial dilation, a mechanism that again relates the AFib effect to the better documented reduction in acute heart failure exacerbations.

“With the diuretic effect, we’d expect less overload at the atrium and less dilation, and the same mechanism would reduce heart failure,” she said in an interview.

“If you reduce preload and afterload you may reduce stress on the ventricle and reduce atrial stretch, and that might have a significant effect on atrial arrhythmia,” agreed Dr. Inzucchi.
 

EMPRISE produces more real-world evidence

A pair of additional reports at the meeting that Dr. Patorno coauthored provided real-world evidence supporting the dramatic heart failure benefit of the SGLT2 inhibitor empagliflozin (Jardiance) in U.S. patients with type 2 diabetes, compared with alternative drug classes. The EMPRISE study used data from the Medicare, Optum Clinformatics, and MarketScan databases during the period from August 2014, when empagliflozin became available, to September 2019. The study used more than 140 variables to match patients treated with either empagliflozin or a comparator agent.

The results showed that, in an analysis of more than 130,000 matched pairs, treatment with empagliflozin was linked to a significant 30% reduction in the incidence of hospitalization for heart failure, compared with patients treated with a GLP-1 receptor agonist. Analysis of more than 116,000 matched pairs of patients showed that treatment with empagliflozin linked with a significant 29%-50% reduced rate of hospitalization for heart failure, compared with matched patients treated with a DPP4 inhibitor.

These findings “add to the pool of information” on the efficacy of agents from the SGLT2 inhibitor class, Dr. Patorno said in an interview. “We wanted to look at the full range of patients with type 2 diabetes who we see in practice,” rather than the more selected group of patients enrolled in randomized trials.

SGLT2 inhibitor use lags even when cost isn’t an issue

Despite all the accumulated evidence for efficacy and safety of the class, usage remains low, Julio A. Lamprea-Montealegre, MD, PhD, a cardiologist at the University of California, San Francisco, reported in a separate talk at the meeting. The study he presented examined records for 1,319,500 adults with type 2 diabetes managed in the VA Healthcare System during 2019 and 2020. Despite being in a system that “removes the influence of cost,” just 10% of these patients received treatment with an SGLT2 inhibitor, and 7% received treatment with a GLP-1 receptor agonist.

Notably, his analysis further showed that treatment with an SGLT2 inhibitor was especially depressed among patients with an estimated glomerular filtration rate (eGFR) of 30-44 mL/min per 1.73m². In this subgroup, usage of a drug from this class was at two-thirds of the rate, compared with patients with an eGFR of at least 90 mL/min per 1.73m2. His findings also documented lower rates of use in patients with higher risk for atherosclerotic cardiovascular disease. Dr. Lamprea-Montealegre called this a “treatment paradox,” in which patients likely to get the most benefit from an SGLT2 inhibitor were also less likely to actually receive it.

While his findings from the VA System suggest that drug cost is not the only factor driving underuse, the high price set for the SGLT2 inhibitor drugs that all currently remain on U.S. patents is widely considered an important factor.

“There is a big problem of affordability,” said Dr. Patorno.

“SGLT2 inhibitors should probably be first-line therapy” for many patients with type 2 diabetes, said Dr. Inzucchi. “The only thing holding it back is cost,” a situation that he hopes will dramatically shift once agents from this class become generic and have substantially lower price tags.

The EMPRISE study received funding from Boehringer Ingelheim, the company that markets empagliflozin (Jardiance). Dr. Patorno had no relevant commercial disclosures. Dr. Inzucchi is an adviser to Abbott Diagnostics, Esperion Therapeutics, and vTv Therapeutics, a consultant to Merck and Pfizer, and has other relationships with AstraZeneca, Boehringer Ingelheim, Lexicon, and Novo Nordisk. Dr. Lamprea-Montealegre had received research funding from Bayer.

NEW ORLEANS – The case continues to grow for prioritizing a sodium-glucose transporter 2 (SGLT2) inhibitor in patients with type 2 diabetes, as real-world evidence of benefit and safety accumulates on top of the data from randomized trials that first established this class as a management pillar.

Another important effect of these agents gaining increasing currency, on top of their well-established benefits in patients with type 2 diabetes for preventing acute heart failure exacerbations and slowing progression of diabetic kidney disease, is that they cut the incidence of new-onset atrial fibrillation (AFib). That effect was confirmed in an analysis of data from about 300,000 U.S. patients included in recent Medicare records, Elisabetta Patorno, MD, reported at the annual scientific sessions of the American Diabetes Association.

Mitchel L. Zoler/MDedge News

But despite documentation like this, real-world evidence also continues to show limited uptake of SGLT2 inhibitors in U.S. patients with type 2 diabetes. Records from more than 1.3 million patients with type 2 diabetes managed in the Veterans Affairs Healthcare System during 2019 or 2022 documented that just 10% of these patients received an agent from this class, even though all were eligible to receive it, according to findings in a separate report at the meeting.

The AFib analysis analyzed two sets of propensity score–matched Medicare patients during 2013-2018 aged 65 years or older with type 2 diabetes and no history of AFib. One analysis focused on 80,475 matched patients who started on treatment with either an SGLT2 inhibitor or a glucagonlike peptide–1 (GLP-1) receptor agonist, and a second on 74,868 matched patients who began either an SGTL2 inhibitor or a dipeptidyl peptidase–4 (DPP4) inhibitor. In both analyses, matching involved more than 130 variables. In both pair sets, patients at baseline averaged about 72 years old, nearly two-thirds were women, about 8%-9% had heart failure, 77%-80% were on metformin, and 20%-25% were using insulin.

The study’s primary endpoint was the incidence of hospitalization for AFib, which occurred a significant 18% less often in the patients who started on an SGLT2, compared with those who started a DPP4 inhibitor during median follow-up of 6.7 months, and a significant 10% less often, compared with those starting a GLP-1 receptor agonist during a median follow-up of 6.0 months, Elisabetta Patorno, MD, DrPH, reported at the meeting. This worked out to 3.7 fewer hospitalizations for AFib per 1,000 patient-years of follow-up among the people who received an SGLT2 inhibitor, compared with a DPP4 inhibitor, and a decrease of 1.8 hospitalizations/1,000 patient-years when compared against patients in a GLP-1 receptor agonist.

Two secondary outcomes showed significantly fewer episodes of newly diagnosed AFib, and significantly fewer patients initiating AFib treatment among those who received an SGLT2 inhibitor relative to the comparator groups. In addition, these associations were consistent across subgroup analyses that divided patients by their age, sex, history of heart failure, and history of atherosclerotic cardiovascular disease.
 

AFib effects add to benefits

The findings “suggest that initiation of an SGLT2 inhibitor may be beneficial in older adults with type 2 diabetes who are at risk for AFib,” said Dr. Patorno, a researcher in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, Boston. “These new findings on AFib may be helpful when weighing the potential risks and benefits of various glucose-lowering drugs in older patients with type 2 diabetes.”

This new evidence follows several prior reports from other research groups of data supporting an AFib benefit from SGLT2 inhibitors. The earlier reports include a post hoc analysis of more than 17,000 patients enrolled in the DECLARE-TIMI 58 cardiovascular outcome trial of dapagliflozin (Farxiga), which showed a 19% relative decrease in the rate of incident AFib or atrial flutter events during a median 4.2 year follow-up.

Other prior reports that found a reduced incidence of AFib events linked with SGLT2 inhibitor treatment include a 2020 meta-analysis based on data from more than 38,000 patients with type 2 diabetes enrolled in any of 16 randomized, controlled trials, which found a 24% relative risk reduction. And an as-yet unpublished report from researchers at the University of Rochester (N.Y.) and their associates presented in November 2021 at the annual scientific sessions of the American Heart Association that documented a significant 24% relative risk reduction in incident AFib events linked to SGLT2 inhibitor treatment in a prospective study of 13,890 patients at several hospitals in Israel or the United States.
 

Evidence ‘convincing’ in totality

The accumulated evidence for a reduced incidence of AFib when patients were on treatment with an SGLT2 inhibitor are “convincing because it’s real world data that complements what we know from clinical trials,” commented Silvio E. Inzucchi, MD, professor of medicine at Yale University and director of the Yale Medicine Diabetes Center in New Haven, Conn., who was not involved with the study.

“If these drugs reduce heart failure, they may also reduce AFib. Heart failure patients easily slip into AFib,” he noted in an interview, but added that “I don’t think this explains all cases” of the reduced AFib incidence.

Dr. Patorno offered a few other possible mechanisms for the observed effect. The class may work by reducing blood pressure, weight, inflammation, and oxidative stress, mitochondrial dysfunction, atrial remodeling, and AFib susceptibility. These agents are also known to cause natriuresis and diuresis, which could reduce atrial dilation, a mechanism that again relates the AFib effect to the better documented reduction in acute heart failure exacerbations.

“With the diuretic effect, we’d expect less overload at the atrium and less dilation, and the same mechanism would reduce heart failure,” she said in an interview.

“If you reduce preload and afterload you may reduce stress on the ventricle and reduce atrial stretch, and that might have a significant effect on atrial arrhythmia,” agreed Dr. Inzucchi.
 

EMPRISE produces more real-world evidence

A pair of additional reports at the meeting that Dr. Patorno coauthored provided real-world evidence supporting the dramatic heart failure benefit of the SGLT2 inhibitor empagliflozin (Jardiance) in U.S. patients with type 2 diabetes, compared with alternative drug classes. The EMPRISE study used data from the Medicare, Optum Clinformatics, and MarketScan databases during the period from August 2014, when empagliflozin became available, to September 2019. The study used more than 140 variables to match patients treated with either empagliflozin or a comparator agent.

The results showed that, in an analysis of more than 130,000 matched pairs, treatment with empagliflozin was linked to a significant 30% reduction in the incidence of hospitalization for heart failure, compared with patients treated with a GLP-1 receptor agonist. Analysis of more than 116,000 matched pairs of patients showed that treatment with empagliflozin linked with a significant 29%-50% reduced rate of hospitalization for heart failure, compared with matched patients treated with a DPP4 inhibitor.

These findings “add to the pool of information” on the efficacy of agents from the SGLT2 inhibitor class, Dr. Patorno said in an interview. “We wanted to look at the full range of patients with type 2 diabetes who we see in practice,” rather than the more selected group of patients enrolled in randomized trials.

SGLT2 inhibitor use lags even when cost isn’t an issue

Despite all the accumulated evidence for efficacy and safety of the class, usage remains low, Julio A. Lamprea-Montealegre, MD, PhD, a cardiologist at the University of California, San Francisco, reported in a separate talk at the meeting. The study he presented examined records for 1,319,500 adults with type 2 diabetes managed in the VA Healthcare System during 2019 and 2020. Despite being in a system that “removes the influence of cost,” just 10% of these patients received treatment with an SGLT2 inhibitor, and 7% received treatment with a GLP-1 receptor agonist.

Notably, his analysis further showed that treatment with an SGLT2 inhibitor was especially depressed among patients with an estimated glomerular filtration rate (eGFR) of 30-44 mL/min per 1.73m². In this subgroup, usage of a drug from this class was at two-thirds of the rate, compared with patients with an eGFR of at least 90 mL/min per 1.73m2. His findings also documented lower rates of use in patients with higher risk for atherosclerotic cardiovascular disease. Dr. Lamprea-Montealegre called this a “treatment paradox,” in which patients likely to get the most benefit from an SGLT2 inhibitor were also less likely to actually receive it.

While his findings from the VA System suggest that drug cost is not the only factor driving underuse, the high price set for the SGLT2 inhibitor drugs that all currently remain on U.S. patents is widely considered an important factor.

“There is a big problem of affordability,” said Dr. Patorno.

“SGLT2 inhibitors should probably be first-line therapy” for many patients with type 2 diabetes, said Dr. Inzucchi. “The only thing holding it back is cost,” a situation that he hopes will dramatically shift once agents from this class become generic and have substantially lower price tags.

The EMPRISE study received funding from Boehringer Ingelheim, the company that markets empagliflozin (Jardiance). Dr. Patorno had no relevant commercial disclosures. Dr. Inzucchi is an adviser to Abbott Diagnostics, Esperion Therapeutics, and vTv Therapeutics, a consultant to Merck and Pfizer, and has other relationships with AstraZeneca, Boehringer Ingelheim, Lexicon, and Novo Nordisk. Dr. Lamprea-Montealegre had received research funding from Bayer.

Goal-directed glycemic management – which may include new technologies for glucose monitoring – for non–critically ill hospitalized patients who have diabetes or newly recognized hyperglycemia can improve outcomes, according to a new practice guideline from the Endocrine Society.  

Even though roughly 35% of hospitalized patients have diabetes or newly discovered hyperglycemia, there is “wide variability in glycemic management in clinical practice,” writing panel chair Mary Korytkowski, MD, from the University of Pittsburgh, said at the annual meeting of the Endocrine Society. “These patients get admitted to every patient service in the hospital, meaning that every clinical service will encounter this group of patients, and their glycemic management can have a major effect on their outcomes. Both short term and long term.”

This guideline provides strategies “to achieve previously recommended glycemic goals while also reducing the risk for hypoglycemia, and this includes inpatient use of insulin pump therapy or continuous glucose monitoring [CGM] devices, among others,” she said.

It also includes “recommendations for preoperative glycemic goals as well as when the use of correctional insulin – well known as sliding scale insulin – may be appropriate” and when it is not.

The document, which replaces a 2012 guideline, was published online in the Journal of Clinical Endocrinology & Metabolism.

A multidisciplinary panel developed the document over the last 3 years to answer 10 clinical practice questions related to management of non–critically ill hospitalized patients with diabetes or newly discovered hyperglycemia.
 

Use of CGM devices in hospital

The first recommendation is: “In adults with insulin-treated diabetes hospitalized for noncritical illness who are at high risk of hypoglycemia, we suggest the use of real-time [CGM] with confirmatory bedside point-of-care blood glucose monitoring for adjustments in insulin dosing rather than point-of-care blood glucose rather than testing alone in hospital settings where resources and training are available.” (Conditional recommendation. Low certainty of evidence).

“We were actually very careful in terms of looking at the data” for use of CGMs, Dr. Korytkowski said in an interview.

Although CGMs are approved by the Food and Drug Administration in the outpatient setting, and that’s becoming the standard of care there, they are not yet approved for in-hospital use.

However, the FDA granted an emergency allowance for use of CGMs in hospitals during the COVID-19 pandemic.

That was “when everyone was scrambling for what to do,” Dr. Korytkowski noted. “There was a shortage of personal protective equipment and a real interest in trying to limit the amount of exposure of healthcare personnel in some of these really critically ill patients for whom intravenous insulin therapy was used to control their glucose level.”

On March 1, the FDA granted Breakthrough Devices Designation for Dexcom CGM use in the hospital setting.

The new guideline suggests CGM be used to detect trends in glycemic management, with insulin dosing decisions made with point-of-care glucose measure (the standard of care).

To implement CGM for glycemic management in hospitals, Dr. Korytkowski said, would require “extensive staff and nursing education to have people with expertise available to provide support to nursing personnel who are both placing these devices, changing these devices, looking at trends, and then knowing when to remove them for certain procedures such as MRI or radiologic procedures.”

“We know that not all hospitals may be readily available to use these devices,” she said. “It is an area of active research. But the use of these devices during the pandemic, in both critical care and non–critical care setting has really provided us with a lot of information that was used to formulate this suggestion in the guideline.”

The document addresses the following areas: CGM, continuous subcutaneous insulin infusion pump therapy, inpatient diabetes education, prespecified preoperative glycemic targets, use of neutral protamine Hagedorn insulin for glucocorticoid or enteral nutrition-associated hyperglycemia, noninsulin therapies, preoperative carbohydrate-containing oral fluids, carbohydrate counting for prandial (mealtime) insulin dosing, and correctional and scheduled (basal or basal bolus) insulin therapies.

Nine key recommendations

Dr. Korytkowski identified nine key recommendations:

• CGM systems can help guide glycemic management with reduced risk for hypoglycemia.
• Patients experiencing glucocorticoid- or enteral nutrition–associated hyperglycemia require scheduled insulin therapy to address anticipated glucose excursions.
• Selected patients using insulin pump therapy prior to a hospital admission can continue to use these devices in the hospital if they have the mental and physical capacity to do so with knowledgeable hospital personnel.
• Diabetes self-management education provided to hospitalized patients can promote improved glycemic control following discharge with reductions in the risk for hospital readmission. “We know that is recommended for patients in the outpatient setting but often they do not get this,” she said. “We were able to observe that this can also impact long-term outcomes “
• Patients with diabetes scheduled for elective surgery may have improved postoperative outcomes when preoperative hemoglobin A1c is 8% or less and preoperative blood glucose is less than 180 mg/dL. “This recommendation answers the question: ‘Where should glycemic goals be for people who are undergoing surgery?’ ”
• Providing preoperative carbohydrate-containing beverages to patients with known diabetes is not recommended.
• Patients with newly recognized hyperglycemia or well-managed diabetes on noninsulin therapy may be treated with correctional insulin alone as initial therapy at hospital admission.
• Some noninsulin diabetes therapies can be used in combination with correction insulin for patients with type 2 diabetes who have mild hyperglycemia.
• Correctional insulin – “otherwise known as sliding-scale insulin” –  can be used as initial therapy for patients with newly recognized hyperglycemia or type 2 diabetes treated with noninsulin therapy prior to hospital admission.
• Scheduled insulin therapy is preferred for patients experiencing persistent blood glucose values greater than 180 mg/dL and is recommended for patients using insulin therapy prior to admission. 

The guideline writers’ hopes

“We hope that this guideline will resolve debates” about appropriate preoperative glycemic management and when sliding-scale insulin can be used and should not be used, said Dr. Korytkowski.

The authors also hope that “it will stimulate research funding for this very important aspect of diabetes care, and that hospitals will recognize the importance of having access to knowledgeable diabetes care and education specialists who can provide staff education regarding inpatient glycemic management, provide oversight for patients using insulin pump therapy or CGM devices, and empower hospital nurses to provide diabetes [self-management] education prior to patient discharge.”

Claire Pegg, the patient representative on the panel, hopes “that this guideline serves as the beginning of a conversation that will allow inpatient caregivers to provide individualized care to patients – some of whom may be self-sufficient with their glycemic management and others who need additional assistance.” 

Development of the guideline was funded by the Endocrine Society. Dr. Korytkowski has reported no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

Goal-directed glycemic management – which may include new technologies for glucose monitoring – for non–critically ill hospitalized patients who have diabetes or newly recognized hyperglycemia can improve outcomes, according to a new practice guideline from the Endocrine Society.  

Even though roughly 35% of hospitalized patients have diabetes or newly discovered hyperglycemia, there is “wide variability in glycemic management in clinical practice,” writing panel chair Mary Korytkowski, MD, from the University of Pittsburgh, said at the annual meeting of the Endocrine Society. “These patients get admitted to every patient service in the hospital, meaning that every clinical service will encounter this group of patients, and their glycemic management can have a major effect on their outcomes. Both short term and long term.”

This guideline provides strategies “to achieve previously recommended glycemic goals while also reducing the risk for hypoglycemia, and this includes inpatient use of insulin pump therapy or continuous glucose monitoring [CGM] devices, among others,” she said.

It also includes “recommendations for preoperative glycemic goals as well as when the use of correctional insulin – well known as sliding scale insulin – may be appropriate” and when it is not.

The document, which replaces a 2012 guideline, was published online in the Journal of Clinical Endocrinology & Metabolism.

A multidisciplinary panel developed the document over the last 3 years to answer 10 clinical practice questions related to management of non–critically ill hospitalized patients with diabetes or newly discovered hyperglycemia.
 

Use of CGM devices in hospital

The first recommendation is: “In adults with insulin-treated diabetes hospitalized for noncritical illness who are at high risk of hypoglycemia, we suggest the use of real-time [CGM] with confirmatory bedside point-of-care blood glucose monitoring for adjustments in insulin dosing rather than point-of-care blood glucose rather than testing alone in hospital settings where resources and training are available.” (Conditional recommendation. Low certainty of evidence).

“We were actually very careful in terms of looking at the data” for use of CGMs, Dr. Korytkowski said in an interview.

Although CGMs are approved by the Food and Drug Administration in the outpatient setting, and that’s becoming the standard of care there, they are not yet approved for in-hospital use.

However, the FDA granted an emergency allowance for use of CGMs in hospitals during the COVID-19 pandemic.

That was “when everyone was scrambling for what to do,” Dr. Korytkowski noted. “There was a shortage of personal protective equipment and a real interest in trying to limit the amount of exposure of healthcare personnel in some of these really critically ill patients for whom intravenous insulin therapy was used to control their glucose level.”

On March 1, the FDA granted Breakthrough Devices Designation for Dexcom CGM use in the hospital setting.

The new guideline suggests CGM be used to detect trends in glycemic management, with insulin dosing decisions made with point-of-care glucose measure (the standard of care).

To implement CGM for glycemic management in hospitals, Dr. Korytkowski said, would require “extensive staff and nursing education to have people with expertise available to provide support to nursing personnel who are both placing these devices, changing these devices, looking at trends, and then knowing when to remove them for certain procedures such as MRI or radiologic procedures.”

“We know that not all hospitals may be readily available to use these devices,” she said. “It is an area of active research. But the use of these devices during the pandemic, in both critical care and non–critical care setting has really provided us with a lot of information that was used to formulate this suggestion in the guideline.”

The document addresses the following areas: CGM, continuous subcutaneous insulin infusion pump therapy, inpatient diabetes education, prespecified preoperative glycemic targets, use of neutral protamine Hagedorn insulin for glucocorticoid or enteral nutrition-associated hyperglycemia, noninsulin therapies, preoperative carbohydrate-containing oral fluids, carbohydrate counting for prandial (mealtime) insulin dosing, and correctional and scheduled (basal or basal bolus) insulin therapies.

Nine key recommendations

Dr. Korytkowski identified nine key recommendations:

• CGM systems can help guide glycemic management with reduced risk for hypoglycemia.
• Patients experiencing glucocorticoid- or enteral nutrition–associated hyperglycemia require scheduled insulin therapy to address anticipated glucose excursions.
• Selected patients using insulin pump therapy prior to a hospital admission can continue to use these devices in the hospital if they have the mental and physical capacity to do so with knowledgeable hospital personnel.
• Diabetes self-management education provided to hospitalized patients can promote improved glycemic control following discharge with reductions in the risk for hospital readmission. “We know that is recommended for patients in the outpatient setting but often they do not get this,” she said. “We were able to observe that this can also impact long-term outcomes “
• Patients with diabetes scheduled for elective surgery may have improved postoperative outcomes when preoperative hemoglobin A1c is 8% or less and preoperative blood glucose is less than 180 mg/dL. “This recommendation answers the question: ‘Where should glycemic goals be for people who are undergoing surgery?’ ”
• Providing preoperative carbohydrate-containing beverages to patients with known diabetes is not recommended.
• Patients with newly recognized hyperglycemia or well-managed diabetes on noninsulin therapy may be treated with correctional insulin alone as initial therapy at hospital admission.
• Some noninsulin diabetes therapies can be used in combination with correction insulin for patients with type 2 diabetes who have mild hyperglycemia.
• Correctional insulin – “otherwise known as sliding-scale insulin” –  can be used as initial therapy for patients with newly recognized hyperglycemia or type 2 diabetes treated with noninsulin therapy prior to hospital admission.
• Scheduled insulin therapy is preferred for patients experiencing persistent blood glucose values greater than 180 mg/dL and is recommended for patients using insulin therapy prior to admission. 

The guideline writers’ hopes

“We hope that this guideline will resolve debates” about appropriate preoperative glycemic management and when sliding-scale insulin can be used and should not be used, said Dr. Korytkowski.

The authors also hope that “it will stimulate research funding for this very important aspect of diabetes care, and that hospitals will recognize the importance of having access to knowledgeable diabetes care and education specialists who can provide staff education regarding inpatient glycemic management, provide oversight for patients using insulin pump therapy or CGM devices, and empower hospital nurses to provide diabetes [self-management] education prior to patient discharge.”

Claire Pegg, the patient representative on the panel, hopes “that this guideline serves as the beginning of a conversation that will allow inpatient caregivers to provide individualized care to patients – some of whom may be self-sufficient with their glycemic management and others who need additional assistance.” 

Development of the guideline was funded by the Endocrine Society. Dr. Korytkowski has reported no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

Goal-directed glycemic management – which may include new technologies for glucose monitoring – for non–critically ill hospitalized patients who have diabetes or newly recognized hyperglycemia can improve outcomes, according to a new practice guideline from the Endocrine Society.  

Even though roughly 35% of hospitalized patients have diabetes or newly discovered hyperglycemia, there is “wide variability in glycemic management in clinical practice,” writing panel chair Mary Korytkowski, MD, from the University of Pittsburgh, said at the annual meeting of the Endocrine Society. “These patients get admitted to every patient service in the hospital, meaning that every clinical service will encounter this group of patients, and their glycemic management can have a major effect on their outcomes. Both short term and long term.”

This guideline provides strategies “to achieve previously recommended glycemic goals while also reducing the risk for hypoglycemia, and this includes inpatient use of insulin pump therapy or continuous glucose monitoring [CGM] devices, among others,” she said.

It also includes “recommendations for preoperative glycemic goals as well as when the use of correctional insulin – well known as sliding scale insulin – may be appropriate” and when it is not.

The document, which replaces a 2012 guideline, was published online in the Journal of Clinical Endocrinology & Metabolism.

A multidisciplinary panel developed the document over the last 3 years to answer 10 clinical practice questions related to management of non–critically ill hospitalized patients with diabetes or newly discovered hyperglycemia.
 

Use of CGM devices in hospital

The first recommendation is: “In adults with insulin-treated diabetes hospitalized for noncritical illness who are at high risk of hypoglycemia, we suggest the use of real-time [CGM] with confirmatory bedside point-of-care blood glucose monitoring for adjustments in insulin dosing rather than point-of-care blood glucose rather than testing alone in hospital settings where resources and training are available.” (Conditional recommendation. Low certainty of evidence).

“We were actually very careful in terms of looking at the data” for use of CGMs, Dr. Korytkowski said in an interview.

Although CGMs are approved by the Food and Drug Administration in the outpatient setting, and that’s becoming the standard of care there, they are not yet approved for in-hospital use.

However, the FDA granted an emergency allowance for use of CGMs in hospitals during the COVID-19 pandemic.

That was “when everyone was scrambling for what to do,” Dr. Korytkowski noted. “There was a shortage of personal protective equipment and a real interest in trying to limit the amount of exposure of healthcare personnel in some of these really critically ill patients for whom intravenous insulin therapy was used to control their glucose level.”

On March 1, the FDA granted Breakthrough Devices Designation for Dexcom CGM use in the hospital setting.

The new guideline suggests CGM be used to detect trends in glycemic management, with insulin dosing decisions made with point-of-care glucose measure (the standard of care).

To implement CGM for glycemic management in hospitals, Dr. Korytkowski said, would require “extensive staff and nursing education to have people with expertise available to provide support to nursing personnel who are both placing these devices, changing these devices, looking at trends, and then knowing when to remove them for certain procedures such as MRI or radiologic procedures.”

“We know that not all hospitals may be readily available to use these devices,” she said. “It is an area of active research. But the use of these devices during the pandemic, in both critical care and non–critical care setting has really provided us with a lot of information that was used to formulate this suggestion in the guideline.”

The document addresses the following areas: CGM, continuous subcutaneous insulin infusion pump therapy, inpatient diabetes education, prespecified preoperative glycemic targets, use of neutral protamine Hagedorn insulin for glucocorticoid or enteral nutrition-associated hyperglycemia, noninsulin therapies, preoperative carbohydrate-containing oral fluids, carbohydrate counting for prandial (mealtime) insulin dosing, and correctional and scheduled (basal or basal bolus) insulin therapies.

Nine key recommendations

Dr. Korytkowski identified nine key recommendations:

• CGM systems can help guide glycemic management with reduced risk for hypoglycemia.
• Patients experiencing glucocorticoid- or enteral nutrition–associated hyperglycemia require scheduled insulin therapy to address anticipated glucose excursions.
• Selected patients using insulin pump therapy prior to a hospital admission can continue to use these devices in the hospital if they have the mental and physical capacity to do so with knowledgeable hospital personnel.
• Diabetes self-management education provided to hospitalized patients can promote improved glycemic control following discharge with reductions in the risk for hospital readmission. “We know that is recommended for patients in the outpatient setting but often they do not get this,” she said. “We were able to observe that this can also impact long-term outcomes “
• Patients with diabetes scheduled for elective surgery may have improved postoperative outcomes when preoperative hemoglobin A1c is 8% or less and preoperative blood glucose is less than 180 mg/dL. “This recommendation answers the question: ‘Where should glycemic goals be for people who are undergoing surgery?’ ”
• Providing preoperative carbohydrate-containing beverages to patients with known diabetes is not recommended.
• Patients with newly recognized hyperglycemia or well-managed diabetes on noninsulin therapy may be treated with correctional insulin alone as initial therapy at hospital admission.
• Some noninsulin diabetes therapies can be used in combination with correction insulin for patients with type 2 diabetes who have mild hyperglycemia.
• Correctional insulin – “otherwise known as sliding-scale insulin” –  can be used as initial therapy for patients with newly recognized hyperglycemia or type 2 diabetes treated with noninsulin therapy prior to hospital admission.
• Scheduled insulin therapy is preferred for patients experiencing persistent blood glucose values greater than 180 mg/dL and is recommended for patients using insulin therapy prior to admission. 

The guideline writers’ hopes

“We hope that this guideline will resolve debates” about appropriate preoperative glycemic management and when sliding-scale insulin can be used and should not be used, said Dr. Korytkowski.

The authors also hope that “it will stimulate research funding for this very important aspect of diabetes care, and that hospitals will recognize the importance of having access to knowledgeable diabetes care and education specialists who can provide staff education regarding inpatient glycemic management, provide oversight for patients using insulin pump therapy or CGM devices, and empower hospital nurses to provide diabetes [self-management] education prior to patient discharge.”

Claire Pegg, the patient representative on the panel, hopes “that this guideline serves as the beginning of a conversation that will allow inpatient caregivers to provide individualized care to patients – some of whom may be self-sufficient with their glycemic management and others who need additional assistance.” 

Development of the guideline was funded by the Endocrine Society. Dr. Korytkowski has reported no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

Following tumor removal in patients with recurrent glioblastoma, an absorbable collagen tile can deliver a controlled and therapeutic dose of radiation that targets remaining tumor cells and spares healthy tissue, new research suggests.

The results showed inserting a collagen matrix containing radioactive seeds into the brain postsurgery did not impede wound healing. It also showed a favorable safety profile, researchers note.

Benefits for patients undergoing this GammaTile (GT) intervention include not having to wait weeks to receive radiation treatment, which in turn improves their quality of life, said study investigator Clark C. Chen, MD, PhD, chair, department of neurosurgery, University of Minnesota Medical School, Minneapolis.

“These initial results are highly promising and offer hope for patients afflicted with an otherwise devastating disease,” Dr. Chen said in an interview.

If replicated in larger trials, GT therapy “could define a new standard of care, and there would really be no reason why patients shouldn’t get this therapy,” he added.

This is the first clinical series describing GT use since its approval by the U.S. Food and Drug Administration (FDA) for recurrent brain cancer.

The findings were presented at the annual meeting of the American Association of Neurological Surgeons (AANS) and were published recently in Neuro-Oncology Advances.

Radioactive seeds

GT therapy is a version of brachytherapy where radioactive sources are placed adjacent to cancerous tissue. It consists of radioactive seeds embedded with a collagen tile.

The neurosurgeon inserts these “tiles” immediately after tumor removal to cover the entire resection cavity, Dr. Chen said. The tiles maintain the cavity architecture to prevent radiation “hot spots” associated with cavity collapse.

Dr. Chen noted the therapy is “short range,” with most of the radiation delivered within 8 millimeters of the radioactive seeds.

The radiation lasts for about a month and the collagen tiles are eventually absorbed within the body. “You put in the tiles and you don’t need to do anything more,” Dr. Chen said.

GT has a number of advantages. Unlike with traditional brachytherapy, the collagen tile provides a buffer around the radiation sources, allowing delivery of the optimal radiation dose while preserving healthy tissue.

It also avoids the up-to-6-weeks patients have to wait postsurgery to get external beam radiation therapy. “If you start radiation too early, it actually compromises wound healing, and in the meantime the tumor is growing,” said Dr. Chen.

“I have several patients where I removed a large tumor and within that 6-week period, the tumor came back entirely,” he added.

With the gamma-tile, however, radiation from the seeds kills the tumor while the body heals.

Safety profile

The study included 22 patients (mean age, 57.7 years; 15 men, 7 women) with wild-type isocitrate dehydrogenase glioblastoma. They were all having surgery for recurrent tumors.

“One of the most challenging aspects of glioblastomas is that not only do the tumors come back, they come back immediately adjacent to where you have done the surgery, and for many patients this is demoralizing,” Dr. Chen said.

Six participants had 0 ⁶ -Methylguanine-DNA methyltranferase (MGMT) methylated glioblastoma, while the others had unmethylated MGMT.

The mean follow-up from initial diagnosis was 733 days (2 years).

Results showed one patient had to be readmitted to the hospital for hydrocephalus, but there were no re-admissions within 30 days attributable to GT.

Despite participants having undergone a second and third resection through the same surgical incision, there were no wound infections. “One of the concerns of giving radiation right after surgery is it can compromise wound healing, and this is why you wait 6 weeks,” Dr. Chen noted.

He stressed that no patient in the study suffered from adverse radiation effects that required medical or surgical intervention.

As the radiation is so short-range, hair loss and skin irritation are not side effects of GT, he added.

“The radiation is inside the brain and highly targeted, so it doesn’t hit hair follicles,” said Dr. Chen. “As best as I can observe in these patients, I did not see toxicity associated with radiation.”

One and done

Among the 22 participants, 18 had neurologic symptoms at baseline. There were no new neurologic deficits that developed after GT placement.

In addition, GT therapy improved “local control” — preventing the tumor from growing back at the site of the surgery. The local control was 86% at 6 months and 81% at 12 months.

The median progression-free survival was about 8 months. The median overall survival was 20 months (about 600 days) for the unmethylated MGMT group and 37.4 months (about 1120 days) for the methylated group.

Outcomes compared favorably to an independent glioblastoma cohort of similar patients who did not receive GT treatment during the study period, Dr. Chen noted.

“This therapy can potentially redefine how we treat glioblastoma patients whose cancer came back,” he said.

A study limitation was that it did not include quality-of-life data, which makes it challenging to assess the therapy’s overall impact, Dr. Chen said. However, he added that from his experience, patients very much appreciate not having to repeatedly take time off work for clinic or hospital visits to receive radiation treatments.

“One of the beauties of this therapy is it’s a one-and-done deal,” he said.

Interesting, timely

Commenting for this news organization, William T. Curry Jr, MD, co-director at MassGeneral Neuroscience and director of neurosurgical oncology at Mass General Cancer Center, Boston, called the study “interesting and timely.”

These new data “underscore that GT is safe in patients that have undergone gross total resection of recurrent glioblastoma and that rates of progression free survival may exceed those treated with resection alone,” said Dr. Curry, who was not involved with the research.

“Surgeons are excited about anything that has the potential to improve outcomes for patients with this very challenging disease, and it is wonderful to be able to offer hope and survival tools to patients,” he added.

However, Dr. Curry noted there are challenges and potential biases when studying survival in cancer patients without conducting a randomization process. The investigators “admit to methodological flaws inherent in the single-arm design in a patient population with recurrent glioblastoma not treated uniformly,” he said.

In addition, he noted overall survival may not have been related to the GT intervention. “Multicenter randomization is probably required to get to the bottom of the survival advantage in different subsets of glioblastoma patients,” Dr. Curry said.

Further research is needed to confirm the efficacy, appropriate indications, and timing of the intervention, but “I would support a randomized multicenter study in patients undergoing near gross total resection of recurrent glioblastoma,” he concluded.

The study received no outside funding. Dr. Chen and Dr. Curry have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Following tumor removal in patients with recurrent glioblastoma, an absorbable collagen tile can deliver a controlled and therapeutic dose of radiation that targets remaining tumor cells and spares healthy tissue, new research suggests.

The results showed inserting a collagen matrix containing radioactive seeds into the brain postsurgery did not impede wound healing. It also showed a favorable safety profile, researchers note.

Benefits for patients undergoing this GammaTile (GT) intervention include not having to wait weeks to receive radiation treatment, which in turn improves their quality of life, said study investigator Clark C. Chen, MD, PhD, chair, department of neurosurgery, University of Minnesota Medical School, Minneapolis.

“These initial results are highly promising and offer hope for patients afflicted with an otherwise devastating disease,” Dr. Chen said in an interview.

If replicated in larger trials, GT therapy “could define a new standard of care, and there would really be no reason why patients shouldn’t get this therapy,” he added.

This is the first clinical series describing GT use since its approval by the U.S. Food and Drug Administration (FDA) for recurrent brain cancer.

The findings were presented at the annual meeting of the American Association of Neurological Surgeons (AANS) and were published recently in Neuro-Oncology Advances.

Radioactive seeds

GT therapy is a version of brachytherapy where radioactive sources are placed adjacent to cancerous tissue. It consists of radioactive seeds embedded with a collagen tile.

The neurosurgeon inserts these “tiles” immediately after tumor removal to cover the entire resection cavity, Dr. Chen said. The tiles maintain the cavity architecture to prevent radiation “hot spots” associated with cavity collapse.

Dr. Chen noted the therapy is “short range,” with most of the radiation delivered within 8 millimeters of the radioactive seeds.

The radiation lasts for about a month and the collagen tiles are eventually absorbed within the body. “You put in the tiles and you don’t need to do anything more,” Dr. Chen said.

GT has a number of advantages. Unlike with traditional brachytherapy, the collagen tile provides a buffer around the radiation sources, allowing delivery of the optimal radiation dose while preserving healthy tissue.

It also avoids the up-to-6-weeks patients have to wait postsurgery to get external beam radiation therapy. “If you start radiation too early, it actually compromises wound healing, and in the meantime the tumor is growing,” said Dr. Chen.

“I have several patients where I removed a large tumor and within that 6-week period, the tumor came back entirely,” he added.

With the gamma-tile, however, radiation from the seeds kills the tumor while the body heals.

Safety profile

The study included 22 patients (mean age, 57.7 years; 15 men, 7 women) with wild-type isocitrate dehydrogenase glioblastoma. They were all having surgery for recurrent tumors.

“One of the most challenging aspects of glioblastomas is that not only do the tumors come back, they come back immediately adjacent to where you have done the surgery, and for many patients this is demoralizing,” Dr. Chen said.

Six participants had 0 ⁶ -Methylguanine-DNA methyltranferase (MGMT) methylated glioblastoma, while the others had unmethylated MGMT.

The mean follow-up from initial diagnosis was 733 days (2 years).

Results showed one patient had to be readmitted to the hospital for hydrocephalus, but there were no re-admissions within 30 days attributable to GT.

Despite participants having undergone a second and third resection through the same surgical incision, there were no wound infections. “One of the concerns of giving radiation right after surgery is it can compromise wound healing, and this is why you wait 6 weeks,” Dr. Chen noted.

He stressed that no patient in the study suffered from adverse radiation effects that required medical or surgical intervention.

As the radiation is so short-range, hair loss and skin irritation are not side effects of GT, he added.

“The radiation is inside the brain and highly targeted, so it doesn’t hit hair follicles,” said Dr. Chen. “As best as I can observe in these patients, I did not see toxicity associated with radiation.”

One and done

Among the 22 participants, 18 had neurologic symptoms at baseline. There were no new neurologic deficits that developed after GT placement.

In addition, GT therapy improved “local control” — preventing the tumor from growing back at the site of the surgery. The local control was 86% at 6 months and 81% at 12 months.

The median progression-free survival was about 8 months. The median overall survival was 20 months (about 600 days) for the unmethylated MGMT group and 37.4 months (about 1120 days) for the methylated group.

Outcomes compared favorably to an independent glioblastoma cohort of similar patients who did not receive GT treatment during the study period, Dr. Chen noted.

“This therapy can potentially redefine how we treat glioblastoma patients whose cancer came back,” he said.

A study limitation was that it did not include quality-of-life data, which makes it challenging to assess the therapy’s overall impact, Dr. Chen said. However, he added that from his experience, patients very much appreciate not having to repeatedly take time off work for clinic or hospital visits to receive radiation treatments.

“One of the beauties of this therapy is it’s a one-and-done deal,” he said.

Interesting, timely

Commenting for this news organization, William T. Curry Jr, MD, co-director at MassGeneral Neuroscience and director of neurosurgical oncology at Mass General Cancer Center, Boston, called the study “interesting and timely.”

These new data “underscore that GT is safe in patients that have undergone gross total resection of recurrent glioblastoma and that rates of progression free survival may exceed those treated with resection alone,” said Dr. Curry, who was not involved with the research.

“Surgeons are excited about anything that has the potential to improve outcomes for patients with this very challenging disease, and it is wonderful to be able to offer hope and survival tools to patients,” he added.

However, Dr. Curry noted there are challenges and potential biases when studying survival in cancer patients without conducting a randomization process. The investigators “admit to methodological flaws inherent in the single-arm design in a patient population with recurrent glioblastoma not treated uniformly,” he said.

In addition, he noted overall survival may not have been related to the GT intervention. “Multicenter randomization is probably required to get to the bottom of the survival advantage in different subsets of glioblastoma patients,” Dr. Curry said.

Further research is needed to confirm the efficacy, appropriate indications, and timing of the intervention, but “I would support a randomized multicenter study in patients undergoing near gross total resection of recurrent glioblastoma,” he concluded.

The study received no outside funding. Dr. Chen and Dr. Curry have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Following tumor removal in patients with recurrent glioblastoma, an absorbable collagen tile can deliver a controlled and therapeutic dose of radiation that targets remaining tumor cells and spares healthy tissue, new research suggests.

The results showed inserting a collagen matrix containing radioactive seeds into the brain postsurgery did not impede wound healing. It also showed a favorable safety profile, researchers note.

Benefits for patients undergoing this GammaTile (GT) intervention include not having to wait weeks to receive radiation treatment, which in turn improves their quality of life, said study investigator Clark C. Chen, MD, PhD, chair, department of neurosurgery, University of Minnesota Medical School, Minneapolis.

“These initial results are highly promising and offer hope for patients afflicted with an otherwise devastating disease,” Dr. Chen said in an interview.

If replicated in larger trials, GT therapy “could define a new standard of care, and there would really be no reason why patients shouldn’t get this therapy,” he added.

This is the first clinical series describing GT use since its approval by the U.S. Food and Drug Administration (FDA) for recurrent brain cancer.

The findings were presented at the annual meeting of the American Association of Neurological Surgeons (AANS) and were published recently in Neuro-Oncology Advances.

Radioactive seeds

GT therapy is a version of brachytherapy where radioactive sources are placed adjacent to cancerous tissue. It consists of radioactive seeds embedded with a collagen tile.

The neurosurgeon inserts these “tiles” immediately after tumor removal to cover the entire resection cavity, Dr. Chen said. The tiles maintain the cavity architecture to prevent radiation “hot spots” associated with cavity collapse.

Dr. Chen noted the therapy is “short range,” with most of the radiation delivered within 8 millimeters of the radioactive seeds.

The radiation lasts for about a month and the collagen tiles are eventually absorbed within the body. “You put in the tiles and you don’t need to do anything more,” Dr. Chen said.

GT has a number of advantages. Unlike with traditional brachytherapy, the collagen tile provides a buffer around the radiation sources, allowing delivery of the optimal radiation dose while preserving healthy tissue.

It also avoids the up-to-6-weeks patients have to wait postsurgery to get external beam radiation therapy. “If you start radiation too early, it actually compromises wound healing, and in the meantime the tumor is growing,” said Dr. Chen.

“I have several patients where I removed a large tumor and within that 6-week period, the tumor came back entirely,” he added.

With the gamma-tile, however, radiation from the seeds kills the tumor while the body heals.

Safety profile

The study included 22 patients (mean age, 57.7 years; 15 men, 7 women) with wild-type isocitrate dehydrogenase glioblastoma. They were all having surgery for recurrent tumors.

“One of the most challenging aspects of glioblastomas is that not only do the tumors come back, they come back immediately adjacent to where you have done the surgery, and for many patients this is demoralizing,” Dr. Chen said.

Six participants had 0 ⁶ -Methylguanine-DNA methyltranferase (MGMT) methylated glioblastoma, while the others had unmethylated MGMT.

The mean follow-up from initial diagnosis was 733 days (2 years).

Results showed one patient had to be readmitted to the hospital for hydrocephalus, but there were no re-admissions within 30 days attributable to GT.

Despite participants having undergone a second and third resection through the same surgical incision, there were no wound infections. “One of the concerns of giving radiation right after surgery is it can compromise wound healing, and this is why you wait 6 weeks,” Dr. Chen noted.

He stressed that no patient in the study suffered from adverse radiation effects that required medical or surgical intervention.

As the radiation is so short-range, hair loss and skin irritation are not side effects of GT, he added.

“The radiation is inside the brain and highly targeted, so it doesn’t hit hair follicles,” said Dr. Chen. “As best as I can observe in these patients, I did not see toxicity associated with radiation.”

One and done

Among the 22 participants, 18 had neurologic symptoms at baseline. There were no new neurologic deficits that developed after GT placement.

In addition, GT therapy improved “local control” — preventing the tumor from growing back at the site of the surgery. The local control was 86% at 6 months and 81% at 12 months.

The median progression-free survival was about 8 months. The median overall survival was 20 months (about 600 days) for the unmethylated MGMT group and 37.4 months (about 1120 days) for the methylated group.

Outcomes compared favorably to an independent glioblastoma cohort of similar patients who did not receive GT treatment during the study period, Dr. Chen noted.

“This therapy can potentially redefine how we treat glioblastoma patients whose cancer came back,” he said.

A study limitation was that it did not include quality-of-life data, which makes it challenging to assess the therapy’s overall impact, Dr. Chen said. However, he added that from his experience, patients very much appreciate not having to repeatedly take time off work for clinic or hospital visits to receive radiation treatments.

“One of the beauties of this therapy is it’s a one-and-done deal,” he said.

Interesting, timely

Commenting for this news organization, William T. Curry Jr, MD, co-director at MassGeneral Neuroscience and director of neurosurgical oncology at Mass General Cancer Center, Boston, called the study “interesting and timely.”

These new data “underscore that GT is safe in patients that have undergone gross total resection of recurrent glioblastoma and that rates of progression free survival may exceed those treated with resection alone,” said Dr. Curry, who was not involved with the research.

“Surgeons are excited about anything that has the potential to improve outcomes for patients with this very challenging disease, and it is wonderful to be able to offer hope and survival tools to patients,” he added.

However, Dr. Curry noted there are challenges and potential biases when studying survival in cancer patients without conducting a randomization process. The investigators “admit to methodological flaws inherent in the single-arm design in a patient population with recurrent glioblastoma not treated uniformly,” he said.

In addition, he noted overall survival may not have been related to the GT intervention. “Multicenter randomization is probably required to get to the bottom of the survival advantage in different subsets of glioblastoma patients,” Dr. Curry said.

Further research is needed to confirm the efficacy, appropriate indications, and timing of the intervention, but “I would support a randomized multicenter study in patients undergoing near gross total resection of recurrent glioblastoma,” he concluded.

The study received no outside funding. Dr. Chen and Dr. Curry have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The American Society for Radiation Oncology (ASTRO) has issued new guidance on the use of radiation therapy for the treatment of brain metastases, an update on its 2012 document.  

“In the decade since the previous ASTRO brain metastases guideline, there has been a tremendous evolution in the way we manage patients’ disease,” said Paul D. Brown, MD, chair of the guideline task force and a professor of radiation oncology at the Mayo Clinic in Rochester, Minn.  

“The development of stereotactic radiosurgery (SRS) has allowed treatment of limited brain metastases alone, often in a single fraction, while largely sparing the surrounding brain,” he elaborated in a statement. Also, novel techniques such as hippocampal avoidance with whole-brain radiation can greatly improve quality of life, he added.

The guideline was published May 6 in Practical Radiation Oncology.

“With the emergence of novel radiotherapy techniques and technologies, brain-penetrating drug therapies and neurosurgical interventions, modern management of brain metastases has become increasingly personalized, complex and multidisciplinary,” Vinai Gondi, MD, vice chair of the guideline task force and director of research and education at the Northwestern Medicine Cancer Center and Proton Center in Chicago, said in a statement.

“We developed this guideline to help inform and guide clinicians in patient-centered, multidisciplinary care for their patients with brain metastases,” he added.

Key recommendations

Overall, the recommendations address a wide range of topics related to radiation therapy in patients with cancer that has spread to the brain,  including delivery techniques for radiation therapy to manage both unresected and resected brain metastases. The guideline also includes treatment algorithms for limited brain metastases and extensive brain metastases.

Key recommendations are as follows:

For patients with intact/unresected brain metastases:

• SRS is recommended for patients with 1-4 brain metastases and reasonable performance status (ECOG performance status 0-2); SRS is conditionally recommended for those with 5-10 brain metastases and reasonable performance status; for patients with tumors exerting mass effect and/or larger size, multidisciplinary discussion with neurosurgery to consider surgical resection is suggested.
• Upfront local therapy (radiation and/or surgery) is strongly recommended for patients with symptomatic brain metastases. 
• For patients with asymptomatic brain metastases who are eligible for central nervous system-directed systemic therapy, multidisciplinary and patient-centered decision-making to determine whether local therapy may be safely deferred is conditionally recommended.
• Whole brain radiation therapy (WBRT) is recommended as a primary treatment for patients with favorable prognosis who have brain metastases that are ineligible for surgery and/or SRS. Hippocampal avoidance (HA) is recommended when appropriate to preserve memory function, as is the addition of memantine to delay neurocognitive decline. Adjuvant WBRT added to SRS routinely is not recommended.
• Supportive care only, without WBRT, should be considered for patients with poor prognosis and brain metastases. Reasonable options for this population include palliative care or hospice, or short-course WBRT for symptomatic brain metastases
• Recommendations also include guidance for SRS and WBRT dosing as well as the use of single-fraction vs hypofractionated SRS. Although SRS use is driven by the number of brain metastases, it is critical that other important factors (eg, total tumor volume and location, patient age, and extracranial disease status) should be taken into consideration during patient-centered decision-making by the multidisciplinary team.

For patients with resected brain metastases:

• Radiation therapy is recommended for all patients after resection in order to improve intracranial control.
• For patients with limited brain metastases after resection, postoperative SRS is recommended over WBRT to preserve the patient’s neurocognitive function and quality of life.
• As a potential alternative to SRS postresection, SRS prior to brain metastasis resection is conditionally recommended.

Updating the guidelines

ASTRO emphasizes that the scope of this paper is limited to the radiotherapeutic management of intact and resected brain metastases resulting from nonhematologic solid tumors. It provides guidance on the reasonable use of modern radiation therapy strategies, including single-fraction and fractionated (ie, hypofractionated SRS) SRS and HA-WBRT, and also discusses clinical considerations in selecting the optimal radiation therapy strategy or in deferring it in favor of best supportive care or close neuro-oncologic surveillance.

The authors note, however, that beyond the scope of this guideline, there are many other important questions that may be the subject of other guidance, such as the appropriate role for CNS-active systemic therapies and/or surgical intervention.

A version of this article was first published on Medscape.com.

The American Society for Radiation Oncology (ASTRO) has issued new guidance on the use of radiation therapy for the treatment of brain metastases, an update on its 2012 document.  

“In the decade since the previous ASTRO brain metastases guideline, there has been a tremendous evolution in the way we manage patients’ disease,” said Paul D. Brown, MD, chair of the guideline task force and a professor of radiation oncology at the Mayo Clinic in Rochester, Minn.  

“The development of stereotactic radiosurgery (SRS) has allowed treatment of limited brain metastases alone, often in a single fraction, while largely sparing the surrounding brain,” he elaborated in a statement. Also, novel techniques such as hippocampal avoidance with whole-brain radiation can greatly improve quality of life, he added.

The guideline was published May 6 in Practical Radiation Oncology.

“With the emergence of novel radiotherapy techniques and technologies, brain-penetrating drug therapies and neurosurgical interventions, modern management of brain metastases has become increasingly personalized, complex and multidisciplinary,” Vinai Gondi, MD, vice chair of the guideline task force and director of research and education at the Northwestern Medicine Cancer Center and Proton Center in Chicago, said in a statement.

“We developed this guideline to help inform and guide clinicians in patient-centered, multidisciplinary care for their patients with brain metastases,” he added.

Key recommendations

Overall, the recommendations address a wide range of topics related to radiation therapy in patients with cancer that has spread to the brain,  including delivery techniques for radiation therapy to manage both unresected and resected brain metastases. The guideline also includes treatment algorithms for limited brain metastases and extensive brain metastases.

Key recommendations are as follows:

For patients with intact/unresected brain metastases:

• SRS is recommended for patients with 1-4 brain metastases and reasonable performance status (ECOG performance status 0-2); SRS is conditionally recommended for those with 5-10 brain metastases and reasonable performance status; for patients with tumors exerting mass effect and/or larger size, multidisciplinary discussion with neurosurgery to consider surgical resection is suggested.
• Upfront local therapy (radiation and/or surgery) is strongly recommended for patients with symptomatic brain metastases. 
• For patients with asymptomatic brain metastases who are eligible for central nervous system-directed systemic therapy, multidisciplinary and patient-centered decision-making to determine whether local therapy may be safely deferred is conditionally recommended.
• Whole brain radiation therapy (WBRT) is recommended as a primary treatment for patients with favorable prognosis who have brain metastases that are ineligible for surgery and/or SRS. Hippocampal avoidance (HA) is recommended when appropriate to preserve memory function, as is the addition of memantine to delay neurocognitive decline. Adjuvant WBRT added to SRS routinely is not recommended.
• Supportive care only, without WBRT, should be considered for patients with poor prognosis and brain metastases. Reasonable options for this population include palliative care or hospice, or short-course WBRT for symptomatic brain metastases
• Recommendations also include guidance for SRS and WBRT dosing as well as the use of single-fraction vs hypofractionated SRS. Although SRS use is driven by the number of brain metastases, it is critical that other important factors (eg, total tumor volume and location, patient age, and extracranial disease status) should be taken into consideration during patient-centered decision-making by the multidisciplinary team.

For patients with resected brain metastases:

• Radiation therapy is recommended for all patients after resection in order to improve intracranial control.
• For patients with limited brain metastases after resection, postoperative SRS is recommended over WBRT to preserve the patient’s neurocognitive function and quality of life.
• As a potential alternative to SRS postresection, SRS prior to brain metastasis resection is conditionally recommended.

Updating the guidelines

ASTRO emphasizes that the scope of this paper is limited to the radiotherapeutic management of intact and resected brain metastases resulting from nonhematologic solid tumors. It provides guidance on the reasonable use of modern radiation therapy strategies, including single-fraction and fractionated (ie, hypofractionated SRS) SRS and HA-WBRT, and also discusses clinical considerations in selecting the optimal radiation therapy strategy or in deferring it in favor of best supportive care or close neuro-oncologic surveillance.

The authors note, however, that beyond the scope of this guideline, there are many other important questions that may be the subject of other guidance, such as the appropriate role for CNS-active systemic therapies and/or surgical intervention.

A version of this article was first published on Medscape.com.

The American Society for Radiation Oncology (ASTRO) has issued new guidance on the use of radiation therapy for the treatment of brain metastases, an update on its 2012 document.  

“In the decade since the previous ASTRO brain metastases guideline, there has been a tremendous evolution in the way we manage patients’ disease,” said Paul D. Brown, MD, chair of the guideline task force and a professor of radiation oncology at the Mayo Clinic in Rochester, Minn.  

“The development of stereotactic radiosurgery (SRS) has allowed treatment of limited brain metastases alone, often in a single fraction, while largely sparing the surrounding brain,” he elaborated in a statement. Also, novel techniques such as hippocampal avoidance with whole-brain radiation can greatly improve quality of life, he added.

The guideline was published May 6 in Practical Radiation Oncology.

“With the emergence of novel radiotherapy techniques and technologies, brain-penetrating drug therapies and neurosurgical interventions, modern management of brain metastases has become increasingly personalized, complex and multidisciplinary,” Vinai Gondi, MD, vice chair of the guideline task force and director of research and education at the Northwestern Medicine Cancer Center and Proton Center in Chicago, said in a statement.

“We developed this guideline to help inform and guide clinicians in patient-centered, multidisciplinary care for their patients with brain metastases,” he added.

Key recommendations

Overall, the recommendations address a wide range of topics related to radiation therapy in patients with cancer that has spread to the brain,  including delivery techniques for radiation therapy to manage both unresected and resected brain metastases. The guideline also includes treatment algorithms for limited brain metastases and extensive brain metastases.

Key recommendations are as follows:

For patients with intact/unresected brain metastases:

• SRS is recommended for patients with 1-4 brain metastases and reasonable performance status (ECOG performance status 0-2); SRS is conditionally recommended for those with 5-10 brain metastases and reasonable performance status; for patients with tumors exerting mass effect and/or larger size, multidisciplinary discussion with neurosurgery to consider surgical resection is suggested.
• Upfront local therapy (radiation and/or surgery) is strongly recommended for patients with symptomatic brain metastases. 
• For patients with asymptomatic brain metastases who are eligible for central nervous system-directed systemic therapy, multidisciplinary and patient-centered decision-making to determine whether local therapy may be safely deferred is conditionally recommended.
• Whole brain radiation therapy (WBRT) is recommended as a primary treatment for patients with favorable prognosis who have brain metastases that are ineligible for surgery and/or SRS. Hippocampal avoidance (HA) is recommended when appropriate to preserve memory function, as is the addition of memantine to delay neurocognitive decline. Adjuvant WBRT added to SRS routinely is not recommended.
• Supportive care only, without WBRT, should be considered for patients with poor prognosis and brain metastases. Reasonable options for this population include palliative care or hospice, or short-course WBRT for symptomatic brain metastases
• Recommendations also include guidance for SRS and WBRT dosing as well as the use of single-fraction vs hypofractionated SRS. Although SRS use is driven by the number of brain metastases, it is critical that other important factors (eg, total tumor volume and location, patient age, and extracranial disease status) should be taken into consideration during patient-centered decision-making by the multidisciplinary team.

For patients with resected brain metastases:

• Radiation therapy is recommended for all patients after resection in order to improve intracranial control.
• For patients with limited brain metastases after resection, postoperative SRS is recommended over WBRT to preserve the patient’s neurocognitive function and quality of life.
• As a potential alternative to SRS postresection, SRS prior to brain metastasis resection is conditionally recommended.

Updating the guidelines

ASTRO emphasizes that the scope of this paper is limited to the radiotherapeutic management of intact and resected brain metastases resulting from nonhematologic solid tumors. It provides guidance on the reasonable use of modern radiation therapy strategies, including single-fraction and fractionated (ie, hypofractionated SRS) SRS and HA-WBRT, and also discusses clinical considerations in selecting the optimal radiation therapy strategy or in deferring it in favor of best supportive care or close neuro-oncologic surveillance.

The authors note, however, that beyond the scope of this guideline, there are many other important questions that may be the subject of other guidance, such as the appropriate role for CNS-active systemic therapies and/or surgical intervention.

A version of this article was first published on Medscape.com.

As it gears up for the first in-person scientific sessions for 3 years, the American Diabetes Association has issued an addendum to its most recent annual clinical practice recommendations published in December 2021, the 2022 Standards of Medical Care in Diabetes, based on recent trial evidence and consensus.

The update informs clinicians about:

• The effect of the nonsteroidal mineralocorticoid antagonist (Kerendia) on cardiovascular outcomes in patients with type 2 diabetes and chronic kidney disease.
• The effect of a sodium-glucose cotransporter 2 (SGLT2) inhibitor on heart failure and renal outcomes in patients with type 2 diabetes.

The National Kidney Foundation and the American Society of Nephrology Task Force recommendation to remove race in the formula for calculating estimated glomerular filtration rate (eGFR).

Checking with Dr Gabbay -- RM 08/16

“This is the fifth year that we are able to update the Standards of Care after it has been published through our Living Standards of Care updates, making it possible to give diabetes care providers the most important information and the latest evidence relevant to their practice,” Robert A. Gabbay, MD, PhD, ADA chief scientific and medical officer, said in a press release from the organization.

The addendum, entitled, “Living Standards of Care,” updates Section 10, “Cardiovascular Disease and Risk Management,” and Section 11, “Chronic Kidney Disease and Risk Management” of the 2022 Standards of Medical Care in Diabetes. 

The amendments were approved by the ADA Professional Practice Committee, which is responsible for developing the Standards of Care. The American College of Cardiology reviewed and endorsed the section on CVD and risk management.

The Living Standards Update was published online in Diabetes Care.
 

CVD and risk management

In the Addendum to Section 10, “Cardiovascular Disease and Risk Management,” the committee writes:

• “For patients with type 2 diabetes and chronic kidney disease treated with maximum tolerated doses of ACE inhibitors or angiotensin receptor blockers, addition of finerenone should be considered to improve cardiovascular outcomes and reduce the risk of chronic kidney disease progression. A”
• “Patients with type 2 diabetes and chronic kidney disease should be considered for treatment with finerenone to reduce cardiovascular outcomes and the risk of chronic kidney disease progression.”
• “In patients with type 2 diabetes and established heart failure with either preserved or reduced ejection fraction, an SGLT2 inhibitor [with proven benefit in this patient population] is recommended to reduce risk of worsening heart failure, hospitalizations for heart failure, and cardiovascular death. ”

In the section “Statin Treatment,” the addendum no longer states that “a prospective trial of a newer fibrate ... is ongoing,” because that trial investigating pemafibrate (Kowa), a novel selective peroxisome proliferator-activated receptor alpha modulator (or fibrate), has been discontinued.
 

Chronic kidney disease and risk management

In the Addendum to Section 11, “Chronic Kidney Disease and Risk Management,” the committee writes: 

• “Traditionally, eGFR is calculated from serum creatinine using a validated formula. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is preferred. ... Historically, a correction factor for muscle mass was included in a modified equation for African Americans; however, due to various issues with inequities, it was decided to the equation such that it applies to all. Hence, a committee was convened, resulting in the recommendation for immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the U.S.” (This is based on an National Kidney Foundation and American Society of Nephrology Task Force recommendation.)
• “Additionally, increased use of cystatin C, especially to confirm estimated GFR in adults who are at risk for or have chronic kidney disease, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone.” 

Evidence from clinical trials

The update is based on findings from the following clinical trials:

• Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease (FIDELIO-DKD)
• Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease (FIGARO-DKD)
• FIDELITY, a prespecified pooled analysis of FIDELIO-DKD and FIGARO-DKD
• Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved)
• Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients with PRESERVED Ejection Fraction Heart Failure (PRESERVED-HF)
• Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT).

A version of this article first appeared on Medscape.com.

As it gears up for the first in-person scientific sessions for 3 years, the American Diabetes Association has issued an addendum to its most recent annual clinical practice recommendations published in December 2021, the 2022 Standards of Medical Care in Diabetes, based on recent trial evidence and consensus.

The update informs clinicians about:

• The effect of the nonsteroidal mineralocorticoid antagonist (Kerendia) on cardiovascular outcomes in patients with type 2 diabetes and chronic kidney disease.
• The effect of a sodium-glucose cotransporter 2 (SGLT2) inhibitor on heart failure and renal outcomes in patients with type 2 diabetes.

The National Kidney Foundation and the American Society of Nephrology Task Force recommendation to remove race in the formula for calculating estimated glomerular filtration rate (eGFR).

Checking with Dr Gabbay -- RM 08/16

“This is the fifth year that we are able to update the Standards of Care after it has been published through our Living Standards of Care updates, making it possible to give diabetes care providers the most important information and the latest evidence relevant to their practice,” Robert A. Gabbay, MD, PhD, ADA chief scientific and medical officer, said in a press release from the organization.

The addendum, entitled, “Living Standards of Care,” updates Section 10, “Cardiovascular Disease and Risk Management,” and Section 11, “Chronic Kidney Disease and Risk Management” of the 2022 Standards of Medical Care in Diabetes. 

The amendments were approved by the ADA Professional Practice Committee, which is responsible for developing the Standards of Care. The American College of Cardiology reviewed and endorsed the section on CVD and risk management.

The Living Standards Update was published online in Diabetes Care.
 

CVD and risk management

In the Addendum to Section 10, “Cardiovascular Disease and Risk Management,” the committee writes:

• “For patients with type 2 diabetes and chronic kidney disease treated with maximum tolerated doses of ACE inhibitors or angiotensin receptor blockers, addition of finerenone should be considered to improve cardiovascular outcomes and reduce the risk of chronic kidney disease progression. A”
• “Patients with type 2 diabetes and chronic kidney disease should be considered for treatment with finerenone to reduce cardiovascular outcomes and the risk of chronic kidney disease progression.”
• “In patients with type 2 diabetes and established heart failure with either preserved or reduced ejection fraction, an SGLT2 inhibitor [with proven benefit in this patient population] is recommended to reduce risk of worsening heart failure, hospitalizations for heart failure, and cardiovascular death. ”

In the section “Statin Treatment,” the addendum no longer states that “a prospective trial of a newer fibrate ... is ongoing,” because that trial investigating pemafibrate (Kowa), a novel selective peroxisome proliferator-activated receptor alpha modulator (or fibrate), has been discontinued.
 

Chronic kidney disease and risk management

In the Addendum to Section 11, “Chronic Kidney Disease and Risk Management,” the committee writes: 

• “Traditionally, eGFR is calculated from serum creatinine using a validated formula. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is preferred. ... Historically, a correction factor for muscle mass was included in a modified equation for African Americans; however, due to various issues with inequities, it was decided to the equation such that it applies to all. Hence, a committee was convened, resulting in the recommendation for immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the U.S.” (This is based on an National Kidney Foundation and American Society of Nephrology Task Force recommendation.)
• “Additionally, increased use of cystatin C, especially to confirm estimated GFR in adults who are at risk for or have chronic kidney disease, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone.” 

Evidence from clinical trials

The update is based on findings from the following clinical trials:

• Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease (FIDELIO-DKD)
• Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease (FIGARO-DKD)
• FIDELITY, a prespecified pooled analysis of FIDELIO-DKD and FIGARO-DKD
• Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved)
• Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients with PRESERVED Ejection Fraction Heart Failure (PRESERVED-HF)
• Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT).

A version of this article first appeared on Medscape.com.

As it gears up for the first in-person scientific sessions for 3 years, the American Diabetes Association has issued an addendum to its most recent annual clinical practice recommendations published in December 2021, the 2022 Standards of Medical Care in Diabetes, based on recent trial evidence and consensus.

The update informs clinicians about:

• The effect of the nonsteroidal mineralocorticoid antagonist (Kerendia) on cardiovascular outcomes in patients with type 2 diabetes and chronic kidney disease.
• The effect of a sodium-glucose cotransporter 2 (SGLT2) inhibitor on heart failure and renal outcomes in patients with type 2 diabetes.

The National Kidney Foundation and the American Society of Nephrology Task Force recommendation to remove race in the formula for calculating estimated glomerular filtration rate (eGFR).

Checking with Dr Gabbay -- RM 08/16

“This is the fifth year that we are able to update the Standards of Care after it has been published through our Living Standards of Care updates, making it possible to give diabetes care providers the most important information and the latest evidence relevant to their practice,” Robert A. Gabbay, MD, PhD, ADA chief scientific and medical officer, said in a press release from the organization.

The addendum, entitled, “Living Standards of Care,” updates Section 10, “Cardiovascular Disease and Risk Management,” and Section 11, “Chronic Kidney Disease and Risk Management” of the 2022 Standards of Medical Care in Diabetes. 

The amendments were approved by the ADA Professional Practice Committee, which is responsible for developing the Standards of Care. The American College of Cardiology reviewed and endorsed the section on CVD and risk management.

The Living Standards Update was published online in Diabetes Care.
 

CVD and risk management

In the Addendum to Section 10, “Cardiovascular Disease and Risk Management,” the committee writes:

• “For patients with type 2 diabetes and chronic kidney disease treated with maximum tolerated doses of ACE inhibitors or angiotensin receptor blockers, addition of finerenone should be considered to improve cardiovascular outcomes and reduce the risk of chronic kidney disease progression. A”
• “Patients with type 2 diabetes and chronic kidney disease should be considered for treatment with finerenone to reduce cardiovascular outcomes and the risk of chronic kidney disease progression.”
• “In patients with type 2 diabetes and established heart failure with either preserved or reduced ejection fraction, an SGLT2 inhibitor [with proven benefit in this patient population] is recommended to reduce risk of worsening heart failure, hospitalizations for heart failure, and cardiovascular death. ”

In the section “Statin Treatment,” the addendum no longer states that “a prospective trial of a newer fibrate ... is ongoing,” because that trial investigating pemafibrate (Kowa), a novel selective peroxisome proliferator-activated receptor alpha modulator (or fibrate), has been discontinued.
 

Chronic kidney disease and risk management

In the Addendum to Section 11, “Chronic Kidney Disease and Risk Management,” the committee writes: 

• “Traditionally, eGFR is calculated from serum creatinine using a validated formula. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is preferred. ... Historically, a correction factor for muscle mass was included in a modified equation for African Americans; however, due to various issues with inequities, it was decided to the equation such that it applies to all. Hence, a committee was convened, resulting in the recommendation for immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the U.S.” (This is based on an National Kidney Foundation and American Society of Nephrology Task Force recommendation.)
• “Additionally, increased use of cystatin C, especially to confirm estimated GFR in adults who are at risk for or have chronic kidney disease, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone.” 

Evidence from clinical trials

The update is based on findings from the following clinical trials:

• Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease (FIDELIO-DKD)
• Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease (FIGARO-DKD)
• FIDELITY, a prespecified pooled analysis of FIDELIO-DKD and FIGARO-DKD
• Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved)
• Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients with PRESERVED Ejection Fraction Heart Failure (PRESERVED-HF)
• Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT).

A version of this article first appeared on Medscape.com.

A novel approach that involves sensors, artificial intelligence, and real-time individualized lifestyle guidance from an app and live coaches led to a high rate of remission of type 2 diabetes in a new study.

Specifically, among 199 patients with type 2 diabetes in India who received the app-delivered lifestyle guidance developed by Twin Health, Mountain View, Calif., mean hemoglobin A1c dropped from 9.0% to 5.7% at 6 months.

This is “huge,” Paramesh Shamanna, MD, told a press briefing at the annual scientific sessions of the American Diabetes Association. The research was presented as three posters by the group at the meeting.

Patients were a mean age of 43 and had diabetes for a mean of 3.7 years and up to 8 years.

An “unprecedented” 84% of patients had remission of diabetes at 6 months, Dr. Shamanna, medical director at Twin Health, noted.

Diabetes remission was defined according to the 2021 joint consensus statement from the ADA and other organizations as an A1c less than 6.5% without the use of diabetes medications for at least 3 months.

Importantly, patients’ time in range (percentage of time spent in target blood glucose range) increased from 53% to 81%, Dr. Shamanna pointed out. On average, patients’ waist circumference decreased by 10 cm (3.9 inches) and their weight dropped from 79 kg (approximately 174 lb) to 68 kg (150 lb).

These results are driven by “the continuous individualized and precise guidance regarding nutrition, activity, and sleep,” Dr. Shamanna said in an interview.
 

Remission is not reversal or cure ...

“Remission” from type 2 diabetes is not “reversal” or a “cure,” Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, stressed to the press. Just like cancer, diabetes can return after remission

Therefore, it is important to follow the lifestyle guidance. Patients may still be at risk for diabetes complications after diabetes remission, so it’s also important to continue to be screened for eye disease, nerve damage, and lipid levels.

However, “remission can be made to last,” Dr. Shamanna said, by continuing to follow the lifestyle advice and getting back on track after a relapse.

“We’re in a different time right now,” Lisa Shah, MD, chief medical officer, Twin Health, noted. “This is very different from management of blood glucose to a certain number.”

This study shows that “remission [from type 2 diabetes] is possible. How you achieve it can be precise for you.”

The program is designed to consider the health and happiness of the patient, added Shashank R. Joshi, MD, chief scientist, Twin Health. “We want remission to be complication free. These findings give patients hope.”

“It’s exciting now that we can really start thinking about remission as an option for people with [type 2] diabetes, and that just provides such incredible hope for all of those living with [type 2] diabetes,” Dr. Gabbay said in an interview.
 

How the intervention works

The Twin Precision Treatment (TPT) intervention integrates multiple data – glucose values from a continuous glucose monitor (CGM); heart rate, activity, and sleep time from a fitness tracker; blood pressure values from a blood pressure cuff; food intake from the patient’s food log; and weight and body fat data from a smart scale – and provides the patient with precise, individualized nutrition and health guidance.

The four most critical sensors are the CGM, the fitness tracker, the smart scale, and the blood pressure cuff, Dr. Shah explained. The system gathers thousands of signals combined with patient self-reported data including mood or anxiety.

The CGM is used to build the initial nutrition guidance during the first 30 days. Once a patient is in remission, he or she can just keep the fitness tracker and smart scale.

The coaches who are part of this program include dietitians who are trained to provide compassionate patient education and help patients avoid diabetes relapse, and they are overseen by a licensed provider.

The program does not restrict calories. “It is not a diet,” Dr. Shah stressed.

The algorithm makes mini adjustments to the food a person is already eating to improve nutrition, Dr. Joshi explained. “This is personalized medicine at its best.” Patients eat food that they like and are guided to make small changes to get glucose under control and avoid glucose spikes.

The program is designed to safely deescalate diabetes medications as A1c decreases, Dr. Shamanna added.

U.S. clinical trial, health insurance coverage

The 1-year results of the current trial are expected in August, and the trial will continue for 2-=5 years, Dr. Shamanna said.

The company has started a clinical trial in the United States, with 5-year results expected in 2027.

“Currently, in the United States, we are partnering with self-insured employers and select health plans that offer [Twin Precision Treatment ] as an available benefit for their members,” Dr. Shah said. It “is suitable for most members living with type 2 diabetes, with rare exclusion situations.”

The study was funded by Twin Health. Dr. Shamanna, Dr. Shah, and Dr. Joshi are employees of Twin Health.

A version of this article first appeared on Medscape.com.

A novel approach that involves sensors, artificial intelligence, and real-time individualized lifestyle guidance from an app and live coaches led to a high rate of remission of type 2 diabetes in a new study.

Specifically, among 199 patients with type 2 diabetes in India who received the app-delivered lifestyle guidance developed by Twin Health, Mountain View, Calif., mean hemoglobin A1c dropped from 9.0% to 5.7% at 6 months.

This is “huge,” Paramesh Shamanna, MD, told a press briefing at the annual scientific sessions of the American Diabetes Association. The research was presented as three posters by the group at the meeting.

Patients were a mean age of 43 and had diabetes for a mean of 3.7 years and up to 8 years.

An “unprecedented” 84% of patients had remission of diabetes at 6 months, Dr. Shamanna, medical director at Twin Health, noted.

Diabetes remission was defined according to the 2021 joint consensus statement from the ADA and other organizations as an A1c less than 6.5% without the use of diabetes medications for at least 3 months.

Importantly, patients’ time in range (percentage of time spent in target blood glucose range) increased from 53% to 81%, Dr. Shamanna pointed out. On average, patients’ waist circumference decreased by 10 cm (3.9 inches) and their weight dropped from 79 kg (approximately 174 lb) to 68 kg (150 lb).

These results are driven by “the continuous individualized and precise guidance regarding nutrition, activity, and sleep,” Dr. Shamanna said in an interview.
 

Remission is not reversal or cure ...

“Remission” from type 2 diabetes is not “reversal” or a “cure,” Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, stressed to the press. Just like cancer, diabetes can return after remission

Therefore, it is important to follow the lifestyle guidance. Patients may still be at risk for diabetes complications after diabetes remission, so it’s also important to continue to be screened for eye disease, nerve damage, and lipid levels.

However, “remission can be made to last,” Dr. Shamanna said, by continuing to follow the lifestyle advice and getting back on track after a relapse.

“We’re in a different time right now,” Lisa Shah, MD, chief medical officer, Twin Health, noted. “This is very different from management of blood glucose to a certain number.”

This study shows that “remission [from type 2 diabetes] is possible. How you achieve it can be precise for you.”

The program is designed to consider the health and happiness of the patient, added Shashank R. Joshi, MD, chief scientist, Twin Health. “We want remission to be complication free. These findings give patients hope.”

“It’s exciting now that we can really start thinking about remission as an option for people with [type 2] diabetes, and that just provides such incredible hope for all of those living with [type 2] diabetes,” Dr. Gabbay said in an interview.
 

How the intervention works

The Twin Precision Treatment (TPT) intervention integrates multiple data – glucose values from a continuous glucose monitor (CGM); heart rate, activity, and sleep time from a fitness tracker; blood pressure values from a blood pressure cuff; food intake from the patient’s food log; and weight and body fat data from a smart scale – and provides the patient with precise, individualized nutrition and health guidance.

The four most critical sensors are the CGM, the fitness tracker, the smart scale, and the blood pressure cuff, Dr. Shah explained. The system gathers thousands of signals combined with patient self-reported data including mood or anxiety.

The CGM is used to build the initial nutrition guidance during the first 30 days. Once a patient is in remission, he or she can just keep the fitness tracker and smart scale.

The coaches who are part of this program include dietitians who are trained to provide compassionate patient education and help patients avoid diabetes relapse, and they are overseen by a licensed provider.

The program does not restrict calories. “It is not a diet,” Dr. Shah stressed.

The algorithm makes mini adjustments to the food a person is already eating to improve nutrition, Dr. Joshi explained. “This is personalized medicine at its best.” Patients eat food that they like and are guided to make small changes to get glucose under control and avoid glucose spikes.

The program is designed to safely deescalate diabetes medications as A1c decreases, Dr. Shamanna added.

U.S. clinical trial, health insurance coverage

The 1-year results of the current trial are expected in August, and the trial will continue for 2-=5 years, Dr. Shamanna said.

The company has started a clinical trial in the United States, with 5-year results expected in 2027.

“Currently, in the United States, we are partnering with self-insured employers and select health plans that offer [Twin Precision Treatment ] as an available benefit for their members,” Dr. Shah said. It “is suitable for most members living with type 2 diabetes, with rare exclusion situations.”

The study was funded by Twin Health. Dr. Shamanna, Dr. Shah, and Dr. Joshi are employees of Twin Health.

A version of this article first appeared on Medscape.com.

A novel approach that involves sensors, artificial intelligence, and real-time individualized lifestyle guidance from an app and live coaches led to a high rate of remission of type 2 diabetes in a new study.

Specifically, among 199 patients with type 2 diabetes in India who received the app-delivered lifestyle guidance developed by Twin Health, Mountain View, Calif., mean hemoglobin A1c dropped from 9.0% to 5.7% at 6 months.

This is “huge,” Paramesh Shamanna, MD, told a press briefing at the annual scientific sessions of the American Diabetes Association. The research was presented as three posters by the group at the meeting.

Patients were a mean age of 43 and had diabetes for a mean of 3.7 years and up to 8 years.

An “unprecedented” 84% of patients had remission of diabetes at 6 months, Dr. Shamanna, medical director at Twin Health, noted.

Diabetes remission was defined according to the 2021 joint consensus statement from the ADA and other organizations as an A1c less than 6.5% without the use of diabetes medications for at least 3 months.

Importantly, patients’ time in range (percentage of time spent in target blood glucose range) increased from 53% to 81%, Dr. Shamanna pointed out. On average, patients’ waist circumference decreased by 10 cm (3.9 inches) and their weight dropped from 79 kg (approximately 174 lb) to 68 kg (150 lb).

These results are driven by “the continuous individualized and precise guidance regarding nutrition, activity, and sleep,” Dr. Shamanna said in an interview.
 

Remission is not reversal or cure ...

“Remission” from type 2 diabetes is not “reversal” or a “cure,” Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, stressed to the press. Just like cancer, diabetes can return after remission

Therefore, it is important to follow the lifestyle guidance. Patients may still be at risk for diabetes complications after diabetes remission, so it’s also important to continue to be screened for eye disease, nerve damage, and lipid levels.

However, “remission can be made to last,” Dr. Shamanna said, by continuing to follow the lifestyle advice and getting back on track after a relapse.

“We’re in a different time right now,” Lisa Shah, MD, chief medical officer, Twin Health, noted. “This is very different from management of blood glucose to a certain number.”

This study shows that “remission [from type 2 diabetes] is possible. How you achieve it can be precise for you.”

The program is designed to consider the health and happiness of the patient, added Shashank R. Joshi, MD, chief scientist, Twin Health. “We want remission to be complication free. These findings give patients hope.”

“It’s exciting now that we can really start thinking about remission as an option for people with [type 2] diabetes, and that just provides such incredible hope for all of those living with [type 2] diabetes,” Dr. Gabbay said in an interview.
 

How the intervention works

The Twin Precision Treatment (TPT) intervention integrates multiple data – glucose values from a continuous glucose monitor (CGM); heart rate, activity, and sleep time from a fitness tracker; blood pressure values from a blood pressure cuff; food intake from the patient’s food log; and weight and body fat data from a smart scale – and provides the patient with precise, individualized nutrition and health guidance.

The four most critical sensors are the CGM, the fitness tracker, the smart scale, and the blood pressure cuff, Dr. Shah explained. The system gathers thousands of signals combined with patient self-reported data including mood or anxiety.

The CGM is used to build the initial nutrition guidance during the first 30 days. Once a patient is in remission, he or she can just keep the fitness tracker and smart scale.

The coaches who are part of this program include dietitians who are trained to provide compassionate patient education and help patients avoid diabetes relapse, and they are overseen by a licensed provider.

The program does not restrict calories. “It is not a diet,” Dr. Shah stressed.

The algorithm makes mini adjustments to the food a person is already eating to improve nutrition, Dr. Joshi explained. “This is personalized medicine at its best.” Patients eat food that they like and are guided to make small changes to get glucose under control and avoid glucose spikes.

The program is designed to safely deescalate diabetes medications as A1c decreases, Dr. Shamanna added.

U.S. clinical trial, health insurance coverage

The 1-year results of the current trial are expected in August, and the trial will continue for 2-=5 years, Dr. Shamanna said.

The company has started a clinical trial in the United States, with 5-year results expected in 2027.

“Currently, in the United States, we are partnering with self-insured employers and select health plans that offer [Twin Precision Treatment ] as an available benefit for their members,” Dr. Shah said. It “is suitable for most members living with type 2 diabetes, with rare exclusion situations.”

The study was funded by Twin Health. Dr. Shamanna, Dr. Shah, and Dr. Joshi are employees of Twin Health.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – High out-of-pocket costs for medications used by patients with diabetes are tied to reduced use of these drugs and ultimately worse clinical outcomes, according to findings from two separate studies.

One study looked at the insurance records of more than 70,000 U.S. patients with type 2 diabetes and established cardiovascular disease who were already on metformin. The findings showed that, after adjustment for confounders, the quartile of patients with the highest out-of-pocket cost for an agent from the sodium-glucose cotransporter 2 (SGLT2)–inhibitor class filled a prescription for one of these drugs a significant 21% less often than did patients from the quartile with the lowest personal expense, after adjustment for a variety of potential confounding factors, reported Jing Luo, MD, at the annual scientific sessions of the American Diabetes Association.

A similar analysis run by Dr. Luo and his associates looking at glucagonlike peptide-1 (GLP-1) receptor agonists showed that the quartile of patients who had to pay the most for one of those drugs had an adjusted 12% lower rate of filling a prescription, compared with those with the lowest out-of-pocket expense, a difference that fell just short of significance.

“If we consistently see that high drug costs affect use of highly effective medications in patients with type 2 diabetes and risk factors, it’s quite problematic because it’s not just a matter of money, but it also makes a difference in the patient’s quality of care,” Dr. Luo said in an interview.

Prevention drug lists can help

Consistency turned up in a second report at the same ADA session that retrospectively reviewed data collected during 2004-2017 by a single large U.S. health insurer to identify 3,315 matched pairs of children and adults with diabetes who all had high-deductible health plans for their medical insurance, along with an associated health savings account.

One set of patients in each matched pair began to receive, at some point during follow-up, coverage with a prevention drug list (PDL; also called a formulary) that provided them with a variety of specified agents at no charge. They included oral antidiabetes agents, insulin, antihypertensives, and lipid-lowering drugs. The other half of the matched pairs of patients received no PDL coverage and had copays for their antidiabetes medications.

The findings showed that the rates of out-of-pocket costs for antidiabetes drugs, antidiabetic medications used, and acute diabetes complications all tracked extremely closely between the matched pairs before half of them started to receive their PDL coverage. However, after PDL coverage kicked in, out of pocket costs dropped by 32% for the people with PDL coverage, compared with those who did not receive this coverage. Oral antidiabetes medication use rose modestly, but acute diabetes complications “declined substantially,” with a 14% relative reduction overall in those with PDL coverage, compared with those without, reported J. Franklin Wharam, MBBCh, a professor and health policy researcher at Duke University in Durham, N.C. In the roughly half of the study cohort who fell into a low-income category based on where they lived, the rate of excess acute diabetes complications was 23% higher for those without a PDL, compared with those who had that coverage.

PDL coverage linked with “large reductions in acute, preventable diabetes complications,” concluded Dr. Wharam. “Policy makers and employers should incentivize PDL uptake among low-income patients with diabetes.”

Newer, more effective drugs cost a lot

“The more comorbidities that patients have, the greater is the strength of the evidence for using newer antidiabetes drugs that are more expensive,” but that would mean spending much more on this part of patient care, noted Dr. Luo, an internal medicine physician and researcher at the University of Pittsburgh. “It will cost a lot of money, and I’m not sure what the solution is. It’s a huge conundrum.”

About 30 million Americans have type 2 diabetes. If every one of them went on an SGLT2 inhibitor, or went on an SGLT2 inhibitor plus a GLP-1 receptor agonist, “it would bankrupt the U.S. health care system, so we can’t do that,” commented Sylvio E. Inzucchi, MD, in an interview. “The only thing holding this back is cost. We target these drugs to the patients most apt to benefit from them. If they were generic they would be used much more widely,” noted Dr. Inzucchi, professor and clinical chief of endocrinology at Yale University in New Haven, Conn.

The study run by Dr. Luo and his associates retrospectively reviewed data from 72,743 U.S. adults included in the Optum Clinformatics database during December 2017–December 2019. All included patients had type 2 diabetes, received metformin monotherapy, and had established atherosclerotic cardiovascular disease. They averaged 72 years of age, 56% were men, and 88% were on a Medicare Advantage plan, while the remainder had commercial insurance. Their average hemoglobin A1c level was 6.8%.

People in the quartile with the lowest copays spent an average of about $20/month for either an SGLT2 inhibitor or a GLP-1 receptor agonist. Those in the quartile with the highest copays spent roughly $100/month for agents from each of these two classes. The analysis followed patients for a median of 914 days.

In addition to finding disparate rates of drug use between these two quartiles, the analysis also showed that higher copays linked with longer times to initially fill prescriptions for these drugs. But while those with higher copays took longer to start both classes than did those with the smallest copays, even those with the lowest out-of-pocket costs averaged about a year to initiate treatment.

Dr. Luo attributed this delay to other factors besides costs to patients, such as clinicians prescribing other classes of second-line oral antidiabetes agents, clinical inertia, and lack of awareness by clinicians of the special benefits of SGLT2 inhibitors and GLP-1 receptor antagonists for patients with type 2 diabetes and cardiovascular disease.

“A lot of clinical and social factors drive medication use,” not just out-of-pocket cost, he explained.

Dr. Luo is a consultant to Alosa Health. Dr. Wharam had no disclosures. Dr. Inzucchi is an adviser to Abbott Diagnostics, Esperion Therapeutics, and vTv Therapeutics, a consultant to Merck and Pfizer, and has other relationships with AstraZeneca, Boehringer Ingelheim, Lexicon, and Novo Nordisk.

NEW ORLEANS – High out-of-pocket costs for medications used by patients with diabetes are tied to reduced use of these drugs and ultimately worse clinical outcomes, according to findings from two separate studies.

One study looked at the insurance records of more than 70,000 U.S. patients with type 2 diabetes and established cardiovascular disease who were already on metformin. The findings showed that, after adjustment for confounders, the quartile of patients with the highest out-of-pocket cost for an agent from the sodium-glucose cotransporter 2 (SGLT2)–inhibitor class filled a prescription for one of these drugs a significant 21% less often than did patients from the quartile with the lowest personal expense, after adjustment for a variety of potential confounding factors, reported Jing Luo, MD, at the annual scientific sessions of the American Diabetes Association.

A similar analysis run by Dr. Luo and his associates looking at glucagonlike peptide-1 (GLP-1) receptor agonists showed that the quartile of patients who had to pay the most for one of those drugs had an adjusted 12% lower rate of filling a prescription, compared with those with the lowest out-of-pocket expense, a difference that fell just short of significance.

“If we consistently see that high drug costs affect use of highly effective medications in patients with type 2 diabetes and risk factors, it’s quite problematic because it’s not just a matter of money, but it also makes a difference in the patient’s quality of care,” Dr. Luo said in an interview.

Prevention drug lists can help

Consistency turned up in a second report at the same ADA session that retrospectively reviewed data collected during 2004-2017 by a single large U.S. health insurer to identify 3,315 matched pairs of children and adults with diabetes who all had high-deductible health plans for their medical insurance, along with an associated health savings account.

One set of patients in each matched pair began to receive, at some point during follow-up, coverage with a prevention drug list (PDL; also called a formulary) that provided them with a variety of specified agents at no charge. They included oral antidiabetes agents, insulin, antihypertensives, and lipid-lowering drugs. The other half of the matched pairs of patients received no PDL coverage and had copays for their antidiabetes medications.

The findings showed that the rates of out-of-pocket costs for antidiabetes drugs, antidiabetic medications used, and acute diabetes complications all tracked extremely closely between the matched pairs before half of them started to receive their PDL coverage. However, after PDL coverage kicked in, out of pocket costs dropped by 32% for the people with PDL coverage, compared with those who did not receive this coverage. Oral antidiabetes medication use rose modestly, but acute diabetes complications “declined substantially,” with a 14% relative reduction overall in those with PDL coverage, compared with those without, reported J. Franklin Wharam, MBBCh, a professor and health policy researcher at Duke University in Durham, N.C. In the roughly half of the study cohort who fell into a low-income category based on where they lived, the rate of excess acute diabetes complications was 23% higher for those without a PDL, compared with those who had that coverage.

PDL coverage linked with “large reductions in acute, preventable diabetes complications,” concluded Dr. Wharam. “Policy makers and employers should incentivize PDL uptake among low-income patients with diabetes.”

Newer, more effective drugs cost a lot

“The more comorbidities that patients have, the greater is the strength of the evidence for using newer antidiabetes drugs that are more expensive,” but that would mean spending much more on this part of patient care, noted Dr. Luo, an internal medicine physician and researcher at the University of Pittsburgh. “It will cost a lot of money, and I’m not sure what the solution is. It’s a huge conundrum.”

About 30 million Americans have type 2 diabetes. If every one of them went on an SGLT2 inhibitor, or went on an SGLT2 inhibitor plus a GLP-1 receptor agonist, “it would bankrupt the U.S. health care system, so we can’t do that,” commented Sylvio E. Inzucchi, MD, in an interview. “The only thing holding this back is cost. We target these drugs to the patients most apt to benefit from them. If they were generic they would be used much more widely,” noted Dr. Inzucchi, professor and clinical chief of endocrinology at Yale University in New Haven, Conn.

The study run by Dr. Luo and his associates retrospectively reviewed data from 72,743 U.S. adults included in the Optum Clinformatics database during December 2017–December 2019. All included patients had type 2 diabetes, received metformin monotherapy, and had established atherosclerotic cardiovascular disease. They averaged 72 years of age, 56% were men, and 88% were on a Medicare Advantage plan, while the remainder had commercial insurance. Their average hemoglobin A1c level was 6.8%.

People in the quartile with the lowest copays spent an average of about $20/month for either an SGLT2 inhibitor or a GLP-1 receptor agonist. Those in the quartile with the highest copays spent roughly $100/month for agents from each of these two classes. The analysis followed patients for a median of 914 days.

In addition to finding disparate rates of drug use between these two quartiles, the analysis also showed that higher copays linked with longer times to initially fill prescriptions for these drugs. But while those with higher copays took longer to start both classes than did those with the smallest copays, even those with the lowest out-of-pocket costs averaged about a year to initiate treatment.

Dr. Luo attributed this delay to other factors besides costs to patients, such as clinicians prescribing other classes of second-line oral antidiabetes agents, clinical inertia, and lack of awareness by clinicians of the special benefits of SGLT2 inhibitors and GLP-1 receptor antagonists for patients with type 2 diabetes and cardiovascular disease.

“A lot of clinical and social factors drive medication use,” not just out-of-pocket cost, he explained.

Dr. Luo is a consultant to Alosa Health. Dr. Wharam had no disclosures. Dr. Inzucchi is an adviser to Abbott Diagnostics, Esperion Therapeutics, and vTv Therapeutics, a consultant to Merck and Pfizer, and has other relationships with AstraZeneca, Boehringer Ingelheim, Lexicon, and Novo Nordisk.

NEW ORLEANS – High out-of-pocket costs for medications used by patients with diabetes are tied to reduced use of these drugs and ultimately worse clinical outcomes, according to findings from two separate studies.

One study looked at the insurance records of more than 70,000 U.S. patients with type 2 diabetes and established cardiovascular disease who were already on metformin. The findings showed that, after adjustment for confounders, the quartile of patients with the highest out-of-pocket cost for an agent from the sodium-glucose cotransporter 2 (SGLT2)–inhibitor class filled a prescription for one of these drugs a significant 21% less often than did patients from the quartile with the lowest personal expense, after adjustment for a variety of potential confounding factors, reported Jing Luo, MD, at the annual scientific sessions of the American Diabetes Association.

A similar analysis run by Dr. Luo and his associates looking at glucagonlike peptide-1 (GLP-1) receptor agonists showed that the quartile of patients who had to pay the most for one of those drugs had an adjusted 12% lower rate of filling a prescription, compared with those with the lowest out-of-pocket expense, a difference that fell just short of significance.

“If we consistently see that high drug costs affect use of highly effective medications in patients with type 2 diabetes and risk factors, it’s quite problematic because it’s not just a matter of money, but it also makes a difference in the patient’s quality of care,” Dr. Luo said in an interview.

Prevention drug lists can help

Consistency turned up in a second report at the same ADA session that retrospectively reviewed data collected during 2004-2017 by a single large U.S. health insurer to identify 3,315 matched pairs of children and adults with diabetes who all had high-deductible health plans for their medical insurance, along with an associated health savings account.

One set of patients in each matched pair began to receive, at some point during follow-up, coverage with a prevention drug list (PDL; also called a formulary) that provided them with a variety of specified agents at no charge. They included oral antidiabetes agents, insulin, antihypertensives, and lipid-lowering drugs. The other half of the matched pairs of patients received no PDL coverage and had copays for their antidiabetes medications.

The findings showed that the rates of out-of-pocket costs for antidiabetes drugs, antidiabetic medications used, and acute diabetes complications all tracked extremely closely between the matched pairs before half of them started to receive their PDL coverage. However, after PDL coverage kicked in, out of pocket costs dropped by 32% for the people with PDL coverage, compared with those who did not receive this coverage. Oral antidiabetes medication use rose modestly, but acute diabetes complications “declined substantially,” with a 14% relative reduction overall in those with PDL coverage, compared with those without, reported J. Franklin Wharam, MBBCh, a professor and health policy researcher at Duke University in Durham, N.C. In the roughly half of the study cohort who fell into a low-income category based on where they lived, the rate of excess acute diabetes complications was 23% higher for those without a PDL, compared with those who had that coverage.

PDL coverage linked with “large reductions in acute, preventable diabetes complications,” concluded Dr. Wharam. “Policy makers and employers should incentivize PDL uptake among low-income patients with diabetes.”

Newer, more effective drugs cost a lot

“The more comorbidities that patients have, the greater is the strength of the evidence for using newer antidiabetes drugs that are more expensive,” but that would mean spending much more on this part of patient care, noted Dr. Luo, an internal medicine physician and researcher at the University of Pittsburgh. “It will cost a lot of money, and I’m not sure what the solution is. It’s a huge conundrum.”

About 30 million Americans have type 2 diabetes. If every one of them went on an SGLT2 inhibitor, or went on an SGLT2 inhibitor plus a GLP-1 receptor agonist, “it would bankrupt the U.S. health care system, so we can’t do that,” commented Sylvio E. Inzucchi, MD, in an interview. “The only thing holding this back is cost. We target these drugs to the patients most apt to benefit from them. If they were generic they would be used much more widely,” noted Dr. Inzucchi, professor and clinical chief of endocrinology at Yale University in New Haven, Conn.

The study run by Dr. Luo and his associates retrospectively reviewed data from 72,743 U.S. adults included in the Optum Clinformatics database during December 2017–December 2019. All included patients had type 2 diabetes, received metformin monotherapy, and had established atherosclerotic cardiovascular disease. They averaged 72 years of age, 56% were men, and 88% were on a Medicare Advantage plan, while the remainder had commercial insurance. Their average hemoglobin A1c level was 6.8%.

People in the quartile with the lowest copays spent an average of about $20/month for either an SGLT2 inhibitor or a GLP-1 receptor agonist. Those in the quartile with the highest copays spent roughly $100/month for agents from each of these two classes. The analysis followed patients for a median of 914 days.

In addition to finding disparate rates of drug use between these two quartiles, the analysis also showed that higher copays linked with longer times to initially fill prescriptions for these drugs. But while those with higher copays took longer to start both classes than did those with the smallest copays, even those with the lowest out-of-pocket costs averaged about a year to initiate treatment.

Dr. Luo attributed this delay to other factors besides costs to patients, such as clinicians prescribing other classes of second-line oral antidiabetes agents, clinical inertia, and lack of awareness by clinicians of the special benefits of SGLT2 inhibitors and GLP-1 receptor antagonists for patients with type 2 diabetes and cardiovascular disease.

“A lot of clinical and social factors drive medication use,” not just out-of-pocket cost, he explained.

Dr. Luo is a consultant to Alosa Health. Dr. Wharam had no disclosures. Dr. Inzucchi is an adviser to Abbott Diagnostics, Esperion Therapeutics, and vTv Therapeutics, a consultant to Merck and Pfizer, and has other relationships with AstraZeneca, Boehringer Ingelheim, Lexicon, and Novo Nordisk.

Another glucagonlike peptide-1 (GLP1) agonist, dulaglutide (Trulicity, Lilly), is poised to be a new option for glycemic control in youth aged 10-18 years with type 2 diabetes, given as a weekly injection, based on the AWARD-PEDS clinical trial.

The U.S. Food and Drug Administration has already approved daily injection liraglutide (Victoza, Novo Nordisk) in 2019 and weekly exenatide (Bydureon/Bydureon BCise, AstraZeneca) in 2021 for glycemic control in young patients with type 2 diabetes, both of which are also GLP-1 agonists.  

AWARD-PEDS showed that youth with type 2 diabetes and obesity treated with or without metformin or basal insulin who received weekly injections of 0.75 mg or 1.5 mg of dulaglutide had lower hemoglobin A1c at 26 weeks than patients who received placebo.

Eli Lilly is now submitting these trial results to the FDA for this indication.

Dulaglutide was cleared for use in adults with type 2 diabetes in the United States in 2014 and was additionally approved for reducing the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes at high risk of such events in 2020.

The most common adverse symptoms were gastrointestinal, and the safety profile was consistent with that in adults. However, the drug had no effect on body mass index.

The study was simultaneously published in the New England Journal of Medicine and presented as a late-breaking poster at the annual scientific sessions of the American Diabetes Association in New Orleans.

Might dulaglutide target pathophysiologic impairments in youth?

Dulaglutide would “offer a new treatment that targets the pathophysiologic impairments of type 2 diabetes in youth,” Silva A. Arslanian, MD, lead investigator, told this news organization.

Exenatide is also given as a weekly injection but is associated with a smaller decrease in A1c and does not improve fasting glucose concentrations, plus it requires more steps compared with the dulaglutide single-use pen, said Dr. Arslanian, who is scientific director at the Center for Pediatric Research in Obesity & Metabolism, UPMC Children’s Hospital of Pittsburgh.

“Liraglutide is a daily injection, and I believe most patients, particularly adolescents, would prefer a weekly injection,” she added.  

Invited to comment, Elvira Isganaitis, MD, MPH, said “the significance of this paper lies in the fact that options for treating type 2 diabetes in children are currently much more limited than in adults – which is a major problem given recent studies that show that type 2 diabetes in youth is much more aggressive and more likely to cause complications early in the disease course.”

Dr. Isganaitis was not involved with the trial but is an investigator for the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study.

“With supply chain shortages and health insurance coverage issues that are common in the U.S., it would be helpful to have more than one FDA-approved option for a weekly GLP-1 receptor agonist in children [and] access to other classes of medications,” added Dr. Isganaitis, a pediatric endocrinologist at the Joslin Diabetes Center, Boston.

Phase 3 trials of sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors in youth with type 2 diabetes are also ongoing, Dr. Arslanian noted, “but as always, recruitment is slow with adolescents.”

“I am not optimistic that DPP4 inhibitors will have a place in the treatment of youth with type 2 diabetes,” she said. A recent study showed the addition of sitagliptin to metformin in youth with type 2 diabetes did not provide durable improvement in glycemic control.

Potentially promising therapy

In their published article, Dr. Arslanian and colleagues write that “considering the progressive increase in [A1c] over time that was observed in the TODAY trial, with 34% of youths having [an A1c] of at least 10% after up to 15 years of follow-up, we believe that the effects of dulaglutide therapy appear to be potentially promising.”

The TODAY trial showed that more than 50% of youth with type 2 diabetes taking metformin failed to maintain glycemic control within a median of 11.5 months, Dr. Arslanian elaborated, and over time their A1c escalated while their beta-cell function deteriorated rapidly, and complications progressed quickly.

“Therefore,” she noted, “considering that dulaglutide and the GLP-1 receptor agonist class of drugs improve A1c, improve beta-cell function, suppress glucagon concentrations, and improve insulin sensitivity, dulaglutide would provide a promising new treatment option for youth with type 2 diabetes.”

Phase 3 superiority trial

The AWARD-PEDS trial included 154 youth with type 2 diabetes and a BMI greater than the 85th percentile for their age and sex at 46 centers in nine countries. Researchers randomized participants 1:1:1 to the two doses of dulaglutide or placebo for 26 weeks, followed by a 26-week open-label study (during which the placebo group received 0.75 mg dulaglutide) and a 4-week safety extension. 

Participants were a mean age of 14.5 years and had a mean BMI of 34 kg/m².

In each of the dulaglutide groups, roughly 66% of patients were female and 58% were White, 18% were Black, and about 57% were Hispanic. They had a mean weight of 91 kg (200 lb) and a mean A1c of about 8%; 62% were taking metformin only, 27% were taking metformin plus basal insulin, 3% were taking basal insulin only, and 10% were on diet and exercise only.

At 26 weeks, mean A1c increased by 0.6% in the placebo group but decreased by 0.6% in the 0.75-mg dulaglutide group and by 0.9% in the 1.5-mg dulaglutide group (P < .001 for both comparisons versus placebo).

Also at 26 weeks, more participants in the pooled dulaglutide groups than in the placebo group had an A1c <7.0% (51% vs. 14%; P < .001).

Fasting glucose concentration increased in the placebo group (+17.1 mg/dL ) and decreased in the pooled dulaglutide groups (–18.9 mg/dL; P < .001).

There were no group differences in BMI or adiposity-related parameters even at 52 weeks.

“I believe adolescents may be somewhat resistant to the weight-reducing effects of GLP-1 agonists in diabetes trials (liraglutide and exenatide youth type 2 diabetes trials showed the same thing) and they may need higher doses,” Dr. Arslanian speculated.

“Only future studies will be able to address this issue,” she concluded.

The study was funded by Eli Lilly. Dr. Arslanian has disclosed being a consultant for Eli Lilly, Novo Nordisk, and Rhythm Pharmaceuticals; participating in data safety monitoring for AstraZeneca and Eli Lilly trials; and receiving institutional research funding from Eli Lilly and Novo Nordisk. Dr. Isganaitis has disclosed receiving research funding (paid to her institution) from Dexcom and AstraZeneca.

A version of this article first appeared on Medscape.com.

Another glucagonlike peptide-1 (GLP1) agonist, dulaglutide (Trulicity, Lilly), is poised to be a new option for glycemic control in youth aged 10-18 years with type 2 diabetes, given as a weekly injection, based on the AWARD-PEDS clinical trial.

The U.S. Food and Drug Administration has already approved daily injection liraglutide (Victoza, Novo Nordisk) in 2019 and weekly exenatide (Bydureon/Bydureon BCise, AstraZeneca) in 2021 for glycemic control in young patients with type 2 diabetes, both of which are also GLP-1 agonists.  

AWARD-PEDS showed that youth with type 2 diabetes and obesity treated with or without metformin or basal insulin who received weekly injections of 0.75 mg or 1.5 mg of dulaglutide had lower hemoglobin A1c at 26 weeks than patients who received placebo.

Eli Lilly is now submitting these trial results to the FDA for this indication.

Dulaglutide was cleared for use in adults with type 2 diabetes in the United States in 2014 and was additionally approved for reducing the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes at high risk of such events in 2020.

The most common adverse symptoms were gastrointestinal, and the safety profile was consistent with that in adults. However, the drug had no effect on body mass index.

The study was simultaneously published in the New England Journal of Medicine and presented as a late-breaking poster at the annual scientific sessions of the American Diabetes Association in New Orleans.

Might dulaglutide target pathophysiologic impairments in youth?

Dulaglutide would “offer a new treatment that targets the pathophysiologic impairments of type 2 diabetes in youth,” Silva A. Arslanian, MD, lead investigator, told this news organization.

Exenatide is also given as a weekly injection but is associated with a smaller decrease in A1c and does not improve fasting glucose concentrations, plus it requires more steps compared with the dulaglutide single-use pen, said Dr. Arslanian, who is scientific director at the Center for Pediatric Research in Obesity & Metabolism, UPMC Children’s Hospital of Pittsburgh.

“Liraglutide is a daily injection, and I believe most patients, particularly adolescents, would prefer a weekly injection,” she added.  

Invited to comment, Elvira Isganaitis, MD, MPH, said “the significance of this paper lies in the fact that options for treating type 2 diabetes in children are currently much more limited than in adults – which is a major problem given recent studies that show that type 2 diabetes in youth is much more aggressive and more likely to cause complications early in the disease course.”

Dr. Isganaitis was not involved with the trial but is an investigator for the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study.

“With supply chain shortages and health insurance coverage issues that are common in the U.S., it would be helpful to have more than one FDA-approved option for a weekly GLP-1 receptor agonist in children [and] access to other classes of medications,” added Dr. Isganaitis, a pediatric endocrinologist at the Joslin Diabetes Center, Boston.

Phase 3 trials of sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors in youth with type 2 diabetes are also ongoing, Dr. Arslanian noted, “but as always, recruitment is slow with adolescents.”

“I am not optimistic that DPP4 inhibitors will have a place in the treatment of youth with type 2 diabetes,” she said. A recent study showed the addition of sitagliptin to metformin in youth with type 2 diabetes did not provide durable improvement in glycemic control.

Potentially promising therapy

In their published article, Dr. Arslanian and colleagues write that “considering the progressive increase in [A1c] over time that was observed in the TODAY trial, with 34% of youths having [an A1c] of at least 10% after up to 15 years of follow-up, we believe that the effects of dulaglutide therapy appear to be potentially promising.”

The TODAY trial showed that more than 50% of youth with type 2 diabetes taking metformin failed to maintain glycemic control within a median of 11.5 months, Dr. Arslanian elaborated, and over time their A1c escalated while their beta-cell function deteriorated rapidly, and complications progressed quickly.

“Therefore,” she noted, “considering that dulaglutide and the GLP-1 receptor agonist class of drugs improve A1c, improve beta-cell function, suppress glucagon concentrations, and improve insulin sensitivity, dulaglutide would provide a promising new treatment option for youth with type 2 diabetes.”

Phase 3 superiority trial

The AWARD-PEDS trial included 154 youth with type 2 diabetes and a BMI greater than the 85th percentile for their age and sex at 46 centers in nine countries. Researchers randomized participants 1:1:1 to the two doses of dulaglutide or placebo for 26 weeks, followed by a 26-week open-label study (during which the placebo group received 0.75 mg dulaglutide) and a 4-week safety extension. 

Participants were a mean age of 14.5 years and had a mean BMI of 34 kg/m².

In each of the dulaglutide groups, roughly 66% of patients were female and 58% were White, 18% were Black, and about 57% were Hispanic. They had a mean weight of 91 kg (200 lb) and a mean A1c of about 8%; 62% were taking metformin only, 27% were taking metformin plus basal insulin, 3% were taking basal insulin only, and 10% were on diet and exercise only.

At 26 weeks, mean A1c increased by 0.6% in the placebo group but decreased by 0.6% in the 0.75-mg dulaglutide group and by 0.9% in the 1.5-mg dulaglutide group (P < .001 for both comparisons versus placebo).

Also at 26 weeks, more participants in the pooled dulaglutide groups than in the placebo group had an A1c <7.0% (51% vs. 14%; P < .001).

Fasting glucose concentration increased in the placebo group (+17.1 mg/dL ) and decreased in the pooled dulaglutide groups (–18.9 mg/dL; P < .001).

There were no group differences in BMI or adiposity-related parameters even at 52 weeks.

“I believe adolescents may be somewhat resistant to the weight-reducing effects of GLP-1 agonists in diabetes trials (liraglutide and exenatide youth type 2 diabetes trials showed the same thing) and they may need higher doses,” Dr. Arslanian speculated.

“Only future studies will be able to address this issue,” she concluded.

The study was funded by Eli Lilly. Dr. Arslanian has disclosed being a consultant for Eli Lilly, Novo Nordisk, and Rhythm Pharmaceuticals; participating in data safety monitoring for AstraZeneca and Eli Lilly trials; and receiving institutional research funding from Eli Lilly and Novo Nordisk. Dr. Isganaitis has disclosed receiving research funding (paid to her institution) from Dexcom and AstraZeneca.

A version of this article first appeared on Medscape.com.

Another glucagonlike peptide-1 (GLP1) agonist, dulaglutide (Trulicity, Lilly), is poised to be a new option for glycemic control in youth aged 10-18 years with type 2 diabetes, given as a weekly injection, based on the AWARD-PEDS clinical trial.

The U.S. Food and Drug Administration has already approved daily injection liraglutide (Victoza, Novo Nordisk) in 2019 and weekly exenatide (Bydureon/Bydureon BCise, AstraZeneca) in 2021 for glycemic control in young patients with type 2 diabetes, both of which are also GLP-1 agonists.  

AWARD-PEDS showed that youth with type 2 diabetes and obesity treated with or without metformin or basal insulin who received weekly injections of 0.75 mg or 1.5 mg of dulaglutide had lower hemoglobin A1c at 26 weeks than patients who received placebo.

Eli Lilly is now submitting these trial results to the FDA for this indication.

Dulaglutide was cleared for use in adults with type 2 diabetes in the United States in 2014 and was additionally approved for reducing the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes at high risk of such events in 2020.

The most common adverse symptoms were gastrointestinal, and the safety profile was consistent with that in adults. However, the drug had no effect on body mass index.

The study was simultaneously published in the New England Journal of Medicine and presented as a late-breaking poster at the annual scientific sessions of the American Diabetes Association in New Orleans.

Might dulaglutide target pathophysiologic impairments in youth?

Dulaglutide would “offer a new treatment that targets the pathophysiologic impairments of type 2 diabetes in youth,” Silva A. Arslanian, MD, lead investigator, told this news organization.

Exenatide is also given as a weekly injection but is associated with a smaller decrease in A1c and does not improve fasting glucose concentrations, plus it requires more steps compared with the dulaglutide single-use pen, said Dr. Arslanian, who is scientific director at the Center for Pediatric Research in Obesity & Metabolism, UPMC Children’s Hospital of Pittsburgh.

“Liraglutide is a daily injection, and I believe most patients, particularly adolescents, would prefer a weekly injection,” she added.  

Invited to comment, Elvira Isganaitis, MD, MPH, said “the significance of this paper lies in the fact that options for treating type 2 diabetes in children are currently much more limited than in adults – which is a major problem given recent studies that show that type 2 diabetes in youth is much more aggressive and more likely to cause complications early in the disease course.”

Dr. Isganaitis was not involved with the trial but is an investigator for the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study.

“With supply chain shortages and health insurance coverage issues that are common in the U.S., it would be helpful to have more than one FDA-approved option for a weekly GLP-1 receptor agonist in children [and] access to other classes of medications,” added Dr. Isganaitis, a pediatric endocrinologist at the Joslin Diabetes Center, Boston.

Phase 3 trials of sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors in youth with type 2 diabetes are also ongoing, Dr. Arslanian noted, “but as always, recruitment is slow with adolescents.”

“I am not optimistic that DPP4 inhibitors will have a place in the treatment of youth with type 2 diabetes,” she said. A recent study showed the addition of sitagliptin to metformin in youth with type 2 diabetes did not provide durable improvement in glycemic control.

Potentially promising therapy

In their published article, Dr. Arslanian and colleagues write that “considering the progressive increase in [A1c] over time that was observed in the TODAY trial, with 34% of youths having [an A1c] of at least 10% after up to 15 years of follow-up, we believe that the effects of dulaglutide therapy appear to be potentially promising.”

The TODAY trial showed that more than 50% of youth with type 2 diabetes taking metformin failed to maintain glycemic control within a median of 11.5 months, Dr. Arslanian elaborated, and over time their A1c escalated while their beta-cell function deteriorated rapidly, and complications progressed quickly.

“Therefore,” she noted, “considering that dulaglutide and the GLP-1 receptor agonist class of drugs improve A1c, improve beta-cell function, suppress glucagon concentrations, and improve insulin sensitivity, dulaglutide would provide a promising new treatment option for youth with type 2 diabetes.”

Phase 3 superiority trial

The AWARD-PEDS trial included 154 youth with type 2 diabetes and a BMI greater than the 85th percentile for their age and sex at 46 centers in nine countries. Researchers randomized participants 1:1:1 to the two doses of dulaglutide or placebo for 26 weeks, followed by a 26-week open-label study (during which the placebo group received 0.75 mg dulaglutide) and a 4-week safety extension. 

Participants were a mean age of 14.5 years and had a mean BMI of 34 kg/m².

In each of the dulaglutide groups, roughly 66% of patients were female and 58% were White, 18% were Black, and about 57% were Hispanic. They had a mean weight of 91 kg (200 lb) and a mean A1c of about 8%; 62% were taking metformin only, 27% were taking metformin plus basal insulin, 3% were taking basal insulin only, and 10% were on diet and exercise only.

At 26 weeks, mean A1c increased by 0.6% in the placebo group but decreased by 0.6% in the 0.75-mg dulaglutide group and by 0.9% in the 1.5-mg dulaglutide group (P < .001 for both comparisons versus placebo).

Also at 26 weeks, more participants in the pooled dulaglutide groups than in the placebo group had an A1c <7.0% (51% vs. 14%; P < .001).

Fasting glucose concentration increased in the placebo group (+17.1 mg/dL ) and decreased in the pooled dulaglutide groups (–18.9 mg/dL; P < .001).

There were no group differences in BMI or adiposity-related parameters even at 52 weeks.

“I believe adolescents may be somewhat resistant to the weight-reducing effects of GLP-1 agonists in diabetes trials (liraglutide and exenatide youth type 2 diabetes trials showed the same thing) and they may need higher doses,” Dr. Arslanian speculated.

“Only future studies will be able to address this issue,” she concluded.

The study was funded by Eli Lilly. Dr. Arslanian has disclosed being a consultant for Eli Lilly, Novo Nordisk, and Rhythm Pharmaceuticals; participating in data safety monitoring for AstraZeneca and Eli Lilly trials; and receiving institutional research funding from Eli Lilly and Novo Nordisk. Dr. Isganaitis has disclosed receiving research funding (paid to her institution) from Dexcom and AstraZeneca.

A version of this article first appeared on Medscape.com.

Adagrasib, an investigational drug that acts as a KRASG12C inhibitor, has shown durable clinical benefit in patients with previously treated, advanced non-small cell lung cancer (NSCLC) with tumors with KRAS G12C mutations.

“KRAS G12C mutations occur in over 10% of patients with NSCL [and] remain difficult to target, and outcomes for this patient population have remained poor,” co-investigator Joshua Sabari, MD, assistant professor of medicine, Perlmutter Cancer Center at NYU Langone, said in a statement.

“Our patients benefited clinically from this agent, and it appears to have improved overall survival (OS), compared with historical outcomes with docetaxel, a standard-of-care chemotherapy regimen, in the second-line setting,” he added.

New data on adagrasib were presented at the annual meeting of the American Society for Clinical Oncology and simultaneously published in the New England Journal of Medicine.

Adagrasib (developed by Mirati) is currently awaiting approval from the U.S. Food and Drug Administration as a treatment for patients with NSCLC harboring the KRAS G12C mutation who have received at least one prior systemic therapy. This would be an accelerated approval based on overall response data from the KRYSTAL-1 study detailed below. The company has an ongoing confirmatory Phase 3 trial, KRYSTAL-12, evaluating adagrasib versus docetaxel in patients previously treated for metastatic NSCLC with a KRAS G12C mutation.

If approved, adagrasib would be the second in this class of agents. The first KRASG12C inhibitor for use in lung cancer was sotorasib (Lumakras), approved by the U.S. Food and Drug Administration in May 2021.  

Dr. Sabari noted that there are several differences between the two drugs. Adagrasib has CNS penetration and is the first KRASG12C inhibitor to demonstrate clinical activity in patients with KRAS G12C-mutated NSCLC with untreated active CNS metastases.
 

Published clinical data

The results published in the New England Journal of Medicine are from the company-funded KRYSTAL-1 clinical trial, which had the primary endpoint of objective response rate.

It was conducted in patients with KRAS G12C-mutated NSCLC who had previously received treatment with at least one platinum-containing chemotherapy regimen and checkpoint inhibitor therapy either sequentially or concurrently.

Patients were treated with oral adagrasib 600 mg twice a day until disease progression, unacceptable toxicity, or death.

On Oct. 15, 2021, the data cutoff date, a total of 116 patients had received at least one dose of adagrasib. At a median follow-up of 12.9 months, the confirmed objective response rate was 42.9% among 112 patients with measurable disease at baseline. One patient achieved a complete response: 42% achieved a partial response, and disease stabilized for a minimum of 6 weeks in over 36% of the group.

Only 5.4% of patients had progressive disease as their best overall response, investigators note. Among those patients who responded to twice-daily KRASG12C inhibition, the median time to response was 1.4 months and the median duration of response was 8.5 months. As of the data cutoff date, one-third of the group were still receiving treatment, the authors note.

Median progression-free survival (PFS) was 6.5 months and median OS was 11.7 months. With a longer median follow-up of 15.6 months, median OS was 12.6 months, and the estimated OS at 1 year was close to 51%.

“The majority of treatment-related adverse events were low-grade, started early in treatment, and quickly resolved after occurrence,” Dr. Sabari noted.

Grade 1-2 treatment-related adverse events occurred in 53% of patients while 45% had grade 3-4 treatment-related adverse events, and there were two fatal grade 5 treatment-related adverse events. The same events led to a dose reduction in 52% of the group overall and dose interruption in 61%, while in 7% of patients, treatment-related adverse events led to discontinuation of the drug.
 

CNS metastases

At baseline, some 42 patients had evidence of central nervous system (CNS) metastases. At a median follow-up of 15.4 months, an intracranial-confirmed objective response was achieved in one-third of this subgroup overall while median duration of the intracranial response was 11.2 months. Again, within the same subgroup, the median PFS was 5.4 months.

As Dr. Sabari noted, CNS metastases from KRAS mutant NSCLC are common. “Adagrasib demonstrated encouraging and durable CNS-specific activity in patients with KRAS G12C-mutant NSCLC and active, untreated CNS metastases,” he said.

The study was funded by Mirati Therapeutics.

A version of this article first appeared on Medscape.com.

Adagrasib, an investigational drug that acts as a KRASG12C inhibitor, has shown durable clinical benefit in patients with previously treated, advanced non-small cell lung cancer (NSCLC) with tumors with KRAS G12C mutations.

“KRAS G12C mutations occur in over 10% of patients with NSCL [and] remain difficult to target, and outcomes for this patient population have remained poor,” co-investigator Joshua Sabari, MD, assistant professor of medicine, Perlmutter Cancer Center at NYU Langone, said in a statement.

“Our patients benefited clinically from this agent, and it appears to have improved overall survival (OS), compared with historical outcomes with docetaxel, a standard-of-care chemotherapy regimen, in the second-line setting,” he added.

New data on adagrasib were presented at the annual meeting of the American Society for Clinical Oncology and simultaneously published in the New England Journal of Medicine.

Adagrasib (developed by Mirati) is currently awaiting approval from the U.S. Food and Drug Administration as a treatment for patients with NSCLC harboring the KRAS G12C mutation who have received at least one prior systemic therapy. This would be an accelerated approval based on overall response data from the KRYSTAL-1 study detailed below. The company has an ongoing confirmatory Phase 3 trial, KRYSTAL-12, evaluating adagrasib versus docetaxel in patients previously treated for metastatic NSCLC with a KRAS G12C mutation.

If approved, adagrasib would be the second in this class of agents. The first KRASG12C inhibitor for use in lung cancer was sotorasib (Lumakras), approved by the U.S. Food and Drug Administration in May 2021.  

Dr. Sabari noted that there are several differences between the two drugs. Adagrasib has CNS penetration and is the first KRASG12C inhibitor to demonstrate clinical activity in patients with KRAS G12C-mutated NSCLC with untreated active CNS metastases.
 

Published clinical data

The results published in the New England Journal of Medicine are from the company-funded KRYSTAL-1 clinical trial, which had the primary endpoint of objective response rate.

It was conducted in patients with KRAS G12C-mutated NSCLC who had previously received treatment with at least one platinum-containing chemotherapy regimen and checkpoint inhibitor therapy either sequentially or concurrently.

Patients were treated with oral adagrasib 600 mg twice a day until disease progression, unacceptable toxicity, or death.

On Oct. 15, 2021, the data cutoff date, a total of 116 patients had received at least one dose of adagrasib. At a median follow-up of 12.9 months, the confirmed objective response rate was 42.9% among 112 patients with measurable disease at baseline. One patient achieved a complete response: 42% achieved a partial response, and disease stabilized for a minimum of 6 weeks in over 36% of the group.

Only 5.4% of patients had progressive disease as their best overall response, investigators note. Among those patients who responded to twice-daily KRASG12C inhibition, the median time to response was 1.4 months and the median duration of response was 8.5 months. As of the data cutoff date, one-third of the group were still receiving treatment, the authors note.

Median progression-free survival (PFS) was 6.5 months and median OS was 11.7 months. With a longer median follow-up of 15.6 months, median OS was 12.6 months, and the estimated OS at 1 year was close to 51%.

“The majority of treatment-related adverse events were low-grade, started early in treatment, and quickly resolved after occurrence,” Dr. Sabari noted.

Grade 1-2 treatment-related adverse events occurred in 53% of patients while 45% had grade 3-4 treatment-related adverse events, and there were two fatal grade 5 treatment-related adverse events. The same events led to a dose reduction in 52% of the group overall and dose interruption in 61%, while in 7% of patients, treatment-related adverse events led to discontinuation of the drug.
 

CNS metastases

At baseline, some 42 patients had evidence of central nervous system (CNS) metastases. At a median follow-up of 15.4 months, an intracranial-confirmed objective response was achieved in one-third of this subgroup overall while median duration of the intracranial response was 11.2 months. Again, within the same subgroup, the median PFS was 5.4 months.

As Dr. Sabari noted, CNS metastases from KRAS mutant NSCLC are common. “Adagrasib demonstrated encouraging and durable CNS-specific activity in patients with KRAS G12C-mutant NSCLC and active, untreated CNS metastases,” he said.

The study was funded by Mirati Therapeutics.

A version of this article first appeared on Medscape.com.

Adagrasib, an investigational drug that acts as a KRASG12C inhibitor, has shown durable clinical benefit in patients with previously treated, advanced non-small cell lung cancer (NSCLC) with tumors with KRAS G12C mutations.

“KRAS G12C mutations occur in over 10% of patients with NSCL [and] remain difficult to target, and outcomes for this patient population have remained poor,” co-investigator Joshua Sabari, MD, assistant professor of medicine, Perlmutter Cancer Center at NYU Langone, said in a statement.

“Our patients benefited clinically from this agent, and it appears to have improved overall survival (OS), compared with historical outcomes with docetaxel, a standard-of-care chemotherapy regimen, in the second-line setting,” he added.

New data on adagrasib were presented at the annual meeting of the American Society for Clinical Oncology and simultaneously published in the New England Journal of Medicine.

Adagrasib (developed by Mirati) is currently awaiting approval from the U.S. Food and Drug Administration as a treatment for patients with NSCLC harboring the KRAS G12C mutation who have received at least one prior systemic therapy. This would be an accelerated approval based on overall response data from the KRYSTAL-1 study detailed below. The company has an ongoing confirmatory Phase 3 trial, KRYSTAL-12, evaluating adagrasib versus docetaxel in patients previously treated for metastatic NSCLC with a KRAS G12C mutation.

If approved, adagrasib would be the second in this class of agents. The first KRASG12C inhibitor for use in lung cancer was sotorasib (Lumakras), approved by the U.S. Food and Drug Administration in May 2021.  

Dr. Sabari noted that there are several differences between the two drugs. Adagrasib has CNS penetration and is the first KRASG12C inhibitor to demonstrate clinical activity in patients with KRAS G12C-mutated NSCLC with untreated active CNS metastases.
 

Published clinical data

The results published in the New England Journal of Medicine are from the company-funded KRYSTAL-1 clinical trial, which had the primary endpoint of objective response rate.

It was conducted in patients with KRAS G12C-mutated NSCLC who had previously received treatment with at least one platinum-containing chemotherapy regimen and checkpoint inhibitor therapy either sequentially or concurrently.

Patients were treated with oral adagrasib 600 mg twice a day until disease progression, unacceptable toxicity, or death.

On Oct. 15, 2021, the data cutoff date, a total of 116 patients had received at least one dose of adagrasib. At a median follow-up of 12.9 months, the confirmed objective response rate was 42.9% among 112 patients with measurable disease at baseline. One patient achieved a complete response: 42% achieved a partial response, and disease stabilized for a minimum of 6 weeks in over 36% of the group.

Only 5.4% of patients had progressive disease as their best overall response, investigators note. Among those patients who responded to twice-daily KRASG12C inhibition, the median time to response was 1.4 months and the median duration of response was 8.5 months. As of the data cutoff date, one-third of the group were still receiving treatment, the authors note.

Median progression-free survival (PFS) was 6.5 months and median OS was 11.7 months. With a longer median follow-up of 15.6 months, median OS was 12.6 months, and the estimated OS at 1 year was close to 51%.

“The majority of treatment-related adverse events were low-grade, started early in treatment, and quickly resolved after occurrence,” Dr. Sabari noted.

Grade 1-2 treatment-related adverse events occurred in 53% of patients while 45% had grade 3-4 treatment-related adverse events, and there were two fatal grade 5 treatment-related adverse events. The same events led to a dose reduction in 52% of the group overall and dose interruption in 61%, while in 7% of patients, treatment-related adverse events led to discontinuation of the drug.
 

CNS metastases

At baseline, some 42 patients had evidence of central nervous system (CNS) metastases. At a median follow-up of 15.4 months, an intracranial-confirmed objective response was achieved in one-third of this subgroup overall while median duration of the intracranial response was 11.2 months. Again, within the same subgroup, the median PFS was 5.4 months.

As Dr. Sabari noted, CNS metastases from KRAS mutant NSCLC are common. “Adagrasib demonstrated encouraging and durable CNS-specific activity in patients with KRAS G12C-mutant NSCLC and active, untreated CNS metastases,” he said.

The study was funded by Mirati Therapeutics.

A version of this article first appeared on Medscape.com.