Diabetes

Serious mental illness (SMI), including bipolar disorder or schizophrenia spectrum disorders, is associated with a twofold increased risk for comorbid physical illness, results of a new meta-analysis showed.

“Although treatment of physical and mental health remains siloed in many health services globally, the high prevalence of physical multimorbidity attests to the urgent need for integrated care models that address both physical and mental health outcomes in people with severe mental illness,” the authors, led by Sean Halstead, MD, of The University of Queensland Medical School in Brisbane, Australia, wrote.

The findings were published online in The Lancet Psychiatry.
 

Shorter Lifespan?

SMI is associated with reduced life expectancy, and experts speculate that additional chronic illnesses — whether physical or psychiatric — may underlie this association.

While previous research has paired SMI with comorbid physical illnesses, the researchers noted that this study is the first to focus on both physical and psychiatric multimorbidity in individuals with SMI.

The investigators conducted a meta-analysis of 82 observational studies comprising 1.6 million individuals with SMI and 13.2 million control subjects to determine the risk for physical or psychiatric multimorbidity.

Studies were included if participants were diagnosed with either a schizophrenia spectrum disorder or bipolar disorder, and the study assessed either physical multimorbidity (at least two physical health conditions) or psychiatric multimorbidity (at least three psychiatric conditions), including the initial SMI.

Investigators found that individuals with SMI had more than a twofold increased risk for physical multimorbidity than those without SMI (odds ratio [OR], 2.40; 95% CI, 1.57-3.65; P = .0009).

Physical multimorbidity, which included cardiovascular, endocrine, neurological rental, gastrointestinal, musculoskeletal, and infectious disorders, was prevalent at similar rates in both schizophrenia spectrum disorder and bipolar disorder.

The ratio of physical multimorbidity was about four times higher in younger populations with SMI (mean age ≤ 40; OR, 3.99; 95% CI, 1.43-11.10) than in older populations (mean age > 40; OR, 1.55; 95% CI, 0.96-2.51; subgroup differences, P = .0013).

In terms of absolute prevalence, 25% of those with SMI had a physical multimorbidity, and 14% had a psychiatric multimorbidity, which were primarily anxiety and substance use disorders.

Investigators speculated that physical multimorbidity in SMI could stem from side effects of psychotropic medications, which are known to cause rapid cardiometabolic changes, including weight gain. In addition, lifestyle factors or nonmodifiable risk factors could also contribute to physical multimorbidity.

The study’s limitations included its small sample sizes for subgroup analyses and insufficient analysis for significant covariates, including smoking rates and symptom severity.

“While health services and treatment guidelines often operate on the assumption that individuals have a single principal diagnosis, these results attest to the clinical complexity many people with severe mental illness face in relation to burden of chronic disease,” the investigators wrote. They added that a greater understanding of the epidemiological manifestations of multimorbidity in SMI is “imperative.”

There was no source of funding for this study. Dr. Halstead is supported by the Australian Research Training Program scholarship. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com .

Serious mental illness (SMI), including bipolar disorder or schizophrenia spectrum disorders, is associated with a twofold increased risk for comorbid physical illness, results of a new meta-analysis showed.

“Although treatment of physical and mental health remains siloed in many health services globally, the high prevalence of physical multimorbidity attests to the urgent need for integrated care models that address both physical and mental health outcomes in people with severe mental illness,” the authors, led by Sean Halstead, MD, of The University of Queensland Medical School in Brisbane, Australia, wrote.

The findings were published online in The Lancet Psychiatry.
 

Shorter Lifespan?

SMI is associated with reduced life expectancy, and experts speculate that additional chronic illnesses — whether physical or psychiatric — may underlie this association.

While previous research has paired SMI with comorbid physical illnesses, the researchers noted that this study is the first to focus on both physical and psychiatric multimorbidity in individuals with SMI.

The investigators conducted a meta-analysis of 82 observational studies comprising 1.6 million individuals with SMI and 13.2 million control subjects to determine the risk for physical or psychiatric multimorbidity.

Studies were included if participants were diagnosed with either a schizophrenia spectrum disorder or bipolar disorder, and the study assessed either physical multimorbidity (at least two physical health conditions) or psychiatric multimorbidity (at least three psychiatric conditions), including the initial SMI.

Investigators found that individuals with SMI had more than a twofold increased risk for physical multimorbidity than those without SMI (odds ratio [OR], 2.40; 95% CI, 1.57-3.65; P = .0009).

Physical multimorbidity, which included cardiovascular, endocrine, neurological rental, gastrointestinal, musculoskeletal, and infectious disorders, was prevalent at similar rates in both schizophrenia spectrum disorder and bipolar disorder.

The ratio of physical multimorbidity was about four times higher in younger populations with SMI (mean age ≤ 40; OR, 3.99; 95% CI, 1.43-11.10) than in older populations (mean age > 40; OR, 1.55; 95% CI, 0.96-2.51; subgroup differences, P = .0013).

In terms of absolute prevalence, 25% of those with SMI had a physical multimorbidity, and 14% had a psychiatric multimorbidity, which were primarily anxiety and substance use disorders.

Investigators speculated that physical multimorbidity in SMI could stem from side effects of psychotropic medications, which are known to cause rapid cardiometabolic changes, including weight gain. In addition, lifestyle factors or nonmodifiable risk factors could also contribute to physical multimorbidity.

The study’s limitations included its small sample sizes for subgroup analyses and insufficient analysis for significant covariates, including smoking rates and symptom severity.

“While health services and treatment guidelines often operate on the assumption that individuals have a single principal diagnosis, these results attest to the clinical complexity many people with severe mental illness face in relation to burden of chronic disease,” the investigators wrote. They added that a greater understanding of the epidemiological manifestations of multimorbidity in SMI is “imperative.”

There was no source of funding for this study. Dr. Halstead is supported by the Australian Research Training Program scholarship. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com .

Serious mental illness (SMI), including bipolar disorder or schizophrenia spectrum disorders, is associated with a twofold increased risk for comorbid physical illness, results of a new meta-analysis showed.

“Although treatment of physical and mental health remains siloed in many health services globally, the high prevalence of physical multimorbidity attests to the urgent need for integrated care models that address both physical and mental health outcomes in people with severe mental illness,” the authors, led by Sean Halstead, MD, of The University of Queensland Medical School in Brisbane, Australia, wrote.

The findings were published online in The Lancet Psychiatry.
 

Shorter Lifespan?

SMI is associated with reduced life expectancy, and experts speculate that additional chronic illnesses — whether physical or psychiatric — may underlie this association.

While previous research has paired SMI with comorbid physical illnesses, the researchers noted that this study is the first to focus on both physical and psychiatric multimorbidity in individuals with SMI.

The investigators conducted a meta-analysis of 82 observational studies comprising 1.6 million individuals with SMI and 13.2 million control subjects to determine the risk for physical or psychiatric multimorbidity.

Studies were included if participants were diagnosed with either a schizophrenia spectrum disorder or bipolar disorder, and the study assessed either physical multimorbidity (at least two physical health conditions) or psychiatric multimorbidity (at least three psychiatric conditions), including the initial SMI.

Investigators found that individuals with SMI had more than a twofold increased risk for physical multimorbidity than those without SMI (odds ratio [OR], 2.40; 95% CI, 1.57-3.65; P = .0009).

Physical multimorbidity, which included cardiovascular, endocrine, neurological rental, gastrointestinal, musculoskeletal, and infectious disorders, was prevalent at similar rates in both schizophrenia spectrum disorder and bipolar disorder.

The ratio of physical multimorbidity was about four times higher in younger populations with SMI (mean age ≤ 40; OR, 3.99; 95% CI, 1.43-11.10) than in older populations (mean age > 40; OR, 1.55; 95% CI, 0.96-2.51; subgroup differences, P = .0013).

In terms of absolute prevalence, 25% of those with SMI had a physical multimorbidity, and 14% had a psychiatric multimorbidity, which were primarily anxiety and substance use disorders.

Investigators speculated that physical multimorbidity in SMI could stem from side effects of psychotropic medications, which are known to cause rapid cardiometabolic changes, including weight gain. In addition, lifestyle factors or nonmodifiable risk factors could also contribute to physical multimorbidity.

The study’s limitations included its small sample sizes for subgroup analyses and insufficient analysis for significant covariates, including smoking rates and symptom severity.

“While health services and treatment guidelines often operate on the assumption that individuals have a single principal diagnosis, these results attest to the clinical complexity many people with severe mental illness face in relation to burden of chronic disease,” the investigators wrote. They added that a greater understanding of the epidemiological manifestations of multimorbidity in SMI is “imperative.”

There was no source of funding for this study. Dr. Halstead is supported by the Australian Research Training Program scholarship. Other disclosures were noted in the original article.

A version of this article appeared on Medscape.com .

VIENNA — With the glucagon-like peptide (GLP) 1 receptor agonist semaglutide (Wegovy) recently shown to significantly induce weight loss in people with osteoarthritis (OA) and obesity in the STEP-9 trial, could drugs traditionally used to treat type 2 diabetes be the next big thing for OA management?

“Hormone-based weight loss drugs are a game changer” for obesity management, Sébastien Czernichow, MD, PhD, said during a plenary session at the OARSI 2024 World Congress.

Sara Freeman/Medscape Medical News

Drugs such as semaglutide may also have a cardioprotective effect, reducing the risk for major adverse cardiovascular events by as much as 20% vs placebo, added Dr. Czernichow, professor of nutrition at Paris Cité University and head of the Department of Nutrition at the George Pompidou European Hospital in Paris, France.

“You have to keep in mind that the short-term side effects are mainly gastrointestinal and [are] manageable. The mid-term side effects are an increased gallbladder [disease] risk, and the long-term benefits and risks are not really well known yet,” Dr. Czernichow said. With regard to that, the effects of these drugs on lean body mass, bone health, and nutritional deficiencies need to be further evaluated and monitored.
 

Weight Loss Benefits

Weight loss is one of the cornerstones of OA management, and in addition to the weight loss seen with the GLP-1 receptor agonists, there have also been changes in body composition, Dr. Czernichow said.

In SURMOUNT-1, for example, the dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide (Zepbound) was shown to significantly reduce total fat mass with a smaller decrease in total lean mass in a subanalysis.

It has been argued that effects on body composition need to be considered when evaluating new weight loss drugs, and that focusing only on the degree of weight reduction is “encouraging inaccurate measures of medication efficacy for both patients and clinicians,” Dr. Czernichow said, citing a viewpoint published in JAMA Internal Medicine.

“The real question is: Are we able to fund these drugs for everyone? Or will only the richest patients be allocated to these drugs?” Dr. Czernichow said.
 

Weight Rebound

Tonia Vincent, MBBS, PhD, professor of musculoskeletal biology and an honorary rheumatologist at The Kennedy Institute of Rheumatology at University of Oxford in England, was concerned about rebound weight gain.

“We hear a lot about this, that people stopping drugs actually get worse weight gain than before they started, and that’s a concern about a drug that is going to have a huge pressure for supply,” Dr. Vincent said following Dr. Czernichow’s presentation.

Another delegate said that calling GLP-1 receptor agonists a “game changer” for weight loss in OA was premature because long-term results are needed.

“You mentioned that the double-digit weight loss is getting very close to the results from bariatric surgery, but bariatric surgery you do once, and for these drugs, to maintain the weight loss, you need to take them continuously,” she said.
 

Weight Loss Affects Bone

Yet another delegate cautioned on the potential effects of significant weight loss on bone and cartilage. There is evidence, he said, that weight loss of 5-10 kg can significantly affect bone turnover, increasing bone resorption and thus putting patients at a risk of becoming osteopenic. “Are we looking at a new population of osteoporosis patients who may then also be at risk for fractures?” he asked.

Separately at OARSI 2024, Anne C. Bay-Jensen, PhD, chief technology officer at Nordic Bioscience in Herlev, Denmark, and colleagues reported data showing that weight loss was associated with an increase in bone and cartilage degradation.

Although Dr. Bay-Jensen and colleagues found that losing weight was associated with improved patient outcomes, there was a 1.58-fold increase in the bone resorption marker CTX-I in people who had lost weight vs a 1.37-fold gain in those whose weight remained stable and 1.11-fold increase in those who gained weight.

Moreover, there was a 1.15-fold increase in the cartilage degradation marker C2M in the weight loss group and 0.84-fold decrease in the interstitial matrix degradation marker C3M.
 

GLP-1 and Bone Effects

Another question is whether GLP-1 receptor agonists might be having direct effects on the bone that may be beneficial in OA. They might, postdoctoral researcher Eda Çiftci, PhD, of AO Research Institute Davos in Switzerland, and collaborators, said during the poster sessions at OARSI 2024.

Dr. Çiftci and researchers reported the findings of an in vitro study that looked at whether liraglutide might have anti-inflammatory and anabolic effects on a human chondrocytes model that had been treated with interleukin (IL)-1-beta to “mimic an inflammatory OA condition.”

The release of the proinflammatory cytokines IL-6 and IL-8 was reduced by treatment with liraglutide when compared with control chondrocytes. Furthermore, the expression of the proteoglycan aggrecan — important for articular cartilage function — also was preserved.

These results suggest that liraglutide does indeed have anabolic and anti-inflammatory effects, Dr. Çiftci and fellow researchers concluded.
 

New Role for Dipeptidyl Transferase Inhibitors?

Researchers are also looking at the potential role for other diabetes medications in OA management, including the dipeptidyl peptidase (DPP) 4 inhibitors.

Although these drugs are considered “weight neutral,” in vitro studies have suggested that the DPP4 enzyme may have a role to play in chondrocyte survival and inflammation, Yu-Hsiu Chen, MD, of the Tri-Service General Hospital and the National Defense Medical Center in Taipei, Taiwan, told this news organization. The DPP4 enzyme inactivates GLP-1, so there is rationale there.

“Last year, we published a paper where we found the concentration of DPP4 in the synovial fluid was correlated with radiographic change in knee OA,” Dr. Chen said. This time, “we’re trying to see if a DPP4 inhibitor can be used as a treatment.”

For their analysis, they used data on people newly diagnosed with type 2 diabetes who were and were not using DPP4 inhibitors obtained from Taiwan’s National Health Insurance Research Database. This database contains information on 99% of the Taiwanese population, Dr. Chen said.

Matching 165,333 DPP4 inhibitor users with an equal number of nonusers showed that there was a significant 58% risk reduction for developing OA with DPP4 inhibitor use (hazard ratio, 0.42; 95% CI, 0.41-0.44).

DPP4 inhibitor use was also associated with a 58% risk lower risk for total knee replacement (TKR) and a 62% lower risk for total hip replacement.

Dr. Chen and colleagues concluded: “These results strongly indicate that DPP4 inhibitors could be considered as a viable treatment approach for individuals with type 2 [diabetes mellitus] who are at risk for developing OA or [who] already have OA.”
 

Could Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors Be Beneficial?

So, what about SGLT2 inhibitors? Do they also have a potential role to play in managing people with OA, regardless of whether there is diabetes present? Perhaps, and their effect may be even greater than what’s been observed for GLP-1 receptor agonists, as data presented by epidemiologist S. Reza Jafarzadeh, DVM, PhD, suggested.

“While GLP-1 receptor agonist drugs have been reported to reduce OA risk, largely attributed to their weight loss effect, SGLT2 inhibitors may provide a greater protective effect on OA outcomes,” said Dr. Jafarzadeh, assistant professor at Boston University.

Sara Freeman/Medscape Medical News

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Czernichow disclosed ties with BariaTek Medical, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Janssen, Jellynov, Lilly, Novo Nordisk, Novartis, and ViiV Healthcare. Dr. Vincent had no relevant disclosures. Dr. Bay-Jensen is the chief technology officer and director of immunoscience at Nordic Bioscience, which funded the work in the poster she presented at OARSI 2024. The work presented by Dr. Çiftci and colleagues was funded by the Eurostars-2 joint program with co-funding from the European Horizon 2020 research and innovation program. Dr. Çiftci had no personal disclosures to report. Dr. Chen’s work was supported by the government of Taiwan, and she had no financial conflicts of interest to disclose. Dr. Jafarzadeh had no conflicts of interest to disclose.

A version of this article appeared on Medscape.com .

VIENNA — With the glucagon-like peptide (GLP) 1 receptor agonist semaglutide (Wegovy) recently shown to significantly induce weight loss in people with osteoarthritis (OA) and obesity in the STEP-9 trial, could drugs traditionally used to treat type 2 diabetes be the next big thing for OA management?

“Hormone-based weight loss drugs are a game changer” for obesity management, Sébastien Czernichow, MD, PhD, said during a plenary session at the OARSI 2024 World Congress.

Sara Freeman/Medscape Medical News

Drugs such as semaglutide may also have a cardioprotective effect, reducing the risk for major adverse cardiovascular events by as much as 20% vs placebo, added Dr. Czernichow, professor of nutrition at Paris Cité University and head of the Department of Nutrition at the George Pompidou European Hospital in Paris, France.

“You have to keep in mind that the short-term side effects are mainly gastrointestinal and [are] manageable. The mid-term side effects are an increased gallbladder [disease] risk, and the long-term benefits and risks are not really well known yet,” Dr. Czernichow said. With regard to that, the effects of these drugs on lean body mass, bone health, and nutritional deficiencies need to be further evaluated and monitored.
 

Weight Loss Benefits

Weight loss is one of the cornerstones of OA management, and in addition to the weight loss seen with the GLP-1 receptor agonists, there have also been changes in body composition, Dr. Czernichow said.

In SURMOUNT-1, for example, the dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide (Zepbound) was shown to significantly reduce total fat mass with a smaller decrease in total lean mass in a subanalysis.

It has been argued that effects on body composition need to be considered when evaluating new weight loss drugs, and that focusing only on the degree of weight reduction is “encouraging inaccurate measures of medication efficacy for both patients and clinicians,” Dr. Czernichow said, citing a viewpoint published in JAMA Internal Medicine.

“The real question is: Are we able to fund these drugs for everyone? Or will only the richest patients be allocated to these drugs?” Dr. Czernichow said.
 

Weight Rebound

Tonia Vincent, MBBS, PhD, professor of musculoskeletal biology and an honorary rheumatologist at The Kennedy Institute of Rheumatology at University of Oxford in England, was concerned about rebound weight gain.

“We hear a lot about this, that people stopping drugs actually get worse weight gain than before they started, and that’s a concern about a drug that is going to have a huge pressure for supply,” Dr. Vincent said following Dr. Czernichow’s presentation.

Another delegate said that calling GLP-1 receptor agonists a “game changer” for weight loss in OA was premature because long-term results are needed.

“You mentioned that the double-digit weight loss is getting very close to the results from bariatric surgery, but bariatric surgery you do once, and for these drugs, to maintain the weight loss, you need to take them continuously,” she said.
 

Weight Loss Affects Bone

Yet another delegate cautioned on the potential effects of significant weight loss on bone and cartilage. There is evidence, he said, that weight loss of 5-10 kg can significantly affect bone turnover, increasing bone resorption and thus putting patients at a risk of becoming osteopenic. “Are we looking at a new population of osteoporosis patients who may then also be at risk for fractures?” he asked.

Separately at OARSI 2024, Anne C. Bay-Jensen, PhD, chief technology officer at Nordic Bioscience in Herlev, Denmark, and colleagues reported data showing that weight loss was associated with an increase in bone and cartilage degradation.

Although Dr. Bay-Jensen and colleagues found that losing weight was associated with improved patient outcomes, there was a 1.58-fold increase in the bone resorption marker CTX-I in people who had lost weight vs a 1.37-fold gain in those whose weight remained stable and 1.11-fold increase in those who gained weight.

Moreover, there was a 1.15-fold increase in the cartilage degradation marker C2M in the weight loss group and 0.84-fold decrease in the interstitial matrix degradation marker C3M.
 

GLP-1 and Bone Effects

Another question is whether GLP-1 receptor agonists might be having direct effects on the bone that may be beneficial in OA. They might, postdoctoral researcher Eda Çiftci, PhD, of AO Research Institute Davos in Switzerland, and collaborators, said during the poster sessions at OARSI 2024.

Dr. Çiftci and researchers reported the findings of an in vitro study that looked at whether liraglutide might have anti-inflammatory and anabolic effects on a human chondrocytes model that had been treated with interleukin (IL)-1-beta to “mimic an inflammatory OA condition.”

The release of the proinflammatory cytokines IL-6 and IL-8 was reduced by treatment with liraglutide when compared with control chondrocytes. Furthermore, the expression of the proteoglycan aggrecan — important for articular cartilage function — also was preserved.

These results suggest that liraglutide does indeed have anabolic and anti-inflammatory effects, Dr. Çiftci and fellow researchers concluded.
 

New Role for Dipeptidyl Transferase Inhibitors?

Researchers are also looking at the potential role for other diabetes medications in OA management, including the dipeptidyl peptidase (DPP) 4 inhibitors.

Although these drugs are considered “weight neutral,” in vitro studies have suggested that the DPP4 enzyme may have a role to play in chondrocyte survival and inflammation, Yu-Hsiu Chen, MD, of the Tri-Service General Hospital and the National Defense Medical Center in Taipei, Taiwan, told this news organization. The DPP4 enzyme inactivates GLP-1, so there is rationale there.

“Last year, we published a paper where we found the concentration of DPP4 in the synovial fluid was correlated with radiographic change in knee OA,” Dr. Chen said. This time, “we’re trying to see if a DPP4 inhibitor can be used as a treatment.”

For their analysis, they used data on people newly diagnosed with type 2 diabetes who were and were not using DPP4 inhibitors obtained from Taiwan’s National Health Insurance Research Database. This database contains information on 99% of the Taiwanese population, Dr. Chen said.

Matching 165,333 DPP4 inhibitor users with an equal number of nonusers showed that there was a significant 58% risk reduction for developing OA with DPP4 inhibitor use (hazard ratio, 0.42; 95% CI, 0.41-0.44).

DPP4 inhibitor use was also associated with a 58% risk lower risk for total knee replacement (TKR) and a 62% lower risk for total hip replacement.

Dr. Chen and colleagues concluded: “These results strongly indicate that DPP4 inhibitors could be considered as a viable treatment approach for individuals with type 2 [diabetes mellitus] who are at risk for developing OA or [who] already have OA.”
 

Could Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors Be Beneficial?

So, what about SGLT2 inhibitors? Do they also have a potential role to play in managing people with OA, regardless of whether there is diabetes present? Perhaps, and their effect may be even greater than what’s been observed for GLP-1 receptor agonists, as data presented by epidemiologist S. Reza Jafarzadeh, DVM, PhD, suggested.

“While GLP-1 receptor agonist drugs have been reported to reduce OA risk, largely attributed to their weight loss effect, SGLT2 inhibitors may provide a greater protective effect on OA outcomes,” said Dr. Jafarzadeh, assistant professor at Boston University.

Sara Freeman/Medscape Medical News

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Czernichow disclosed ties with BariaTek Medical, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Janssen, Jellynov, Lilly, Novo Nordisk, Novartis, and ViiV Healthcare. Dr. Vincent had no relevant disclosures. Dr. Bay-Jensen is the chief technology officer and director of immunoscience at Nordic Bioscience, which funded the work in the poster she presented at OARSI 2024. The work presented by Dr. Çiftci and colleagues was funded by the Eurostars-2 joint program with co-funding from the European Horizon 2020 research and innovation program. Dr. Çiftci had no personal disclosures to report. Dr. Chen’s work was supported by the government of Taiwan, and she had no financial conflicts of interest to disclose. Dr. Jafarzadeh had no conflicts of interest to disclose.

A version of this article appeared on Medscape.com .

VIENNA — With the glucagon-like peptide (GLP) 1 receptor agonist semaglutide (Wegovy) recently shown to significantly induce weight loss in people with osteoarthritis (OA) and obesity in the STEP-9 trial, could drugs traditionally used to treat type 2 diabetes be the next big thing for OA management?

“Hormone-based weight loss drugs are a game changer” for obesity management, Sébastien Czernichow, MD, PhD, said during a plenary session at the OARSI 2024 World Congress.

Sara Freeman/Medscape Medical News

Drugs such as semaglutide may also have a cardioprotective effect, reducing the risk for major adverse cardiovascular events by as much as 20% vs placebo, added Dr. Czernichow, professor of nutrition at Paris Cité University and head of the Department of Nutrition at the George Pompidou European Hospital in Paris, France.

“You have to keep in mind that the short-term side effects are mainly gastrointestinal and [are] manageable. The mid-term side effects are an increased gallbladder [disease] risk, and the long-term benefits and risks are not really well known yet,” Dr. Czernichow said. With regard to that, the effects of these drugs on lean body mass, bone health, and nutritional deficiencies need to be further evaluated and monitored.
 

Weight Loss Benefits

Weight loss is one of the cornerstones of OA management, and in addition to the weight loss seen with the GLP-1 receptor agonists, there have also been changes in body composition, Dr. Czernichow said.

In SURMOUNT-1, for example, the dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide (Zepbound) was shown to significantly reduce total fat mass with a smaller decrease in total lean mass in a subanalysis.

It has been argued that effects on body composition need to be considered when evaluating new weight loss drugs, and that focusing only on the degree of weight reduction is “encouraging inaccurate measures of medication efficacy for both patients and clinicians,” Dr. Czernichow said, citing a viewpoint published in JAMA Internal Medicine.

“The real question is: Are we able to fund these drugs for everyone? Or will only the richest patients be allocated to these drugs?” Dr. Czernichow said.
 

Weight Rebound

Tonia Vincent, MBBS, PhD, professor of musculoskeletal biology and an honorary rheumatologist at The Kennedy Institute of Rheumatology at University of Oxford in England, was concerned about rebound weight gain.

“We hear a lot about this, that people stopping drugs actually get worse weight gain than before they started, and that’s a concern about a drug that is going to have a huge pressure for supply,” Dr. Vincent said following Dr. Czernichow’s presentation.

Another delegate said that calling GLP-1 receptor agonists a “game changer” for weight loss in OA was premature because long-term results are needed.

“You mentioned that the double-digit weight loss is getting very close to the results from bariatric surgery, but bariatric surgery you do once, and for these drugs, to maintain the weight loss, you need to take them continuously,” she said.
 

Weight Loss Affects Bone

Yet another delegate cautioned on the potential effects of significant weight loss on bone and cartilage. There is evidence, he said, that weight loss of 5-10 kg can significantly affect bone turnover, increasing bone resorption and thus putting patients at a risk of becoming osteopenic. “Are we looking at a new population of osteoporosis patients who may then also be at risk for fractures?” he asked.

Separately at OARSI 2024, Anne C. Bay-Jensen, PhD, chief technology officer at Nordic Bioscience in Herlev, Denmark, and colleagues reported data showing that weight loss was associated with an increase in bone and cartilage degradation.

Although Dr. Bay-Jensen and colleagues found that losing weight was associated with improved patient outcomes, there was a 1.58-fold increase in the bone resorption marker CTX-I in people who had lost weight vs a 1.37-fold gain in those whose weight remained stable and 1.11-fold increase in those who gained weight.

Moreover, there was a 1.15-fold increase in the cartilage degradation marker C2M in the weight loss group and 0.84-fold decrease in the interstitial matrix degradation marker C3M.
 

GLP-1 and Bone Effects

Another question is whether GLP-1 receptor agonists might be having direct effects on the bone that may be beneficial in OA. They might, postdoctoral researcher Eda Çiftci, PhD, of AO Research Institute Davos in Switzerland, and collaborators, said during the poster sessions at OARSI 2024.

Dr. Çiftci and researchers reported the findings of an in vitro study that looked at whether liraglutide might have anti-inflammatory and anabolic effects on a human chondrocytes model that had been treated with interleukin (IL)-1-beta to “mimic an inflammatory OA condition.”

The release of the proinflammatory cytokines IL-6 and IL-8 was reduced by treatment with liraglutide when compared with control chondrocytes. Furthermore, the expression of the proteoglycan aggrecan — important for articular cartilage function — also was preserved.

These results suggest that liraglutide does indeed have anabolic and anti-inflammatory effects, Dr. Çiftci and fellow researchers concluded.
 

New Role for Dipeptidyl Transferase Inhibitors?

Researchers are also looking at the potential role for other diabetes medications in OA management, including the dipeptidyl peptidase (DPP) 4 inhibitors.

Although these drugs are considered “weight neutral,” in vitro studies have suggested that the DPP4 enzyme may have a role to play in chondrocyte survival and inflammation, Yu-Hsiu Chen, MD, of the Tri-Service General Hospital and the National Defense Medical Center in Taipei, Taiwan, told this news organization. The DPP4 enzyme inactivates GLP-1, so there is rationale there.

“Last year, we published a paper where we found the concentration of DPP4 in the synovial fluid was correlated with radiographic change in knee OA,” Dr. Chen said. This time, “we’re trying to see if a DPP4 inhibitor can be used as a treatment.”

For their analysis, they used data on people newly diagnosed with type 2 diabetes who were and were not using DPP4 inhibitors obtained from Taiwan’s National Health Insurance Research Database. This database contains information on 99% of the Taiwanese population, Dr. Chen said.

Matching 165,333 DPP4 inhibitor users with an equal number of nonusers showed that there was a significant 58% risk reduction for developing OA with DPP4 inhibitor use (hazard ratio, 0.42; 95% CI, 0.41-0.44).

DPP4 inhibitor use was also associated with a 58% risk lower risk for total knee replacement (TKR) and a 62% lower risk for total hip replacement.

Dr. Chen and colleagues concluded: “These results strongly indicate that DPP4 inhibitors could be considered as a viable treatment approach for individuals with type 2 [diabetes mellitus] who are at risk for developing OA or [who] already have OA.”
 

Could Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors Be Beneficial?

So, what about SGLT2 inhibitors? Do they also have a potential role to play in managing people with OA, regardless of whether there is diabetes present? Perhaps, and their effect may be even greater than what’s been observed for GLP-1 receptor agonists, as data presented by epidemiologist S. Reza Jafarzadeh, DVM, PhD, suggested.

“While GLP-1 receptor agonist drugs have been reported to reduce OA risk, largely attributed to their weight loss effect, SGLT2 inhibitors may provide a greater protective effect on OA outcomes,” said Dr. Jafarzadeh, assistant professor at Boston University.

Sara Freeman/Medscape Medical News

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Czernichow disclosed ties with BariaTek Medical, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Janssen, Jellynov, Lilly, Novo Nordisk, Novartis, and ViiV Healthcare. Dr. Vincent had no relevant disclosures. Dr. Bay-Jensen is the chief technology officer and director of immunoscience at Nordic Bioscience, which funded the work in the poster she presented at OARSI 2024. The work presented by Dr. Çiftci and colleagues was funded by the Eurostars-2 joint program with co-funding from the European Horizon 2020 research and innovation program. Dr. Çiftci had no personal disclosures to report. Dr. Chen’s work was supported by the government of Taiwan, and she had no financial conflicts of interest to disclose. Dr. Jafarzadeh had no conflicts of interest to disclose.

A version of this article appeared on Medscape.com .

DENVER — In addition to the established gastrointestinal side effects common with the highly effective anti-obesity drugs, there is growing discussion around their potential to contribute to the loss of lean mass, necessary to keep the metabolic engine running full-steam.

And although measures should be recommended to prevent those effects, experts also want to remind clinicians that the loss of lean mass is indeed expected with most weight loss interventions — when they’re successful.

“The bottom line is if you’re successful with weight loss, it’s a normal process that you’re going to lose some lean mass,” Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center in Boston, said during a presentation on the issue at Obesity Medicine 2024.

“It’s what we would expect to see if you successfully lost weight with bariatric surgery or with an intense lifestyle intervention,” said Dr. Fitch, past president of the Obesity Medicine Association.

“The difference is, there haven’t been nearly as many people being successful with weight loss with those other interventions,” she noted. “But with the popularity of the glucagon-like peptide 1 (GLP-1) medications, people are hearing this for the first time and saying, ‘Oh my gosh, 30% of the weight loss is muscle mass — that’s horrible.’ “

An underlying goal in the treatment of obesity is the reduction of fat mass, and significant fat mass reduction can provide benefits exceeding the drawbacks resulting from lean mass loss, which have been reported in clinical trials of the GLP-1s semaglutide and the dual glucose-dependent insulinotropic polypeptide tirzepatide to range from about 25% to 40%, respectively, of weight loss.

“Excess adiposity is what makes us sick — not our weight,” Dr. Fitch underscored. “The amount of fat that people are losing [with anti-obesity medications] is far more beneficial than maybe the potential that they’ve lost a little bit of lean mass,” she said.

She cited research suggesting that significant weight loss from bariatric surgery is linked to increases in life expectancy, cardiovascular risk reduction, cancer risk reduction, and a wide array of other positive effects — despite the loss of lean mass that occurs with the weight loss.

Opportunity for Awareness

The increased attention on issues of body composition accompanying weight loss importantly provides clinicians the chance to underscore to patients the importance of offsetting the loss of lean mass through strength training, nutritional choices, and other measures.

However, patients should be prepared that achieving these goals can be more challenging than expected, said Dr. Fitch.

“It can be very hard to be in an energy deficit (due to a weight loss regimen) and gain muscle mass,” she said. “When athletes are trying to gain muscle mass, they’re increasing their intake to do so. It doesn’t come naturally in today’s world.”

Nevertheless, patients can be reassured that the losses can be reversed with some effort, Dr. Fitch noted.

She cautioned that for those who succeed in building or rebuilding lean mass, the evidence may be reflected on the scale, with numbers going up, not down — something they may not wish to see.

“Patients tend to freak out when they see the scale going up after losing all of that weight, but you can reassure them that it’s okay — this is healthier weight gain.”

Special Considerations in Older Patients

Efforts at staving off lean mass loss are particularly important in older patients, who are already most vulnerable to experiencing it naturally with age, even if not on a weight loss regimen.

But Dr. Fitch offered that age does not necessarily have to be a barrier in tackling those effects.

She described two cases of treating patients in their mid-70s, a male and female, with GLP-1s for obesity. Not only were they able to achieve substantial reductions in body mass index over nearly a year on treatment, but they were also able to avoid skeletal muscle mass loss during a period when it would have likely naturally occurred.

She noted the need to augment strength training with protein intake to help build muscle, citing recommendations including consumption of 1.4-2.0 g of protein per kg of body weight for building muscle and maintaining muscle mass.

Importantly, “make sure patients aren’t too appetite suppressed so they can keep up with their nutrition,” Dr. Fitch said.

A key condition to watch for in these patients is sarcopenia. Definitions of sarcopenia vary, but it is distinguished by low skeletal muscle mass and either low muscle strength — measured, for instance, with hand grip — or low muscle performance, such as reduced walking speed or muscle power, Dr. Fitch said.

In such cases, patients may need special considerations, including avoiding significant caloric deficits and whether the risks of medication outweigh the benefits.

‘Super-Responders’ and Other Lean Mass Loss Scenarios

Further addressing the issues of body composition and weight loss at the meeting, Robert F. Kushner, MD, professor of medicine and medicine education at Northwestern University in Chicago, noted that one area of concern regarding lean mass loss is “super-responders” — patients who have exceptionally high weight loss on GLP-1s.

“We are concerned about individuals who experience very high weight loss responses to medication, [specifically] 25% or more weight loss, as well as individuals at higher risk of losing lean body mass [muscle mass], specifically people in their 50s, 60s, and 70s,” Dr. Kushner told this news organization.

“Lifestyle counseling, particularly regarding safety and body composition, is recommended in these patients,” he said, adding that in managing these patients, “the approach is to use close patient monitoring, dose reduction if needed, and emphasizing a high-protein diet accompanied by aerobic and resistance physical activity.”

Potentially dramatic lean mass loss can occur in obesity whether or not patients are on obesity medications. As evidence of this, Dr. Kushner cited a subanalysis of the Look AHEAD trial of 1019 overweight or obese patients who had a mean age of 58 years at baseline. Patients were randomized to either a physical activity and reduced calorie intervention group or simply education.

Although the results showed that fat losses in the intervention group were generally regained over 8 years, a striking, steady decline was observed in lean mass in both the intervention and control groups, including men and women.

Dr. Fitch disclosed ties to Eli Lilly, Novo Nordisk, Currax, Vivus, SideKick Health, Jenny Craig, Carmot, and Seca. Dr. Kushner is on the advisory boards of Novo Nordisk, Weight Watchers, Lilly, Boehringer Ingelheim, and Altimmune.

A version of this article appeared on Medscape.com.

DENVER — In addition to the established gastrointestinal side effects common with the highly effective anti-obesity drugs, there is growing discussion around their potential to contribute to the loss of lean mass, necessary to keep the metabolic engine running full-steam.

And although measures should be recommended to prevent those effects, experts also want to remind clinicians that the loss of lean mass is indeed expected with most weight loss interventions — when they’re successful.

“The bottom line is if you’re successful with weight loss, it’s a normal process that you’re going to lose some lean mass,” Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center in Boston, said during a presentation on the issue at Obesity Medicine 2024.

“It’s what we would expect to see if you successfully lost weight with bariatric surgery or with an intense lifestyle intervention,” said Dr. Fitch, past president of the Obesity Medicine Association.

“The difference is, there haven’t been nearly as many people being successful with weight loss with those other interventions,” she noted. “But with the popularity of the glucagon-like peptide 1 (GLP-1) medications, people are hearing this for the first time and saying, ‘Oh my gosh, 30% of the weight loss is muscle mass — that’s horrible.’ “

An underlying goal in the treatment of obesity is the reduction of fat mass, and significant fat mass reduction can provide benefits exceeding the drawbacks resulting from lean mass loss, which have been reported in clinical trials of the GLP-1s semaglutide and the dual glucose-dependent insulinotropic polypeptide tirzepatide to range from about 25% to 40%, respectively, of weight loss.

“Excess adiposity is what makes us sick — not our weight,” Dr. Fitch underscored. “The amount of fat that people are losing [with anti-obesity medications] is far more beneficial than maybe the potential that they’ve lost a little bit of lean mass,” she said.

She cited research suggesting that significant weight loss from bariatric surgery is linked to increases in life expectancy, cardiovascular risk reduction, cancer risk reduction, and a wide array of other positive effects — despite the loss of lean mass that occurs with the weight loss.

Opportunity for Awareness

The increased attention on issues of body composition accompanying weight loss importantly provides clinicians the chance to underscore to patients the importance of offsetting the loss of lean mass through strength training, nutritional choices, and other measures.

However, patients should be prepared that achieving these goals can be more challenging than expected, said Dr. Fitch.

“It can be very hard to be in an energy deficit (due to a weight loss regimen) and gain muscle mass,” she said. “When athletes are trying to gain muscle mass, they’re increasing their intake to do so. It doesn’t come naturally in today’s world.”

Nevertheless, patients can be reassured that the losses can be reversed with some effort, Dr. Fitch noted.

She cautioned that for those who succeed in building or rebuilding lean mass, the evidence may be reflected on the scale, with numbers going up, not down — something they may not wish to see.

“Patients tend to freak out when they see the scale going up after losing all of that weight, but you can reassure them that it’s okay — this is healthier weight gain.”

Special Considerations in Older Patients

Efforts at staving off lean mass loss are particularly important in older patients, who are already most vulnerable to experiencing it naturally with age, even if not on a weight loss regimen.

But Dr. Fitch offered that age does not necessarily have to be a barrier in tackling those effects.

She described two cases of treating patients in their mid-70s, a male and female, with GLP-1s for obesity. Not only were they able to achieve substantial reductions in body mass index over nearly a year on treatment, but they were also able to avoid skeletal muscle mass loss during a period when it would have likely naturally occurred.

She noted the need to augment strength training with protein intake to help build muscle, citing recommendations including consumption of 1.4-2.0 g of protein per kg of body weight for building muscle and maintaining muscle mass.

Importantly, “make sure patients aren’t too appetite suppressed so they can keep up with their nutrition,” Dr. Fitch said.

A key condition to watch for in these patients is sarcopenia. Definitions of sarcopenia vary, but it is distinguished by low skeletal muscle mass and either low muscle strength — measured, for instance, with hand grip — or low muscle performance, such as reduced walking speed or muscle power, Dr. Fitch said.

In such cases, patients may need special considerations, including avoiding significant caloric deficits and whether the risks of medication outweigh the benefits.

‘Super-Responders’ and Other Lean Mass Loss Scenarios

Further addressing the issues of body composition and weight loss at the meeting, Robert F. Kushner, MD, professor of medicine and medicine education at Northwestern University in Chicago, noted that one area of concern regarding lean mass loss is “super-responders” — patients who have exceptionally high weight loss on GLP-1s.

“We are concerned about individuals who experience very high weight loss responses to medication, [specifically] 25% or more weight loss, as well as individuals at higher risk of losing lean body mass [muscle mass], specifically people in their 50s, 60s, and 70s,” Dr. Kushner told this news organization.

“Lifestyle counseling, particularly regarding safety and body composition, is recommended in these patients,” he said, adding that in managing these patients, “the approach is to use close patient monitoring, dose reduction if needed, and emphasizing a high-protein diet accompanied by aerobic and resistance physical activity.”

Potentially dramatic lean mass loss can occur in obesity whether or not patients are on obesity medications. As evidence of this, Dr. Kushner cited a subanalysis of the Look AHEAD trial of 1019 overweight or obese patients who had a mean age of 58 years at baseline. Patients were randomized to either a physical activity and reduced calorie intervention group or simply education.

Although the results showed that fat losses in the intervention group were generally regained over 8 years, a striking, steady decline was observed in lean mass in both the intervention and control groups, including men and women.

Dr. Fitch disclosed ties to Eli Lilly, Novo Nordisk, Currax, Vivus, SideKick Health, Jenny Craig, Carmot, and Seca. Dr. Kushner is on the advisory boards of Novo Nordisk, Weight Watchers, Lilly, Boehringer Ingelheim, and Altimmune.

A version of this article appeared on Medscape.com.

DENVER — In addition to the established gastrointestinal side effects common with the highly effective anti-obesity drugs, there is growing discussion around their potential to contribute to the loss of lean mass, necessary to keep the metabolic engine running full-steam.

And although measures should be recommended to prevent those effects, experts also want to remind clinicians that the loss of lean mass is indeed expected with most weight loss interventions — when they’re successful.

“The bottom line is if you’re successful with weight loss, it’s a normal process that you’re going to lose some lean mass,” Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center in Boston, said during a presentation on the issue at Obesity Medicine 2024.

“It’s what we would expect to see if you successfully lost weight with bariatric surgery or with an intense lifestyle intervention,” said Dr. Fitch, past president of the Obesity Medicine Association.

“The difference is, there haven’t been nearly as many people being successful with weight loss with those other interventions,” she noted. “But with the popularity of the glucagon-like peptide 1 (GLP-1) medications, people are hearing this for the first time and saying, ‘Oh my gosh, 30% of the weight loss is muscle mass — that’s horrible.’ “

An underlying goal in the treatment of obesity is the reduction of fat mass, and significant fat mass reduction can provide benefits exceeding the drawbacks resulting from lean mass loss, which have been reported in clinical trials of the GLP-1s semaglutide and the dual glucose-dependent insulinotropic polypeptide tirzepatide to range from about 25% to 40%, respectively, of weight loss.

“Excess adiposity is what makes us sick — not our weight,” Dr. Fitch underscored. “The amount of fat that people are losing [with anti-obesity medications] is far more beneficial than maybe the potential that they’ve lost a little bit of lean mass,” she said.

She cited research suggesting that significant weight loss from bariatric surgery is linked to increases in life expectancy, cardiovascular risk reduction, cancer risk reduction, and a wide array of other positive effects — despite the loss of lean mass that occurs with the weight loss.

Opportunity for Awareness

The increased attention on issues of body composition accompanying weight loss importantly provides clinicians the chance to underscore to patients the importance of offsetting the loss of lean mass through strength training, nutritional choices, and other measures.

However, patients should be prepared that achieving these goals can be more challenging than expected, said Dr. Fitch.

“It can be very hard to be in an energy deficit (due to a weight loss regimen) and gain muscle mass,” she said. “When athletes are trying to gain muscle mass, they’re increasing their intake to do so. It doesn’t come naturally in today’s world.”

Nevertheless, patients can be reassured that the losses can be reversed with some effort, Dr. Fitch noted.

She cautioned that for those who succeed in building or rebuilding lean mass, the evidence may be reflected on the scale, with numbers going up, not down — something they may not wish to see.

“Patients tend to freak out when they see the scale going up after losing all of that weight, but you can reassure them that it’s okay — this is healthier weight gain.”

Special Considerations in Older Patients

Efforts at staving off lean mass loss are particularly important in older patients, who are already most vulnerable to experiencing it naturally with age, even if not on a weight loss regimen.

But Dr. Fitch offered that age does not necessarily have to be a barrier in tackling those effects.

She described two cases of treating patients in their mid-70s, a male and female, with GLP-1s for obesity. Not only were they able to achieve substantial reductions in body mass index over nearly a year on treatment, but they were also able to avoid skeletal muscle mass loss during a period when it would have likely naturally occurred.

She noted the need to augment strength training with protein intake to help build muscle, citing recommendations including consumption of 1.4-2.0 g of protein per kg of body weight for building muscle and maintaining muscle mass.

Importantly, “make sure patients aren’t too appetite suppressed so they can keep up with their nutrition,” Dr. Fitch said.

A key condition to watch for in these patients is sarcopenia. Definitions of sarcopenia vary, but it is distinguished by low skeletal muscle mass and either low muscle strength — measured, for instance, with hand grip — or low muscle performance, such as reduced walking speed or muscle power, Dr. Fitch said.

In such cases, patients may need special considerations, including avoiding significant caloric deficits and whether the risks of medication outweigh the benefits.

‘Super-Responders’ and Other Lean Mass Loss Scenarios

Further addressing the issues of body composition and weight loss at the meeting, Robert F. Kushner, MD, professor of medicine and medicine education at Northwestern University in Chicago, noted that one area of concern regarding lean mass loss is “super-responders” — patients who have exceptionally high weight loss on GLP-1s.

“We are concerned about individuals who experience very high weight loss responses to medication, [specifically] 25% or more weight loss, as well as individuals at higher risk of losing lean body mass [muscle mass], specifically people in their 50s, 60s, and 70s,” Dr. Kushner told this news organization.

“Lifestyle counseling, particularly regarding safety and body composition, is recommended in these patients,” he said, adding that in managing these patients, “the approach is to use close patient monitoring, dose reduction if needed, and emphasizing a high-protein diet accompanied by aerobic and resistance physical activity.”

Potentially dramatic lean mass loss can occur in obesity whether or not patients are on obesity medications. As evidence of this, Dr. Kushner cited a subanalysis of the Look AHEAD trial of 1019 overweight or obese patients who had a mean age of 58 years at baseline. Patients were randomized to either a physical activity and reduced calorie intervention group or simply education.

Although the results showed that fat losses in the intervention group were generally regained over 8 years, a striking, steady decline was observed in lean mass in both the intervention and control groups, including men and women.

Dr. Fitch disclosed ties to Eli Lilly, Novo Nordisk, Currax, Vivus, SideKick Health, Jenny Craig, Carmot, and Seca. Dr. Kushner is on the advisory boards of Novo Nordisk, Weight Watchers, Lilly, Boehringer Ingelheim, and Altimmune.

A version of this article appeared on Medscape.com.

TOPLINE:

Nearly 90% of adults were at risk of developing cardiovascular-kidney-metabolic (CKM) syndrome between 2011 and 2020, according to new research published in JAMA.

METHODOLOGY:

• In 2023, the American Heart Association defined  to acknowledge how heart and kidney diseases, diabetes, and obesity interact and are increasingly co-occurring conditions.
• Researchers used data from the National Health and Nutrition Examination Survey between 2011 and 2020.
• More than 10,000 adults over age 20 years were included; all of them received a physical and fasting laboratory measurements and self-reported their cardiovascular disease (CVD) status.
• Researchers created categories for risk, ranging from 0 (no risk factors) to 4, using factors such as kidney disease, obesity, and hypertension.

TAKEAWAY:

• Nearly 90% of participants met the criteria for having a stage of the CKM syndrome, with rates remaining steady throughout the study period.Almost half of people met the criteria for stage 2 (having metabolic risk factors like hypertension or moderate- to high-risk chronic kidney disease).
• 14.6% met the criteria for advanced stage 3 (very high-risk chronic kidney disease or a high risk for 10-year CVD) and stage 4 CKM syndrome (established CVD) combined.
• Men, adults over age 65 years, and Black individuals were at a greater risk for advanced stages of the CKM syndrome.
• Almost half of people met the criteria for stage 2 (having metabolic risk factors like hypertension or moderate- to high-risk chronic kidney disease).
   
• 14.6% met the criteria for advanced stage 3 (very high-risk chronic kidney disease or a high risk for 10-year CVD) and stage 4 CKM syndrome (established CVD) combined.
   
• Men, adults over age 65 years, and Black individuals were at a greater risk for advanced stages of the CKM syndrome.

IN PRACTICE:

“Equitable health care approaches prioritizing CKM health are urgently needed,” the study authors wrote.

SOURCE:

The study was led by Muthiah Vaduganathan, MD, MPH, cardiologist and researcher at Brigham and Women’s Hospital, Harvard Medical School, Boston.

LIMITATIONS: 

Established CVD statuses were self-reported. Some data that would indicate advanced CKM stages were not available (eg, cardiac biomarkers, echocardiography, and coronary angiography), which may have led to an underestimation of rates.

DISCLOSURES:

One author received grants from Bristol Myers Squibb–Pfizer outside the submitted work. Dr. Vaduganathan received grants from and was an adviser and committee trial member for various pharmaceutical companies outside the submitted work. The authors reported no other disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Nearly 90% of adults were at risk of developing cardiovascular-kidney-metabolic (CKM) syndrome between 2011 and 2020, according to new research published in JAMA.

METHODOLOGY:

• In 2023, the American Heart Association defined  to acknowledge how heart and kidney diseases, diabetes, and obesity interact and are increasingly co-occurring conditions.
• Researchers used data from the National Health and Nutrition Examination Survey between 2011 and 2020.
• More than 10,000 adults over age 20 years were included; all of them received a physical and fasting laboratory measurements and self-reported their cardiovascular disease (CVD) status.
• Researchers created categories for risk, ranging from 0 (no risk factors) to 4, using factors such as kidney disease, obesity, and hypertension.

TAKEAWAY:

• Nearly 90% of participants met the criteria for having a stage of the CKM syndrome, with rates remaining steady throughout the study period.Almost half of people met the criteria for stage 2 (having metabolic risk factors like hypertension or moderate- to high-risk chronic kidney disease).
• 14.6% met the criteria for advanced stage 3 (very high-risk chronic kidney disease or a high risk for 10-year CVD) and stage 4 CKM syndrome (established CVD) combined.
• Men, adults over age 65 years, and Black individuals were at a greater risk for advanced stages of the CKM syndrome.
• Almost half of people met the criteria for stage 2 (having metabolic risk factors like hypertension or moderate- to high-risk chronic kidney disease).
   
• 14.6% met the criteria for advanced stage 3 (very high-risk chronic kidney disease or a high risk for 10-year CVD) and stage 4 CKM syndrome (established CVD) combined.
   
• Men, adults over age 65 years, and Black individuals were at a greater risk for advanced stages of the CKM syndrome.

IN PRACTICE:

“Equitable health care approaches prioritizing CKM health are urgently needed,” the study authors wrote.

SOURCE:

The study was led by Muthiah Vaduganathan, MD, MPH, cardiologist and researcher at Brigham and Women’s Hospital, Harvard Medical School, Boston.

LIMITATIONS: 

Established CVD statuses were self-reported. Some data that would indicate advanced CKM stages were not available (eg, cardiac biomarkers, echocardiography, and coronary angiography), which may have led to an underestimation of rates.

DISCLOSURES:

One author received grants from Bristol Myers Squibb–Pfizer outside the submitted work. Dr. Vaduganathan received grants from and was an adviser and committee trial member for various pharmaceutical companies outside the submitted work. The authors reported no other disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Nearly 90% of adults were at risk of developing cardiovascular-kidney-metabolic (CKM) syndrome between 2011 and 2020, according to new research published in JAMA.

METHODOLOGY:

• In 2023, the American Heart Association defined  to acknowledge how heart and kidney diseases, diabetes, and obesity interact and are increasingly co-occurring conditions.
• Researchers used data from the National Health and Nutrition Examination Survey between 2011 and 2020.
• More than 10,000 adults over age 20 years were included; all of them received a physical and fasting laboratory measurements and self-reported their cardiovascular disease (CVD) status.
• Researchers created categories for risk, ranging from 0 (no risk factors) to 4, using factors such as kidney disease, obesity, and hypertension.

TAKEAWAY:

• Nearly 90% of participants met the criteria for having a stage of the CKM syndrome, with rates remaining steady throughout the study period.Almost half of people met the criteria for stage 2 (having metabolic risk factors like hypertension or moderate- to high-risk chronic kidney disease).
• 14.6% met the criteria for advanced stage 3 (very high-risk chronic kidney disease or a high risk for 10-year CVD) and stage 4 CKM syndrome (established CVD) combined.
• Men, adults over age 65 years, and Black individuals were at a greater risk for advanced stages of the CKM syndrome.
• Almost half of people met the criteria for stage 2 (having metabolic risk factors like hypertension or moderate- to high-risk chronic kidney disease).
   
• 14.6% met the criteria for advanced stage 3 (very high-risk chronic kidney disease or a high risk for 10-year CVD) and stage 4 CKM syndrome (established CVD) combined.
   
• Men, adults over age 65 years, and Black individuals were at a greater risk for advanced stages of the CKM syndrome.

IN PRACTICE:

“Equitable health care approaches prioritizing CKM health are urgently needed,” the study authors wrote.

SOURCE:

The study was led by Muthiah Vaduganathan, MD, MPH, cardiologist and researcher at Brigham and Women’s Hospital, Harvard Medical School, Boston.

LIMITATIONS: 

Established CVD statuses were self-reported. Some data that would indicate advanced CKM stages were not available (eg, cardiac biomarkers, echocardiography, and coronary angiography), which may have led to an underestimation of rates.

DISCLOSURES:

One author received grants from Bristol Myers Squibb–Pfizer outside the submitted work. Dr. Vaduganathan received grants from and was an adviser and committee trial member for various pharmaceutical companies outside the submitted work. The authors reported no other disclosures.

A version of this article appeared on Medscape.com.

CHICAGO — The diabetes/weight loss drug semaglutide is associated with a significantly greater risk for repeat operations in patients with diabetes who require lumbar surgery, a new study suggests.

The risk for additional surgeries was even higher among patients taking the popular weight loss and diabetes drug for longer periods of time.

Investigators say the study provides the first evidence on the impact of semaglutide on spine surgery. 

“The expectation was [that] we would see patients doing better after surgery, less wound complications, and other things, and in our diabetic patients we did not see that and saw increased odds of needing additional surgeries,” investigator Syed I. Khalid, MD, neurosurgery resident at University of Illinois Chicago, told this news organization.

The findings were presented on May 3 at the American Association of Neurological Surgeons (AANS) 2024 Annual Meeting.
 

Additional Surgery at Year 1

The new study used the all-payer Mariner database to identify patients aged 18-74 years with type 2 diabetes who underwent elective one- to three-level transforaminal lumbar interbody fusions (TLIFs) between January 2018 and October 2022. 

Patients were matched in a 3:1 ratio for age, sex, hypertension, obesity, smoking history, chronic kidney disease, osteoporosis, insulin use, and spinal fusion level, resulting in 447 patients with semaglutide use and 1334 with no semaglutide use. More than half (56%) were female, 62% used insulin, and 81% underwent single-level TLIF.

Total medical complications were higher in the semaglutide group, at 13.4%, compared with 7.7% in the no-semaglutide group (odds ratio [OR], 1.85). This was driven by higher rates of urinary tract infection (6.7% vs 2.5%) and acute kidney injury (6.3% vs 3.9%), two complications observed with semaglutide in other studies, Dr. Khalid said.

Total surgical complications, however, were lower in patients taking semaglutide, at 3.8% vs 5.2% in those who did not (OR, 0.73). 

Patients taking semaglutide vs those who were not using semaglutide had fewer wound healing complications (5 vs 31), hematoma (1 vs 9), surgical-site infections (12 vs 44), and cerebrospinal fluid leaks (2 vs 3).

Still, people taking semaglutide were nearly 12 times more likely to have an additional lumbar surgery at 1 year than did those who did not use the drug (27.3% vs 3.1%; OR, 11.79; 95% CI, 8.17-17.33).

Kaplan-Meier plots revealed a striking divergence of these populations when semaglutide exposure for more than or less than 9 months was examined (log-rank P < .0001).

Currently under review for publication, this study provides the first evidence on the impact of semaglutide on spine surgery, Dr. Khalid said. A second follow-up paper, also under review, looked only at patients with patients morbidly obesity without diabetes who had taken semaglutide for weight loss. 

“In nondiabetic, morbidly obese patients undergoing spine surgery, we see a similar trend,” Dr. Khalid said.
 

Sarcopenia the Cause?

The additional surgeries were primarily extensions of constructs, with additional surgery and fusion at more levels, Dr. Khalid noted. 

“The idea is that it could be the fact there is sarcopenia or muscle loss that’s taking place in conjunction with fat loss that’s causing that to happen,” Dr. Khalid said.

The mechanism remains speculative, but evidence from other areas examining frailty states has shown that those patients have weaker bones, sarcopenia, and worse outcomes with spine surgery, he noted. 

The investigators plan to use artificial intelligence to evaluate changes in body composition after semaglutide use in patients who underwent imaging prior to spine surgery or even before back pain occurred. Because these medications are uptitrated over time, follow-up studies will also look at whether this change takes place with a certain dose, Dr. Khalid added. 

On the basis of the current analysis of generic semaglutide alone, it’s not possible to say whether the use of other glucagon-like peptide 1 (GLP-1) receptor agonists will result in similar findings, but “the odds of a class effect are high,” Dr. Khalid said. 

Commenting on the findings, Walavan Sivakumar, MD, director of neurosurgery at Pacific Neuroscience Institute, Los Angeles, noted that the timing of surgery is already an issue for patients taking semaglutide and other GLP-1 receptor agonists following recent guidance from the American Society of Anesthesiologists that suggests stopping GLP-1 receptor agonists prior to elective surgery to reduce the risk for complications associated with anesthesia.

“It’s an incredibly topical point and seems to be something showing up on a daily basis for clinicians all throughout neurosurgery,” Dr. Sivakumar said. “It’s thought-provoking and a great first start.” 

Dr. Sivakumar also observed that frailty is a hot topic in all of neurosurgery. “That’s a major, major point that’s showing an impact on all surgical outcomes and it’s being heavily studied in the neurosurgical subsets right now. So that’s definitely a possible correlating factor.”

Dr. Khalid reported no financial relationships. Dr. Sivakumar reported serving as a consultant for Stryker. 
 

A version of this article appeared on Medscape.com.

CHICAGO — The diabetes/weight loss drug semaglutide is associated with a significantly greater risk for repeat operations in patients with diabetes who require lumbar surgery, a new study suggests.

The risk for additional surgeries was even higher among patients taking the popular weight loss and diabetes drug for longer periods of time.

Investigators say the study provides the first evidence on the impact of semaglutide on spine surgery. 

“The expectation was [that] we would see patients doing better after surgery, less wound complications, and other things, and in our diabetic patients we did not see that and saw increased odds of needing additional surgeries,” investigator Syed I. Khalid, MD, neurosurgery resident at University of Illinois Chicago, told this news organization.

The findings were presented on May 3 at the American Association of Neurological Surgeons (AANS) 2024 Annual Meeting.
 

Additional Surgery at Year 1

The new study used the all-payer Mariner database to identify patients aged 18-74 years with type 2 diabetes who underwent elective one- to three-level transforaminal lumbar interbody fusions (TLIFs) between January 2018 and October 2022. 

Patients were matched in a 3:1 ratio for age, sex, hypertension, obesity, smoking history, chronic kidney disease, osteoporosis, insulin use, and spinal fusion level, resulting in 447 patients with semaglutide use and 1334 with no semaglutide use. More than half (56%) were female, 62% used insulin, and 81% underwent single-level TLIF.

Total medical complications were higher in the semaglutide group, at 13.4%, compared with 7.7% in the no-semaglutide group (odds ratio [OR], 1.85). This was driven by higher rates of urinary tract infection (6.7% vs 2.5%) and acute kidney injury (6.3% vs 3.9%), two complications observed with semaglutide in other studies, Dr. Khalid said.

Total surgical complications, however, were lower in patients taking semaglutide, at 3.8% vs 5.2% in those who did not (OR, 0.73). 

Patients taking semaglutide vs those who were not using semaglutide had fewer wound healing complications (5 vs 31), hematoma (1 vs 9), surgical-site infections (12 vs 44), and cerebrospinal fluid leaks (2 vs 3).

Still, people taking semaglutide were nearly 12 times more likely to have an additional lumbar surgery at 1 year than did those who did not use the drug (27.3% vs 3.1%; OR, 11.79; 95% CI, 8.17-17.33).

Kaplan-Meier plots revealed a striking divergence of these populations when semaglutide exposure for more than or less than 9 months was examined (log-rank P < .0001).

Currently under review for publication, this study provides the first evidence on the impact of semaglutide on spine surgery, Dr. Khalid said. A second follow-up paper, also under review, looked only at patients with patients morbidly obesity without diabetes who had taken semaglutide for weight loss. 

“In nondiabetic, morbidly obese patients undergoing spine surgery, we see a similar trend,” Dr. Khalid said.
 

Sarcopenia the Cause?

The additional surgeries were primarily extensions of constructs, with additional surgery and fusion at more levels, Dr. Khalid noted. 

“The idea is that it could be the fact there is sarcopenia or muscle loss that’s taking place in conjunction with fat loss that’s causing that to happen,” Dr. Khalid said.

The mechanism remains speculative, but evidence from other areas examining frailty states has shown that those patients have weaker bones, sarcopenia, and worse outcomes with spine surgery, he noted. 

The investigators plan to use artificial intelligence to evaluate changes in body composition after semaglutide use in patients who underwent imaging prior to spine surgery or even before back pain occurred. Because these medications are uptitrated over time, follow-up studies will also look at whether this change takes place with a certain dose, Dr. Khalid added. 

On the basis of the current analysis of generic semaglutide alone, it’s not possible to say whether the use of other glucagon-like peptide 1 (GLP-1) receptor agonists will result in similar findings, but “the odds of a class effect are high,” Dr. Khalid said. 

Commenting on the findings, Walavan Sivakumar, MD, director of neurosurgery at Pacific Neuroscience Institute, Los Angeles, noted that the timing of surgery is already an issue for patients taking semaglutide and other GLP-1 receptor agonists following recent guidance from the American Society of Anesthesiologists that suggests stopping GLP-1 receptor agonists prior to elective surgery to reduce the risk for complications associated with anesthesia.

“It’s an incredibly topical point and seems to be something showing up on a daily basis for clinicians all throughout neurosurgery,” Dr. Sivakumar said. “It’s thought-provoking and a great first start.” 

Dr. Sivakumar also observed that frailty is a hot topic in all of neurosurgery. “That’s a major, major point that’s showing an impact on all surgical outcomes and it’s being heavily studied in the neurosurgical subsets right now. So that’s definitely a possible correlating factor.”

Dr. Khalid reported no financial relationships. Dr. Sivakumar reported serving as a consultant for Stryker. 
 

A version of this article appeared on Medscape.com.

CHICAGO — The diabetes/weight loss drug semaglutide is associated with a significantly greater risk for repeat operations in patients with diabetes who require lumbar surgery, a new study suggests.

The risk for additional surgeries was even higher among patients taking the popular weight loss and diabetes drug for longer periods of time.

Investigators say the study provides the first evidence on the impact of semaglutide on spine surgery. 

“The expectation was [that] we would see patients doing better after surgery, less wound complications, and other things, and in our diabetic patients we did not see that and saw increased odds of needing additional surgeries,” investigator Syed I. Khalid, MD, neurosurgery resident at University of Illinois Chicago, told this news organization.

The findings were presented on May 3 at the American Association of Neurological Surgeons (AANS) 2024 Annual Meeting.
 

Additional Surgery at Year 1

The new study used the all-payer Mariner database to identify patients aged 18-74 years with type 2 diabetes who underwent elective one- to three-level transforaminal lumbar interbody fusions (TLIFs) between January 2018 and October 2022. 

Patients were matched in a 3:1 ratio for age, sex, hypertension, obesity, smoking history, chronic kidney disease, osteoporosis, insulin use, and spinal fusion level, resulting in 447 patients with semaglutide use and 1334 with no semaglutide use. More than half (56%) were female, 62% used insulin, and 81% underwent single-level TLIF.

Total medical complications were higher in the semaglutide group, at 13.4%, compared with 7.7% in the no-semaglutide group (odds ratio [OR], 1.85). This was driven by higher rates of urinary tract infection (6.7% vs 2.5%) and acute kidney injury (6.3% vs 3.9%), two complications observed with semaglutide in other studies, Dr. Khalid said.

Total surgical complications, however, were lower in patients taking semaglutide, at 3.8% vs 5.2% in those who did not (OR, 0.73). 

Patients taking semaglutide vs those who were not using semaglutide had fewer wound healing complications (5 vs 31), hematoma (1 vs 9), surgical-site infections (12 vs 44), and cerebrospinal fluid leaks (2 vs 3).

Still, people taking semaglutide were nearly 12 times more likely to have an additional lumbar surgery at 1 year than did those who did not use the drug (27.3% vs 3.1%; OR, 11.79; 95% CI, 8.17-17.33).

Kaplan-Meier plots revealed a striking divergence of these populations when semaglutide exposure for more than or less than 9 months was examined (log-rank P < .0001).

Currently under review for publication, this study provides the first evidence on the impact of semaglutide on spine surgery, Dr. Khalid said. A second follow-up paper, also under review, looked only at patients with patients morbidly obesity without diabetes who had taken semaglutide for weight loss. 

“In nondiabetic, morbidly obese patients undergoing spine surgery, we see a similar trend,” Dr. Khalid said.
 

Sarcopenia the Cause?

The additional surgeries were primarily extensions of constructs, with additional surgery and fusion at more levels, Dr. Khalid noted. 

“The idea is that it could be the fact there is sarcopenia or muscle loss that’s taking place in conjunction with fat loss that’s causing that to happen,” Dr. Khalid said.

The mechanism remains speculative, but evidence from other areas examining frailty states has shown that those patients have weaker bones, sarcopenia, and worse outcomes with spine surgery, he noted. 

The investigators plan to use artificial intelligence to evaluate changes in body composition after semaglutide use in patients who underwent imaging prior to spine surgery or even before back pain occurred. Because these medications are uptitrated over time, follow-up studies will also look at whether this change takes place with a certain dose, Dr. Khalid added. 

On the basis of the current analysis of generic semaglutide alone, it’s not possible to say whether the use of other glucagon-like peptide 1 (GLP-1) receptor agonists will result in similar findings, but “the odds of a class effect are high,” Dr. Khalid said. 

Commenting on the findings, Walavan Sivakumar, MD, director of neurosurgery at Pacific Neuroscience Institute, Los Angeles, noted that the timing of surgery is already an issue for patients taking semaglutide and other GLP-1 receptor agonists following recent guidance from the American Society of Anesthesiologists that suggests stopping GLP-1 receptor agonists prior to elective surgery to reduce the risk for complications associated with anesthesia.

“It’s an incredibly topical point and seems to be something showing up on a daily basis for clinicians all throughout neurosurgery,” Dr. Sivakumar said. “It’s thought-provoking and a great first start.” 

Dr. Sivakumar also observed that frailty is a hot topic in all of neurosurgery. “That’s a major, major point that’s showing an impact on all surgical outcomes and it’s being heavily studied in the neurosurgical subsets right now. So that’s definitely a possible correlating factor.”

Dr. Khalid reported no financial relationships. Dr. Sivakumar reported serving as a consultant for Stryker. 
 

A version of this article appeared on Medscape.com.

Pharmaceutical giant Eli Lilly recently announced that its newly approved weight loss medication Zepbound — a glucagon-like peptide 1 receptor agonist (GLP-1 RA) akin to Mounjaro, Ozempic, and Wegovy — will be prescribed by independent telehealth providers on a platform managed by the company itself. The drug can be subsequently shipped direct to consumer (DTC), allowing delivery straight to patients’ homes. 

This arrangement raises serious concerns about an inherent conflict of interest, as we previously discussed. What happens when a pharmaceutical company influences access to remote providers who prescribe the very medications it manufactures? Will these remote providers truly put the patient’s interest first when debating their safety and appropriate use? Whom will patients consult if they have concerns after initiating the medication?

Without new guardrails, the potential for misleading messaging to result in dangerous prescribing patterns looms large. The United States is one of only two countries to allow DTC advertising of prescription drugs, and the explosion in demand for GLP-1 RAs is partly attributable to this model (Oh, oh, Ozempic, anyone?). Americans spent over $78 billion on weight loss goods and services in 2019; time-intensive approaches such as diet and exercise are understandably difficult, and the public has always looked for a magic cure. Although GLP-1 RAs are promising, they may present a path to disaster without proper supervision.

LillyDirect, which in addition to Zepbound offers migraine medications and other products in the company’s catalogue, primarily aims to increase access to medication and reduce costs of the drugs for consumers. The stated mission is noble: By cutting out the middlemen of traditional pharmacies and benefit managers, administrative costs drop. LillyDirect goes a step further by reducing the need for patients to visit their regular family doctor to receive these medications.

On the surface, this design appears promising. Wait times for doctor’s appointments will fall. Patients can order drugs from the comfort of their home. Everyone benefits. Or do they? 

Although easier access and reduced cost may be an apparent win for patients, DTC arrangements complicate the ethics of prescriptions and patient follow-up. This model reminds us of the roots of the opioid crisis, where powerful advertising and relationships between prescribers and drugmakers led to great harm. Providers often faced a conflict of interest when prescribing dangerous drugs to patients who requested them. We must learn from these mistakes to ensure there is critical oversight into the independence of prescribers used by LillyDirect and other DTC platforms.

Adding to these parallels, once a patient begins a GLP-1 medication such as Zepbound, stopping treatment will probably lead to regaining lost weight, serving as negative reinforcement. Hence, patients may decide never to discontinue these medications.

Obtaining what amounts to a lifelong prescription from a telehealth provider who may never follow a patient sets a dangerous precedent that will be difficult to unravel once begun. Recent challenges in access to medications such as Zepbound have been complicated by supply chain and manufacturing issues, leading to potential interruptions in patient access, ultimately affecting compliance. The rapid increase in online providers indicates competition for distribution channels has sharply increased and poses a threat to Lilly’s DTC site. 

Furthermore, the lack of a regular physician to monitor patients introduces uncertainty in safety and continuity of care. These are important tenets in protecting patients, especially patients who are not diabetic and desire a quick fix. We have already seen a huge, arguably unrestrained, rise in prescriptions of GLP-1 RAs for weight loss — up to a 352% increase in 2023.

These drugs have shown great promise and are generally safe when used in the right patient, but important contraindications exist — namely, serious gastrointestinal side effects and low blood glucose in nondiabetic persons — that an astute physician must consider. Patients desiring these medications often must undergo comprehensive laboratory testing and cardiac evaluation, both before initiation and during regular follow-up, to check for comorbidities.

The American College of Physicians cautioned against such prescribing practices in a recent position statement, emphasizing that the lack of an established care provider could adversely affect patients. We note that the potential harms of DTC sales would concentrate in economically and racially underserved communities, where obesity, lack of insurance, and low health literacy are more common. 

But the DTC genie is out of the pill bottle, and as such platforms become more common, patients will inherently take more ownership over their medical care. Remote providers will of course not be following these patients and evaluating for side effects. As a result, we in medical practice must be abreast of new downsides of these medications if and when they arise. 

Every clinician must be aware of the medications a patient is taking, even those that they did not prescribe. They should educate their patients about drug-drug interactions and side effects and order lab tests to monitor for side effects. 

Independent physicians abide by an underlying oath: First, do no harm. They serve as a trusted check on industry and a valuable long-term partner for patients. Where are the guardrails to protect patients and ensure that pharmaceutical companies are not essentially pushing prescriptions for their own products? Will traditional healthcare providers be effectively relegated to a bystander role in Lilly’s transactional approach to medication distribution? Unlike other commercial goods, pharmacologics have great nuance; not every approved medication is meant for every patient.

A version of this article appeared on Medscape.com.

Pharmaceutical giant Eli Lilly recently announced that its newly approved weight loss medication Zepbound — a glucagon-like peptide 1 receptor agonist (GLP-1 RA) akin to Mounjaro, Ozempic, and Wegovy — will be prescribed by independent telehealth providers on a platform managed by the company itself. The drug can be subsequently shipped direct to consumer (DTC), allowing delivery straight to patients’ homes. 

This arrangement raises serious concerns about an inherent conflict of interest, as we previously discussed. What happens when a pharmaceutical company influences access to remote providers who prescribe the very medications it manufactures? Will these remote providers truly put the patient’s interest first when debating their safety and appropriate use? Whom will patients consult if they have concerns after initiating the medication?

Without new guardrails, the potential for misleading messaging to result in dangerous prescribing patterns looms large. The United States is one of only two countries to allow DTC advertising of prescription drugs, and the explosion in demand for GLP-1 RAs is partly attributable to this model (Oh, oh, Ozempic, anyone?). Americans spent over $78 billion on weight loss goods and services in 2019; time-intensive approaches such as diet and exercise are understandably difficult, and the public has always looked for a magic cure. Although GLP-1 RAs are promising, they may present a path to disaster without proper supervision.

LillyDirect, which in addition to Zepbound offers migraine medications and other products in the company’s catalogue, primarily aims to increase access to medication and reduce costs of the drugs for consumers. The stated mission is noble: By cutting out the middlemen of traditional pharmacies and benefit managers, administrative costs drop. LillyDirect goes a step further by reducing the need for patients to visit their regular family doctor to receive these medications.

On the surface, this design appears promising. Wait times for doctor’s appointments will fall. Patients can order drugs from the comfort of their home. Everyone benefits. Or do they? 

Although easier access and reduced cost may be an apparent win for patients, DTC arrangements complicate the ethics of prescriptions and patient follow-up. This model reminds us of the roots of the opioid crisis, where powerful advertising and relationships between prescribers and drugmakers led to great harm. Providers often faced a conflict of interest when prescribing dangerous drugs to patients who requested them. We must learn from these mistakes to ensure there is critical oversight into the independence of prescribers used by LillyDirect and other DTC platforms.

Adding to these parallels, once a patient begins a GLP-1 medication such as Zepbound, stopping treatment will probably lead to regaining lost weight, serving as negative reinforcement. Hence, patients may decide never to discontinue these medications.

Obtaining what amounts to a lifelong prescription from a telehealth provider who may never follow a patient sets a dangerous precedent that will be difficult to unravel once begun. Recent challenges in access to medications such as Zepbound have been complicated by supply chain and manufacturing issues, leading to potential interruptions in patient access, ultimately affecting compliance. The rapid increase in online providers indicates competition for distribution channels has sharply increased and poses a threat to Lilly’s DTC site. 

Furthermore, the lack of a regular physician to monitor patients introduces uncertainty in safety and continuity of care. These are important tenets in protecting patients, especially patients who are not diabetic and desire a quick fix. We have already seen a huge, arguably unrestrained, rise in prescriptions of GLP-1 RAs for weight loss — up to a 352% increase in 2023.

These drugs have shown great promise and are generally safe when used in the right patient, but important contraindications exist — namely, serious gastrointestinal side effects and low blood glucose in nondiabetic persons — that an astute physician must consider. Patients desiring these medications often must undergo comprehensive laboratory testing and cardiac evaluation, both before initiation and during regular follow-up, to check for comorbidities.

The American College of Physicians cautioned against such prescribing practices in a recent position statement, emphasizing that the lack of an established care provider could adversely affect patients. We note that the potential harms of DTC sales would concentrate in economically and racially underserved communities, where obesity, lack of insurance, and low health literacy are more common. 

But the DTC genie is out of the pill bottle, and as such platforms become more common, patients will inherently take more ownership over their medical care. Remote providers will of course not be following these patients and evaluating for side effects. As a result, we in medical practice must be abreast of new downsides of these medications if and when they arise. 

Every clinician must be aware of the medications a patient is taking, even those that they did not prescribe. They should educate their patients about drug-drug interactions and side effects and order lab tests to monitor for side effects. 

Independent physicians abide by an underlying oath: First, do no harm. They serve as a trusted check on industry and a valuable long-term partner for patients. Where are the guardrails to protect patients and ensure that pharmaceutical companies are not essentially pushing prescriptions for their own products? Will traditional healthcare providers be effectively relegated to a bystander role in Lilly’s transactional approach to medication distribution? Unlike other commercial goods, pharmacologics have great nuance; not every approved medication is meant for every patient.

A version of this article appeared on Medscape.com.

Pharmaceutical giant Eli Lilly recently announced that its newly approved weight loss medication Zepbound — a glucagon-like peptide 1 receptor agonist (GLP-1 RA) akin to Mounjaro, Ozempic, and Wegovy — will be prescribed by independent telehealth providers on a platform managed by the company itself. The drug can be subsequently shipped direct to consumer (DTC), allowing delivery straight to patients’ homes. 

This arrangement raises serious concerns about an inherent conflict of interest, as we previously discussed. What happens when a pharmaceutical company influences access to remote providers who prescribe the very medications it manufactures? Will these remote providers truly put the patient’s interest first when debating their safety and appropriate use? Whom will patients consult if they have concerns after initiating the medication?

Without new guardrails, the potential for misleading messaging to result in dangerous prescribing patterns looms large. The United States is one of only two countries to allow DTC advertising of prescription drugs, and the explosion in demand for GLP-1 RAs is partly attributable to this model (Oh, oh, Ozempic, anyone?). Americans spent over $78 billion on weight loss goods and services in 2019; time-intensive approaches such as diet and exercise are understandably difficult, and the public has always looked for a magic cure. Although GLP-1 RAs are promising, they may present a path to disaster without proper supervision.

LillyDirect, which in addition to Zepbound offers migraine medications and other products in the company’s catalogue, primarily aims to increase access to medication and reduce costs of the drugs for consumers. The stated mission is noble: By cutting out the middlemen of traditional pharmacies and benefit managers, administrative costs drop. LillyDirect goes a step further by reducing the need for patients to visit their regular family doctor to receive these medications.

On the surface, this design appears promising. Wait times for doctor’s appointments will fall. Patients can order drugs from the comfort of their home. Everyone benefits. Or do they? 

Although easier access and reduced cost may be an apparent win for patients, DTC arrangements complicate the ethics of prescriptions and patient follow-up. This model reminds us of the roots of the opioid crisis, where powerful advertising and relationships between prescribers and drugmakers led to great harm. Providers often faced a conflict of interest when prescribing dangerous drugs to patients who requested them. We must learn from these mistakes to ensure there is critical oversight into the independence of prescribers used by LillyDirect and other DTC platforms.

Adding to these parallels, once a patient begins a GLP-1 medication such as Zepbound, stopping treatment will probably lead to regaining lost weight, serving as negative reinforcement. Hence, patients may decide never to discontinue these medications.

Obtaining what amounts to a lifelong prescription from a telehealth provider who may never follow a patient sets a dangerous precedent that will be difficult to unravel once begun. Recent challenges in access to medications such as Zepbound have been complicated by supply chain and manufacturing issues, leading to potential interruptions in patient access, ultimately affecting compliance. The rapid increase in online providers indicates competition for distribution channels has sharply increased and poses a threat to Lilly’s DTC site. 

Furthermore, the lack of a regular physician to monitor patients introduces uncertainty in safety and continuity of care. These are important tenets in protecting patients, especially patients who are not diabetic and desire a quick fix. We have already seen a huge, arguably unrestrained, rise in prescriptions of GLP-1 RAs for weight loss — up to a 352% increase in 2023.

These drugs have shown great promise and are generally safe when used in the right patient, but important contraindications exist — namely, serious gastrointestinal side effects and low blood glucose in nondiabetic persons — that an astute physician must consider. Patients desiring these medications often must undergo comprehensive laboratory testing and cardiac evaluation, both before initiation and during regular follow-up, to check for comorbidities.

The American College of Physicians cautioned against such prescribing practices in a recent position statement, emphasizing that the lack of an established care provider could adversely affect patients. We note that the potential harms of DTC sales would concentrate in economically and racially underserved communities, where obesity, lack of insurance, and low health literacy are more common. 

But the DTC genie is out of the pill bottle, and as such platforms become more common, patients will inherently take more ownership over their medical care. Remote providers will of course not be following these patients and evaluating for side effects. As a result, we in medical practice must be abreast of new downsides of these medications if and when they arise. 

Every clinician must be aware of the medications a patient is taking, even those that they did not prescribe. They should educate their patients about drug-drug interactions and side effects and order lab tests to monitor for side effects. 

Independent physicians abide by an underlying oath: First, do no harm. They serve as a trusted check on industry and a valuable long-term partner for patients. Where are the guardrails to protect patients and ensure that pharmaceutical companies are not essentially pushing prescriptions for their own products? Will traditional healthcare providers be effectively relegated to a bystander role in Lilly’s transactional approach to medication distribution? Unlike other commercial goods, pharmacologics have great nuance; not every approved medication is meant for every patient.

A version of this article appeared on Medscape.com.

People with diabetes don’t have higher gastric volumes than those without diabetes after following standard preoperative fasting instructions, suggested a study from a team of anesthesiologist researchers.

However, an endocrinologist faulted the study in part because the participants appeared to be healthier than typical populations with type 1 and type 2 diabetes. Moreover, the issue is now further complicated by the widespread use of glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of both type 2 diabetes and weight loss. These drugs, which were introduced after the study’s enrollment period, work in part by delaying gastric emptying.

The new data come from a prospective study of 84 people with diabetes (85% with type 2) and 96 without diabetes, all with a body mass index (BMI) < 40, who were undergoing elective surgery. A gastric ultrasound was used to assess their gastric contents after they had followed the standard preoperative fasting guidelines of stopping solids 8 hours prior to the procedure and clearing liquids 2 hours prior.

There was no significant difference between the two groups in gastric volume (0.81 mL/kg with diabetes vs 0.87 mL/kg without) or in the proportion with “full stomach,” as designated by the American Society of Anesthesiologists (ASA) guidelines (any solid content or > 1.5 mL/kg of clear fluid), which was seen in 13 with diabetes (15.5%) and 11 (11.5%) without.

Published in Anesthesiology, the findings offer reassurance that different fasting instructions generally aren’t needed for people with diabetes in order to minimize the risk for perioperative pulmonary aspiration, lead author Anahi Perlas, MD, professor of anesthesiology and pain medicine at the University of Toronto, told this news organization.

“We never change practice completely based on a single study, but I think in general, based on our findings, that most diabetic patients aren’t any different from nondiabetics when it comes to their gastric content after fasting, and our standard fasting instructions seem to be just as effective in ensuring an empty stomach.”

But, she added, “If someone has symptoms of gastroparesis or when in doubt, we can always do a gastric ultrasound exam at the bedside and see whether the stomach is full or empty ... it’s very quick, and it’s not difficult to do.”
 

Expert Identifies Noteworthy Study Limitations

In an accompanying editorial, Mark A. Warner, MD, professor of anesthesiology at the Mayo Clinic in Rochester, Minnesota, said the findings “will be very helpful to anesthesiologists,” although he noted that the exclusion of people with a BMI > 40 is a limitation.

However, Michael Horowitz, MBBS, PhD, FRACP, director of the Endocrine and Metabolic Unit at the Royal Adelaide Hospital and professor of medicine at Adelaide Medical School in Adelaide, Australia, disputed the study’s conclusions. He noted that the sample was small, and the participants had an average A1c of 7.2%. Fewer than half had microvascular or neuropathic complications. Thus, they were healthier than the general population with diabetes.

“They’ve picked the wrong group of diabetics,” said Dr. Horowitz, who specializes in gastrointestinal complications of diabetes. “This is not a group where you would expect a very high prevalence of delayed emptying.”

Gastric emptying of solids and liquids varies widely even among healthy people and more so in those with type 2 diabetes. About a third of those with above-target A1c levels have gastroparesis, while those more in the target range tend to have accelerated emptying, he explained.

And regarding the use of gastric ultrasound for those who are symptomatic, Dr. Horowitz said, “The relationship of symptoms such as nausea, vomiting, fullness, whatever it may be, with the rate of gastric emptying is weak at best. The association is not simply cause and effect.”
 

Are the Fasting Guidelines Flawed, Regardless of Diabetes Status?

Dr. Horowitz also faulted the ASA’s 2017 guidance revision for allowing clear liquids to be consumed up to 2 hours in advance of anesthesia because it doesn’t distinguish between liquids with and without calories.

“Whether you have diabetes or not, if you are allowed to have a sugar drink up to 2 hours before your operation, the majority of people empty at about 4 kcal/min, so they will still have some of that drink in their stomach,” he said. “If you want an empty stomach, the ASA guidelines are wrong.”

That explains why the study found relatively high rates of “full stomach” in both groups, 15.5% of those with diabetes and 11.5% of those without, he said.
 

The GLP-1 Agonist Factor

Although the study didn’t address GLP-1 receptor agonist use, Dr. Warner did in his accompanying editorial, noting that the drugs’ rapid expansion “will likely change how we use perioperative fasting guidelines. With these medications delaying gastric emptying times, we now have another risk factor for pulmonary aspiration to consider when applying fasting guidelines. The inconsistent impact of GLP-1 agonists on gastric emptying, ranging from little to significant, makes it difficult for anesthesiologists to gauge whether or not patients taking GLP-1 agonists are likely to have preoperative gastric liquid or solid contents that could cause subsequent damage if regurgitated.”

Gastric ultrasound can be helpful in this situation, Dr. Warner wrote. In addition, he endorsed the 2023 ASA guidance, which calls for withholding daily-dosed GLP-1 agonists on the day of the surgery and the weekly formulations for a week. And if gastrointestinal symptoms are present, delay elective procedures.

But Dr. Horowitz said those recommendations are likely insufficient as well, pointing to data suggesting that daily liraglutide can delay gastric emptying for up to 16 weeks in about a third of patients. Such studies haven’t been conducted by the manufacturers, particularly on the once-weekly formulations, and the ensuing risk for aspiration isn’t known.

“The slowing occurs in much lower doses than are used for glucose lowering,” Dr. Horowitz said. “It is very likely that plasma levels will need to be extremely low to avoid gastric slowing. The current guidelines fail to appreciate this. So, to withhold the short-acting drugs for 1 day is probably wrong. And to stop long-acting drugs for 1 week is almost certainly wrong too.”

But as for what should be done, he said, “I don’t actually know what you do about it. And no one does because there are no data available to answer the question.”

The study received funding from the Physicians’ Services Incorporated Foundation and the Canadian Society of Anesthesiologists. Dr. Perlas received support for nonclinical time through a merit award from the Department of Anesthesiology and Pain Medicine, University of Toronto, and the Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network. She is an executive editor of the journal Regional Anesthesia and Pain Medicine and does consulting work for FujiFilm SonoSite. Dr. Horowitz had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

People with diabetes don’t have higher gastric volumes than those without diabetes after following standard preoperative fasting instructions, suggested a study from a team of anesthesiologist researchers.

However, an endocrinologist faulted the study in part because the participants appeared to be healthier than typical populations with type 1 and type 2 diabetes. Moreover, the issue is now further complicated by the widespread use of glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of both type 2 diabetes and weight loss. These drugs, which were introduced after the study’s enrollment period, work in part by delaying gastric emptying.

The new data come from a prospective study of 84 people with diabetes (85% with type 2) and 96 without diabetes, all with a body mass index (BMI) < 40, who were undergoing elective surgery. A gastric ultrasound was used to assess their gastric contents after they had followed the standard preoperative fasting guidelines of stopping solids 8 hours prior to the procedure and clearing liquids 2 hours prior.

There was no significant difference between the two groups in gastric volume (0.81 mL/kg with diabetes vs 0.87 mL/kg without) or in the proportion with “full stomach,” as designated by the American Society of Anesthesiologists (ASA) guidelines (any solid content or > 1.5 mL/kg of clear fluid), which was seen in 13 with diabetes (15.5%) and 11 (11.5%) without.

Published in Anesthesiology, the findings offer reassurance that different fasting instructions generally aren’t needed for people with diabetes in order to minimize the risk for perioperative pulmonary aspiration, lead author Anahi Perlas, MD, professor of anesthesiology and pain medicine at the University of Toronto, told this news organization.

“We never change practice completely based on a single study, but I think in general, based on our findings, that most diabetic patients aren’t any different from nondiabetics when it comes to their gastric content after fasting, and our standard fasting instructions seem to be just as effective in ensuring an empty stomach.”

But, she added, “If someone has symptoms of gastroparesis or when in doubt, we can always do a gastric ultrasound exam at the bedside and see whether the stomach is full or empty ... it’s very quick, and it’s not difficult to do.”
 

Expert Identifies Noteworthy Study Limitations

In an accompanying editorial, Mark A. Warner, MD, professor of anesthesiology at the Mayo Clinic in Rochester, Minnesota, said the findings “will be very helpful to anesthesiologists,” although he noted that the exclusion of people with a BMI > 40 is a limitation.

However, Michael Horowitz, MBBS, PhD, FRACP, director of the Endocrine and Metabolic Unit at the Royal Adelaide Hospital and professor of medicine at Adelaide Medical School in Adelaide, Australia, disputed the study’s conclusions. He noted that the sample was small, and the participants had an average A1c of 7.2%. Fewer than half had microvascular or neuropathic complications. Thus, they were healthier than the general population with diabetes.

“They’ve picked the wrong group of diabetics,” said Dr. Horowitz, who specializes in gastrointestinal complications of diabetes. “This is not a group where you would expect a very high prevalence of delayed emptying.”

Gastric emptying of solids and liquids varies widely even among healthy people and more so in those with type 2 diabetes. About a third of those with above-target A1c levels have gastroparesis, while those more in the target range tend to have accelerated emptying, he explained.

And regarding the use of gastric ultrasound for those who are symptomatic, Dr. Horowitz said, “The relationship of symptoms such as nausea, vomiting, fullness, whatever it may be, with the rate of gastric emptying is weak at best. The association is not simply cause and effect.”
 

Are the Fasting Guidelines Flawed, Regardless of Diabetes Status?

Dr. Horowitz also faulted the ASA’s 2017 guidance revision for allowing clear liquids to be consumed up to 2 hours in advance of anesthesia because it doesn’t distinguish between liquids with and without calories.

“Whether you have diabetes or not, if you are allowed to have a sugar drink up to 2 hours before your operation, the majority of people empty at about 4 kcal/min, so they will still have some of that drink in their stomach,” he said. “If you want an empty stomach, the ASA guidelines are wrong.”

That explains why the study found relatively high rates of “full stomach” in both groups, 15.5% of those with diabetes and 11.5% of those without, he said.
 

The GLP-1 Agonist Factor

Although the study didn’t address GLP-1 receptor agonist use, Dr. Warner did in his accompanying editorial, noting that the drugs’ rapid expansion “will likely change how we use perioperative fasting guidelines. With these medications delaying gastric emptying times, we now have another risk factor for pulmonary aspiration to consider when applying fasting guidelines. The inconsistent impact of GLP-1 agonists on gastric emptying, ranging from little to significant, makes it difficult for anesthesiologists to gauge whether or not patients taking GLP-1 agonists are likely to have preoperative gastric liquid or solid contents that could cause subsequent damage if regurgitated.”

Gastric ultrasound can be helpful in this situation, Dr. Warner wrote. In addition, he endorsed the 2023 ASA guidance, which calls for withholding daily-dosed GLP-1 agonists on the day of the surgery and the weekly formulations for a week. And if gastrointestinal symptoms are present, delay elective procedures.

But Dr. Horowitz said those recommendations are likely insufficient as well, pointing to data suggesting that daily liraglutide can delay gastric emptying for up to 16 weeks in about a third of patients. Such studies haven’t been conducted by the manufacturers, particularly on the once-weekly formulations, and the ensuing risk for aspiration isn’t known.

“The slowing occurs in much lower doses than are used for glucose lowering,” Dr. Horowitz said. “It is very likely that plasma levels will need to be extremely low to avoid gastric slowing. The current guidelines fail to appreciate this. So, to withhold the short-acting drugs for 1 day is probably wrong. And to stop long-acting drugs for 1 week is almost certainly wrong too.”

But as for what should be done, he said, “I don’t actually know what you do about it. And no one does because there are no data available to answer the question.”

The study received funding from the Physicians’ Services Incorporated Foundation and the Canadian Society of Anesthesiologists. Dr. Perlas received support for nonclinical time through a merit award from the Department of Anesthesiology and Pain Medicine, University of Toronto, and the Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network. She is an executive editor of the journal Regional Anesthesia and Pain Medicine and does consulting work for FujiFilm SonoSite. Dr. Horowitz had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

People with diabetes don’t have higher gastric volumes than those without diabetes after following standard preoperative fasting instructions, suggested a study from a team of anesthesiologist researchers.

However, an endocrinologist faulted the study in part because the participants appeared to be healthier than typical populations with type 1 and type 2 diabetes. Moreover, the issue is now further complicated by the widespread use of glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of both type 2 diabetes and weight loss. These drugs, which were introduced after the study’s enrollment period, work in part by delaying gastric emptying.

The new data come from a prospective study of 84 people with diabetes (85% with type 2) and 96 without diabetes, all with a body mass index (BMI) < 40, who were undergoing elective surgery. A gastric ultrasound was used to assess their gastric contents after they had followed the standard preoperative fasting guidelines of stopping solids 8 hours prior to the procedure and clearing liquids 2 hours prior.

There was no significant difference between the two groups in gastric volume (0.81 mL/kg with diabetes vs 0.87 mL/kg without) or in the proportion with “full stomach,” as designated by the American Society of Anesthesiologists (ASA) guidelines (any solid content or > 1.5 mL/kg of clear fluid), which was seen in 13 with diabetes (15.5%) and 11 (11.5%) without.

Published in Anesthesiology, the findings offer reassurance that different fasting instructions generally aren’t needed for people with diabetes in order to minimize the risk for perioperative pulmonary aspiration, lead author Anahi Perlas, MD, professor of anesthesiology and pain medicine at the University of Toronto, told this news organization.

“We never change practice completely based on a single study, but I think in general, based on our findings, that most diabetic patients aren’t any different from nondiabetics when it comes to their gastric content after fasting, and our standard fasting instructions seem to be just as effective in ensuring an empty stomach.”

But, she added, “If someone has symptoms of gastroparesis or when in doubt, we can always do a gastric ultrasound exam at the bedside and see whether the stomach is full or empty ... it’s very quick, and it’s not difficult to do.”
 

Expert Identifies Noteworthy Study Limitations

In an accompanying editorial, Mark A. Warner, MD, professor of anesthesiology at the Mayo Clinic in Rochester, Minnesota, said the findings “will be very helpful to anesthesiologists,” although he noted that the exclusion of people with a BMI > 40 is a limitation.

However, Michael Horowitz, MBBS, PhD, FRACP, director of the Endocrine and Metabolic Unit at the Royal Adelaide Hospital and professor of medicine at Adelaide Medical School in Adelaide, Australia, disputed the study’s conclusions. He noted that the sample was small, and the participants had an average A1c of 7.2%. Fewer than half had microvascular or neuropathic complications. Thus, they were healthier than the general population with diabetes.

“They’ve picked the wrong group of diabetics,” said Dr. Horowitz, who specializes in gastrointestinal complications of diabetes. “This is not a group where you would expect a very high prevalence of delayed emptying.”

Gastric emptying of solids and liquids varies widely even among healthy people and more so in those with type 2 diabetes. About a third of those with above-target A1c levels have gastroparesis, while those more in the target range tend to have accelerated emptying, he explained.

And regarding the use of gastric ultrasound for those who are symptomatic, Dr. Horowitz said, “The relationship of symptoms such as nausea, vomiting, fullness, whatever it may be, with the rate of gastric emptying is weak at best. The association is not simply cause and effect.”
 

Are the Fasting Guidelines Flawed, Regardless of Diabetes Status?

Dr. Horowitz also faulted the ASA’s 2017 guidance revision for allowing clear liquids to be consumed up to 2 hours in advance of anesthesia because it doesn’t distinguish between liquids with and without calories.

“Whether you have diabetes or not, if you are allowed to have a sugar drink up to 2 hours before your operation, the majority of people empty at about 4 kcal/min, so they will still have some of that drink in their stomach,” he said. “If you want an empty stomach, the ASA guidelines are wrong.”

That explains why the study found relatively high rates of “full stomach” in both groups, 15.5% of those with diabetes and 11.5% of those without, he said.
 

The GLP-1 Agonist Factor

Although the study didn’t address GLP-1 receptor agonist use, Dr. Warner did in his accompanying editorial, noting that the drugs’ rapid expansion “will likely change how we use perioperative fasting guidelines. With these medications delaying gastric emptying times, we now have another risk factor for pulmonary aspiration to consider when applying fasting guidelines. The inconsistent impact of GLP-1 agonists on gastric emptying, ranging from little to significant, makes it difficult for anesthesiologists to gauge whether or not patients taking GLP-1 agonists are likely to have preoperative gastric liquid or solid contents that could cause subsequent damage if regurgitated.”

Gastric ultrasound can be helpful in this situation, Dr. Warner wrote. In addition, he endorsed the 2023 ASA guidance, which calls for withholding daily-dosed GLP-1 agonists on the day of the surgery and the weekly formulations for a week. And if gastrointestinal symptoms are present, delay elective procedures.

But Dr. Horowitz said those recommendations are likely insufficient as well, pointing to data suggesting that daily liraglutide can delay gastric emptying for up to 16 weeks in about a third of patients. Such studies haven’t been conducted by the manufacturers, particularly on the once-weekly formulations, and the ensuing risk for aspiration isn’t known.

“The slowing occurs in much lower doses than are used for glucose lowering,” Dr. Horowitz said. “It is very likely that plasma levels will need to be extremely low to avoid gastric slowing. The current guidelines fail to appreciate this. So, to withhold the short-acting drugs for 1 day is probably wrong. And to stop long-acting drugs for 1 week is almost certainly wrong too.”

But as for what should be done, he said, “I don’t actually know what you do about it. And no one does because there are no data available to answer the question.”

The study received funding from the Physicians’ Services Incorporated Foundation and the Canadian Society of Anesthesiologists. Dr. Perlas received support for nonclinical time through a merit award from the Department of Anesthesiology and Pain Medicine, University of Toronto, and the Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network. She is an executive editor of the journal Regional Anesthesia and Pain Medicine and does consulting work for FujiFilm SonoSite. Dr. Horowitz had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Two professional societies have issued new guidance for type 2 diabetes management in primary care, with one focused specifically on the use of the newer medications.

On April 19, 2024, the American College of Physicians (ACP) published Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians. The internal medicine group recommends the use of glucagon-like peptide-1 (GLP-1) agonists, and sodium–glucose cotransporter-2 (SGLT2) inhibitors as second-line treatment after metformin. They also advise against the use of dipeptidyl peptidase-4 (DPP-4) inhibitors. 

The document was also presented simultaneously at the ACP annual meeting. 

And on April 15, the American Diabetes Association (ADA) posted its comprehensive Standards of Care in Diabetes—2024 Abridged for Primary Care Professionals as a follow-up to the December 2023 publication of its full-length Standards. Section 9, Pharmacologic Approaches to Glycemic Treatment, covers the same ground as the ACP guidelines.
 

General Agreement but Some Differences

The recommendations generally agree regarding medication use, although there are some differences. Both societies continue to endorse metformin and lifestyle modification as first-line therapy for glycemic management in type 2 diabetes. However, while ADA also gives the option of initial combination therapy with prioritization of avoiding hypoglycemia, ACP advises adding new medications only if glycemic goals aren’t met with lifestyle and metformin alone. 

The new ACP document gives two general recommendations:

1. Add an SGLT2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control. 

*Use an SGLT2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure.

*Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke.

2. ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality.

Both ADA and ACP advise using SGLT2 inhibitors in patients with congestive heart failure and/or chronic kidney disease, and using GLP-1 agonists in patients for whom weight management is a priority. The ADA also advises using agents of either drug class with proven cardiovascular benefit for people with type 2 diabetes who have established cardiovascular disease or who are at high risk.

ADA doesn’t advise against the use of DPP-4 inhibitors but doesn’t prioritize them either. Both insulin and sulfonylureas remain options for both, but they also are lower priority due to their potential for causing hypoglycemia. ACP says that sulfonylureas and long-acting insulin are “inferior to SGLT2 inhibitors and GLP-1 agonists in reducing all-cause mortality and morbidity but may still have some limited value for glycemic control.” 

The two groups continue to differ regarding A1c goals, although both recommend individualization. The ACP generally advises levels between 7% and 8% for most adults with type 2 diabetes, and de-intensification of pharmacologic agents for those with A1c levels below 6.5%. On the other hand, ADA recommends A1c levels < 7% as long as that can be achieved safely. 

This is the first time ACP has addressed this topic in a guideline, panel chair Carolyn J. Crandall, MD, told this news organization. “Diabetes treatment, of course, is our bread and butter…but what we had done before was based on the need to identify a target, like glycosylated hemoglobin. What patients and physicians really want to know now is, who should receive these new drugs? Should they receive these new drugs? And what benefits do they have?”

Added Dr. Crandall, who is professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles. “At ACP we have a complicated process that I’m actually very proud of, where we’ve asked a lay public panel, as well at the members of our guideline committee, to rank what’s most important in terms of the health outcomes for this condition…And then we look at how to balance those risks and benefits to make the recommendations.” 

In the same Annals of Internal Medicine issue are two systematic reviews/meta-analyses that informed the new document, one on drug effectiveness and the other on cost-effectiveness. 

In the accompanying editorial from Fatima Z. Syed, MD, an internist and medical weight management specialist at Duke University Division of General Internal Medicine, Durham, North Carolina, she notes, “the potential added benefits of these newer medications, including weight loss and cardiovascular and renal benefits, motivate their prescription, but cost and prior authorization hurdles can bar their use.”

Dr. Syed cites as “missing” from the ACP guidelines an analysis of comorbidities, including obesity. The reason for that, according to the document, is that “weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis.”

However, Dr. Syed notes that factoring in weight loss could improve the cost-effectiveness of the newer medications. She points out that the ADA Standards suggest a GLP-1 agonist with or without metformin as initial therapy options for people with newly diagnosed type 2 diabetes who might benefit from weight loss.

“The ACP guidelines strengthen the case for metformin as first-line medication for diabetes when comorbid conditions are not present. Metformin is cost-effective and has excellent hemoglobin A1c reduction. The accompanying economic analysis tells us that in the absence of comorbidity, the newer medication classes do not seem to be cost-effective. However, given that many patients with type 2 diabetes have obesity or existing cardiovascular or renal disease, the choice and accessibility of newer medications can be nuanced. The cost-effectiveness of GLP1 agonists and SGLT2 inhibitors as initial diabetes therapy in the setting of various comorbid conditions warrants careful exploration.”

Dr. Crandall has no disclosures. Dr. Syed disclosed that her husband is employed by Blue Cross Blue Shield of North Carolina.

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

Two professional societies have issued new guidance for type 2 diabetes management in primary care, with one focused specifically on the use of the newer medications.

On April 19, 2024, the American College of Physicians (ACP) published Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians. The internal medicine group recommends the use of glucagon-like peptide-1 (GLP-1) agonists, and sodium–glucose cotransporter-2 (SGLT2) inhibitors as second-line treatment after metformin. They also advise against the use of dipeptidyl peptidase-4 (DPP-4) inhibitors. 

The document was also presented simultaneously at the ACP annual meeting. 

And on April 15, the American Diabetes Association (ADA) posted its comprehensive Standards of Care in Diabetes—2024 Abridged for Primary Care Professionals as a follow-up to the December 2023 publication of its full-length Standards. Section 9, Pharmacologic Approaches to Glycemic Treatment, covers the same ground as the ACP guidelines.
 

General Agreement but Some Differences

The recommendations generally agree regarding medication use, although there are some differences. Both societies continue to endorse metformin and lifestyle modification as first-line therapy for glycemic management in type 2 diabetes. However, while ADA also gives the option of initial combination therapy with prioritization of avoiding hypoglycemia, ACP advises adding new medications only if glycemic goals aren’t met with lifestyle and metformin alone. 

The new ACP document gives two general recommendations:

1. Add an SGLT2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control. 

*Use an SGLT2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure.

*Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke.

2. ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality.

Both ADA and ACP advise using SGLT2 inhibitors in patients with congestive heart failure and/or chronic kidney disease, and using GLP-1 agonists in patients for whom weight management is a priority. The ADA also advises using agents of either drug class with proven cardiovascular benefit for people with type 2 diabetes who have established cardiovascular disease or who are at high risk.

ADA doesn’t advise against the use of DPP-4 inhibitors but doesn’t prioritize them either. Both insulin and sulfonylureas remain options for both, but they also are lower priority due to their potential for causing hypoglycemia. ACP says that sulfonylureas and long-acting insulin are “inferior to SGLT2 inhibitors and GLP-1 agonists in reducing all-cause mortality and morbidity but may still have some limited value for glycemic control.” 

The two groups continue to differ regarding A1c goals, although both recommend individualization. The ACP generally advises levels between 7% and 8% for most adults with type 2 diabetes, and de-intensification of pharmacologic agents for those with A1c levels below 6.5%. On the other hand, ADA recommends A1c levels < 7% as long as that can be achieved safely. 

This is the first time ACP has addressed this topic in a guideline, panel chair Carolyn J. Crandall, MD, told this news organization. “Diabetes treatment, of course, is our bread and butter…but what we had done before was based on the need to identify a target, like glycosylated hemoglobin. What patients and physicians really want to know now is, who should receive these new drugs? Should they receive these new drugs? And what benefits do they have?”

Added Dr. Crandall, who is professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles. “At ACP we have a complicated process that I’m actually very proud of, where we’ve asked a lay public panel, as well at the members of our guideline committee, to rank what’s most important in terms of the health outcomes for this condition…And then we look at how to balance those risks and benefits to make the recommendations.” 

In the same Annals of Internal Medicine issue are two systematic reviews/meta-analyses that informed the new document, one on drug effectiveness and the other on cost-effectiveness. 

In the accompanying editorial from Fatima Z. Syed, MD, an internist and medical weight management specialist at Duke University Division of General Internal Medicine, Durham, North Carolina, she notes, “the potential added benefits of these newer medications, including weight loss and cardiovascular and renal benefits, motivate their prescription, but cost and prior authorization hurdles can bar their use.”

Dr. Syed cites as “missing” from the ACP guidelines an analysis of comorbidities, including obesity. The reason for that, according to the document, is that “weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis.”

However, Dr. Syed notes that factoring in weight loss could improve the cost-effectiveness of the newer medications. She points out that the ADA Standards suggest a GLP-1 agonist with or without metformin as initial therapy options for people with newly diagnosed type 2 diabetes who might benefit from weight loss.

“The ACP guidelines strengthen the case for metformin as first-line medication for diabetes when comorbid conditions are not present. Metformin is cost-effective and has excellent hemoglobin A1c reduction. The accompanying economic analysis tells us that in the absence of comorbidity, the newer medication classes do not seem to be cost-effective. However, given that many patients with type 2 diabetes have obesity or existing cardiovascular or renal disease, the choice and accessibility of newer medications can be nuanced. The cost-effectiveness of GLP1 agonists and SGLT2 inhibitors as initial diabetes therapy in the setting of various comorbid conditions warrants careful exploration.”

Dr. Crandall has no disclosures. Dr. Syed disclosed that her husband is employed by Blue Cross Blue Shield of North Carolina.

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

Two professional societies have issued new guidance for type 2 diabetes management in primary care, with one focused specifically on the use of the newer medications.

On April 19, 2024, the American College of Physicians (ACP) published Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians. The internal medicine group recommends the use of glucagon-like peptide-1 (GLP-1) agonists, and sodium–glucose cotransporter-2 (SGLT2) inhibitors as second-line treatment after metformin. They also advise against the use of dipeptidyl peptidase-4 (DPP-4) inhibitors. 

The document was also presented simultaneously at the ACP annual meeting. 

And on April 15, the American Diabetes Association (ADA) posted its comprehensive Standards of Care in Diabetes—2024 Abridged for Primary Care Professionals as a follow-up to the December 2023 publication of its full-length Standards. Section 9, Pharmacologic Approaches to Glycemic Treatment, covers the same ground as the ACP guidelines.
 

General Agreement but Some Differences

The recommendations generally agree regarding medication use, although there are some differences. Both societies continue to endorse metformin and lifestyle modification as first-line therapy for glycemic management in type 2 diabetes. However, while ADA also gives the option of initial combination therapy with prioritization of avoiding hypoglycemia, ACP advises adding new medications only if glycemic goals aren’t met with lifestyle and metformin alone. 

The new ACP document gives two general recommendations:

1. Add an SGLT2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control. 

*Use an SGLT2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure.

*Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke.

2. ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality.

Both ADA and ACP advise using SGLT2 inhibitors in patients with congestive heart failure and/or chronic kidney disease, and using GLP-1 agonists in patients for whom weight management is a priority. The ADA also advises using agents of either drug class with proven cardiovascular benefit for people with type 2 diabetes who have established cardiovascular disease or who are at high risk.

ADA doesn’t advise against the use of DPP-4 inhibitors but doesn’t prioritize them either. Both insulin and sulfonylureas remain options for both, but they also are lower priority due to their potential for causing hypoglycemia. ACP says that sulfonylureas and long-acting insulin are “inferior to SGLT2 inhibitors and GLP-1 agonists in reducing all-cause mortality and morbidity but may still have some limited value for glycemic control.” 

The two groups continue to differ regarding A1c goals, although both recommend individualization. The ACP generally advises levels between 7% and 8% for most adults with type 2 diabetes, and de-intensification of pharmacologic agents for those with A1c levels below 6.5%. On the other hand, ADA recommends A1c levels < 7% as long as that can be achieved safely. 

This is the first time ACP has addressed this topic in a guideline, panel chair Carolyn J. Crandall, MD, told this news organization. “Diabetes treatment, of course, is our bread and butter…but what we had done before was based on the need to identify a target, like glycosylated hemoglobin. What patients and physicians really want to know now is, who should receive these new drugs? Should they receive these new drugs? And what benefits do they have?”

Added Dr. Crandall, who is professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles. “At ACP we have a complicated process that I’m actually very proud of, where we’ve asked a lay public panel, as well at the members of our guideline committee, to rank what’s most important in terms of the health outcomes for this condition…And then we look at how to balance those risks and benefits to make the recommendations.” 

In the same Annals of Internal Medicine issue are two systematic reviews/meta-analyses that informed the new document, one on drug effectiveness and the other on cost-effectiveness. 

In the accompanying editorial from Fatima Z. Syed, MD, an internist and medical weight management specialist at Duke University Division of General Internal Medicine, Durham, North Carolina, she notes, “the potential added benefits of these newer medications, including weight loss and cardiovascular and renal benefits, motivate their prescription, but cost and prior authorization hurdles can bar their use.”

Dr. Syed cites as “missing” from the ACP guidelines an analysis of comorbidities, including obesity. The reason for that, according to the document, is that “weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis.”

However, Dr. Syed notes that factoring in weight loss could improve the cost-effectiveness of the newer medications. She points out that the ADA Standards suggest a GLP-1 agonist with or without metformin as initial therapy options for people with newly diagnosed type 2 diabetes who might benefit from weight loss.

“The ACP guidelines strengthen the case for metformin as first-line medication for diabetes when comorbid conditions are not present. Metformin is cost-effective and has excellent hemoglobin A1c reduction. The accompanying economic analysis tells us that in the absence of comorbidity, the newer medication classes do not seem to be cost-effective. However, given that many patients with type 2 diabetes have obesity or existing cardiovascular or renal disease, the choice and accessibility of newer medications can be nuanced. The cost-effectiveness of GLP1 agonists and SGLT2 inhibitors as initial diabetes therapy in the setting of various comorbid conditions warrants careful exploration.”

Dr. Crandall has no disclosures. Dr. Syed disclosed that her husband is employed by Blue Cross Blue Shield of North Carolina.

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

The US Food and Drug Administration (FDA) has designated the Eversense (Sensionics, Inc; Ascencia Diabetes Care) implanted continuous glucose monitor (CGM) an “integrated CGM,” meaning it can be used in conjunction with insulin pumps as part of an automated insulin delivery system (AID). 

The Eversense now joins Dexcom’s G6 and G7 and the Freestyle Libre 2 Plus in being compatible with multiple different branded insulin pumps as part of AID systems, and it is the only implantable one. 

The sensor device is inserted under the skin of the patient’s upper arm by a healthcare provider and a transmitter is worn over it on the skin. The FDA approved the Eversense in June 2018 for 3-month use and in February 2022  for use up to 6 months. It is indicated for people with diabetes aged 18 years and older.

Fingerstick blood glucose measurements are still required for calibration once a day after day 21, when symptoms don’t match the CGM information, or when taking tetracycline medications. 

According to Sensionics, the Eversense is “the most accurate CGM in the critical low glucose ranges with essentially no compression lows.” The latter refers to ‘false low’ alarms that sometimes occur when a person presses on the device, such as during sleep.

“As we look ahead, we are focused on progressing our partnership discussions and software developments, and look forward to providing more updates,” Sensionics said in a statement.
 

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

The US Food and Drug Administration (FDA) has designated the Eversense (Sensionics, Inc; Ascencia Diabetes Care) implanted continuous glucose monitor (CGM) an “integrated CGM,” meaning it can be used in conjunction with insulin pumps as part of an automated insulin delivery system (AID). 

The Eversense now joins Dexcom’s G6 and G7 and the Freestyle Libre 2 Plus in being compatible with multiple different branded insulin pumps as part of AID systems, and it is the only implantable one. 

The sensor device is inserted under the skin of the patient’s upper arm by a healthcare provider and a transmitter is worn over it on the skin. The FDA approved the Eversense in June 2018 for 3-month use and in February 2022  for use up to 6 months. It is indicated for people with diabetes aged 18 years and older.

Fingerstick blood glucose measurements are still required for calibration once a day after day 21, when symptoms don’t match the CGM information, or when taking tetracycline medications. 

According to Sensionics, the Eversense is “the most accurate CGM in the critical low glucose ranges with essentially no compression lows.” The latter refers to ‘false low’ alarms that sometimes occur when a person presses on the device, such as during sleep.

“As we look ahead, we are focused on progressing our partnership discussions and software developments, and look forward to providing more updates,” Sensionics said in a statement.
 

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

The US Food and Drug Administration (FDA) has designated the Eversense (Sensionics, Inc; Ascencia Diabetes Care) implanted continuous glucose monitor (CGM) an “integrated CGM,” meaning it can be used in conjunction with insulin pumps as part of an automated insulin delivery system (AID). 

The Eversense now joins Dexcom’s G6 and G7 and the Freestyle Libre 2 Plus in being compatible with multiple different branded insulin pumps as part of AID systems, and it is the only implantable one. 

The sensor device is inserted under the skin of the patient’s upper arm by a healthcare provider and a transmitter is worn over it on the skin. The FDA approved the Eversense in June 2018 for 3-month use and in February 2022  for use up to 6 months. It is indicated for people with diabetes aged 18 years and older.

Fingerstick blood glucose measurements are still required for calibration once a day after day 21, when symptoms don’t match the CGM information, or when taking tetracycline medications. 

According to Sensionics, the Eversense is “the most accurate CGM in the critical low glucose ranges with essentially no compression lows.” The latter refers to ‘false low’ alarms that sometimes occur when a person presses on the device, such as during sleep.

“As we look ahead, we are focused on progressing our partnership discussions and software developments, and look forward to providing more updates,” Sensionics said in a statement.
 

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

Older men with chronic kidney disease (CKD) show higher resting muscle sympathetic nerve activity, but not vascular stiffness, compared with older women, offering clues to the underlying reasons why men with CKD have a higher cardiovascular risk than do women with the disease.

“Although it is well established that sympathetic nerve system activity is chronically elevated in patients with impaired kidney function, we show for the first time that males with CKD have higher resting muscle sympathetic nerve activity compared with females with CKD,” report the authors on research published in the American Journal of Physiology-Renal Physiology.

“For clinicians, the key takeaway is the importance of recognizing sex-specific differences in sympathetic activity and vascular function when assessing cardiovascular risk in CKD patients,” first author Matias G. Zanuzzi, MD, of the Division of Renal Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, told this news organization.

In the general population, cardiovascular risk is lower in younger women vs men, but their risks converge in older age as women develop similar levels of sympathetic overactivity, vascular stiffness, and cardiovascular risk.

However, an exception to that pattern is seen in the CKD population, where men continue to have a higher cardiovascular mortality risk vs women even in older age.

Studies evaluating the reasons for that have been conflicting, with some reporting a tendency of higher muscle sympathetic nerve activity in older women compared with men and others suggest the opposite finding — lower activity vs men.

To further investigate, Dr. Zanuzzi and colleagues enrolled 129 participants, including 96 men and 33 women with stage III or IV CKD.

The mean age of the study participants was 64 years for men and65 years for women. Most had obesity, and importantly, more than 80% of participants in each group was Black. There were no significant differences between the groups in terms of body mass index or comorbidities, including smoking, diabetes, or hypertension.

At two separate study visits, vascular stiffness was assessed with carotid-femoral pulse wave velocity measurement, and resting muscle sympathetic nerve activity was measured using microneurography. 

The results showed that men with CKD had significantly higher resting muscle sympathetic nerve activity compared with women with CKD (68 vs 55 bursts per 100 heartbeats; P = .005), whereas no differences in vascular stiffness were observed between the genders (P = .248).

“The findings suggest that the higher cardiovascular disease risk observed in older males with CKD may be influenced by elevated sympathetic activity,” Dr. Zanuzzi explained.

“However, the lack of significant differences in vascular stiffness between genders implies that additional factors beyond vascular remodeling may contribute to the observed sex-specific differences in cardiovascular risk,” he said.

Of note, resting vascular stiffness was not associated with muscular sympathetic nerve activity in either men or women, which was surprising to the authors, Dr. Zanuzzi noted.

“This underscores the multifactorial nature of vascular pathophysiology in CKD and underscores the need for further research to unravel the underlying mechanisms.”

In other findings, although prior studies have shown a positive correlation between age and resting muscle sympathetic nerve activity in White, healthy women and men without obesity,, no similar relationship was observed in men or women with CKD.

“These findings suggest that the protective effect of younger age on sympathetic function may not be present in the setting of decreased kidney function in both males and females,” the authors note.

In addition, whereas previous research has shown a clear association between sympathetic overactivity and a wide variety of measures of obesity, in the current study, that association was only observed in men with CKD.

Important limitations of the study include the cross-sectional design and that the population was predominantly Black, Dr. Zanuzzi noted.

“Generalizability to other demographic groups may be limited, and future longitudinal studies are needed to validate these findings and explore potential causal relationships,” he said.

The findings underscore “the need for novel therapeutic approaches targeting sympathetic overactivity and vascular stiffness in CKD patients, especially considering the observed sex-specific differences,” Dr. Zanuzzi added. 

“Potential interventions may include pharmacological agents that modulate sympathetic tone or vascular remodeling pathways,” he said.

“Lifestyle modifications focusing on stress reduction and cardiovascular health promotion could also play a crucial role in mitigating cardiovascular risk.”

Dr. Zanuzzi concluded that “tailoring treatment strategies to address these differences may lead to more personalized and effective management approaches, ultimately improving clinical outcomes in this high-risk population.”

The authors had no disclosures to report.

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

Older men with chronic kidney disease (CKD) show higher resting muscle sympathetic nerve activity, but not vascular stiffness, compared with older women, offering clues to the underlying reasons why men with CKD have a higher cardiovascular risk than do women with the disease.

“Although it is well established that sympathetic nerve system activity is chronically elevated in patients with impaired kidney function, we show for the first time that males with CKD have higher resting muscle sympathetic nerve activity compared with females with CKD,” report the authors on research published in the American Journal of Physiology-Renal Physiology.

“For clinicians, the key takeaway is the importance of recognizing sex-specific differences in sympathetic activity and vascular function when assessing cardiovascular risk in CKD patients,” first author Matias G. Zanuzzi, MD, of the Division of Renal Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, told this news organization.

In the general population, cardiovascular risk is lower in younger women vs men, but their risks converge in older age as women develop similar levels of sympathetic overactivity, vascular stiffness, and cardiovascular risk.

However, an exception to that pattern is seen in the CKD population, where men continue to have a higher cardiovascular mortality risk vs women even in older age.

Studies evaluating the reasons for that have been conflicting, with some reporting a tendency of higher muscle sympathetic nerve activity in older women compared with men and others suggest the opposite finding — lower activity vs men.

To further investigate, Dr. Zanuzzi and colleagues enrolled 129 participants, including 96 men and 33 women with stage III or IV CKD.

The mean age of the study participants was 64 years for men and65 years for women. Most had obesity, and importantly, more than 80% of participants in each group was Black. There were no significant differences between the groups in terms of body mass index or comorbidities, including smoking, diabetes, or hypertension.

At two separate study visits, vascular stiffness was assessed with carotid-femoral pulse wave velocity measurement, and resting muscle sympathetic nerve activity was measured using microneurography. 

The results showed that men with CKD had significantly higher resting muscle sympathetic nerve activity compared with women with CKD (68 vs 55 bursts per 100 heartbeats; P = .005), whereas no differences in vascular stiffness were observed between the genders (P = .248).

“The findings suggest that the higher cardiovascular disease risk observed in older males with CKD may be influenced by elevated sympathetic activity,” Dr. Zanuzzi explained.

“However, the lack of significant differences in vascular stiffness between genders implies that additional factors beyond vascular remodeling may contribute to the observed sex-specific differences in cardiovascular risk,” he said.

Of note, resting vascular stiffness was not associated with muscular sympathetic nerve activity in either men or women, which was surprising to the authors, Dr. Zanuzzi noted.

“This underscores the multifactorial nature of vascular pathophysiology in CKD and underscores the need for further research to unravel the underlying mechanisms.”

In other findings, although prior studies have shown a positive correlation between age and resting muscle sympathetic nerve activity in White, healthy women and men without obesity,, no similar relationship was observed in men or women with CKD.

“These findings suggest that the protective effect of younger age on sympathetic function may not be present in the setting of decreased kidney function in both males and females,” the authors note.

In addition, whereas previous research has shown a clear association between sympathetic overactivity and a wide variety of measures of obesity, in the current study, that association was only observed in men with CKD.

Important limitations of the study include the cross-sectional design and that the population was predominantly Black, Dr. Zanuzzi noted.

“Generalizability to other demographic groups may be limited, and future longitudinal studies are needed to validate these findings and explore potential causal relationships,” he said.

The findings underscore “the need for novel therapeutic approaches targeting sympathetic overactivity and vascular stiffness in CKD patients, especially considering the observed sex-specific differences,” Dr. Zanuzzi added. 

“Potential interventions may include pharmacological agents that modulate sympathetic tone or vascular remodeling pathways,” he said.

“Lifestyle modifications focusing on stress reduction and cardiovascular health promotion could also play a crucial role in mitigating cardiovascular risk.”

Dr. Zanuzzi concluded that “tailoring treatment strategies to address these differences may lead to more personalized and effective management approaches, ultimately improving clinical outcomes in this high-risk population.”

The authors had no disclosures to report.

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

Older men with chronic kidney disease (CKD) show higher resting muscle sympathetic nerve activity, but not vascular stiffness, compared with older women, offering clues to the underlying reasons why men with CKD have a higher cardiovascular risk than do women with the disease.

“Although it is well established that sympathetic nerve system activity is chronically elevated in patients with impaired kidney function, we show for the first time that males with CKD have higher resting muscle sympathetic nerve activity compared with females with CKD,” report the authors on research published in the American Journal of Physiology-Renal Physiology.

“For clinicians, the key takeaway is the importance of recognizing sex-specific differences in sympathetic activity and vascular function when assessing cardiovascular risk in CKD patients,” first author Matias G. Zanuzzi, MD, of the Division of Renal Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, told this news organization.

In the general population, cardiovascular risk is lower in younger women vs men, but their risks converge in older age as women develop similar levels of sympathetic overactivity, vascular stiffness, and cardiovascular risk.

However, an exception to that pattern is seen in the CKD population, where men continue to have a higher cardiovascular mortality risk vs women even in older age.

Studies evaluating the reasons for that have been conflicting, with some reporting a tendency of higher muscle sympathetic nerve activity in older women compared with men and others suggest the opposite finding — lower activity vs men.

To further investigate, Dr. Zanuzzi and colleagues enrolled 129 participants, including 96 men and 33 women with stage III or IV CKD.

The mean age of the study participants was 64 years for men and65 years for women. Most had obesity, and importantly, more than 80% of participants in each group was Black. There were no significant differences between the groups in terms of body mass index or comorbidities, including smoking, diabetes, or hypertension.

At two separate study visits, vascular stiffness was assessed with carotid-femoral pulse wave velocity measurement, and resting muscle sympathetic nerve activity was measured using microneurography. 

The results showed that men with CKD had significantly higher resting muscle sympathetic nerve activity compared with women with CKD (68 vs 55 bursts per 100 heartbeats; P = .005), whereas no differences in vascular stiffness were observed between the genders (P = .248).

“The findings suggest that the higher cardiovascular disease risk observed in older males with CKD may be influenced by elevated sympathetic activity,” Dr. Zanuzzi explained.

“However, the lack of significant differences in vascular stiffness between genders implies that additional factors beyond vascular remodeling may contribute to the observed sex-specific differences in cardiovascular risk,” he said.

Of note, resting vascular stiffness was not associated with muscular sympathetic nerve activity in either men or women, which was surprising to the authors, Dr. Zanuzzi noted.

“This underscores the multifactorial nature of vascular pathophysiology in CKD and underscores the need for further research to unravel the underlying mechanisms.”

In other findings, although prior studies have shown a positive correlation between age and resting muscle sympathetic nerve activity in White, healthy women and men without obesity,, no similar relationship was observed in men or women with CKD.

“These findings suggest that the protective effect of younger age on sympathetic function may not be present in the setting of decreased kidney function in both males and females,” the authors note.

In addition, whereas previous research has shown a clear association between sympathetic overactivity and a wide variety of measures of obesity, in the current study, that association was only observed in men with CKD.

Important limitations of the study include the cross-sectional design and that the population was predominantly Black, Dr. Zanuzzi noted.

“Generalizability to other demographic groups may be limited, and future longitudinal studies are needed to validate these findings and explore potential causal relationships,” he said.

The findings underscore “the need for novel therapeutic approaches targeting sympathetic overactivity and vascular stiffness in CKD patients, especially considering the observed sex-specific differences,” Dr. Zanuzzi added. 

“Potential interventions may include pharmacological agents that modulate sympathetic tone or vascular remodeling pathways,” he said.

“Lifestyle modifications focusing on stress reduction and cardiovascular health promotion could also play a crucial role in mitigating cardiovascular risk.”

Dr. Zanuzzi concluded that “tailoring treatment strategies to address these differences may lead to more personalized and effective management approaches, ultimately improving clinical outcomes in this high-risk population.”

The authors had no disclosures to report.

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