Exercise recommendations typically focus on the duration of physical activity. For example, the World Health Organization advises at least 150 minutes of moderate physical activity per week. A new analysis of data from the Women’s Health Study, published in JAMA Internal Medicine, suggested that step count could also be a useful metric. For some, such a recommendation might be easier to follow.

“It’s not so easy to keep track of how long you’ve been moderately active in a given week,” Cary P. Gross, MD, from the Department of Medicine at Yale University in New Haven, Connecticut, wrote in an editorial. “Counting steps might be easier for some people, especially since most carry a phone that can serve as a pedometer.”
 

The 10,000-Step Recommendation

However, there are no well-founded recommendations for step counts, partly due to a lack of scientific evidence linking steps with mortality and cardiovascular diseases. The often-cited 10,000 steps per day originated from a marketing campaign in Japan in the 1960s.

The research team led by Rikuta Hamaya, MD, from the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston, analyzed data from participants in the Women’s Health Study. This clinical trial in the United States from 1992 to 2004 investigated the use of aspirin and vitamin E for cancer and cardiovascular disease prevention.

The current analysis included 14,399 women who were aged ≥ 62 years and had not developed cardiovascular disease or cancer. Between 2011 and 2015, they measured their physical activity and step count over 7 days using an accelerometer. They were followed-up for an average of 9 years.
 

Risk Reduction With Both Parameters

Moderate physical activity among the participants amounted to a median of 62 minutes per week, with a median daily step count of 5183. Hamaya and his colleagues found that both physical activity parameters were associated with lower mortality and reduced risk for cardiovascular diseases.

Participants who engaged in more than the recommended 150 minutes of moderate-intensity activity per week had a 32% lower mortality risk than those who were the least physically active. Women with > 7000 steps per day had a 42% lower mortality risk than those with the lowest daily step count.

Women in the top three quartiles of physical activity outlived those in the lowest quartile by an average of 2.22 months (time) or 2.36 months (steps), according to Hamaya and his team. The survival advantage was independent of body mass index.

For the endpoint of cardiovascular diseases (heart attack, stroke, and cardiovascular mortality), the researchers observed similar results as for mortality.
 

More Ways to Reach the Goal

Dr. Hamaya emphasized the importance of offering multiple ways to meet exercise recommendations: “For some, especially younger people, physical activity includes sports like tennis, soccer, walking, or jogging. All these can be tracked well with step counting. But for others, activity means cycling or swimming, which is easier to measure by duration.”

For Dr. Gross, the new findings provide a basis for using step counts to set physical activity goals — both in individual patient counseling and in formal guidelines. However, he stressed that further studies are necessary.

“The results need to be replicated in various populations, not just among men and younger people but also among ethnic minorities and lower-income populations, who often have less time and space for structured physical activity.”
 

This story was translated from Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Exercise recommendations typically focus on the duration of physical activity. For example, the World Health Organization advises at least 150 minutes of moderate physical activity per week. A new analysis of data from the Women’s Health Study, published in JAMA Internal Medicine, suggested that step count could also be a useful metric. For some, such a recommendation might be easier to follow.

“It’s not so easy to keep track of how long you’ve been moderately active in a given week,” Cary P. Gross, MD, from the Department of Medicine at Yale University in New Haven, Connecticut, wrote in an editorial. “Counting steps might be easier for some people, especially since most carry a phone that can serve as a pedometer.”
 

The 10,000-Step Recommendation

However, there are no well-founded recommendations for step counts, partly due to a lack of scientific evidence linking steps with mortality and cardiovascular diseases. The often-cited 10,000 steps per day originated from a marketing campaign in Japan in the 1960s.

The research team led by Rikuta Hamaya, MD, from the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston, analyzed data from participants in the Women’s Health Study. This clinical trial in the United States from 1992 to 2004 investigated the use of aspirin and vitamin E for cancer and cardiovascular disease prevention.

The current analysis included 14,399 women who were aged ≥ 62 years and had not developed cardiovascular disease or cancer. Between 2011 and 2015, they measured their physical activity and step count over 7 days using an accelerometer. They were followed-up for an average of 9 years.
 

Risk Reduction With Both Parameters

Moderate physical activity among the participants amounted to a median of 62 minutes per week, with a median daily step count of 5183. Hamaya and his colleagues found that both physical activity parameters were associated with lower mortality and reduced risk for cardiovascular diseases.

Participants who engaged in more than the recommended 150 minutes of moderate-intensity activity per week had a 32% lower mortality risk than those who were the least physically active. Women with > 7000 steps per day had a 42% lower mortality risk than those with the lowest daily step count.

Women in the top three quartiles of physical activity outlived those in the lowest quartile by an average of 2.22 months (time) or 2.36 months (steps), according to Hamaya and his team. The survival advantage was independent of body mass index.

For the endpoint of cardiovascular diseases (heart attack, stroke, and cardiovascular mortality), the researchers observed similar results as for mortality.
 

More Ways to Reach the Goal

Dr. Hamaya emphasized the importance of offering multiple ways to meet exercise recommendations: “For some, especially younger people, physical activity includes sports like tennis, soccer, walking, or jogging. All these can be tracked well with step counting. But for others, activity means cycling or swimming, which is easier to measure by duration.”

For Dr. Gross, the new findings provide a basis for using step counts to set physical activity goals — both in individual patient counseling and in formal guidelines. However, he stressed that further studies are necessary.

“The results need to be replicated in various populations, not just among men and younger people but also among ethnic minorities and lower-income populations, who often have less time and space for structured physical activity.”
 

This story was translated from Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Exercise recommendations typically focus on the duration of physical activity. For example, the World Health Organization advises at least 150 minutes of moderate physical activity per week. A new analysis of data from the Women’s Health Study, published in JAMA Internal Medicine, suggested that step count could also be a useful metric. For some, such a recommendation might be easier to follow.

“It’s not so easy to keep track of how long you’ve been moderately active in a given week,” Cary P. Gross, MD, from the Department of Medicine at Yale University in New Haven, Connecticut, wrote in an editorial. “Counting steps might be easier for some people, especially since most carry a phone that can serve as a pedometer.”
 

The 10,000-Step Recommendation

However, there are no well-founded recommendations for step counts, partly due to a lack of scientific evidence linking steps with mortality and cardiovascular diseases. The often-cited 10,000 steps per day originated from a marketing campaign in Japan in the 1960s.

The research team led by Rikuta Hamaya, MD, from the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston, analyzed data from participants in the Women’s Health Study. This clinical trial in the United States from 1992 to 2004 investigated the use of aspirin and vitamin E for cancer and cardiovascular disease prevention.

The current analysis included 14,399 women who were aged ≥ 62 years and had not developed cardiovascular disease or cancer. Between 2011 and 2015, they measured their physical activity and step count over 7 days using an accelerometer. They were followed-up for an average of 9 years.
 

Risk Reduction With Both Parameters

Moderate physical activity among the participants amounted to a median of 62 minutes per week, with a median daily step count of 5183. Hamaya and his colleagues found that both physical activity parameters were associated with lower mortality and reduced risk for cardiovascular diseases.

Participants who engaged in more than the recommended 150 minutes of moderate-intensity activity per week had a 32% lower mortality risk than those who were the least physically active. Women with > 7000 steps per day had a 42% lower mortality risk than those with the lowest daily step count.

Women in the top three quartiles of physical activity outlived those in the lowest quartile by an average of 2.22 months (time) or 2.36 months (steps), according to Hamaya and his team. The survival advantage was independent of body mass index.

For the endpoint of cardiovascular diseases (heart attack, stroke, and cardiovascular mortality), the researchers observed similar results as for mortality.
 

More Ways to Reach the Goal

Dr. Hamaya emphasized the importance of offering multiple ways to meet exercise recommendations: “For some, especially younger people, physical activity includes sports like tennis, soccer, walking, or jogging. All these can be tracked well with step counting. But for others, activity means cycling or swimming, which is easier to measure by duration.”

For Dr. Gross, the new findings provide a basis for using step counts to set physical activity goals — both in individual patient counseling and in formal guidelines. However, he stressed that further studies are necessary.

“The results need to be replicated in various populations, not just among men and younger people but also among ethnic minorities and lower-income populations, who often have less time and space for structured physical activity.”
 

This story was translated from Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

BOSTON — An investigational male contraceptive gel suppresses sperm more rapidly than previous products in development, new data suggested.

The product, 8 mg segesterone acetate (Nestorone) combined with 74 mg testosterone (“NesT”) is a gel that a man applies daily to both shoulders. The progesterone blocks spermatogenesis, and the testosterone restores blood levels to maintain sexual function. It is under development by the National Institute of Child Health and Human Development (NICHD) in collaboration with the Population Council, the Los Angeles Biomedical Research Institute, and the University of Washington School of Medicine.

Currently, the only available male contraceptives are vasectomy, which isn’t easily reversible, and condoms, which have a high failure rate. Previous attempts to develop a “male pill” have been unsuccessful for a variety of reasons, but so far, this product appears effective and safe, Diana Blithe, PhD, chief of the Contraceptive Development Program at NICHD, said at a press briefing held on June 2, 2024, during the annual meeting of the Endocrine Society.

“It’s been a long time coming. … Men need and want more contraceptive options such as an effective reversible method,” she told this news organization.

New phase 2b data show that among 222 couples in which the man initially had normal (> 15 million/mL) sperm counts, the median time to suppression (< 1 million/mL) was less than 8 weeks with NesT compared with 9-15 weeks seen in previous trials of injected male hormonal contraceptives. Nearly all (86%) had achieved suppression by 15 weeks.

After two consecutive counts of < 1 million/mL, the couples entered the trial’s ongoing 2-year efficacy phase. There have been no major safety concerns thus far, but “we need more data,” Dr. Blithe noted.

Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “certainly, I think it’s a big advance on what we have so far. … I think it’s showing great promise.”

Dr. Hayes did caution, though, that “with real-world use, daily application of a gel might be a bit more challenging than taking an injection…an injection is more consistent. With a gel, patients might forget or shower it off. But I don’t think 1 day of interruption would be a significant thing.”

Transference of the topical to a partner or a child is another potential concern, Dr. Hayes noted, although this is true of current testosterone gel products as well. During the briefing, Dr. Blithe said that this issue is why the product is recommended to be placed on the upper arms rather than the abdomen or another spot more likely to come into contact with another person. Also, in the trial, men were instructed to wear shirts during intercourse.

Regarding the rapidity of sperm suppression, Dr. Hayes said, “It’s surprising. It looks great as a reversible contraceptive. … Normally, you think of the life cycle of the sperm being about 72 days. So to see 50% suppression by 8 weeks, and then 85%-90% by 15 weeks, that’s very rapid. It may be that the progesterone that they’re using is very potent. Progestins can have some negative effects on lipids and mood. We didn’t really see the safety data in this presentation. So that will be interesting to see.”

During the briefing, Dr. Blithe said that the phase 2b trial is expected to finish by the end of this year, and in the meantime, the researchers are communicating with the US Food and Drug Administration about the design of a phase 3 trial because this is an unprecedented area. “They don’t have guidelines yet. They’ll need to develop them first.”

Dr. Blithe has been the NICHD principal investigator on cooperative research and development agreements with HRA Pharma and Daré Bioscience. Dr. Hayes had no disclosures.

A version of this article appeared on Medscape.com .

BOSTON — An investigational male contraceptive gel suppresses sperm more rapidly than previous products in development, new data suggested.

The product, 8 mg segesterone acetate (Nestorone) combined with 74 mg testosterone (“NesT”) is a gel that a man applies daily to both shoulders. The progesterone blocks spermatogenesis, and the testosterone restores blood levels to maintain sexual function. It is under development by the National Institute of Child Health and Human Development (NICHD) in collaboration with the Population Council, the Los Angeles Biomedical Research Institute, and the University of Washington School of Medicine.

Currently, the only available male contraceptives are vasectomy, which isn’t easily reversible, and condoms, which have a high failure rate. Previous attempts to develop a “male pill” have been unsuccessful for a variety of reasons, but so far, this product appears effective and safe, Diana Blithe, PhD, chief of the Contraceptive Development Program at NICHD, said at a press briefing held on June 2, 2024, during the annual meeting of the Endocrine Society.

“It’s been a long time coming. … Men need and want more contraceptive options such as an effective reversible method,” she told this news organization.

New phase 2b data show that among 222 couples in which the man initially had normal (> 15 million/mL) sperm counts, the median time to suppression (< 1 million/mL) was less than 8 weeks with NesT compared with 9-15 weeks seen in previous trials of injected male hormonal contraceptives. Nearly all (86%) had achieved suppression by 15 weeks.

After two consecutive counts of < 1 million/mL, the couples entered the trial’s ongoing 2-year efficacy phase. There have been no major safety concerns thus far, but “we need more data,” Dr. Blithe noted.

Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “certainly, I think it’s a big advance on what we have so far. … I think it’s showing great promise.”

Dr. Hayes did caution, though, that “with real-world use, daily application of a gel might be a bit more challenging than taking an injection…an injection is more consistent. With a gel, patients might forget or shower it off. But I don’t think 1 day of interruption would be a significant thing.”

Transference of the topical to a partner or a child is another potential concern, Dr. Hayes noted, although this is true of current testosterone gel products as well. During the briefing, Dr. Blithe said that this issue is why the product is recommended to be placed on the upper arms rather than the abdomen or another spot more likely to come into contact with another person. Also, in the trial, men were instructed to wear shirts during intercourse.

Regarding the rapidity of sperm suppression, Dr. Hayes said, “It’s surprising. It looks great as a reversible contraceptive. … Normally, you think of the life cycle of the sperm being about 72 days. So to see 50% suppression by 8 weeks, and then 85%-90% by 15 weeks, that’s very rapid. It may be that the progesterone that they’re using is very potent. Progestins can have some negative effects on lipids and mood. We didn’t really see the safety data in this presentation. So that will be interesting to see.”

During the briefing, Dr. Blithe said that the phase 2b trial is expected to finish by the end of this year, and in the meantime, the researchers are communicating with the US Food and Drug Administration about the design of a phase 3 trial because this is an unprecedented area. “They don’t have guidelines yet. They’ll need to develop them first.”

Dr. Blithe has been the NICHD principal investigator on cooperative research and development agreements with HRA Pharma and Daré Bioscience. Dr. Hayes had no disclosures.

A version of this article appeared on Medscape.com .

BOSTON — An investigational male contraceptive gel suppresses sperm more rapidly than previous products in development, new data suggested.

The product, 8 mg segesterone acetate (Nestorone) combined with 74 mg testosterone (“NesT”) is a gel that a man applies daily to both shoulders. The progesterone blocks spermatogenesis, and the testosterone restores blood levels to maintain sexual function. It is under development by the National Institute of Child Health and Human Development (NICHD) in collaboration with the Population Council, the Los Angeles Biomedical Research Institute, and the University of Washington School of Medicine.

Currently, the only available male contraceptives are vasectomy, which isn’t easily reversible, and condoms, which have a high failure rate. Previous attempts to develop a “male pill” have been unsuccessful for a variety of reasons, but so far, this product appears effective and safe, Diana Blithe, PhD, chief of the Contraceptive Development Program at NICHD, said at a press briefing held on June 2, 2024, during the annual meeting of the Endocrine Society.

“It’s been a long time coming. … Men need and want more contraceptive options such as an effective reversible method,” she told this news organization.

New phase 2b data show that among 222 couples in which the man initially had normal (> 15 million/mL) sperm counts, the median time to suppression (< 1 million/mL) was less than 8 weeks with NesT compared with 9-15 weeks seen in previous trials of injected male hormonal contraceptives. Nearly all (86%) had achieved suppression by 15 weeks.

After two consecutive counts of < 1 million/mL, the couples entered the trial’s ongoing 2-year efficacy phase. There have been no major safety concerns thus far, but “we need more data,” Dr. Blithe noted.

Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “certainly, I think it’s a big advance on what we have so far. … I think it’s showing great promise.”

Dr. Hayes did caution, though, that “with real-world use, daily application of a gel might be a bit more challenging than taking an injection…an injection is more consistent. With a gel, patients might forget or shower it off. But I don’t think 1 day of interruption would be a significant thing.”

Transference of the topical to a partner or a child is another potential concern, Dr. Hayes noted, although this is true of current testosterone gel products as well. During the briefing, Dr. Blithe said that this issue is why the product is recommended to be placed on the upper arms rather than the abdomen or another spot more likely to come into contact with another person. Also, in the trial, men were instructed to wear shirts during intercourse.

Regarding the rapidity of sperm suppression, Dr. Hayes said, “It’s surprising. It looks great as a reversible contraceptive. … Normally, you think of the life cycle of the sperm being about 72 days. So to see 50% suppression by 8 weeks, and then 85%-90% by 15 weeks, that’s very rapid. It may be that the progesterone that they’re using is very potent. Progestins can have some negative effects on lipids and mood. We didn’t really see the safety data in this presentation. So that will be interesting to see.”

During the briefing, Dr. Blithe said that the phase 2b trial is expected to finish by the end of this year, and in the meantime, the researchers are communicating with the US Food and Drug Administration about the design of a phase 3 trial because this is an unprecedented area. “They don’t have guidelines yet. They’ll need to develop them first.”

Dr. Blithe has been the NICHD principal investigator on cooperative research and development agreements with HRA Pharma and Daré Bioscience. Dr. Hayes had no disclosures.

A version of this article appeared on Medscape.com .

TOPLINE:

A diet rich in green, leafy, cruciferous, and colorful vegetables may improve glucose tolerance and insulin sensitivity, whereas a high intake of potato fries or chips may worsen these outcomes, an Australian study shows.

METHODOLOGY:

• Researchers assessed the association between the intake of vegetables and potatoes with markers of type 2 diabetes (T2D) in 8009 participants (median age, 52 years; 55% women) from the Australian Diabetes, Obesity, and Lifestyle Study.
• A self-administered 74-item food frequency questionnaire was used to assess participants’ eating habits over 12 months prior to baseline.
• Participants were categorized into four quartiles of vegetable intake, from the highest intake (Q4) to the lowest intake (Q1).
• The association between vegetable intake and various metabolic markers such as fasting plasma glucose (FPG), 2-hour post-load plasma glucose, updated homeostasis model assessment of beta cell function (HOMA2-%beta), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin were evaluated over a 12-year follow-up period.

TAKEAWAY:

• The post-load glucose was 3% lower in participants in the highest vs lowest quartile of total vegetable intake (ratio of means [RoM], 0.97; 95% CI, 0.96-0.99).
• Post-load glucose was 4% lower (RoM, 0.96; 95% CI, 0.95-0.98), HOMA2-%beta was 3% lower (RoM, 0.97; 95% CI, 0.96-0.99), and serum insulin was 5% lower (RoM, 0.95; 95% CI, 0.93-0.98) in those in the highest vs lowest quartile of green leafy vegetable intake.
• Those in the highest vs lowest quartile of potato fries or chips intake had 1% higher FPG, 3% higher HOMA2-%beta, and 8% higher serum insulin but 6% lower HOMA2-%S, revealing a negative impact on glucose tolerance and insulin sensitivity.
• The risk for T2D over 12 years was 26% and 25% lower among those in the highest and moderate quartiles of cruciferous vegetable intake, respectively, than among those in the lowest quartile of cruciferous vegetable intake.

IN PRACTICE:

The authors wrote that their study “sheds light on the physiological alterations in insulin regulation and glucose tolerance resulting from higher vegetable and subgroups of vegetable intake and supports the notion that vegetable subgroups may act differently in regulating insulin and blood glucose levels.”

SOURCE:

The study was led by Pratik Pokharel, MPH, Nutrition & Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia, and was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s observational nature precluded the inference of causality. Potential measurement errors in dietary exposures and recall bias linked to the food frequency questionnaire could have affected the findings. The overrepresentation of participants from higher education and socioeconomic subgroups and loss to follow-up could limit the generalizability of the findings.

DISCLOSURES:

The study was funded by the National Health and Medical Research Council, National Heart Foundation of Australia, and Royal Perth Hospital Medical Research Foundation. Several authors reported receiving grants from various sources during the conduct of this study. The other authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A diet rich in green, leafy, cruciferous, and colorful vegetables may improve glucose tolerance and insulin sensitivity, whereas a high intake of potato fries or chips may worsen these outcomes, an Australian study shows.

METHODOLOGY:

• Researchers assessed the association between the intake of vegetables and potatoes with markers of type 2 diabetes (T2D) in 8009 participants (median age, 52 years; 55% women) from the Australian Diabetes, Obesity, and Lifestyle Study.
• A self-administered 74-item food frequency questionnaire was used to assess participants’ eating habits over 12 months prior to baseline.
• Participants were categorized into four quartiles of vegetable intake, from the highest intake (Q4) to the lowest intake (Q1).
• The association between vegetable intake and various metabolic markers such as fasting plasma glucose (FPG), 2-hour post-load plasma glucose, updated homeostasis model assessment of beta cell function (HOMA2-%beta), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin were evaluated over a 12-year follow-up period.

TAKEAWAY:

• The post-load glucose was 3% lower in participants in the highest vs lowest quartile of total vegetable intake (ratio of means [RoM], 0.97; 95% CI, 0.96-0.99).
• Post-load glucose was 4% lower (RoM, 0.96; 95% CI, 0.95-0.98), HOMA2-%beta was 3% lower (RoM, 0.97; 95% CI, 0.96-0.99), and serum insulin was 5% lower (RoM, 0.95; 95% CI, 0.93-0.98) in those in the highest vs lowest quartile of green leafy vegetable intake.
• Those in the highest vs lowest quartile of potato fries or chips intake had 1% higher FPG, 3% higher HOMA2-%beta, and 8% higher serum insulin but 6% lower HOMA2-%S, revealing a negative impact on glucose tolerance and insulin sensitivity.
• The risk for T2D over 12 years was 26% and 25% lower among those in the highest and moderate quartiles of cruciferous vegetable intake, respectively, than among those in the lowest quartile of cruciferous vegetable intake.

IN PRACTICE:

The authors wrote that their study “sheds light on the physiological alterations in insulin regulation and glucose tolerance resulting from higher vegetable and subgroups of vegetable intake and supports the notion that vegetable subgroups may act differently in regulating insulin and blood glucose levels.”

SOURCE:

The study was led by Pratik Pokharel, MPH, Nutrition & Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia, and was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s observational nature precluded the inference of causality. Potential measurement errors in dietary exposures and recall bias linked to the food frequency questionnaire could have affected the findings. The overrepresentation of participants from higher education and socioeconomic subgroups and loss to follow-up could limit the generalizability of the findings.

DISCLOSURES:

The study was funded by the National Health and Medical Research Council, National Heart Foundation of Australia, and Royal Perth Hospital Medical Research Foundation. Several authors reported receiving grants from various sources during the conduct of this study. The other authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A diet rich in green, leafy, cruciferous, and colorful vegetables may improve glucose tolerance and insulin sensitivity, whereas a high intake of potato fries or chips may worsen these outcomes, an Australian study shows.

METHODOLOGY:

• Researchers assessed the association between the intake of vegetables and potatoes with markers of type 2 diabetes (T2D) in 8009 participants (median age, 52 years; 55% women) from the Australian Diabetes, Obesity, and Lifestyle Study.
• A self-administered 74-item food frequency questionnaire was used to assess participants’ eating habits over 12 months prior to baseline.
• Participants were categorized into four quartiles of vegetable intake, from the highest intake (Q4) to the lowest intake (Q1).
• The association between vegetable intake and various metabolic markers such as fasting plasma glucose (FPG), 2-hour post-load plasma glucose, updated homeostasis model assessment of beta cell function (HOMA2-%beta), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin were evaluated over a 12-year follow-up period.

TAKEAWAY:

• The post-load glucose was 3% lower in participants in the highest vs lowest quartile of total vegetable intake (ratio of means [RoM], 0.97; 95% CI, 0.96-0.99).
• Post-load glucose was 4% lower (RoM, 0.96; 95% CI, 0.95-0.98), HOMA2-%beta was 3% lower (RoM, 0.97; 95% CI, 0.96-0.99), and serum insulin was 5% lower (RoM, 0.95; 95% CI, 0.93-0.98) in those in the highest vs lowest quartile of green leafy vegetable intake.
• Those in the highest vs lowest quartile of potato fries or chips intake had 1% higher FPG, 3% higher HOMA2-%beta, and 8% higher serum insulin but 6% lower HOMA2-%S, revealing a negative impact on glucose tolerance and insulin sensitivity.
• The risk for T2D over 12 years was 26% and 25% lower among those in the highest and moderate quartiles of cruciferous vegetable intake, respectively, than among those in the lowest quartile of cruciferous vegetable intake.

IN PRACTICE:

The authors wrote that their study “sheds light on the physiological alterations in insulin regulation and glucose tolerance resulting from higher vegetable and subgroups of vegetable intake and supports the notion that vegetable subgroups may act differently in regulating insulin and blood glucose levels.”

SOURCE:

The study was led by Pratik Pokharel, MPH, Nutrition & Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia, and was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s observational nature precluded the inference of causality. Potential measurement errors in dietary exposures and recall bias linked to the food frequency questionnaire could have affected the findings. The overrepresentation of participants from higher education and socioeconomic subgroups and loss to follow-up could limit the generalizability of the findings.

DISCLOSURES:

The study was funded by the National Health and Medical Research Council, National Heart Foundation of Australia, and Royal Perth Hospital Medical Research Foundation. Several authors reported receiving grants from various sources during the conduct of this study. The other authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Investigators found that the use of oral contraceptives (OCs) may be associated with an increased risk for frontal fibrosing alopecia (FFA) in women with a common variant in the CYP1B1 gene.

METHODOLOGY:

• OC use has been considered a possible factor behind the increased incidence of FFA because it was first documented in 1994, and a recent genome-wide association study of FFA identified a signal for an association with a variant in CYP1B1.
• The same researchers conducted a gene-environment interaction study with a case-control design involving 489 White female patients (mean age, 65.8 years) with FFA and 34,254 controls, matched for age and genetic ancestry.
• Data were collected from July 2015 to September 2017 and analyzed from October 2022 to December 2023.
• The study aimed to investigate the modulatory effect of OC use on the CYP1B1 variant’s impact on FFA risk, using logistic regression models for analysis.

TAKEAWAY:

• The use of OCs was associated with a 1.9 times greater risk for FFA in individuals with the specific CYP1B1 genetic variant, but there was no association among those with no history of OC use.
• The study suggests a significant gene-environment interaction, indicating that OC use may influence FFA risk in genetically predisposed individuals.

IN PRACTICE:

“This gene-environment interaction analysis suggests that the protective effect of the CYPIB1 missense variant on FFA risk might be mediated by exposure” to OCs, the authors wrote. The study, they added, “underscores the importance of considering genetic predispositions and environmental factors, such as oral contraceptive use, in understanding and managing frontal fibrosing alopecia.”

SOURCE:

Tuntas Rayinda, MD, MSc, PhD, of St. John’s Institute of Dermatology, King’s College London, led the study, which was published online May 29, 2024, in JAMA Dermatology.

LIMITATIONS:

The study’s reliance on self-reported OC use may have introduced recall and differences in ascertainment of OC use between patient and control groups and could have affected the study’s findings. The study also did not collect information on the type of OC used, which could have influenced the observed interaction.

DISCLOSURES:

The study was supported by the British Skin Foundation Young Investigator Award. One investigator reported being a subinvestigator on an alopecia areata study funded by Pfizer. No other disclosures were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. 

A version of this article appeared on Medscape.com.

TOPLINE:

Investigators found that the use of oral contraceptives (OCs) may be associated with an increased risk for frontal fibrosing alopecia (FFA) in women with a common variant in the CYP1B1 gene.

METHODOLOGY:

• OC use has been considered a possible factor behind the increased incidence of FFA because it was first documented in 1994, and a recent genome-wide association study of FFA identified a signal for an association with a variant in CYP1B1.
• The same researchers conducted a gene-environment interaction study with a case-control design involving 489 White female patients (mean age, 65.8 years) with FFA and 34,254 controls, matched for age and genetic ancestry.
• Data were collected from July 2015 to September 2017 and analyzed from October 2022 to December 2023.
• The study aimed to investigate the modulatory effect of OC use on the CYP1B1 variant’s impact on FFA risk, using logistic regression models for analysis.

TAKEAWAY:

• The use of OCs was associated with a 1.9 times greater risk for FFA in individuals with the specific CYP1B1 genetic variant, but there was no association among those with no history of OC use.
• The study suggests a significant gene-environment interaction, indicating that OC use may influence FFA risk in genetically predisposed individuals.

IN PRACTICE:

“This gene-environment interaction analysis suggests that the protective effect of the CYPIB1 missense variant on FFA risk might be mediated by exposure” to OCs, the authors wrote. The study, they added, “underscores the importance of considering genetic predispositions and environmental factors, such as oral contraceptive use, in understanding and managing frontal fibrosing alopecia.”

SOURCE:

Tuntas Rayinda, MD, MSc, PhD, of St. John’s Institute of Dermatology, King’s College London, led the study, which was published online May 29, 2024, in JAMA Dermatology.

LIMITATIONS:

The study’s reliance on self-reported OC use may have introduced recall and differences in ascertainment of OC use between patient and control groups and could have affected the study’s findings. The study also did not collect information on the type of OC used, which could have influenced the observed interaction.

DISCLOSURES:

The study was supported by the British Skin Foundation Young Investigator Award. One investigator reported being a subinvestigator on an alopecia areata study funded by Pfizer. No other disclosures were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. 

A version of this article appeared on Medscape.com.

TOPLINE:

Investigators found that the use of oral contraceptives (OCs) may be associated with an increased risk for frontal fibrosing alopecia (FFA) in women with a common variant in the CYP1B1 gene.

METHODOLOGY:

• OC use has been considered a possible factor behind the increased incidence of FFA because it was first documented in 1994, and a recent genome-wide association study of FFA identified a signal for an association with a variant in CYP1B1.
• The same researchers conducted a gene-environment interaction study with a case-control design involving 489 White female patients (mean age, 65.8 years) with FFA and 34,254 controls, matched for age and genetic ancestry.
• Data were collected from July 2015 to September 2017 and analyzed from October 2022 to December 2023.
• The study aimed to investigate the modulatory effect of OC use on the CYP1B1 variant’s impact on FFA risk, using logistic regression models for analysis.

TAKEAWAY:

• The use of OCs was associated with a 1.9 times greater risk for FFA in individuals with the specific CYP1B1 genetic variant, but there was no association among those with no history of OC use.
• The study suggests a significant gene-environment interaction, indicating that OC use may influence FFA risk in genetically predisposed individuals.

IN PRACTICE:

“This gene-environment interaction analysis suggests that the protective effect of the CYPIB1 missense variant on FFA risk might be mediated by exposure” to OCs, the authors wrote. The study, they added, “underscores the importance of considering genetic predispositions and environmental factors, such as oral contraceptive use, in understanding and managing frontal fibrosing alopecia.”

SOURCE:

Tuntas Rayinda, MD, MSc, PhD, of St. John’s Institute of Dermatology, King’s College London, led the study, which was published online May 29, 2024, in JAMA Dermatology.

LIMITATIONS:

The study’s reliance on self-reported OC use may have introduced recall and differences in ascertainment of OC use between patient and control groups and could have affected the study’s findings. The study also did not collect information on the type of OC used, which could have influenced the observed interaction.

DISCLOSURES:

The study was supported by the British Skin Foundation Young Investigator Award. One investigator reported being a subinvestigator on an alopecia areata study funded by Pfizer. No other disclosures were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. 

A version of this article appeared on Medscape.com.

Exercise interventions are recommended to help prevent falls and fall-related morbidity in community-dwelling adults aged 65 years and older who are at increased risk of falls, according to a new recommendation statement from the U.S. Preventive Services Task Force (USPSTF) (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.8481).

Falls remain the leading cause of injury-related morbidity and mortality among older adults in the United States, with approximately 27% of community-dwelling individuals aged 65 years and older reporting at least one fall in the past year, wrote lead author Wanda K. Nicholson, MD, of George Washington University, Washington, and colleagues.

The task force concluded with moderate certainty that exercise interventions yielded a moderate benefit in fall reduction among older adults at risk (grade B recommendation).

The decision to offer multifactorial fall prevention interventions to older adults at risk for falls should be individualized based on assessment of potential risks and benefits of these interventions, including circumstances of prior falls, presence of comorbid medical conditions, and the patient’s values and preferences (grade C recommendation), the authors wrote.

The exercise intervention could include individual or group activity, although most of the studies in the systematic review involved group exercise, the authors noted.

The recommendation was based on data from a systematic evidence review published in JAMA (2024 Jun 4. doi: 10.1001/jama.2024.4166). The task force reviewed data from 83 randomized trials published between January 1, 2016, and May 8, 2023, deemed fair to good quality that examined six types of fall prevention interventions in a total of 48,839 individuals. Of these, 28 studies involved multifactorial interventions and 27 involved exercise interventions.

Overall, multifactorial interventions and exercise interventions were associated with a significant reduction in falls (incidence rate ratio 0.84 and 0.85, respectively).

Exercise interventions were significantly associated with reduced individual risk of one or more falls and injurious falls, but not with reduced individual risk of injurious falls. However, multifactorial interventions were not significantly associated with reductions in risk of one or more falls, injurious falls, fall-related fractures, individual risk of injurious falls, or individual risk of fall-related fractures.

Although teasing out the specific exercise components that are most effective for fall prevention is challenging, the most commonly studied components associated with reduced risk of falls included gait training, balance training, and functional training, followed by strength and resistance training, the task force noted.

Duration of exercise interventions in the reviewed studies ranged from 2 to 30 months and the most common frequency of sessions was 2 to 3 per week.

Based on these findings, the task force found that exercise had the most consistent benefits for reduced risk across several fall-related outcomes. Although individuals in the studies of multifactorial interventions were at increased risk for falls, the multistep process of interventions to address an individual’s multiple risk factors limited their effectiveness, in part because of logistical challenges and inconsistent adherence, the authors wrote.

The results of the review were limited by several factors, including the focus on studies with a primary or secondary aim of fall prevention, the fact that the recommendation does not apply to many subgroups of older adults, and the lack of data on health outcomes unrelated to falls that were associated with the interventions, the authors noted.

The new recommendation is consistent with and replaces the 2018 USPSTF recommendation on interventions for fall prevention in community-dwelling older adults, but without the recommendation against vitamin D supplementation as a fall prevention intervention. The new recommendation does not address vitamin D use; evidence will be examined in a separate recommendation, the task force wrote.
 

How to Get Older Adults Moving

“The biggest obstacle to exercise is patient inertia and choice to engage in other sedentary activities,” David B. Reuben, MD, and David A. Ganz, MD, both of the University of California, Los Angeles, wrote in an accompanying editorial (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.9063).

“Given the demonstrated benefits of exercise for cardiovascular disease, cognitive function, and favorable associations with all-cause, cardiovascular, and cancer mortality, specific fall prevention exercise recommendations need to be considered in the context of universal exercise recommendations, including aerobic and muscle strengthening exercise,” the authors wrote. However, maintaining regular exercise is a challenge for many older adults, and more research is needed on factors that drive exercise initiation and adherence in this population, they said.

Multifactorial fall assessments in particular take time, and more fall prevention programs are needed that include multifactorial assessments and interventions, the editorialists said. “Even if primary care clinicians faithfully implement the USPSTF recommendations, a significant reduction in falls and their resulting injuries is still far off,” in part, because of the need for more programs and policies, and the need to improve access to exercise programs and provide insurance coverage for them, they noted.

“Above all, older persons need to be active participants in exercise and reduction of risk factors for falls,” the editorialists concluded.

The research for the recommendation was funded by the Agency for Healthcare Research and Quality (AHRQ). The authors had no financial conflicts to disclose. Dr. Ganz disclosed serving as an author of the 2022 World Guidelines for Falls Prevention and Management for Older Adults.

Exercise interventions are recommended to help prevent falls and fall-related morbidity in community-dwelling adults aged 65 years and older who are at increased risk of falls, according to a new recommendation statement from the U.S. Preventive Services Task Force (USPSTF) (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.8481).

Falls remain the leading cause of injury-related morbidity and mortality among older adults in the United States, with approximately 27% of community-dwelling individuals aged 65 years and older reporting at least one fall in the past year, wrote lead author Wanda K. Nicholson, MD, of George Washington University, Washington, and colleagues.

The task force concluded with moderate certainty that exercise interventions yielded a moderate benefit in fall reduction among older adults at risk (grade B recommendation).

The decision to offer multifactorial fall prevention interventions to older adults at risk for falls should be individualized based on assessment of potential risks and benefits of these interventions, including circumstances of prior falls, presence of comorbid medical conditions, and the patient’s values and preferences (grade C recommendation), the authors wrote.

The exercise intervention could include individual or group activity, although most of the studies in the systematic review involved group exercise, the authors noted.

The recommendation was based on data from a systematic evidence review published in JAMA (2024 Jun 4. doi: 10.1001/jama.2024.4166). The task force reviewed data from 83 randomized trials published between January 1, 2016, and May 8, 2023, deemed fair to good quality that examined six types of fall prevention interventions in a total of 48,839 individuals. Of these, 28 studies involved multifactorial interventions and 27 involved exercise interventions.

Overall, multifactorial interventions and exercise interventions were associated with a significant reduction in falls (incidence rate ratio 0.84 and 0.85, respectively).

Exercise interventions were significantly associated with reduced individual risk of one or more falls and injurious falls, but not with reduced individual risk of injurious falls. However, multifactorial interventions were not significantly associated with reductions in risk of one or more falls, injurious falls, fall-related fractures, individual risk of injurious falls, or individual risk of fall-related fractures.

Although teasing out the specific exercise components that are most effective for fall prevention is challenging, the most commonly studied components associated with reduced risk of falls included gait training, balance training, and functional training, followed by strength and resistance training, the task force noted.

Duration of exercise interventions in the reviewed studies ranged from 2 to 30 months and the most common frequency of sessions was 2 to 3 per week.

Based on these findings, the task force found that exercise had the most consistent benefits for reduced risk across several fall-related outcomes. Although individuals in the studies of multifactorial interventions were at increased risk for falls, the multistep process of interventions to address an individual’s multiple risk factors limited their effectiveness, in part because of logistical challenges and inconsistent adherence, the authors wrote.

The results of the review were limited by several factors, including the focus on studies with a primary or secondary aim of fall prevention, the fact that the recommendation does not apply to many subgroups of older adults, and the lack of data on health outcomes unrelated to falls that were associated with the interventions, the authors noted.

The new recommendation is consistent with and replaces the 2018 USPSTF recommendation on interventions for fall prevention in community-dwelling older adults, but without the recommendation against vitamin D supplementation as a fall prevention intervention. The new recommendation does not address vitamin D use; evidence will be examined in a separate recommendation, the task force wrote.
 

How to Get Older Adults Moving

“The biggest obstacle to exercise is patient inertia and choice to engage in other sedentary activities,” David B. Reuben, MD, and David A. Ganz, MD, both of the University of California, Los Angeles, wrote in an accompanying editorial (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.9063).

“Given the demonstrated benefits of exercise for cardiovascular disease, cognitive function, and favorable associations with all-cause, cardiovascular, and cancer mortality, specific fall prevention exercise recommendations need to be considered in the context of universal exercise recommendations, including aerobic and muscle strengthening exercise,” the authors wrote. However, maintaining regular exercise is a challenge for many older adults, and more research is needed on factors that drive exercise initiation and adherence in this population, they said.

Multifactorial fall assessments in particular take time, and more fall prevention programs are needed that include multifactorial assessments and interventions, the editorialists said. “Even if primary care clinicians faithfully implement the USPSTF recommendations, a significant reduction in falls and their resulting injuries is still far off,” in part, because of the need for more programs and policies, and the need to improve access to exercise programs and provide insurance coverage for them, they noted.

“Above all, older persons need to be active participants in exercise and reduction of risk factors for falls,” the editorialists concluded.

The research for the recommendation was funded by the Agency for Healthcare Research and Quality (AHRQ). The authors had no financial conflicts to disclose. Dr. Ganz disclosed serving as an author of the 2022 World Guidelines for Falls Prevention and Management for Older Adults.

Exercise interventions are recommended to help prevent falls and fall-related morbidity in community-dwelling adults aged 65 years and older who are at increased risk of falls, according to a new recommendation statement from the U.S. Preventive Services Task Force (USPSTF) (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.8481).

Falls remain the leading cause of injury-related morbidity and mortality among older adults in the United States, with approximately 27% of community-dwelling individuals aged 65 years and older reporting at least one fall in the past year, wrote lead author Wanda K. Nicholson, MD, of George Washington University, Washington, and colleagues.

The task force concluded with moderate certainty that exercise interventions yielded a moderate benefit in fall reduction among older adults at risk (grade B recommendation).

The decision to offer multifactorial fall prevention interventions to older adults at risk for falls should be individualized based on assessment of potential risks and benefits of these interventions, including circumstances of prior falls, presence of comorbid medical conditions, and the patient’s values and preferences (grade C recommendation), the authors wrote.

The exercise intervention could include individual or group activity, although most of the studies in the systematic review involved group exercise, the authors noted.

The recommendation was based on data from a systematic evidence review published in JAMA (2024 Jun 4. doi: 10.1001/jama.2024.4166). The task force reviewed data from 83 randomized trials published between January 1, 2016, and May 8, 2023, deemed fair to good quality that examined six types of fall prevention interventions in a total of 48,839 individuals. Of these, 28 studies involved multifactorial interventions and 27 involved exercise interventions.

Overall, multifactorial interventions and exercise interventions were associated with a significant reduction in falls (incidence rate ratio 0.84 and 0.85, respectively).

Exercise interventions were significantly associated with reduced individual risk of one or more falls and injurious falls, but not with reduced individual risk of injurious falls. However, multifactorial interventions were not significantly associated with reductions in risk of one or more falls, injurious falls, fall-related fractures, individual risk of injurious falls, or individual risk of fall-related fractures.

Although teasing out the specific exercise components that are most effective for fall prevention is challenging, the most commonly studied components associated with reduced risk of falls included gait training, balance training, and functional training, followed by strength and resistance training, the task force noted.

Duration of exercise interventions in the reviewed studies ranged from 2 to 30 months and the most common frequency of sessions was 2 to 3 per week.

Based on these findings, the task force found that exercise had the most consistent benefits for reduced risk across several fall-related outcomes. Although individuals in the studies of multifactorial interventions were at increased risk for falls, the multistep process of interventions to address an individual’s multiple risk factors limited their effectiveness, in part because of logistical challenges and inconsistent adherence, the authors wrote.

The results of the review were limited by several factors, including the focus on studies with a primary or secondary aim of fall prevention, the fact that the recommendation does not apply to many subgroups of older adults, and the lack of data on health outcomes unrelated to falls that were associated with the interventions, the authors noted.

The new recommendation is consistent with and replaces the 2018 USPSTF recommendation on interventions for fall prevention in community-dwelling older adults, but without the recommendation against vitamin D supplementation as a fall prevention intervention. The new recommendation does not address vitamin D use; evidence will be examined in a separate recommendation, the task force wrote.
 

How to Get Older Adults Moving

“The biggest obstacle to exercise is patient inertia and choice to engage in other sedentary activities,” David B. Reuben, MD, and David A. Ganz, MD, both of the University of California, Los Angeles, wrote in an accompanying editorial (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.9063).

“Given the demonstrated benefits of exercise for cardiovascular disease, cognitive function, and favorable associations with all-cause, cardiovascular, and cancer mortality, specific fall prevention exercise recommendations need to be considered in the context of universal exercise recommendations, including aerobic and muscle strengthening exercise,” the authors wrote. However, maintaining regular exercise is a challenge for many older adults, and more research is needed on factors that drive exercise initiation and adherence in this population, they said.

Multifactorial fall assessments in particular take time, and more fall prevention programs are needed that include multifactorial assessments and interventions, the editorialists said. “Even if primary care clinicians faithfully implement the USPSTF recommendations, a significant reduction in falls and their resulting injuries is still far off,” in part, because of the need for more programs and policies, and the need to improve access to exercise programs and provide insurance coverage for them, they noted.

“Above all, older persons need to be active participants in exercise and reduction of risk factors for falls,” the editorialists concluded.

The research for the recommendation was funded by the Agency for Healthcare Research and Quality (AHRQ). The authors had no financial conflicts to disclose. Dr. Ganz disclosed serving as an author of the 2022 World Guidelines for Falls Prevention and Management for Older Adults.

A reformulation of the multiple cancer drugs in the combination treatment known as BEACOPP boosted progression free survival vs. the original therapy in adult patients with advanced-stage classical Hodgkin lymphoma, a large, open-label, phase III trial found.

At a median follow-up of 4 years, progression-free survival for the new treatment, known as BrECADD, was 94.3% vs. 90.9% for BEACOPP (hazard ratio, 0.66, 95% CI, P = .035), researchers led by Peter Borchmann, MD, assistant medical director of hematology and oncology at the University Hospital of Cologne, Germany, reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

“These results are really striking,” said hematologist-oncologist Oreofe O. Odejide, MD, MPH, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, who was not involved in the study and commented on it during an ASCO news briefing. “This is really poised to impact the standard-of-care treatment for patients with advanced-stage classical Hodgkin lymphoma.”

As Dr. Borchmann explained at the briefing, Hodgkin lymphoma is the most common cancer among young adults. “The median age at onset is around 30 years, and it can be primarily cured with chemotherapy. Intensified chemotherapy probably is better primary lymphoma control than less intensive treatment, but this comes at the cost of treatment-related adverse events.”

Dr. Borchmann and colleagues developed the existing treatment known as BEACOPP, a combination of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone. “It’s our standard of care due to its high primary cure rate, which is reflected by compelling progression-free survival,” he said.

However, he said, “it’s a high burden of treatment.” The investigational treatment, BrECADD, includes six drugs instead of seven: brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone. Two of the additions — brentuximab vedotin and dacarbazine — are cancer drugs, and dexamethasone is a steroid. There is one fewer cancer drug in the new formulation.

In the international HD21 trial (9 countries, 233 sites), researchers recruited patients aged 18-60 who received four or six cycles of either BEACOPP or BrECADD. The doses were guided by PET2 findings.

In the intention-to-treat cohort of 1,482 subjects (median age 31.1, 44% female), 742 were assigned to BrECADD and 740 to BEACOPP.

There were few early treatment failures in the BrECADD group vs. BEACOPP. The numbers who had primary progression within the first 3 months were 5 vs. 15, respectively, and the numbers reaching early relapse between months 3 and 12 were 11 vs. 23, respectively.

Four-year overall survival rates in the groups were nearly identical at 98.5% for BrECADD and 98.2% for BEACOPP. In regard to fertility, follicle-stimulating hormone recovery rates after 1 year were higher in the BrECADD group in both men (67% vs. 24%, respectively) and women (89% vs. 68%, respectively). Birth rates were also higher in the BrECADD group (n = 60 vs. n = 43 in the BEACOPP group).

Nearly two-thirds of those in BrECADD group (64%) required 12 weeks of therapy — four cycles. As for treatment-related morbidity toxicities, they were less common in the BrECADD group vs. the BEACOPP group (42% vs. 59%, respectively, P < .0001), and 1% of BrECADD-treated had them at 1 year.

Oncologist Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, welcomed the findings at the ACO news briefing. “By replacing some pretty toxic chemo with an antibody-drug conjugate [brentuximab vedotin], and changing the regimen a bit, and using PET scan to determine the number of cycles received, the long-term outcomes were maintained, if not even improved upon,” said Dr. Dr. Gralow, who was not involved in the study.

In addition, she said, the findings about fertility are good news because “these are young people who probably haven’t started a family yet, and we’re increasing the odds that they will be able to do so after survival.”

Moving forward, she said, “we will need to have some discussion on how this relates to ABVD, which is a more commonly used regimen in the United States right now.” ABVD refers to a combination of doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine.

Takeda funded the study. Dr. Borchmann reported ties with BMS, GmbH & Co, Incyte, MSD/Merck, Roche, Takeda/Millennium, Miltenyi, Amgen, and Novartis. Some of the other study authors reported various disclosures. Dr. Odejide and Dr. Gralow have no disclosures.

A reformulation of the multiple cancer drugs in the combination treatment known as BEACOPP boosted progression free survival vs. the original therapy in adult patients with advanced-stage classical Hodgkin lymphoma, a large, open-label, phase III trial found.

At a median follow-up of 4 years, progression-free survival for the new treatment, known as BrECADD, was 94.3% vs. 90.9% for BEACOPP (hazard ratio, 0.66, 95% CI, P = .035), researchers led by Peter Borchmann, MD, assistant medical director of hematology and oncology at the University Hospital of Cologne, Germany, reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

“These results are really striking,” said hematologist-oncologist Oreofe O. Odejide, MD, MPH, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, who was not involved in the study and commented on it during an ASCO news briefing. “This is really poised to impact the standard-of-care treatment for patients with advanced-stage classical Hodgkin lymphoma.”

As Dr. Borchmann explained at the briefing, Hodgkin lymphoma is the most common cancer among young adults. “The median age at onset is around 30 years, and it can be primarily cured with chemotherapy. Intensified chemotherapy probably is better primary lymphoma control than less intensive treatment, but this comes at the cost of treatment-related adverse events.”

Dr. Borchmann and colleagues developed the existing treatment known as BEACOPP, a combination of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone. “It’s our standard of care due to its high primary cure rate, which is reflected by compelling progression-free survival,” he said.

However, he said, “it’s a high burden of treatment.” The investigational treatment, BrECADD, includes six drugs instead of seven: brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone. Two of the additions — brentuximab vedotin and dacarbazine — are cancer drugs, and dexamethasone is a steroid. There is one fewer cancer drug in the new formulation.

In the international HD21 trial (9 countries, 233 sites), researchers recruited patients aged 18-60 who received four or six cycles of either BEACOPP or BrECADD. The doses were guided by PET2 findings.

In the intention-to-treat cohort of 1,482 subjects (median age 31.1, 44% female), 742 were assigned to BrECADD and 740 to BEACOPP.

There were few early treatment failures in the BrECADD group vs. BEACOPP. The numbers who had primary progression within the first 3 months were 5 vs. 15, respectively, and the numbers reaching early relapse between months 3 and 12 were 11 vs. 23, respectively.

Four-year overall survival rates in the groups were nearly identical at 98.5% for BrECADD and 98.2% for BEACOPP. In regard to fertility, follicle-stimulating hormone recovery rates after 1 year were higher in the BrECADD group in both men (67% vs. 24%, respectively) and women (89% vs. 68%, respectively). Birth rates were also higher in the BrECADD group (n = 60 vs. n = 43 in the BEACOPP group).

Nearly two-thirds of those in BrECADD group (64%) required 12 weeks of therapy — four cycles. As for treatment-related morbidity toxicities, they were less common in the BrECADD group vs. the BEACOPP group (42% vs. 59%, respectively, P < .0001), and 1% of BrECADD-treated had them at 1 year.

Oncologist Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, welcomed the findings at the ACO news briefing. “By replacing some pretty toxic chemo with an antibody-drug conjugate [brentuximab vedotin], and changing the regimen a bit, and using PET scan to determine the number of cycles received, the long-term outcomes were maintained, if not even improved upon,” said Dr. Dr. Gralow, who was not involved in the study.

In addition, she said, the findings about fertility are good news because “these are young people who probably haven’t started a family yet, and we’re increasing the odds that they will be able to do so after survival.”

Moving forward, she said, “we will need to have some discussion on how this relates to ABVD, which is a more commonly used regimen in the United States right now.” ABVD refers to a combination of doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine.

Takeda funded the study. Dr. Borchmann reported ties with BMS, GmbH & Co, Incyte, MSD/Merck, Roche, Takeda/Millennium, Miltenyi, Amgen, and Novartis. Some of the other study authors reported various disclosures. Dr. Odejide and Dr. Gralow have no disclosures.

A reformulation of the multiple cancer drugs in the combination treatment known as BEACOPP boosted progression free survival vs. the original therapy in adult patients with advanced-stage classical Hodgkin lymphoma, a large, open-label, phase III trial found.

At a median follow-up of 4 years, progression-free survival for the new treatment, known as BrECADD, was 94.3% vs. 90.9% for BEACOPP (hazard ratio, 0.66, 95% CI, P = .035), researchers led by Peter Borchmann, MD, assistant medical director of hematology and oncology at the University Hospital of Cologne, Germany, reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

“These results are really striking,” said hematologist-oncologist Oreofe O. Odejide, MD, MPH, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, who was not involved in the study and commented on it during an ASCO news briefing. “This is really poised to impact the standard-of-care treatment for patients with advanced-stage classical Hodgkin lymphoma.”

As Dr. Borchmann explained at the briefing, Hodgkin lymphoma is the most common cancer among young adults. “The median age at onset is around 30 years, and it can be primarily cured with chemotherapy. Intensified chemotherapy probably is better primary lymphoma control than less intensive treatment, but this comes at the cost of treatment-related adverse events.”

Dr. Borchmann and colleagues developed the existing treatment known as BEACOPP, a combination of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone. “It’s our standard of care due to its high primary cure rate, which is reflected by compelling progression-free survival,” he said.

However, he said, “it’s a high burden of treatment.” The investigational treatment, BrECADD, includes six drugs instead of seven: brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone. Two of the additions — brentuximab vedotin and dacarbazine — are cancer drugs, and dexamethasone is a steroid. There is one fewer cancer drug in the new formulation.

In the international HD21 trial (9 countries, 233 sites), researchers recruited patients aged 18-60 who received four or six cycles of either BEACOPP or BrECADD. The doses were guided by PET2 findings.

In the intention-to-treat cohort of 1,482 subjects (median age 31.1, 44% female), 742 were assigned to BrECADD and 740 to BEACOPP.

There were few early treatment failures in the BrECADD group vs. BEACOPP. The numbers who had primary progression within the first 3 months were 5 vs. 15, respectively, and the numbers reaching early relapse between months 3 and 12 were 11 vs. 23, respectively.

Four-year overall survival rates in the groups were nearly identical at 98.5% for BrECADD and 98.2% for BEACOPP. In regard to fertility, follicle-stimulating hormone recovery rates after 1 year were higher in the BrECADD group in both men (67% vs. 24%, respectively) and women (89% vs. 68%, respectively). Birth rates were also higher in the BrECADD group (n = 60 vs. n = 43 in the BEACOPP group).

Nearly two-thirds of those in BrECADD group (64%) required 12 weeks of therapy — four cycles. As for treatment-related morbidity toxicities, they were less common in the BrECADD group vs. the BEACOPP group (42% vs. 59%, respectively, P < .0001), and 1% of BrECADD-treated had them at 1 year.

Oncologist Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, welcomed the findings at the ACO news briefing. “By replacing some pretty toxic chemo with an antibody-drug conjugate [brentuximab vedotin], and changing the regimen a bit, and using PET scan to determine the number of cycles received, the long-term outcomes were maintained, if not even improved upon,” said Dr. Dr. Gralow, who was not involved in the study.

In addition, she said, the findings about fertility are good news because “these are young people who probably haven’t started a family yet, and we’re increasing the odds that they will be able to do so after survival.”

Moving forward, she said, “we will need to have some discussion on how this relates to ABVD, which is a more commonly used regimen in the United States right now.” ABVD refers to a combination of doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine.

Takeda funded the study. Dr. Borchmann reported ties with BMS, GmbH & Co, Incyte, MSD/Merck, Roche, Takeda/Millennium, Miltenyi, Amgen, and Novartis. Some of the other study authors reported various disclosures. Dr. Odejide and Dr. Gralow have no disclosures.

Asciminib, a first-in-class tyrosine kinase inhibitor (TKI), shows efficacy and significantly improved tolerability compared with standard of care TKIs as a frontline treatment of newly diagnosed chronic myeloid leukemia (CML), primary results from the pivotal ASC4FIRST trial show.

“In the ASC4FIRST trial, asciminib is the first and only agent to demonstrate statistically significant efficacy versus standard-of-care frontline TKIs in newly diagnosed CML patients,” said senior author Jorge E. Cortes, MD, director of the Georgia Cancer Center at Augusta University in Georgia, in presenting the findings at a press briefing for the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

”Asciminib’s strong benefit-risk profile may transform the CML treatment paradigm,” Dr. Cortes said.

The study was published concurrently in The New England Journal of Medicine.

While TKIs have transformed the treatment of CML, improving the 5-year survival rates from 22% in the 1970s to 70% in recent years, nearly half of patients do not achieve a major molecular response within a year, due to either resistance or intolerance, causing the common switching of drugs.

Long-term use is further associated with common side effects, including gastrointestinal and cardiovascular events, due to off-target effects.

Asciminib is a potent and highly specific agent is an allosteric inhibitor targeting ABL myristoyl pocket, which is important in avoiding off-target effects that cause the common side effects.

The drug already has approval from the US Food and Drug Administration (FDA) for the treatment of patients with chronic phase CML who are resistant or intolerant to at least 2 prior TKIs or those with T315I mutation.

For the current pivotal phase 3 ASC4FIRST trial to evaluate the drug as a frontline therapy in recently diagnosed patients with chronic phase CML, 405 patients from cancer centers in 29 countries were enrolled.

The participants were randomized to treatment either with asciminib 80 mg once daily (n = 201) or to an investigator-selected TKI (n = 204), determined based on factors including patient age, preference, and overall health.

In the latter group, 102 patients were receiving imatinib and an equal number receive a stronger, second-generation TKI.

Overall, the patients had a median age of 52 and 65% were male. About 54% were White and 44% were Asian. Those receiving second-generation TKIs were more likely to be younger and without additional health concerns, allowing them to tolerate the more potent drugs.

The median follow-up was 16.3 months in the asciminib group and 15.7 months in the other TKIs group.

For the primary outcome, a major molecular response occurred at week 48 among 67.7% of patients in the asciminib group, compared with 49% in the combined TKI arm of imatinib and second-generation TKI groups (P < .001).

In a subanalysis of patients who were randomized to receive imatinib, a major molecular response occurred at week 48 in 69.3% in the asciminib group versus 40.2% of patients in the imatinib arm (P < .001).

The corresponding rates in the comparison of patients on second-generation TKIs were 66.0% and 57.8%, which was not a statistically significant difference.

Furthermore, a deep molecular response, which may lead to remission and discontinuation of treatment, occurred at week 48 in among 38.8% in the asciminib arm compared with the 20.6% in the combined investigator-selected TKI arm.

In the imatinib comparison analysis, the deep molecular response occurred in 42.6% of patients in the asciminib arm versus 17.8% in the imatinib arm, and in the second-generation TKI arm, the deep molecular response occurred in 35% versus 26.5%, respectively.

Importantly, in the TKI-treated group, significantly more patients in the asciminib group — 86%, remained on therapy at the data cut-off, compared with 62% of those receiving imatinib and 75% of those receiving a second generation TKI.

Adverse events of grade 3 or higher that led to discontinuation were lower with asciminib versus imatinib and second-generation TKIs (38% vs 44.4% and 54.9%, respectively), as were events leading to discontinuation (4.5% versus 11.1% and 9.8%, respectively).

The most common adverse events occurring with asciminib were low platelet count (13%) and low neutrophil count (10%). In terms of severe side effects, blood clots, a known severe side effect of TKIs, occurred in only 1% of patients.

In addition, dose adjustments and treatment interruptions were also more significantly less common in the asciminib group.

Overall, the results indicate that “asciminib has the potential to become a therapy of choice for patients with newly diagnosed chronic phase CML,” said first author Timothy P. Hughes, MD, of South Australian Health and Medical Research Institute and University of Adelaide, Australia, in presenting the findings.

Commenting on the study in an interview, Dr. Cortes underscored the importance of molecular responses as indicators of longer-term responses.

“Early responses correlate with better long-term outcomes,” he said. “Most importantly, they are associated with better probabilities of having a deep molecular response, a requirement for considerations of treatment discontinuation,” which is a highly desirable goal for many patients, he noted.

“If we can get more patients to be eligible for treatment discontinuation and to discontinue successfully, this could be a major advance,” Dr. Cortes emphasized.

“Also, for the patients who do have to stay on therapy for the rest of their lives, a treatment option that has fewer adverse events would be very desirable,” he said.

“We need to see that longer follow-up confirms the current trends, but we are very encouraged by what we see so far.”
 

Impressive Results; Financial Toxicity Concerns

In discussing the significance of the findings at the meeting, Pankit Vachhani, MD, assistant professor of medicine at the University of Alabama at Birmingham, said the efficacy and toxicity profiles with asciminib were impressive.

“The nearly 70% major molecular response is one of the highest rates that we have seen in clinical trials at week 48,” he said. “That’s great and maybe we will see deeper responses with time.”

He added that the toxicity profile “was better than imagined — frankly I did not expect that, so that’s a welcome surprise, but we do need longer-term data especially on arterial occlusive events not to mention some other adverse events as well.”

“The question to ask ourselves, though, is whether the use of lower dose first- or second-generation TKIs leads to comparable amounts of toxicities.”

Dr. Vachhani raised the concern of cost: “There is the issue of financial toxicity,” he noted. “At current prices, treatment using asciminib would come to approximately $260,000 per year in terms of the cost to the healthcare system,” he said.

“Meanwhile, imatinib right now, in the US, can be obtained for $500 per year, and additional TKIs are going generic [soon],” he said, noting that survival differences remain unclear.

Further commenting, Eunice Wang, MD, associate professor of medicine at the Roswell Park Cancer Institute in Buffalo, New York, agreed that the results are impressive, saying the trial supports asciminib as “the new standard of care of first line therapy of newly diagnosed CML based on both efficacy.”

Dr. Wang, who moderated the ASCO session, noted the caveat that “given the chronicity of this disease, it is important to continue to follow the patients enrolled on this study for longevity and durability of these efficacy endpoints.”

Nevertheless, “given the lower discontinuation rates versus other TKIs and the fact that, in my opinion, most patients who stop drug will do so in the first 6-12 months if not tolerated, these results are highly promising,” she said.

Dr. Wang also agreed, however, that the rising costs of the TKIs are an important concern.

“All of the BCR-ABL TKIs except imatinib already cost several thousand dollars per month, but there is a trend that newer agents are priced higher than prior,” she said. “This needs to be addressed as $10-$20K per month is not reasonable, and the pharmaceutical companies need to be aware.

“Yes, the data with asciminib is better, but if many patients who respond to imatinib just take longer and there is no difference in overall or disease-free survival long-term, the financial costs are a serious topic of discussion,” Dr. Wang noted.

The study was funded by Novartis. Dr. Cortes disclosed ties with Ascentage Pharma, Bio-Path Holdings, BMS, Novartis, Pfizer, Rigel Pharmeuticals, Sun Pharmaceutical Industries, and Takeda Oncology. Dr. Vachhani and Dr. Wang reported various disclosures.

Asciminib, a first-in-class tyrosine kinase inhibitor (TKI), shows efficacy and significantly improved tolerability compared with standard of care TKIs as a frontline treatment of newly diagnosed chronic myeloid leukemia (CML), primary results from the pivotal ASC4FIRST trial show.

“In the ASC4FIRST trial, asciminib is the first and only agent to demonstrate statistically significant efficacy versus standard-of-care frontline TKIs in newly diagnosed CML patients,” said senior author Jorge E. Cortes, MD, director of the Georgia Cancer Center at Augusta University in Georgia, in presenting the findings at a press briefing for the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

”Asciminib’s strong benefit-risk profile may transform the CML treatment paradigm,” Dr. Cortes said.

The study was published concurrently in The New England Journal of Medicine.

While TKIs have transformed the treatment of CML, improving the 5-year survival rates from 22% in the 1970s to 70% in recent years, nearly half of patients do not achieve a major molecular response within a year, due to either resistance or intolerance, causing the common switching of drugs.

Long-term use is further associated with common side effects, including gastrointestinal and cardiovascular events, due to off-target effects.

Asciminib is a potent and highly specific agent is an allosteric inhibitor targeting ABL myristoyl pocket, which is important in avoiding off-target effects that cause the common side effects.

The drug already has approval from the US Food and Drug Administration (FDA) for the treatment of patients with chronic phase CML who are resistant or intolerant to at least 2 prior TKIs or those with T315I mutation.

For the current pivotal phase 3 ASC4FIRST trial to evaluate the drug as a frontline therapy in recently diagnosed patients with chronic phase CML, 405 patients from cancer centers in 29 countries were enrolled.

The participants were randomized to treatment either with asciminib 80 mg once daily (n = 201) or to an investigator-selected TKI (n = 204), determined based on factors including patient age, preference, and overall health.

In the latter group, 102 patients were receiving imatinib and an equal number receive a stronger, second-generation TKI.

Overall, the patients had a median age of 52 and 65% were male. About 54% were White and 44% were Asian. Those receiving second-generation TKIs were more likely to be younger and without additional health concerns, allowing them to tolerate the more potent drugs.

The median follow-up was 16.3 months in the asciminib group and 15.7 months in the other TKIs group.

For the primary outcome, a major molecular response occurred at week 48 among 67.7% of patients in the asciminib group, compared with 49% in the combined TKI arm of imatinib and second-generation TKI groups (P < .001).

In a subanalysis of patients who were randomized to receive imatinib, a major molecular response occurred at week 48 in 69.3% in the asciminib group versus 40.2% of patients in the imatinib arm (P < .001).

The corresponding rates in the comparison of patients on second-generation TKIs were 66.0% and 57.8%, which was not a statistically significant difference.

Furthermore, a deep molecular response, which may lead to remission and discontinuation of treatment, occurred at week 48 in among 38.8% in the asciminib arm compared with the 20.6% in the combined investigator-selected TKI arm.

In the imatinib comparison analysis, the deep molecular response occurred in 42.6% of patients in the asciminib arm versus 17.8% in the imatinib arm, and in the second-generation TKI arm, the deep molecular response occurred in 35% versus 26.5%, respectively.

Importantly, in the TKI-treated group, significantly more patients in the asciminib group — 86%, remained on therapy at the data cut-off, compared with 62% of those receiving imatinib and 75% of those receiving a second generation TKI.

Adverse events of grade 3 or higher that led to discontinuation were lower with asciminib versus imatinib and second-generation TKIs (38% vs 44.4% and 54.9%, respectively), as were events leading to discontinuation (4.5% versus 11.1% and 9.8%, respectively).

The most common adverse events occurring with asciminib were low platelet count (13%) and low neutrophil count (10%). In terms of severe side effects, blood clots, a known severe side effect of TKIs, occurred in only 1% of patients.

In addition, dose adjustments and treatment interruptions were also more significantly less common in the asciminib group.

Overall, the results indicate that “asciminib has the potential to become a therapy of choice for patients with newly diagnosed chronic phase CML,” said first author Timothy P. Hughes, MD, of South Australian Health and Medical Research Institute and University of Adelaide, Australia, in presenting the findings.

Commenting on the study in an interview, Dr. Cortes underscored the importance of molecular responses as indicators of longer-term responses.

“Early responses correlate with better long-term outcomes,” he said. “Most importantly, they are associated with better probabilities of having a deep molecular response, a requirement for considerations of treatment discontinuation,” which is a highly desirable goal for many patients, he noted.

“If we can get more patients to be eligible for treatment discontinuation and to discontinue successfully, this could be a major advance,” Dr. Cortes emphasized.

“Also, for the patients who do have to stay on therapy for the rest of their lives, a treatment option that has fewer adverse events would be very desirable,” he said.

“We need to see that longer follow-up confirms the current trends, but we are very encouraged by what we see so far.”
 

Impressive Results; Financial Toxicity Concerns

In discussing the significance of the findings at the meeting, Pankit Vachhani, MD, assistant professor of medicine at the University of Alabama at Birmingham, said the efficacy and toxicity profiles with asciminib were impressive.

“The nearly 70% major molecular response is one of the highest rates that we have seen in clinical trials at week 48,” he said. “That’s great and maybe we will see deeper responses with time.”

He added that the toxicity profile “was better than imagined — frankly I did not expect that, so that’s a welcome surprise, but we do need longer-term data especially on arterial occlusive events not to mention some other adverse events as well.”

“The question to ask ourselves, though, is whether the use of lower dose first- or second-generation TKIs leads to comparable amounts of toxicities.”

Dr. Vachhani raised the concern of cost: “There is the issue of financial toxicity,” he noted. “At current prices, treatment using asciminib would come to approximately $260,000 per year in terms of the cost to the healthcare system,” he said.

“Meanwhile, imatinib right now, in the US, can be obtained for $500 per year, and additional TKIs are going generic [soon],” he said, noting that survival differences remain unclear.

Further commenting, Eunice Wang, MD, associate professor of medicine at the Roswell Park Cancer Institute in Buffalo, New York, agreed that the results are impressive, saying the trial supports asciminib as “the new standard of care of first line therapy of newly diagnosed CML based on both efficacy.”

Dr. Wang, who moderated the ASCO session, noted the caveat that “given the chronicity of this disease, it is important to continue to follow the patients enrolled on this study for longevity and durability of these efficacy endpoints.”

Nevertheless, “given the lower discontinuation rates versus other TKIs and the fact that, in my opinion, most patients who stop drug will do so in the first 6-12 months if not tolerated, these results are highly promising,” she said.

Dr. Wang also agreed, however, that the rising costs of the TKIs are an important concern.

“All of the BCR-ABL TKIs except imatinib already cost several thousand dollars per month, but there is a trend that newer agents are priced higher than prior,” she said. “This needs to be addressed as $10-$20K per month is not reasonable, and the pharmaceutical companies need to be aware.

“Yes, the data with asciminib is better, but if many patients who respond to imatinib just take longer and there is no difference in overall or disease-free survival long-term, the financial costs are a serious topic of discussion,” Dr. Wang noted.

The study was funded by Novartis. Dr. Cortes disclosed ties with Ascentage Pharma, Bio-Path Holdings, BMS, Novartis, Pfizer, Rigel Pharmeuticals, Sun Pharmaceutical Industries, and Takeda Oncology. Dr. Vachhani and Dr. Wang reported various disclosures.

Asciminib, a first-in-class tyrosine kinase inhibitor (TKI), shows efficacy and significantly improved tolerability compared with standard of care TKIs as a frontline treatment of newly diagnosed chronic myeloid leukemia (CML), primary results from the pivotal ASC4FIRST trial show.

“In the ASC4FIRST trial, asciminib is the first and only agent to demonstrate statistically significant efficacy versus standard-of-care frontline TKIs in newly diagnosed CML patients,” said senior author Jorge E. Cortes, MD, director of the Georgia Cancer Center at Augusta University in Georgia, in presenting the findings at a press briefing for the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

”Asciminib’s strong benefit-risk profile may transform the CML treatment paradigm,” Dr. Cortes said.

The study was published concurrently in The New England Journal of Medicine.

While TKIs have transformed the treatment of CML, improving the 5-year survival rates from 22% in the 1970s to 70% in recent years, nearly half of patients do not achieve a major molecular response within a year, due to either resistance or intolerance, causing the common switching of drugs.

Long-term use is further associated with common side effects, including gastrointestinal and cardiovascular events, due to off-target effects.

Asciminib is a potent and highly specific agent is an allosteric inhibitor targeting ABL myristoyl pocket, which is important in avoiding off-target effects that cause the common side effects.

The drug already has approval from the US Food and Drug Administration (FDA) for the treatment of patients with chronic phase CML who are resistant or intolerant to at least 2 prior TKIs or those with T315I mutation.

For the current pivotal phase 3 ASC4FIRST trial to evaluate the drug as a frontline therapy in recently diagnosed patients with chronic phase CML, 405 patients from cancer centers in 29 countries were enrolled.

The participants were randomized to treatment either with asciminib 80 mg once daily (n = 201) or to an investigator-selected TKI (n = 204), determined based on factors including patient age, preference, and overall health.

In the latter group, 102 patients were receiving imatinib and an equal number receive a stronger, second-generation TKI.

Overall, the patients had a median age of 52 and 65% were male. About 54% were White and 44% were Asian. Those receiving second-generation TKIs were more likely to be younger and without additional health concerns, allowing them to tolerate the more potent drugs.

The median follow-up was 16.3 months in the asciminib group and 15.7 months in the other TKIs group.

For the primary outcome, a major molecular response occurred at week 48 among 67.7% of patients in the asciminib group, compared with 49% in the combined TKI arm of imatinib and second-generation TKI groups (P < .001).

In a subanalysis of patients who were randomized to receive imatinib, a major molecular response occurred at week 48 in 69.3% in the asciminib group versus 40.2% of patients in the imatinib arm (P < .001).

The corresponding rates in the comparison of patients on second-generation TKIs were 66.0% and 57.8%, which was not a statistically significant difference.

Furthermore, a deep molecular response, which may lead to remission and discontinuation of treatment, occurred at week 48 in among 38.8% in the asciminib arm compared with the 20.6% in the combined investigator-selected TKI arm.

In the imatinib comparison analysis, the deep molecular response occurred in 42.6% of patients in the asciminib arm versus 17.8% in the imatinib arm, and in the second-generation TKI arm, the deep molecular response occurred in 35% versus 26.5%, respectively.

Importantly, in the TKI-treated group, significantly more patients in the asciminib group — 86%, remained on therapy at the data cut-off, compared with 62% of those receiving imatinib and 75% of those receiving a second generation TKI.

Adverse events of grade 3 or higher that led to discontinuation were lower with asciminib versus imatinib and second-generation TKIs (38% vs 44.4% and 54.9%, respectively), as were events leading to discontinuation (4.5% versus 11.1% and 9.8%, respectively).

The most common adverse events occurring with asciminib were low platelet count (13%) and low neutrophil count (10%). In terms of severe side effects, blood clots, a known severe side effect of TKIs, occurred in only 1% of patients.

In addition, dose adjustments and treatment interruptions were also more significantly less common in the asciminib group.

Overall, the results indicate that “asciminib has the potential to become a therapy of choice for patients with newly diagnosed chronic phase CML,” said first author Timothy P. Hughes, MD, of South Australian Health and Medical Research Institute and University of Adelaide, Australia, in presenting the findings.

Commenting on the study in an interview, Dr. Cortes underscored the importance of molecular responses as indicators of longer-term responses.

“Early responses correlate with better long-term outcomes,” he said. “Most importantly, they are associated with better probabilities of having a deep molecular response, a requirement for considerations of treatment discontinuation,” which is a highly desirable goal for many patients, he noted.

“If we can get more patients to be eligible for treatment discontinuation and to discontinue successfully, this could be a major advance,” Dr. Cortes emphasized.

“Also, for the patients who do have to stay on therapy for the rest of their lives, a treatment option that has fewer adverse events would be very desirable,” he said.

“We need to see that longer follow-up confirms the current trends, but we are very encouraged by what we see so far.”
 

Impressive Results; Financial Toxicity Concerns

In discussing the significance of the findings at the meeting, Pankit Vachhani, MD, assistant professor of medicine at the University of Alabama at Birmingham, said the efficacy and toxicity profiles with asciminib were impressive.

“The nearly 70% major molecular response is one of the highest rates that we have seen in clinical trials at week 48,” he said. “That’s great and maybe we will see deeper responses with time.”

He added that the toxicity profile “was better than imagined — frankly I did not expect that, so that’s a welcome surprise, but we do need longer-term data especially on arterial occlusive events not to mention some other adverse events as well.”

“The question to ask ourselves, though, is whether the use of lower dose first- or second-generation TKIs leads to comparable amounts of toxicities.”

Dr. Vachhani raised the concern of cost: “There is the issue of financial toxicity,” he noted. “At current prices, treatment using asciminib would come to approximately $260,000 per year in terms of the cost to the healthcare system,” he said.

“Meanwhile, imatinib right now, in the US, can be obtained for $500 per year, and additional TKIs are going generic [soon],” he said, noting that survival differences remain unclear.

Further commenting, Eunice Wang, MD, associate professor of medicine at the Roswell Park Cancer Institute in Buffalo, New York, agreed that the results are impressive, saying the trial supports asciminib as “the new standard of care of first line therapy of newly diagnosed CML based on both efficacy.”

Dr. Wang, who moderated the ASCO session, noted the caveat that “given the chronicity of this disease, it is important to continue to follow the patients enrolled on this study for longevity and durability of these efficacy endpoints.”

Nevertheless, “given the lower discontinuation rates versus other TKIs and the fact that, in my opinion, most patients who stop drug will do so in the first 6-12 months if not tolerated, these results are highly promising,” she said.

Dr. Wang also agreed, however, that the rising costs of the TKIs are an important concern.

“All of the BCR-ABL TKIs except imatinib already cost several thousand dollars per month, but there is a trend that newer agents are priced higher than prior,” she said. “This needs to be addressed as $10-$20K per month is not reasonable, and the pharmaceutical companies need to be aware.

“Yes, the data with asciminib is better, but if many patients who respond to imatinib just take longer and there is no difference in overall or disease-free survival long-term, the financial costs are a serious topic of discussion,” Dr. Wang noted.

The study was funded by Novartis. Dr. Cortes disclosed ties with Ascentage Pharma, Bio-Path Holdings, BMS, Novartis, Pfizer, Rigel Pharmeuticals, Sun Pharmaceutical Industries, and Takeda Oncology. Dr. Vachhani and Dr. Wang reported various disclosures.

How does the presence of the JAK2 V617F mutation affect the diagnosis and classification of myeloproliferative neoplasms?

Dr. Richard: The JAK2 V617F mutation is found in > 90% of patients with polycythemia vera (PV). The remaining patients with PV have mutations in a different portion of the JAK2 gene. Since JAK2 mutations are found in virtually all patients with PV, having the mutation helps make the diagnosis, but does not carry prognostic significance. Some studies suggest that the allele burden of the mutated JAK2 V617F could be used to identify aggressive disease, but that finding is not universally accepted across all health care entities or practitioners. Variations in acceptance may be due to factors such as evolution of knowledge based on the latest evidence, clinical practice variability and priorities, availability of testing, and complexity of disease management.

This is not true of the 2 other classical myeloproliferative neoplasms (MPNs) that we see commonly in our clinics: essential thrombocytosis (ET) and myelofibrosis (MF). The CALR mutation can be seen in patients with ET and MF and signals a less aggressive form of the disease.

The presence of JAK2 V617F is critical for prognosis. Although it does not directly help to inform the patient of what to expect, identifying the mutation provides us with important information about the patient’s prognosis, which helps guide treatment decisions such as the intensity of therapy and monitoring for thrombotic events.

What are the potential implications of the JAK2 V617F mutation in the treatment of PV?

Dr. Richard: The discovery of the JAK2 V617F mutation in MPNs in 2005 led to the hope that perhaps there would be targeted therapy that could result in disease remissions. We had all hoped that the spectacular responses observed in patients with chronic myelogenous leukemia (CML) treated with imatinib could be replicated with JAK2 inhibitors. It turned out that blocking JAK2 was insufficient to reverse the disease. Studies are still ongoing whether drugs that can decrease the JAK2 V617F allele burden could be used to achieve a type of remission. Perhaps combination therapies will need to be developed.

I am hopeful that in the future we do see advancements that provide improved diagnosis and monitoring to help facilitate early detection, personalized treatment approaches to offer more effective and well tolerated therapies, risk stratification and prognostication to help identify higher risk progression, combination therapies to possibly improve efficacy and adherence, and novel therapeutic targets to help discover new treatments and provide improved outcomes.

How can JAK2 V617F lead to 3 different forms of myeloproliferative neoplasms?

Dr. Richard: The short answer is no one knows exactly. The phenotypic differences between PV and the other 2 MPN variants are most likely determined by the integration of other signaling pathways that are activated by the corresponding driver mutation, and interactions with other mutations. What also seems to matter is the sequence in which the individual mutations are acquired.

There have been documented cases of post-polycythemic leukemia that no longer have the JAK2 V617F mutation. However, at some point that mutation was lost, and the cells acquired other driver mutations that resulted in leukemia.

What we do know now is that there are several potential interactions that can coexist with JAK2 V617F. There is MPL mutation, which contributes to disease pathogenesis and thrombotic risk. Independent of JAK2 V617F pathways is CALR mutation, which is another driver of MPNs. In addition are other JAK mutations, epigenetic alterations, and microenvironmental factors. All of these have the potential to influence clinical manifestations by impacting clinical outcomes, affecting expression patterns and signaling inflammation within the bone marrow microenvironment.

Are there any ongoing research efforts or clinical trials exploring targeted therapies that specifically address the JAK2 V617F mutation in patients with PV?

Dr. Richard: The ongoing research efforts to address JAK2-targeted therapies are looking at options like novel JAK inhibitors, combination therapies, resistance mechanisms, improved safety profiles, biomarker identification, exploring new indications, and preclinical studies that involve the development and testing of new JAK inhibitors.

Other JAK2-targeted therapies continue to be in development. At this time, we have ruxolitinib, pacritinib, fedratinib, and momelotinib. None of them appear to be a magic bullet the way imatinib was with CML. Perhaps a better disease comparison is chronic lymphocytic leukemia (CLL). In CLL, targeted therapies against Bruton tyrosine kinase and BCL2 are being combined to result in many years of disease control. JAK2 inhibition may need to be combined with another active drug, perhaps against a mutation or pathway that has not yet been identified.

How does the presence of the JAK2 V617F mutation affect the diagnosis and classification of myeloproliferative neoplasms?

Dr. Richard: The JAK2 V617F mutation is found in > 90% of patients with polycythemia vera (PV). The remaining patients with PV have mutations in a different portion of the JAK2 gene. Since JAK2 mutations are found in virtually all patients with PV, having the mutation helps make the diagnosis, but does not carry prognostic significance. Some studies suggest that the allele burden of the mutated JAK2 V617F could be used to identify aggressive disease, but that finding is not universally accepted across all health care entities or practitioners. Variations in acceptance may be due to factors such as evolution of knowledge based on the latest evidence, clinical practice variability and priorities, availability of testing, and complexity of disease management.

This is not true of the 2 other classical myeloproliferative neoplasms (MPNs) that we see commonly in our clinics: essential thrombocytosis (ET) and myelofibrosis (MF). The CALR mutation can be seen in patients with ET and MF and signals a less aggressive form of the disease.

The presence of JAK2 V617F is critical for prognosis. Although it does not directly help to inform the patient of what to expect, identifying the mutation provides us with important information about the patient’s prognosis, which helps guide treatment decisions such as the intensity of therapy and monitoring for thrombotic events.

What are the potential implications of the JAK2 V617F mutation in the treatment of PV?

Dr. Richard: The discovery of the JAK2 V617F mutation in MPNs in 2005 led to the hope that perhaps there would be targeted therapy that could result in disease remissions. We had all hoped that the spectacular responses observed in patients with chronic myelogenous leukemia (CML) treated with imatinib could be replicated with JAK2 inhibitors. It turned out that blocking JAK2 was insufficient to reverse the disease. Studies are still ongoing whether drugs that can decrease the JAK2 V617F allele burden could be used to achieve a type of remission. Perhaps combination therapies will need to be developed.

I am hopeful that in the future we do see advancements that provide improved diagnosis and monitoring to help facilitate early detection, personalized treatment approaches to offer more effective and well tolerated therapies, risk stratification and prognostication to help identify higher risk progression, combination therapies to possibly improve efficacy and adherence, and novel therapeutic targets to help discover new treatments and provide improved outcomes.

How can JAK2 V617F lead to 3 different forms of myeloproliferative neoplasms?

Dr. Richard: The short answer is no one knows exactly. The phenotypic differences between PV and the other 2 MPN variants are most likely determined by the integration of other signaling pathways that are activated by the corresponding driver mutation, and interactions with other mutations. What also seems to matter is the sequence in which the individual mutations are acquired.

There have been documented cases of post-polycythemic leukemia that no longer have the JAK2 V617F mutation. However, at some point that mutation was lost, and the cells acquired other driver mutations that resulted in leukemia.

What we do know now is that there are several potential interactions that can coexist with JAK2 V617F. There is MPL mutation, which contributes to disease pathogenesis and thrombotic risk. Independent of JAK2 V617F pathways is CALR mutation, which is another driver of MPNs. In addition are other JAK mutations, epigenetic alterations, and microenvironmental factors. All of these have the potential to influence clinical manifestations by impacting clinical outcomes, affecting expression patterns and signaling inflammation within the bone marrow microenvironment.

Are there any ongoing research efforts or clinical trials exploring targeted therapies that specifically address the JAK2 V617F mutation in patients with PV?

Dr. Richard: The ongoing research efforts to address JAK2-targeted therapies are looking at options like novel JAK inhibitors, combination therapies, resistance mechanisms, improved safety profiles, biomarker identification, exploring new indications, and preclinical studies that involve the development and testing of new JAK inhibitors.

Other JAK2-targeted therapies continue to be in development. At this time, we have ruxolitinib, pacritinib, fedratinib, and momelotinib. None of them appear to be a magic bullet the way imatinib was with CML. Perhaps a better disease comparison is chronic lymphocytic leukemia (CLL). In CLL, targeted therapies against Bruton tyrosine kinase and BCL2 are being combined to result in many years of disease control. JAK2 inhibition may need to be combined with another active drug, perhaps against a mutation or pathway that has not yet been identified.

How does the presence of the JAK2 V617F mutation affect the diagnosis and classification of myeloproliferative neoplasms?

Dr. Richard: The JAK2 V617F mutation is found in > 90% of patients with polycythemia vera (PV). The remaining patients with PV have mutations in a different portion of the JAK2 gene. Since JAK2 mutations are found in virtually all patients with PV, having the mutation helps make the diagnosis, but does not carry prognostic significance. Some studies suggest that the allele burden of the mutated JAK2 V617F could be used to identify aggressive disease, but that finding is not universally accepted across all health care entities or practitioners. Variations in acceptance may be due to factors such as evolution of knowledge based on the latest evidence, clinical practice variability and priorities, availability of testing, and complexity of disease management.

This is not true of the 2 other classical myeloproliferative neoplasms (MPNs) that we see commonly in our clinics: essential thrombocytosis (ET) and myelofibrosis (MF). The CALR mutation can be seen in patients with ET and MF and signals a less aggressive form of the disease.

The presence of JAK2 V617F is critical for prognosis. Although it does not directly help to inform the patient of what to expect, identifying the mutation provides us with important information about the patient’s prognosis, which helps guide treatment decisions such as the intensity of therapy and monitoring for thrombotic events.

What are the potential implications of the JAK2 V617F mutation in the treatment of PV?

Dr. Richard: The discovery of the JAK2 V617F mutation in MPNs in 2005 led to the hope that perhaps there would be targeted therapy that could result in disease remissions. We had all hoped that the spectacular responses observed in patients with chronic myelogenous leukemia (CML) treated with imatinib could be replicated with JAK2 inhibitors. It turned out that blocking JAK2 was insufficient to reverse the disease. Studies are still ongoing whether drugs that can decrease the JAK2 V617F allele burden could be used to achieve a type of remission. Perhaps combination therapies will need to be developed.

I am hopeful that in the future we do see advancements that provide improved diagnosis and monitoring to help facilitate early detection, personalized treatment approaches to offer more effective and well tolerated therapies, risk stratification and prognostication to help identify higher risk progression, combination therapies to possibly improve efficacy and adherence, and novel therapeutic targets to help discover new treatments and provide improved outcomes.

How can JAK2 V617F lead to 3 different forms of myeloproliferative neoplasms?

Dr. Richard: The short answer is no one knows exactly. The phenotypic differences between PV and the other 2 MPN variants are most likely determined by the integration of other signaling pathways that are activated by the corresponding driver mutation, and interactions with other mutations. What also seems to matter is the sequence in which the individual mutations are acquired.

There have been documented cases of post-polycythemic leukemia that no longer have the JAK2 V617F mutation. However, at some point that mutation was lost, and the cells acquired other driver mutations that resulted in leukemia.

What we do know now is that there are several potential interactions that can coexist with JAK2 V617F. There is MPL mutation, which contributes to disease pathogenesis and thrombotic risk. Independent of JAK2 V617F pathways is CALR mutation, which is another driver of MPNs. In addition are other JAK mutations, epigenetic alterations, and microenvironmental factors. All of these have the potential to influence clinical manifestations by impacting clinical outcomes, affecting expression patterns and signaling inflammation within the bone marrow microenvironment.

Are there any ongoing research efforts or clinical trials exploring targeted therapies that specifically address the JAK2 V617F mutation in patients with PV?

Dr. Richard: The ongoing research efforts to address JAK2-targeted therapies are looking at options like novel JAK inhibitors, combination therapies, resistance mechanisms, improved safety profiles, biomarker identification, exploring new indications, and preclinical studies that involve the development and testing of new JAK inhibitors.

Other JAK2-targeted therapies continue to be in development. At this time, we have ruxolitinib, pacritinib, fedratinib, and momelotinib. None of them appear to be a magic bullet the way imatinib was with CML. Perhaps a better disease comparison is chronic lymphocytic leukemia (CLL). In CLL, targeted therapies against Bruton tyrosine kinase and BCL2 are being combined to result in many years of disease control. JAK2 inhibition may need to be combined with another active drug, perhaps against a mutation or pathway that has not yet been identified.

This transcript has been edited for clarity.

Jorge Plutzky, MD: Hi. I'm Dr Jorge Plutzky, director of preventive cardiology at the Brigham and Women's Hospital, and in that setting I direct our lipid clinic. I'm pleased to be here today to talk about how we communicate about cholesterol. And I'm pleased to be able to do that today with a patient of mine, Brian McMahon.

Brian, thank you for being here. 

Brian McMahon: Thank you, Doctor. 

Plutzky: Why don't you tell people listening how we came to connect in the first place. 

McMahon: Well, it was around statins. I had been prescribed one probably 10 years ago, and I had an adverse reaction to it — a violent reaction. And the doctor just told me to stop taking it. So I did. And I never asked another question.

And then 10 years later, my GP in Connecticut said, "You should go get a calcium score exam. Insurance doesn't cover it. It's 90 bucks, and it'll be the best 90 bucks you ever spent." And then the numbers were not good. That led me to come and talk to you about what do I do now? What are my options? I had an adverse reaction to statins. I didn't think I could even take them. 

Plutzky: That's so important. Really, the failure was in your physician not getting that initial follow-up: Okay, so you had this reaction; what are the potential explanations for that, and what could be the next steps?

It really should not fall upon you as a patient to have to push that. But in fact, when people are better educated about the issues in our system, sometimes you do have to be your own advocate and ask, "What's next?" And it's important for us in communicating these issues during that first encounter, which might be with a primary care physician or a cardiologist, but more often it's with a primary care physician.

We're more motivated when someone's already had an event — secondary prevention. Let's not have another one because the patient has now been through something scary: a heart attack or a stent or even bypass surgery or a stroke. Those really motivate people. But even in that setting, we often find that patients don't necessarily stay on treatment or don't necessarily get treated aggressively enough to the right LDL level.

So that becomes important to set the stage early about why we are doing this, and let's come up with options that are safe, usually well tolerated, and have been extensively studied. 

McMahon: I think the key is that it is a silent killer, so you don't feel bad, you don't have a rash, you don't have a scratch. It's not painful, but it could kill you. But the very fact that it's just that the statin doesn't agree with you — that was a real mess, in my estimation. 

Plutzky: Often in settings of primary prevention, you're trying to conjure up the future for someone, saying, "You know what? If we don't do something, we're going to run into issues." But those patients don't feel bad. You're right that it is silent, but that's where the huge opportunity exists: early intervention — identifying what that risk is and how many different options we have, like if someone doesn't succeed on or has an issue with a statin. We know that's uncommon, but people often do well with some of these other alternatives, including just a different statin, which was the case with you. 

McMahon: Right. And I had no idea that that was even available to me. That was an eye-opener, that there are options available to me, that I can find different things that work; but for goodness' sake, you should be on it. 

Plutzky: Yes, we often have patients do well on a statin. Some patients really can't take a statin.

We'll go through a couple different options. I often will lay out for people who think they're having an issue with the statin that there are three possibilities: One, it's not the statin, because in the clinical trials we see people who quit the placebo as often as they quit the statin. Sharing that with patients matters. It's possible that what one felt wasn't even related to the statin. Two, sometimes reactions are statin specific. We try a different statin and then someone does well. Sometimes that may be influenced by the fact that we've laid out the data and explained to a patient, "We know that statins are safe, effective, and well tolerated, and here's the benefit for you down the road."

Is that part of why that second statin now works? It's hard to know. I've had many physician patients who say, "I didn't feel great on that one, but now I'm on a different statin and I'm feeling, much better." So, everyone reacts differently.

McMahon: I love that you walked me into it too. It wasn't just, "Here's 20 mg. We started at 5 mg, then we went to 10 mg, now we're at 20 mg." You took the time to say, "I hear you and I heard what happened to you. So, let's walk into this." I lost 10 years of taking statins, which would have put me in a different place.

Plutzky: The fact is that the first dose of the statin has the biggest impact on reducing your LDL. And then as you titrate it up, which we do all the time — we have with you — the effect on the lowering of LDL is less impactful. That's why it can be a way in with people to say, "Let's start with this low dose." At least they're on something. And people often say, "Wow! I really feel completely fine on this." There are people who either just can't take a statin at all or who, once they're on the statin, aren't getting to a low enough or appropriate LDL number, and it's good to have those alternatives.

One of them is specifically theoretically designed for people who think they've had muscle issues with statin. Your issues were different, but bempedoic acid is an alternative. And even going beyond that, we now have injectable medicines that really are very effective at bringing down LDL.

When people hear injections, they're like, "Oh my gosh, I don't want to take an injection," but explain to people how easy it is to do those injections. It's basically just a pen against your skin. That really reduces their fear and their anxiety. But it's important to realize that we do have many tools for lowering LDL. If someone runs into a problem with the statin that you can't overcome, then it's important to move on. 

So we should recognize how important it is to lower LDL. Realizing how many tools we have allows people to begin working through the process where the objective is: I want to get my LDL down, and if we can do it with a statin, then we're taking advantage of all this data we have about their benefits. But if that turns out not to work for a given patient, even after trying and explaining things, then let's move on. But let's get to that ultimate goal of lowering LDL as one component of risk. 

I think there's nothing more empowering for the person you're dealing with than to share with them what it is that you know; that you know, based upon medical science and clinical trials, what that rationale is, because no one is trying to hurt themselves. If someone comes in who doesn't want to take a statin, it's not because they're trying to have a heart attack. They're not trying to hurt themselves. There's some barrier to what's motivating them, to what's keeping them from this therapy. We just have to better communicate what the goal is and what the basis is for pursuing this, and then finding your way through the woods of saying, "Well, that worked great and we've made it" vs "We've run into something, so let's go on a different path." 

McMahon: I think that to me was the light-bulb moment, which was that experience with statin: Don't take it anymore. And then 10 years go by and now I'm in trouble. And then I find out that there is a wealth of opportunities. There are so many arrows in your quiver — not to make a Cupid joke, but there are so many arrows available to fix this, and I didn't know it. Now I do.

Plutzky: Yes, it's empowering. I think there's a challenge for us as caregivers to more broadly share what we know so that people are motivated and empowered to say, "I want to get treated. I want to do better. And I understand the extent to which this is a risk for me if I don't do better."

McMahon: Right.

Plutzky: So often there's a family history associated with that, too. Sometimes when I'm communicating with patients the idea of "You need to do this," especially patients with young kids, I'm communicating, "How you eat and your activity level is sending a very powerful message to your kids."

McMahon: Yes. 

Plutzky: We're trying to eat healthy. We're more oriented toward vegetables. We're being active. Let's go for a walk. Let's go for a family run. Let's have a sport that we do together. Or even just the kids seeing you leave the house to say, "I'm off." "Where are you going, Dad?" "I'm going to play tennis." "Can I come with you?" And then…

McMahon: It creates a lifestyle.

Plutzky: Yes. 

McMahon: Well, it comes back to: You have one heart. 

Plutzky: Yes. Well, it's been a pleasure to have a chance to discuss what are really important topics. I mean, this is really impactful. Far beyond just your experience, it's the chance for other people to realize that these are issues that need to be recognized, dealt with; that people need to be empowered; and that ultimately it comes down to us about how to better communicate.

I'm always very focused on how can a patient know what I know and what I think matters based upon evidence, data, clinical trials. How do we share that and share that in very limited time windows? It's been a privilege to work with you, Brian, in a clinical setting, and I'm very appreciative of your taking the time to join us today.

McMahon: Thank you for getting me on the right path. I'm grateful. 

Plutzky: Well, you've done that for yourself. Good talking to you. 

McMahon: Likewise.

Jorge Plutzky, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: Altimmune; Boehringer Ingelheim; Esperion; New Amsterdam; Novo Nordisk

Received research grant from: Boehringer Ingelheim; Novartis

Serve(d) on clinical trial committee for: Esperion; Novo Nordisk

Brian McMahon has disclosed no relevant financial relationships.

This transcript has been edited for clarity.

Jorge Plutzky, MD: Hi. I'm Dr Jorge Plutzky, director of preventive cardiology at the Brigham and Women's Hospital, and in that setting I direct our lipid clinic. I'm pleased to be here today to talk about how we communicate about cholesterol. And I'm pleased to be able to do that today with a patient of mine, Brian McMahon.

Brian, thank you for being here. 

Brian McMahon: Thank you, Doctor. 

Plutzky: Why don't you tell people listening how we came to connect in the first place. 

McMahon: Well, it was around statins. I had been prescribed one probably 10 years ago, and I had an adverse reaction to it — a violent reaction. And the doctor just told me to stop taking it. So I did. And I never asked another question.

And then 10 years later, my GP in Connecticut said, "You should go get a calcium score exam. Insurance doesn't cover it. It's 90 bucks, and it'll be the best 90 bucks you ever spent." And then the numbers were not good. That led me to come and talk to you about what do I do now? What are my options? I had an adverse reaction to statins. I didn't think I could even take them. 

Plutzky: That's so important. Really, the failure was in your physician not getting that initial follow-up: Okay, so you had this reaction; what are the potential explanations for that, and what could be the next steps?

It really should not fall upon you as a patient to have to push that. But in fact, when people are better educated about the issues in our system, sometimes you do have to be your own advocate and ask, "What's next?" And it's important for us in communicating these issues during that first encounter, which might be with a primary care physician or a cardiologist, but more often it's with a primary care physician.

We're more motivated when someone's already had an event — secondary prevention. Let's not have another one because the patient has now been through something scary: a heart attack or a stent or even bypass surgery or a stroke. Those really motivate people. But even in that setting, we often find that patients don't necessarily stay on treatment or don't necessarily get treated aggressively enough to the right LDL level.

So that becomes important to set the stage early about why we are doing this, and let's come up with options that are safe, usually well tolerated, and have been extensively studied. 

McMahon: I think the key is that it is a silent killer, so you don't feel bad, you don't have a rash, you don't have a scratch. It's not painful, but it could kill you. But the very fact that it's just that the statin doesn't agree with you — that was a real mess, in my estimation. 

Plutzky: Often in settings of primary prevention, you're trying to conjure up the future for someone, saying, "You know what? If we don't do something, we're going to run into issues." But those patients don't feel bad. You're right that it is silent, but that's where the huge opportunity exists: early intervention — identifying what that risk is and how many different options we have, like if someone doesn't succeed on or has an issue with a statin. We know that's uncommon, but people often do well with some of these other alternatives, including just a different statin, which was the case with you. 

McMahon: Right. And I had no idea that that was even available to me. That was an eye-opener, that there are options available to me, that I can find different things that work; but for goodness' sake, you should be on it. 

Plutzky: Yes, we often have patients do well on a statin. Some patients really can't take a statin.

We'll go through a couple different options. I often will lay out for people who think they're having an issue with the statin that there are three possibilities: One, it's not the statin, because in the clinical trials we see people who quit the placebo as often as they quit the statin. Sharing that with patients matters. It's possible that what one felt wasn't even related to the statin. Two, sometimes reactions are statin specific. We try a different statin and then someone does well. Sometimes that may be influenced by the fact that we've laid out the data and explained to a patient, "We know that statins are safe, effective, and well tolerated, and here's the benefit for you down the road."

Is that part of why that second statin now works? It's hard to know. I've had many physician patients who say, "I didn't feel great on that one, but now I'm on a different statin and I'm feeling, much better." So, everyone reacts differently.

McMahon: I love that you walked me into it too. It wasn't just, "Here's 20 mg. We started at 5 mg, then we went to 10 mg, now we're at 20 mg." You took the time to say, "I hear you and I heard what happened to you. So, let's walk into this." I lost 10 years of taking statins, which would have put me in a different place.

Plutzky: The fact is that the first dose of the statin has the biggest impact on reducing your LDL. And then as you titrate it up, which we do all the time — we have with you — the effect on the lowering of LDL is less impactful. That's why it can be a way in with people to say, "Let's start with this low dose." At least they're on something. And people often say, "Wow! I really feel completely fine on this." There are people who either just can't take a statin at all or who, once they're on the statin, aren't getting to a low enough or appropriate LDL number, and it's good to have those alternatives.

One of them is specifically theoretically designed for people who think they've had muscle issues with statin. Your issues were different, but bempedoic acid is an alternative. And even going beyond that, we now have injectable medicines that really are very effective at bringing down LDL.

When people hear injections, they're like, "Oh my gosh, I don't want to take an injection," but explain to people how easy it is to do those injections. It's basically just a pen against your skin. That really reduces their fear and their anxiety. But it's important to realize that we do have many tools for lowering LDL. If someone runs into a problem with the statin that you can't overcome, then it's important to move on. 

So we should recognize how important it is to lower LDL. Realizing how many tools we have allows people to begin working through the process where the objective is: I want to get my LDL down, and if we can do it with a statin, then we're taking advantage of all this data we have about their benefits. But if that turns out not to work for a given patient, even after trying and explaining things, then let's move on. But let's get to that ultimate goal of lowering LDL as one component of risk. 

I think there's nothing more empowering for the person you're dealing with than to share with them what it is that you know; that you know, based upon medical science and clinical trials, what that rationale is, because no one is trying to hurt themselves. If someone comes in who doesn't want to take a statin, it's not because they're trying to have a heart attack. They're not trying to hurt themselves. There's some barrier to what's motivating them, to what's keeping them from this therapy. We just have to better communicate what the goal is and what the basis is for pursuing this, and then finding your way through the woods of saying, "Well, that worked great and we've made it" vs "We've run into something, so let's go on a different path." 

McMahon: I think that to me was the light-bulb moment, which was that experience with statin: Don't take it anymore. And then 10 years go by and now I'm in trouble. And then I find out that there is a wealth of opportunities. There are so many arrows in your quiver — not to make a Cupid joke, but there are so many arrows available to fix this, and I didn't know it. Now I do.

Plutzky: Yes, it's empowering. I think there's a challenge for us as caregivers to more broadly share what we know so that people are motivated and empowered to say, "I want to get treated. I want to do better. And I understand the extent to which this is a risk for me if I don't do better."

McMahon: Right.

Plutzky: So often there's a family history associated with that, too. Sometimes when I'm communicating with patients the idea of "You need to do this," especially patients with young kids, I'm communicating, "How you eat and your activity level is sending a very powerful message to your kids."

McMahon: Yes. 

Plutzky: We're trying to eat healthy. We're more oriented toward vegetables. We're being active. Let's go for a walk. Let's go for a family run. Let's have a sport that we do together. Or even just the kids seeing you leave the house to say, "I'm off." "Where are you going, Dad?" "I'm going to play tennis." "Can I come with you?" And then…

McMahon: It creates a lifestyle.

Plutzky: Yes. 

McMahon: Well, it comes back to: You have one heart. 

Plutzky: Yes. Well, it's been a pleasure to have a chance to discuss what are really important topics. I mean, this is really impactful. Far beyond just your experience, it's the chance for other people to realize that these are issues that need to be recognized, dealt with; that people need to be empowered; and that ultimately it comes down to us about how to better communicate.

I'm always very focused on how can a patient know what I know and what I think matters based upon evidence, data, clinical trials. How do we share that and share that in very limited time windows? It's been a privilege to work with you, Brian, in a clinical setting, and I'm very appreciative of your taking the time to join us today.

McMahon: Thank you for getting me on the right path. I'm grateful. 

Plutzky: Well, you've done that for yourself. Good talking to you. 

McMahon: Likewise.

Jorge Plutzky, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: Altimmune; Boehringer Ingelheim; Esperion; New Amsterdam; Novo Nordisk

Received research grant from: Boehringer Ingelheim; Novartis

Serve(d) on clinical trial committee for: Esperion; Novo Nordisk

Brian McMahon has disclosed no relevant financial relationships.

This transcript has been edited for clarity.

Jorge Plutzky, MD: Hi. I'm Dr Jorge Plutzky, director of preventive cardiology at the Brigham and Women's Hospital, and in that setting I direct our lipid clinic. I'm pleased to be here today to talk about how we communicate about cholesterol. And I'm pleased to be able to do that today with a patient of mine, Brian McMahon.

Brian, thank you for being here. 

Brian McMahon: Thank you, Doctor. 

Plutzky: Why don't you tell people listening how we came to connect in the first place. 

McMahon: Well, it was around statins. I had been prescribed one probably 10 years ago, and I had an adverse reaction to it — a violent reaction. And the doctor just told me to stop taking it. So I did. And I never asked another question.

And then 10 years later, my GP in Connecticut said, "You should go get a calcium score exam. Insurance doesn't cover it. It's 90 bucks, and it'll be the best 90 bucks you ever spent." And then the numbers were not good. That led me to come and talk to you about what do I do now? What are my options? I had an adverse reaction to statins. I didn't think I could even take them. 

Plutzky: That's so important. Really, the failure was in your physician not getting that initial follow-up: Okay, so you had this reaction; what are the potential explanations for that, and what could be the next steps?

It really should not fall upon you as a patient to have to push that. But in fact, when people are better educated about the issues in our system, sometimes you do have to be your own advocate and ask, "What's next?" And it's important for us in communicating these issues during that first encounter, which might be with a primary care physician or a cardiologist, but more often it's with a primary care physician.

We're more motivated when someone's already had an event — secondary prevention. Let's not have another one because the patient has now been through something scary: a heart attack or a stent or even bypass surgery or a stroke. Those really motivate people. But even in that setting, we often find that patients don't necessarily stay on treatment or don't necessarily get treated aggressively enough to the right LDL level.

So that becomes important to set the stage early about why we are doing this, and let's come up with options that are safe, usually well tolerated, and have been extensively studied. 

McMahon: I think the key is that it is a silent killer, so you don't feel bad, you don't have a rash, you don't have a scratch. It's not painful, but it could kill you. But the very fact that it's just that the statin doesn't agree with you — that was a real mess, in my estimation. 

Plutzky: Often in settings of primary prevention, you're trying to conjure up the future for someone, saying, "You know what? If we don't do something, we're going to run into issues." But those patients don't feel bad. You're right that it is silent, but that's where the huge opportunity exists: early intervention — identifying what that risk is and how many different options we have, like if someone doesn't succeed on or has an issue with a statin. We know that's uncommon, but people often do well with some of these other alternatives, including just a different statin, which was the case with you. 

McMahon: Right. And I had no idea that that was even available to me. That was an eye-opener, that there are options available to me, that I can find different things that work; but for goodness' sake, you should be on it. 

Plutzky: Yes, we often have patients do well on a statin. Some patients really can't take a statin.

We'll go through a couple different options. I often will lay out for people who think they're having an issue with the statin that there are three possibilities: One, it's not the statin, because in the clinical trials we see people who quit the placebo as often as they quit the statin. Sharing that with patients matters. It's possible that what one felt wasn't even related to the statin. Two, sometimes reactions are statin specific. We try a different statin and then someone does well. Sometimes that may be influenced by the fact that we've laid out the data and explained to a patient, "We know that statins are safe, effective, and well tolerated, and here's the benefit for you down the road."

Is that part of why that second statin now works? It's hard to know. I've had many physician patients who say, "I didn't feel great on that one, but now I'm on a different statin and I'm feeling, much better." So, everyone reacts differently.

McMahon: I love that you walked me into it too. It wasn't just, "Here's 20 mg. We started at 5 mg, then we went to 10 mg, now we're at 20 mg." You took the time to say, "I hear you and I heard what happened to you. So, let's walk into this." I lost 10 years of taking statins, which would have put me in a different place.

Plutzky: The fact is that the first dose of the statin has the biggest impact on reducing your LDL. And then as you titrate it up, which we do all the time — we have with you — the effect on the lowering of LDL is less impactful. That's why it can be a way in with people to say, "Let's start with this low dose." At least they're on something. And people often say, "Wow! I really feel completely fine on this." There are people who either just can't take a statin at all or who, once they're on the statin, aren't getting to a low enough or appropriate LDL number, and it's good to have those alternatives.

One of them is specifically theoretically designed for people who think they've had muscle issues with statin. Your issues were different, but bempedoic acid is an alternative. And even going beyond that, we now have injectable medicines that really are very effective at bringing down LDL.

When people hear injections, they're like, "Oh my gosh, I don't want to take an injection," but explain to people how easy it is to do those injections. It's basically just a pen against your skin. That really reduces their fear and their anxiety. But it's important to realize that we do have many tools for lowering LDL. If someone runs into a problem with the statin that you can't overcome, then it's important to move on. 

So we should recognize how important it is to lower LDL. Realizing how many tools we have allows people to begin working through the process where the objective is: I want to get my LDL down, and if we can do it with a statin, then we're taking advantage of all this data we have about their benefits. But if that turns out not to work for a given patient, even after trying and explaining things, then let's move on. But let's get to that ultimate goal of lowering LDL as one component of risk. 

I think there's nothing more empowering for the person you're dealing with than to share with them what it is that you know; that you know, based upon medical science and clinical trials, what that rationale is, because no one is trying to hurt themselves. If someone comes in who doesn't want to take a statin, it's not because they're trying to have a heart attack. They're not trying to hurt themselves. There's some barrier to what's motivating them, to what's keeping them from this therapy. We just have to better communicate what the goal is and what the basis is for pursuing this, and then finding your way through the woods of saying, "Well, that worked great and we've made it" vs "We've run into something, so let's go on a different path." 

McMahon: I think that to me was the light-bulb moment, which was that experience with statin: Don't take it anymore. And then 10 years go by and now I'm in trouble. And then I find out that there is a wealth of opportunities. There are so many arrows in your quiver — not to make a Cupid joke, but there are so many arrows available to fix this, and I didn't know it. Now I do.

Plutzky: Yes, it's empowering. I think there's a challenge for us as caregivers to more broadly share what we know so that people are motivated and empowered to say, "I want to get treated. I want to do better. And I understand the extent to which this is a risk for me if I don't do better."

McMahon: Right.

Plutzky: So often there's a family history associated with that, too. Sometimes when I'm communicating with patients the idea of "You need to do this," especially patients with young kids, I'm communicating, "How you eat and your activity level is sending a very powerful message to your kids."

McMahon: Yes. 

Plutzky: We're trying to eat healthy. We're more oriented toward vegetables. We're being active. Let's go for a walk. Let's go for a family run. Let's have a sport that we do together. Or even just the kids seeing you leave the house to say, "I'm off." "Where are you going, Dad?" "I'm going to play tennis." "Can I come with you?" And then…

McMahon: It creates a lifestyle.

Plutzky: Yes. 

McMahon: Well, it comes back to: You have one heart. 

Plutzky: Yes. Well, it's been a pleasure to have a chance to discuss what are really important topics. I mean, this is really impactful. Far beyond just your experience, it's the chance for other people to realize that these are issues that need to be recognized, dealt with; that people need to be empowered; and that ultimately it comes down to us about how to better communicate.

I'm always very focused on how can a patient know what I know and what I think matters based upon evidence, data, clinical trials. How do we share that and share that in very limited time windows? It's been a privilege to work with you, Brian, in a clinical setting, and I'm very appreciative of your taking the time to join us today.

McMahon: Thank you for getting me on the right path. I'm grateful. 

Plutzky: Well, you've done that for yourself. Good talking to you. 

McMahon: Likewise.

Jorge Plutzky, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: Altimmune; Boehringer Ingelheim; Esperion; New Amsterdam; Novo Nordisk

Received research grant from: Boehringer Ingelheim; Novartis

Serve(d) on clinical trial committee for: Esperion; Novo Nordisk

Brian McMahon has disclosed no relevant financial relationships.

BERLIN — What is the best way to help patients with diabetes, heart problems, and obesity lose weight and improve their outcomes? Is it exercise or medication (such as glucagon-like peptide 1 or gastric inhibitory polypeptide receptor agonists)? This was the focus of a “Battle of Experts” at the 2024 Diabetes Congress in Berlin.

Benefits of Exercise

“Exercise is ‘omnipotent,’ ” said Christine Joisten, MD, general, sports, and nutrition physician at the Sports University in Cologne, Germany. She pointed out that exercise not only helps with weight loss but also improves overall fitness, body composition, eating habits, cardiometabolic health, and quality of life, listing the benefits of exercise.

In a conversation with this news organization, Stephan Kress, MD, a diabetologist at Vinzentius Hospital in Landau, Germany, and first chair of the German Diabetes Society’s Diabetes, Sports, and Exercise Working Group, referred to a study by Pedersen et al. that examined the effect of exercise on 26 conditions. It indicated that exercise had moderate to strong positive effects on disease progression. The benefits of exercise extended beyond metabolic, cardiological, pneumological, and musculoskeletal diseases to neurological and psychiatric conditions.

The so-called myokines, which are “good” cytokines released by muscles, could play a role in this process, according to a presentation by study author Bente Klarlund Pedersen, MD, of Rigshospitalet in Copenhagen, Denmark.

For example, exercise could elevate mood in patients with depression and reduce inflammation in individuals with chronic inflammatory diseases, said Dr. Kress. Many patients, including those with diabetes, could benefit from physical activity even if their A1c levels do not decrease as desired.
 

Exercise As a Snack

Fat loss can be achieved with prolonged activity or with “short and intense” sessions if followed by refraining from eating immediately afterward, Dr. Joisten explained during the expert battle at the Diabetes Congress.

Different recommendations exist regarding how much exercise is necessary. According to the World Health Organization’s (WHO) recommendation, “Every step counts.” “As sports physicians, we consider physical activity to be any form of energy expenditure achieved through muscle activity,” said Dr. Joisten.

This means that even occasional standing up, walking around, climbing stairs, and everyday activities are a start. They help motivate stigmatized, discouraged patients with obesity. Dr. Joisten highlighted a clear advantage of exercise over the “weight loss injection.” “You can promise your patients that when they start or resume physical activity, they will experience the greatest increase in fitness and health right from the start.”

Just 500 more steps per day can decrease cardiovascular mortality by 7%, while a daily increase of 1000 steps reduces overall mortality by 15%, according to a recent meta-analysis. For movement in a confined space, such as a home office, one can engage in “exercise snacks.” To do this, one interrupts sedentary activities throughout the day with short bursts of movement, said Dr. Joisten.

Dr. Kress agreed with this introductory concept. “With lower intensity and longer duration, you can achieve even more than with short, intense exercise sessions,” he told this news organization. For starters, he recommended “walking without panting,” such as walking or jogging at a pace that allows for conversation.

Even the first walk improves the condition of coronary arteries, Dr. Kress explained. Fragmented exercise sessions, such as three times for 10 min/d, benefit circulation and fitness, the expert emphasized. Moderate aerobic training also ensures effective fat burning and prevents lactic acid buildup.
 

The Next Step

Gradual progression can lead to longer or brisker walks. The goal does not always have to be 10,000 steps per day, as shown in a meta-analysis presented by Dr. Joisten. In individuals aged < 60 years, 8000-10,000 steps significantly reduced mortality. For those aged > 60 years, 6000-8000 steps were sufficient.

More exercise is even better. The WHO recommends 150-300 min/wk of exercise for adults, including seniors, equivalent to 30-60 min/d for 5 days a week. Additionally, strength training is recommended on 2 days a week — or for seniors, 3 days of combined training sessions with strength and balance components.

In a network meta-analysis, the following exercise regimens were compared for overweight or obese individuals:

• Interval training (very high intensity, 2-3 d/wk, averaging 91 min/wk)
• Strength training (2-3 d/wk, averaging 126 min/wk)
• Continuous endurance training (moderate intensity, 3-5 d/wk, averaging 176 min/wk)
• Combined training (3-4 d/wk, averaging 187 min/wk)
• Hybrid training (high intensity, such as dancing, jumping rope, ball sports, etc., 2-3 d/wk, averaging 128 min/wk).

Participants in the combined training group (which included the longest weekly training times) performed the best in all five endpoints: Body composition, blood lipid levels, blood sugar control, blood pressure, and cardiorespiratory fitness. However, hybrid training also produced good results.
 

First, Visit the Doctor

Patients who wish to exercise and have not done so in a while or who have cardiac-respiratory or orthopedic conditions should first undergo a medical checkup, Dr. Kress told this news organization.

In most cases, a test on a stationary bicycle at the primary care physician’s office would be sufficient. If higher athletic goals are sought, a sports physician or a cardiologist should be consulted.

However, when looking at weight loss alone, exercise may not go very far, said Dr. Joisten. Approximately 1.5-3.5 kg of body weight can be lost, as shown in a meta-analysis. Of this amount, about 1.3-2.6 kg is fat mass. Only 330-560 g of this total is visceral fat, which matters the most.
 

A Direct Comparison

Matthias Blüher, MD, an endocrinologist and diabetologist at the University Hospital Leipzig in Leipzig, Germany, represented the pro-injection position. He initially focused on body weight and presented a highly publicized study by Lundgren et al., which showed that treatment with 3.0 mg/d liraglutide was significantly more effective in terms of weight loss than moderate to intensive physical activity. After 12 months, patients who received the injection lost 6.8 kg, while those who exercised lost only 4.1 kg. “The injection wins in a direct comparison,” said Dr. Blüher.

The diabetologist also pointed out the risk for injury associated with exercise. Patients may become less active after a sports injury, he noted.

The LOOK-AHEAD study investigated whether a lifestyle program involving exercise and dietary changes brought cardiovascular benefits. In the long run, it did not. Patients regained weight after some time, and the combined cardiovascular endpoint did not differ between the group with an active, healthy lifestyle and the inactive control group. The study was discontinued.

The SELECT study compared the effect of treatment with once-weekly semaglutide 2.4 mg and placebo on cardiovascular events in patients with cardiovascular conditions and overweight or obesity (n = 17,604). Patients in the semaglutide arm had significantly fewer cardiovascular events over nearly 3 years than the comparison patients receiving placebo (6.5% vs 8.0%). Although the study participants did not have diabetes, they had relatively high baseline A1c levels; two thirds of the patients (n = 11,696) had prediabetes, with an A1c level ≥ 5.7%. Semaglutide significantly delayed the onset of diabetes in these patients, said Dr. Blüher.

A review in which Dr. Blüher was involved showed that treatment with 2.4 mg semaglutide or 15 mg tirzepatide over 12 months was more effective than many older medications (including orlistat) but not as effective as bariatric surgery. Participants in the Exercise and Nutrition study performed even worse than with the older medications.
 

Combination Therapy

Dr. Blüher and Dr. Joisten agreed that the combined prescription and use of exercise and incretin-based medications yields the best results for relevant endpoints such as weight loss and blood sugar control.

For example, data from the Lundgren study mentioned previously showed that participants in the combination group with liraglutide plus exercise lost an average of 9.5 kg of body weight. In addition, the A1c level, insulin sensitivity, and cardiorespiratory fitness of the participants in the combination group improved significantly over the course of the study.

The suggestion of an interval therapy (alternating between exercise and injections) enjoyed widespread approval during the audience discussion. Dr. Kress also supported the idea of interval therapy with incretin-based injections because it minimizes costs and could enhance insurance companies’ acceptance of this therapy.

But exercise should not be interrupted, he said, and perhaps patients would not want to take breaks either, hoping that “once someone has lost weight (for example, even under injection therapy) they gain new motivation to move and achieve more.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

BERLIN — What is the best way to help patients with diabetes, heart problems, and obesity lose weight and improve their outcomes? Is it exercise or medication (such as glucagon-like peptide 1 or gastric inhibitory polypeptide receptor agonists)? This was the focus of a “Battle of Experts” at the 2024 Diabetes Congress in Berlin.

Benefits of Exercise

“Exercise is ‘omnipotent,’ ” said Christine Joisten, MD, general, sports, and nutrition physician at the Sports University in Cologne, Germany. She pointed out that exercise not only helps with weight loss but also improves overall fitness, body composition, eating habits, cardiometabolic health, and quality of life, listing the benefits of exercise.

In a conversation with this news organization, Stephan Kress, MD, a diabetologist at Vinzentius Hospital in Landau, Germany, and first chair of the German Diabetes Society’s Diabetes, Sports, and Exercise Working Group, referred to a study by Pedersen et al. that examined the effect of exercise on 26 conditions. It indicated that exercise had moderate to strong positive effects on disease progression. The benefits of exercise extended beyond metabolic, cardiological, pneumological, and musculoskeletal diseases to neurological and psychiatric conditions.

The so-called myokines, which are “good” cytokines released by muscles, could play a role in this process, according to a presentation by study author Bente Klarlund Pedersen, MD, of Rigshospitalet in Copenhagen, Denmark.

For example, exercise could elevate mood in patients with depression and reduce inflammation in individuals with chronic inflammatory diseases, said Dr. Kress. Many patients, including those with diabetes, could benefit from physical activity even if their A1c levels do not decrease as desired.
 

Exercise As a Snack

Fat loss can be achieved with prolonged activity or with “short and intense” sessions if followed by refraining from eating immediately afterward, Dr. Joisten explained during the expert battle at the Diabetes Congress.

Different recommendations exist regarding how much exercise is necessary. According to the World Health Organization’s (WHO) recommendation, “Every step counts.” “As sports physicians, we consider physical activity to be any form of energy expenditure achieved through muscle activity,” said Dr. Joisten.

This means that even occasional standing up, walking around, climbing stairs, and everyday activities are a start. They help motivate stigmatized, discouraged patients with obesity. Dr. Joisten highlighted a clear advantage of exercise over the “weight loss injection.” “You can promise your patients that when they start or resume physical activity, they will experience the greatest increase in fitness and health right from the start.”

Just 500 more steps per day can decrease cardiovascular mortality by 7%, while a daily increase of 1000 steps reduces overall mortality by 15%, according to a recent meta-analysis. For movement in a confined space, such as a home office, one can engage in “exercise snacks.” To do this, one interrupts sedentary activities throughout the day with short bursts of movement, said Dr. Joisten.

Dr. Kress agreed with this introductory concept. “With lower intensity and longer duration, you can achieve even more than with short, intense exercise sessions,” he told this news organization. For starters, he recommended “walking without panting,” such as walking or jogging at a pace that allows for conversation.

Even the first walk improves the condition of coronary arteries, Dr. Kress explained. Fragmented exercise sessions, such as three times for 10 min/d, benefit circulation and fitness, the expert emphasized. Moderate aerobic training also ensures effective fat burning and prevents lactic acid buildup.
 

The Next Step

Gradual progression can lead to longer or brisker walks. The goal does not always have to be 10,000 steps per day, as shown in a meta-analysis presented by Dr. Joisten. In individuals aged < 60 years, 8000-10,000 steps significantly reduced mortality. For those aged > 60 years, 6000-8000 steps were sufficient.

More exercise is even better. The WHO recommends 150-300 min/wk of exercise for adults, including seniors, equivalent to 30-60 min/d for 5 days a week. Additionally, strength training is recommended on 2 days a week — or for seniors, 3 days of combined training sessions with strength and balance components.

In a network meta-analysis, the following exercise regimens were compared for overweight or obese individuals:

• Interval training (very high intensity, 2-3 d/wk, averaging 91 min/wk)
• Strength training (2-3 d/wk, averaging 126 min/wk)
• Continuous endurance training (moderate intensity, 3-5 d/wk, averaging 176 min/wk)
• Combined training (3-4 d/wk, averaging 187 min/wk)
• Hybrid training (high intensity, such as dancing, jumping rope, ball sports, etc., 2-3 d/wk, averaging 128 min/wk).

Participants in the combined training group (which included the longest weekly training times) performed the best in all five endpoints: Body composition, blood lipid levels, blood sugar control, blood pressure, and cardiorespiratory fitness. However, hybrid training also produced good results.
 

First, Visit the Doctor

Patients who wish to exercise and have not done so in a while or who have cardiac-respiratory or orthopedic conditions should first undergo a medical checkup, Dr. Kress told this news organization.

In most cases, a test on a stationary bicycle at the primary care physician’s office would be sufficient. If higher athletic goals are sought, a sports physician or a cardiologist should be consulted.

However, when looking at weight loss alone, exercise may not go very far, said Dr. Joisten. Approximately 1.5-3.5 kg of body weight can be lost, as shown in a meta-analysis. Of this amount, about 1.3-2.6 kg is fat mass. Only 330-560 g of this total is visceral fat, which matters the most.
 

A Direct Comparison

Matthias Blüher, MD, an endocrinologist and diabetologist at the University Hospital Leipzig in Leipzig, Germany, represented the pro-injection position. He initially focused on body weight and presented a highly publicized study by Lundgren et al., which showed that treatment with 3.0 mg/d liraglutide was significantly more effective in terms of weight loss than moderate to intensive physical activity. After 12 months, patients who received the injection lost 6.8 kg, while those who exercised lost only 4.1 kg. “The injection wins in a direct comparison,” said Dr. Blüher.

The diabetologist also pointed out the risk for injury associated with exercise. Patients may become less active after a sports injury, he noted.

The LOOK-AHEAD study investigated whether a lifestyle program involving exercise and dietary changes brought cardiovascular benefits. In the long run, it did not. Patients regained weight after some time, and the combined cardiovascular endpoint did not differ between the group with an active, healthy lifestyle and the inactive control group. The study was discontinued.

The SELECT study compared the effect of treatment with once-weekly semaglutide 2.4 mg and placebo on cardiovascular events in patients with cardiovascular conditions and overweight or obesity (n = 17,604). Patients in the semaglutide arm had significantly fewer cardiovascular events over nearly 3 years than the comparison patients receiving placebo (6.5% vs 8.0%). Although the study participants did not have diabetes, they had relatively high baseline A1c levels; two thirds of the patients (n = 11,696) had prediabetes, with an A1c level ≥ 5.7%. Semaglutide significantly delayed the onset of diabetes in these patients, said Dr. Blüher.

A review in which Dr. Blüher was involved showed that treatment with 2.4 mg semaglutide or 15 mg tirzepatide over 12 months was more effective than many older medications (including orlistat) but not as effective as bariatric surgery. Participants in the Exercise and Nutrition study performed even worse than with the older medications.
 

Combination Therapy

Dr. Blüher and Dr. Joisten agreed that the combined prescription and use of exercise and incretin-based medications yields the best results for relevant endpoints such as weight loss and blood sugar control.

For example, data from the Lundgren study mentioned previously showed that participants in the combination group with liraglutide plus exercise lost an average of 9.5 kg of body weight. In addition, the A1c level, insulin sensitivity, and cardiorespiratory fitness of the participants in the combination group improved significantly over the course of the study.

The suggestion of an interval therapy (alternating between exercise and injections) enjoyed widespread approval during the audience discussion. Dr. Kress also supported the idea of interval therapy with incretin-based injections because it minimizes costs and could enhance insurance companies’ acceptance of this therapy.

But exercise should not be interrupted, he said, and perhaps patients would not want to take breaks either, hoping that “once someone has lost weight (for example, even under injection therapy) they gain new motivation to move and achieve more.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

BERLIN — What is the best way to help patients with diabetes, heart problems, and obesity lose weight and improve their outcomes? Is it exercise or medication (such as glucagon-like peptide 1 or gastric inhibitory polypeptide receptor agonists)? This was the focus of a “Battle of Experts” at the 2024 Diabetes Congress in Berlin.

Benefits of Exercise

“Exercise is ‘omnipotent,’ ” said Christine Joisten, MD, general, sports, and nutrition physician at the Sports University in Cologne, Germany. She pointed out that exercise not only helps with weight loss but also improves overall fitness, body composition, eating habits, cardiometabolic health, and quality of life, listing the benefits of exercise.

In a conversation with this news organization, Stephan Kress, MD, a diabetologist at Vinzentius Hospital in Landau, Germany, and first chair of the German Diabetes Society’s Diabetes, Sports, and Exercise Working Group, referred to a study by Pedersen et al. that examined the effect of exercise on 26 conditions. It indicated that exercise had moderate to strong positive effects on disease progression. The benefits of exercise extended beyond metabolic, cardiological, pneumological, and musculoskeletal diseases to neurological and psychiatric conditions.

The so-called myokines, which are “good” cytokines released by muscles, could play a role in this process, according to a presentation by study author Bente Klarlund Pedersen, MD, of Rigshospitalet in Copenhagen, Denmark.

For example, exercise could elevate mood in patients with depression and reduce inflammation in individuals with chronic inflammatory diseases, said Dr. Kress. Many patients, including those with diabetes, could benefit from physical activity even if their A1c levels do not decrease as desired.
 

Exercise As a Snack

Fat loss can be achieved with prolonged activity or with “short and intense” sessions if followed by refraining from eating immediately afterward, Dr. Joisten explained during the expert battle at the Diabetes Congress.

Different recommendations exist regarding how much exercise is necessary. According to the World Health Organization’s (WHO) recommendation, “Every step counts.” “As sports physicians, we consider physical activity to be any form of energy expenditure achieved through muscle activity,” said Dr. Joisten.

This means that even occasional standing up, walking around, climbing stairs, and everyday activities are a start. They help motivate stigmatized, discouraged patients with obesity. Dr. Joisten highlighted a clear advantage of exercise over the “weight loss injection.” “You can promise your patients that when they start or resume physical activity, they will experience the greatest increase in fitness and health right from the start.”

Just 500 more steps per day can decrease cardiovascular mortality by 7%, while a daily increase of 1000 steps reduces overall mortality by 15%, according to a recent meta-analysis. For movement in a confined space, such as a home office, one can engage in “exercise snacks.” To do this, one interrupts sedentary activities throughout the day with short bursts of movement, said Dr. Joisten.

Dr. Kress agreed with this introductory concept. “With lower intensity and longer duration, you can achieve even more than with short, intense exercise sessions,” he told this news organization. For starters, he recommended “walking without panting,” such as walking or jogging at a pace that allows for conversation.

Even the first walk improves the condition of coronary arteries, Dr. Kress explained. Fragmented exercise sessions, such as three times for 10 min/d, benefit circulation and fitness, the expert emphasized. Moderate aerobic training also ensures effective fat burning and prevents lactic acid buildup.
 

The Next Step

Gradual progression can lead to longer or brisker walks. The goal does not always have to be 10,000 steps per day, as shown in a meta-analysis presented by Dr. Joisten. In individuals aged < 60 years, 8000-10,000 steps significantly reduced mortality. For those aged > 60 years, 6000-8000 steps were sufficient.

More exercise is even better. The WHO recommends 150-300 min/wk of exercise for adults, including seniors, equivalent to 30-60 min/d for 5 days a week. Additionally, strength training is recommended on 2 days a week — or for seniors, 3 days of combined training sessions with strength and balance components.

In a network meta-analysis, the following exercise regimens were compared for overweight or obese individuals:

• Interval training (very high intensity, 2-3 d/wk, averaging 91 min/wk)
• Strength training (2-3 d/wk, averaging 126 min/wk)
• Continuous endurance training (moderate intensity, 3-5 d/wk, averaging 176 min/wk)
• Combined training (3-4 d/wk, averaging 187 min/wk)
• Hybrid training (high intensity, such as dancing, jumping rope, ball sports, etc., 2-3 d/wk, averaging 128 min/wk).

Participants in the combined training group (which included the longest weekly training times) performed the best in all five endpoints: Body composition, blood lipid levels, blood sugar control, blood pressure, and cardiorespiratory fitness. However, hybrid training also produced good results.
 

First, Visit the Doctor

Patients who wish to exercise and have not done so in a while or who have cardiac-respiratory or orthopedic conditions should first undergo a medical checkup, Dr. Kress told this news organization.

In most cases, a test on a stationary bicycle at the primary care physician’s office would be sufficient. If higher athletic goals are sought, a sports physician or a cardiologist should be consulted.

However, when looking at weight loss alone, exercise may not go very far, said Dr. Joisten. Approximately 1.5-3.5 kg of body weight can be lost, as shown in a meta-analysis. Of this amount, about 1.3-2.6 kg is fat mass. Only 330-560 g of this total is visceral fat, which matters the most.
 

A Direct Comparison

Matthias Blüher, MD, an endocrinologist and diabetologist at the University Hospital Leipzig in Leipzig, Germany, represented the pro-injection position. He initially focused on body weight and presented a highly publicized study by Lundgren et al., which showed that treatment with 3.0 mg/d liraglutide was significantly more effective in terms of weight loss than moderate to intensive physical activity. After 12 months, patients who received the injection lost 6.8 kg, while those who exercised lost only 4.1 kg. “The injection wins in a direct comparison,” said Dr. Blüher.

The diabetologist also pointed out the risk for injury associated with exercise. Patients may become less active after a sports injury, he noted.

The LOOK-AHEAD study investigated whether a lifestyle program involving exercise and dietary changes brought cardiovascular benefits. In the long run, it did not. Patients regained weight after some time, and the combined cardiovascular endpoint did not differ between the group with an active, healthy lifestyle and the inactive control group. The study was discontinued.

The SELECT study compared the effect of treatment with once-weekly semaglutide 2.4 mg and placebo on cardiovascular events in patients with cardiovascular conditions and overweight or obesity (n = 17,604). Patients in the semaglutide arm had significantly fewer cardiovascular events over nearly 3 years than the comparison patients receiving placebo (6.5% vs 8.0%). Although the study participants did not have diabetes, they had relatively high baseline A1c levels; two thirds of the patients (n = 11,696) had prediabetes, with an A1c level ≥ 5.7%. Semaglutide significantly delayed the onset of diabetes in these patients, said Dr. Blüher.

A review in which Dr. Blüher was involved showed that treatment with 2.4 mg semaglutide or 15 mg tirzepatide over 12 months was more effective than many older medications (including orlistat) but not as effective as bariatric surgery. Participants in the Exercise and Nutrition study performed even worse than with the older medications.
 

Combination Therapy

Dr. Blüher and Dr. Joisten agreed that the combined prescription and use of exercise and incretin-based medications yields the best results for relevant endpoints such as weight loss and blood sugar control.

For example, data from the Lundgren study mentioned previously showed that participants in the combination group with liraglutide plus exercise lost an average of 9.5 kg of body weight. In addition, the A1c level, insulin sensitivity, and cardiorespiratory fitness of the participants in the combination group improved significantly over the course of the study.

The suggestion of an interval therapy (alternating between exercise and injections) enjoyed widespread approval during the audience discussion. Dr. Kress also supported the idea of interval therapy with incretin-based injections because it minimizes costs and could enhance insurance companies’ acceptance of this therapy.

But exercise should not be interrupted, he said, and perhaps patients would not want to take breaks either, hoping that “once someone has lost weight (for example, even under injection therapy) they gain new motivation to move and achieve more.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.