Common Antidepressants Ranked by Potential for Weight Gain

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Eight commonly used antidepressants have been ranked by their weight gain potential. 

Results of a large observational study showed small differences in short- and long-term weight change in patients prescribed one of eight antidepressants, with bupropion associated with the lowest weight gain and escitalopramparoxetine, and duloxetine associated with the greatest. 

Escitalopram, paroxetine, and duloxetine users were 10%-15% more likely to gain at least 5% of their baseline weight compared with those taking sertraline, which was used as a comparator. 

Investigators noted that the more clinicians and patients know about how a particular antidepressant may affect patients’ weight, the better informed they can be about which antidepressants to prescribe. 

“Patients and their clinicians often have several options when starting an antidepressant for the first time. This study provides important real-world evidence regarding the amount of weight gain that should be expected after starting some of the most common antidepressants,” lead author Joshua Petimar, ScD, assistant professor of population medicine in the Harvard Pilgrim Health Care Institute at Harvard Medical School, Boston, said in a press release. 

The findings were published online in Annals of Internal Medicine


 

Real-World Data

Though weight gain is a commonly reported side effect of antidepressant use and may lead to medication nonadherence and worse outcomes, there is a lack of real-world data about weight change across specific medications. 

Investigators used electronic health records from eight health care systems across the United States spanning from 2010 to 2019. The analysis included information on 183,118 adults aged 20-80 years who were new users of one of eight common first-line antidepressants. Investigators measured their weight at baseline and at 6, 12, and 24 months after initiation to estimate intention-to-treat (ITT) effects of weight change.

At baseline, participants were randomly assigned to begin sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, or venlafaxine

The most common antidepressants prescribed were sertraline, citalopram, and bupropion. Approximately 36% of participants had a diagnosis of depression, and 39% were diagnosed with anxiety.

Among selective serotonin reuptake inhibitors (SSRIs), escitalopram and paroxetine were associated with the greatest 6-month weight gain, whereas bupropion was associated with the least weight gain across all analyses.

Using sertraline as a comparator, 6-month weight change was lower for bupropion (difference, 0.22 kg) and higher for escitalopram (difference, 0.41 kg), duloxetine (difference, 0.34 kg), paroxetine (difference, 0.37 kg), and venlafaxine (difference, 0.17 kg).

Escitalopram, paroxetine, and duloxetine users were 10%-15% more likely to gain at least 5% of their baseline weight compared with sertraline users.

Investigators noted little difference in adherence levels between medications during the study except at 6 months, when it was higher for those who took bupropion (41%) than for those taking other antidepressants (28%-36%).

The study included data only on prescriptions and investigators could not verify whether the medications were dispensed or taken as prescribed. Other limitations included missing weight information because most patients did not encounter the health system at exactly 6, 12, and 24 months; only 15%-30% had weight measurements in those months. 

Finally, the low adherence rates made it difficult to attribute relative weight change at the 12- and 24-month time points to the specific medications of interest.

“Clinicians and patients could consider these differences when making decisions about specific antidepressants, especially given the complex relationships of obesity and depression with health, quality of life, and stigma,” the authors wrote. 

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Disclosures are noted in the original article. 

A version of this article appeared on Medscape.com.

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Eight commonly used antidepressants have been ranked by their weight gain potential. 

Results of a large observational study showed small differences in short- and long-term weight change in patients prescribed one of eight antidepressants, with bupropion associated with the lowest weight gain and escitalopramparoxetine, and duloxetine associated with the greatest. 

Escitalopram, paroxetine, and duloxetine users were 10%-15% more likely to gain at least 5% of their baseline weight compared with those taking sertraline, which was used as a comparator. 

Investigators noted that the more clinicians and patients know about how a particular antidepressant may affect patients’ weight, the better informed they can be about which antidepressants to prescribe. 

“Patients and their clinicians often have several options when starting an antidepressant for the first time. This study provides important real-world evidence regarding the amount of weight gain that should be expected after starting some of the most common antidepressants,” lead author Joshua Petimar, ScD, assistant professor of population medicine in the Harvard Pilgrim Health Care Institute at Harvard Medical School, Boston, said in a press release. 

The findings were published online in Annals of Internal Medicine


 

Real-World Data

Though weight gain is a commonly reported side effect of antidepressant use and may lead to medication nonadherence and worse outcomes, there is a lack of real-world data about weight change across specific medications. 

Investigators used electronic health records from eight health care systems across the United States spanning from 2010 to 2019. The analysis included information on 183,118 adults aged 20-80 years who were new users of one of eight common first-line antidepressants. Investigators measured their weight at baseline and at 6, 12, and 24 months after initiation to estimate intention-to-treat (ITT) effects of weight change.

At baseline, participants were randomly assigned to begin sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, or venlafaxine

The most common antidepressants prescribed were sertraline, citalopram, and bupropion. Approximately 36% of participants had a diagnosis of depression, and 39% were diagnosed with anxiety.

Among selective serotonin reuptake inhibitors (SSRIs), escitalopram and paroxetine were associated with the greatest 6-month weight gain, whereas bupropion was associated with the least weight gain across all analyses.

Using sertraline as a comparator, 6-month weight change was lower for bupropion (difference, 0.22 kg) and higher for escitalopram (difference, 0.41 kg), duloxetine (difference, 0.34 kg), paroxetine (difference, 0.37 kg), and venlafaxine (difference, 0.17 kg).

Escitalopram, paroxetine, and duloxetine users were 10%-15% more likely to gain at least 5% of their baseline weight compared with sertraline users.

Investigators noted little difference in adherence levels between medications during the study except at 6 months, when it was higher for those who took bupropion (41%) than for those taking other antidepressants (28%-36%).

The study included data only on prescriptions and investigators could not verify whether the medications were dispensed or taken as prescribed. Other limitations included missing weight information because most patients did not encounter the health system at exactly 6, 12, and 24 months; only 15%-30% had weight measurements in those months. 

Finally, the low adherence rates made it difficult to attribute relative weight change at the 12- and 24-month time points to the specific medications of interest.

“Clinicians and patients could consider these differences when making decisions about specific antidepressants, especially given the complex relationships of obesity and depression with health, quality of life, and stigma,” the authors wrote. 

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Disclosures are noted in the original article. 

A version of this article appeared on Medscape.com.

 

Eight commonly used antidepressants have been ranked by their weight gain potential. 

Results of a large observational study showed small differences in short- and long-term weight change in patients prescribed one of eight antidepressants, with bupropion associated with the lowest weight gain and escitalopramparoxetine, and duloxetine associated with the greatest. 

Escitalopram, paroxetine, and duloxetine users were 10%-15% more likely to gain at least 5% of their baseline weight compared with those taking sertraline, which was used as a comparator. 

Investigators noted that the more clinicians and patients know about how a particular antidepressant may affect patients’ weight, the better informed they can be about which antidepressants to prescribe. 

“Patients and their clinicians often have several options when starting an antidepressant for the first time. This study provides important real-world evidence regarding the amount of weight gain that should be expected after starting some of the most common antidepressants,” lead author Joshua Petimar, ScD, assistant professor of population medicine in the Harvard Pilgrim Health Care Institute at Harvard Medical School, Boston, said in a press release. 

The findings were published online in Annals of Internal Medicine


 

Real-World Data

Though weight gain is a commonly reported side effect of antidepressant use and may lead to medication nonadherence and worse outcomes, there is a lack of real-world data about weight change across specific medications. 

Investigators used electronic health records from eight health care systems across the United States spanning from 2010 to 2019. The analysis included information on 183,118 adults aged 20-80 years who were new users of one of eight common first-line antidepressants. Investigators measured their weight at baseline and at 6, 12, and 24 months after initiation to estimate intention-to-treat (ITT) effects of weight change.

At baseline, participants were randomly assigned to begin sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, or venlafaxine

The most common antidepressants prescribed were sertraline, citalopram, and bupropion. Approximately 36% of participants had a diagnosis of depression, and 39% were diagnosed with anxiety.

Among selective serotonin reuptake inhibitors (SSRIs), escitalopram and paroxetine were associated with the greatest 6-month weight gain, whereas bupropion was associated with the least weight gain across all analyses.

Using sertraline as a comparator, 6-month weight change was lower for bupropion (difference, 0.22 kg) and higher for escitalopram (difference, 0.41 kg), duloxetine (difference, 0.34 kg), paroxetine (difference, 0.37 kg), and venlafaxine (difference, 0.17 kg).

Escitalopram, paroxetine, and duloxetine users were 10%-15% more likely to gain at least 5% of their baseline weight compared with sertraline users.

Investigators noted little difference in adherence levels between medications during the study except at 6 months, when it was higher for those who took bupropion (41%) than for those taking other antidepressants (28%-36%).

The study included data only on prescriptions and investigators could not verify whether the medications were dispensed or taken as prescribed. Other limitations included missing weight information because most patients did not encounter the health system at exactly 6, 12, and 24 months; only 15%-30% had weight measurements in those months. 

Finally, the low adherence rates made it difficult to attribute relative weight change at the 12- and 24-month time points to the specific medications of interest.

“Clinicians and patients could consider these differences when making decisions about specific antidepressants, especially given the complex relationships of obesity and depression with health, quality of life, and stigma,” the authors wrote. 

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Disclosures are noted in the original article. 

A version of this article appeared on Medscape.com.

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Semaglutide May Increase Risk of Disease Causing Vision Loss

Article Type
Changed
Tue, 07/09/2024 - 14:50

 

TOPLINE: 

Patients with type 2 diabetes, overweight, or obesity taking the glucagon-like peptide receptor agonist (GLP-1 RA) semaglutide appear to have an increased risk for an uncommon condition that can cause vision loss. 
 

METHODOLOGY:

  • Researchers conducted a retrospective study of 16,827 patients at Massachusetts Eye and Ear in Boston.
  • Their analysis focused on 710 patients with type 2 diabetes (194 of whom had been prescribed semaglutide) and 979 patients with overweight or obesity (361 prescribed semaglutide).
  • The researchers compared patients prescribed semaglutide with those prescribed a medication other than a GLP-1 agent. They matched patients by factors such as age and sex and whether they had hypertension, obstructive sleep apnea, or coronary artery disease.
  • They assessed the cumulative incidence of nonarteritic anterior ischemic optic neuropathy (NAION) during 36 months of follow-up. 
  •  

TAKEAWAY: 

  • Semaglutide use was associated with a higher risk for NAION in patients with type 2 diabetes (hazard ratio [HR], 4.28; 95% CI, 1.62-11.29).
  • In patients with overweight or obesity, semaglutide again was linked to a higher risk for NAION (HR, 7.64; 95% CI, 2.21-26.36).
  • Among patients with type 2 diabetes, the cumulative incidence of NAION over 36 months was 8.9% for those prescribed semaglutide vs 1.8% among those taking non–GLP-1 medications.
  • For patients with overweight or obesity, the cumulative incidence of NAION over 36 months was 6.7% for the semaglutide cohort vs 0.8% for those in the other group. 

IN PRACTICE:

Semaglutide has “provided very significant benefits in many ways, but future discussions between a patient and their physician should include NAION as a potential risk,” study leader Joseph Rizzo, MD, with Mass Eye and Ear and Harvard Medical School, said in a news release about the findings. “It is important to appreciate, however, that the increased risk relates to a disorder that is relatively uncommon.”

“Given the numbers of participants who have been recruited to clinical trials and the large number of people globally who use GLP-1 RAs, we should be confident that if corroborated, the absolute risk of developing NAION in direct relation to taking semaglutide must indeed be rare,” Susan P. Mollan, MBcHB, of University Hospitals Birmingham NHS Foundation Trust, in England, wrote in a commentary published with the study. 
 

SOURCE:

The study was published online on July 3 in JAMA Ophthalmology.
 

LIMITATIONS: 

The patients were seen at a hospital that specializes in ophthalmology and has a specialized neuro-ophthalmology service, so the results may not fully apply to other settings. The results were driven by a relatively small number of NAION cases in the patients exposed to semaglutide. The study does not establish that semaglutide directly causes NAION, the researchers noted. “The best approaches to confirm, refute, or refine our findings would be to conduct a much larger, retrospective, multicenter population-based cohort study; a prospective, randomized clinical study; or a postmarket analysis of all GLP-1 RA drugs,” they wrote.

 

DISCLOSURES:

The study was supported by a grant from Research to Prevent Blindness. 
 

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

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TOPLINE: 

Patients with type 2 diabetes, overweight, or obesity taking the glucagon-like peptide receptor agonist (GLP-1 RA) semaglutide appear to have an increased risk for an uncommon condition that can cause vision loss. 
 

METHODOLOGY:

  • Researchers conducted a retrospective study of 16,827 patients at Massachusetts Eye and Ear in Boston.
  • Their analysis focused on 710 patients with type 2 diabetes (194 of whom had been prescribed semaglutide) and 979 patients with overweight or obesity (361 prescribed semaglutide).
  • The researchers compared patients prescribed semaglutide with those prescribed a medication other than a GLP-1 agent. They matched patients by factors such as age and sex and whether they had hypertension, obstructive sleep apnea, or coronary artery disease.
  • They assessed the cumulative incidence of nonarteritic anterior ischemic optic neuropathy (NAION) during 36 months of follow-up. 
  •  

TAKEAWAY: 

  • Semaglutide use was associated with a higher risk for NAION in patients with type 2 diabetes (hazard ratio [HR], 4.28; 95% CI, 1.62-11.29).
  • In patients with overweight or obesity, semaglutide again was linked to a higher risk for NAION (HR, 7.64; 95% CI, 2.21-26.36).
  • Among patients with type 2 diabetes, the cumulative incidence of NAION over 36 months was 8.9% for those prescribed semaglutide vs 1.8% among those taking non–GLP-1 medications.
  • For patients with overweight or obesity, the cumulative incidence of NAION over 36 months was 6.7% for the semaglutide cohort vs 0.8% for those in the other group. 

IN PRACTICE:

Semaglutide has “provided very significant benefits in many ways, but future discussions between a patient and their physician should include NAION as a potential risk,” study leader Joseph Rizzo, MD, with Mass Eye and Ear and Harvard Medical School, said in a news release about the findings. “It is important to appreciate, however, that the increased risk relates to a disorder that is relatively uncommon.”

“Given the numbers of participants who have been recruited to clinical trials and the large number of people globally who use GLP-1 RAs, we should be confident that if corroborated, the absolute risk of developing NAION in direct relation to taking semaglutide must indeed be rare,” Susan P. Mollan, MBcHB, of University Hospitals Birmingham NHS Foundation Trust, in England, wrote in a commentary published with the study. 
 

SOURCE:

The study was published online on July 3 in JAMA Ophthalmology.
 

LIMITATIONS: 

The patients were seen at a hospital that specializes in ophthalmology and has a specialized neuro-ophthalmology service, so the results may not fully apply to other settings. The results were driven by a relatively small number of NAION cases in the patients exposed to semaglutide. The study does not establish that semaglutide directly causes NAION, the researchers noted. “The best approaches to confirm, refute, or refine our findings would be to conduct a much larger, retrospective, multicenter population-based cohort study; a prospective, randomized clinical study; or a postmarket analysis of all GLP-1 RA drugs,” they wrote.

 

DISCLOSURES:

The study was supported by a grant from Research to Prevent Blindness. 
 

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

 

TOPLINE: 

Patients with type 2 diabetes, overweight, or obesity taking the glucagon-like peptide receptor agonist (GLP-1 RA) semaglutide appear to have an increased risk for an uncommon condition that can cause vision loss. 
 

METHODOLOGY:

  • Researchers conducted a retrospective study of 16,827 patients at Massachusetts Eye and Ear in Boston.
  • Their analysis focused on 710 patients with type 2 diabetes (194 of whom had been prescribed semaglutide) and 979 patients with overweight or obesity (361 prescribed semaglutide).
  • The researchers compared patients prescribed semaglutide with those prescribed a medication other than a GLP-1 agent. They matched patients by factors such as age and sex and whether they had hypertension, obstructive sleep apnea, or coronary artery disease.
  • They assessed the cumulative incidence of nonarteritic anterior ischemic optic neuropathy (NAION) during 36 months of follow-up. 
  •  

TAKEAWAY: 

  • Semaglutide use was associated with a higher risk for NAION in patients with type 2 diabetes (hazard ratio [HR], 4.28; 95% CI, 1.62-11.29).
  • In patients with overweight or obesity, semaglutide again was linked to a higher risk for NAION (HR, 7.64; 95% CI, 2.21-26.36).
  • Among patients with type 2 diabetes, the cumulative incidence of NAION over 36 months was 8.9% for those prescribed semaglutide vs 1.8% among those taking non–GLP-1 medications.
  • For patients with overweight or obesity, the cumulative incidence of NAION over 36 months was 6.7% for the semaglutide cohort vs 0.8% for those in the other group. 

IN PRACTICE:

Semaglutide has “provided very significant benefits in many ways, but future discussions between a patient and their physician should include NAION as a potential risk,” study leader Joseph Rizzo, MD, with Mass Eye and Ear and Harvard Medical School, said in a news release about the findings. “It is important to appreciate, however, that the increased risk relates to a disorder that is relatively uncommon.”

“Given the numbers of participants who have been recruited to clinical trials and the large number of people globally who use GLP-1 RAs, we should be confident that if corroborated, the absolute risk of developing NAION in direct relation to taking semaglutide must indeed be rare,” Susan P. Mollan, MBcHB, of University Hospitals Birmingham NHS Foundation Trust, in England, wrote in a commentary published with the study. 
 

SOURCE:

The study was published online on July 3 in JAMA Ophthalmology.
 

LIMITATIONS: 

The patients were seen at a hospital that specializes in ophthalmology and has a specialized neuro-ophthalmology service, so the results may not fully apply to other settings. The results were driven by a relatively small number of NAION cases in the patients exposed to semaglutide. The study does not establish that semaglutide directly causes NAION, the researchers noted. “The best approaches to confirm, refute, or refine our findings would be to conduct a much larger, retrospective, multicenter population-based cohort study; a prospective, randomized clinical study; or a postmarket analysis of all GLP-1 RA drugs,” they wrote.

 

DISCLOSURES:

The study was supported by a grant from Research to Prevent Blindness. 
 

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

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Weight Loss Drugs Cut Cancer Risk in Diabetes Patients

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Recent research on popular weight loss drugs has uncovered surprising benefits beyond their intended use, like lowering the risk of fatal heart attacks. And now there may be another unforeseen advantage: People with type 2 diabetes who took these drugs had a lower risk of having 10 out of 13 obesity-related cancers, compared to those who used insulin therapy.

That’s according to a study published July 5 in JAMA Network Open where researchers studied glucagon-like peptide receptor agonists (known as GLP-1RAs), a class of drugs used to treat diabetes and obesity. Ozempic, Wegovy, Mounjaro, and Zepbound, which have become well-known recently because they are linked to rapid weight loss, contain GLP-1RAs.

For the study, they looked at electronic health records of 1.7 million patients who had type 2 diabetes, no prior diagnosis of obesity-related cancers, and had been prescribed GLP-1RAs, insulins, or metformin from March 2005 to November 2018.

The scientists found that compared to patients who took insulin, people who took GLP-1RAs had a “significant risk reduction” in 10 of 13 obesity-related cancers. Those 10 cancers were esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma.

Compared with patients taking insulin, patients taking GLP-1RAs showed no statistically significant reduction in stomach cancer and no reduced risk of breast and thyroid cancers, the study said.

But the study found no decrease in cancer risk with GLP-1RAs compared with metformin.

While the study results suggest that these drugs may reduce the risk of certain obesity-related cancers better than insulins, more research is needed, they said.

A version of this article appeared on WebMD.com.

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Recent research on popular weight loss drugs has uncovered surprising benefits beyond their intended use, like lowering the risk of fatal heart attacks. And now there may be another unforeseen advantage: People with type 2 diabetes who took these drugs had a lower risk of having 10 out of 13 obesity-related cancers, compared to those who used insulin therapy.

That’s according to a study published July 5 in JAMA Network Open where researchers studied glucagon-like peptide receptor agonists (known as GLP-1RAs), a class of drugs used to treat diabetes and obesity. Ozempic, Wegovy, Mounjaro, and Zepbound, which have become well-known recently because they are linked to rapid weight loss, contain GLP-1RAs.

For the study, they looked at electronic health records of 1.7 million patients who had type 2 diabetes, no prior diagnosis of obesity-related cancers, and had been prescribed GLP-1RAs, insulins, or metformin from March 2005 to November 2018.

The scientists found that compared to patients who took insulin, people who took GLP-1RAs had a “significant risk reduction” in 10 of 13 obesity-related cancers. Those 10 cancers were esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma.

Compared with patients taking insulin, patients taking GLP-1RAs showed no statistically significant reduction in stomach cancer and no reduced risk of breast and thyroid cancers, the study said.

But the study found no decrease in cancer risk with GLP-1RAs compared with metformin.

While the study results suggest that these drugs may reduce the risk of certain obesity-related cancers better than insulins, more research is needed, they said.

A version of this article appeared on WebMD.com.

Recent research on popular weight loss drugs has uncovered surprising benefits beyond their intended use, like lowering the risk of fatal heart attacks. And now there may be another unforeseen advantage: People with type 2 diabetes who took these drugs had a lower risk of having 10 out of 13 obesity-related cancers, compared to those who used insulin therapy.

That’s according to a study published July 5 in JAMA Network Open where researchers studied glucagon-like peptide receptor agonists (known as GLP-1RAs), a class of drugs used to treat diabetes and obesity. Ozempic, Wegovy, Mounjaro, and Zepbound, which have become well-known recently because they are linked to rapid weight loss, contain GLP-1RAs.

For the study, they looked at electronic health records of 1.7 million patients who had type 2 diabetes, no prior diagnosis of obesity-related cancers, and had been prescribed GLP-1RAs, insulins, or metformin from March 2005 to November 2018.

The scientists found that compared to patients who took insulin, people who took GLP-1RAs had a “significant risk reduction” in 10 of 13 obesity-related cancers. Those 10 cancers were esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma.

Compared with patients taking insulin, patients taking GLP-1RAs showed no statistically significant reduction in stomach cancer and no reduced risk of breast and thyroid cancers, the study said.

But the study found no decrease in cancer risk with GLP-1RAs compared with metformin.

While the study results suggest that these drugs may reduce the risk of certain obesity-related cancers better than insulins, more research is needed, they said.

A version of this article appeared on WebMD.com.

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Can Response to Semaglutide Be Predicted With a Genetic Test?

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Mon, 07/08/2024 - 10:29

— An analysis of data from 137 patients suggested testing whether people have a trait known as abnormal postprandial satiety (APS), or hungry gut, can predict how well they may respond to the obesity drug semaglutide, although it failed to establish this link for the somewhat similar tirzepatide.

At the American Diabetes Association (ADA) Scientific Sessions, Maria Daniela Hurtado Andrade, MD, PhD, of the Mayo Clinic, Jacksonville, Florida, presented results of a study using the MyPhenome Hungry Gut test, which was developed through machine learning, a form of artificial intelligence. 

The test is part of the MyPhenome obesity phenotyping portfolio from Phenomix Sciences, a company founded by Mayo Clinic physicians, scientists, and researchers Andres Acosta, MD, PhD, and Michael Camilleri, MD, DSc. 

At the ADA meeting, Dr. Hurtado Andrade discussed a test of 137 adults: 91 were considered to have a positive biomarker for abnormal postprandial satiety (APS+), and 46 who did not have it were classified as APS−. These were patients of the Mayo Clinic who were already taking obesity drugs and agreed to phenotyping. Of this group, 113 were on semaglutide and 24 on tirzepatide.

At 12 months, among those taking semaglutide, patients classified as APS+ achieved a mean 18% body weight loss compared with 10% in those classified as APS−. But the test didn’t find these kinds of differences for the tirzepatide group, with a mean 19.4% body weight loss in the APS+ group and a mean loss of 22.1% in the APS− group.

Further studies are warranted to assess the clinical utility of these biomarkers, Dr. Hurtado Andrade said. But these findings do support “the use of precision medicine for obesity based on an individual’s genetic background,” she said.

Dr. Hurtado Andrade’s presentation impressed fellow researchers who noted it as an early step toward the long-sought goal of more personalized medicine.

Daniel S. Hsia, MD, of Emory University, Atlanta, who led the ADA session at which Dr. Hurtado Andrade presented, said it was good to see new information being presented about using genetic risk scoring in obesity.

“The numbers were very small for the tirzepatide group as compared to the semaglutide group, so it’s a little hard to really come to any significant conclusions,” Dr. Hsia said in an interview.

At the ADA meeting, Ajay D. Rao, MD, MMSc, of Temple University, Philadelphia, said clinicians are excited about the idea of having biomarkers to aid in decisions about approaches to obesity.

In a follow-up interview with this news organization, Dr. Rao said he too is looking to see more testing of this approach to care, while describing Hurtado Andrade’s work as a “very well-done study.”

“We still need to see more large-scale studies of responsiveness to certain interventions,” he said. 

Dr. Hurtado Andrade noted that researchers at academic centers such as Mayo can try to hone in the combination of genetic and other factors that led to obesity, such as emotional eating patterns and abnormal postprandial satiety. 

But this approach is not widely scalable, as it demands resources of time and staffing that not all clinicians and patients enjoy.

“To overcome this challenge, our team has been working on developing biomarkers” such as the machine-learning gene risk score used to predict abnormal postprandial satiety, she said.

Findings for a related project were presented in May at Digestive Disease Week, as this news organization reported earlier. In that study, researchers calculated the genetic risk score for 84 adults undergoing weight loss interventions at Mayo Clinic who were prescribed the glucagon-like peptide 1 receptor agonist semaglutide.

This news organization separately asked Phenomix about the sales of MyPhenome Test kits. These cost $499, and about 500 tests have been sold since commercialization started last year, a spokesperson said.

The study was funded by Phenomix Sciences. Separately, Dr. Hurtado Andrade has worked as a consultant for Novo Nordisk and received research support from the National Institutes of Health. 

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

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— An analysis of data from 137 patients suggested testing whether people have a trait known as abnormal postprandial satiety (APS), or hungry gut, can predict how well they may respond to the obesity drug semaglutide, although it failed to establish this link for the somewhat similar tirzepatide.

At the American Diabetes Association (ADA) Scientific Sessions, Maria Daniela Hurtado Andrade, MD, PhD, of the Mayo Clinic, Jacksonville, Florida, presented results of a study using the MyPhenome Hungry Gut test, which was developed through machine learning, a form of artificial intelligence. 

The test is part of the MyPhenome obesity phenotyping portfolio from Phenomix Sciences, a company founded by Mayo Clinic physicians, scientists, and researchers Andres Acosta, MD, PhD, and Michael Camilleri, MD, DSc. 

At the ADA meeting, Dr. Hurtado Andrade discussed a test of 137 adults: 91 were considered to have a positive biomarker for abnormal postprandial satiety (APS+), and 46 who did not have it were classified as APS−. These were patients of the Mayo Clinic who were already taking obesity drugs and agreed to phenotyping. Of this group, 113 were on semaglutide and 24 on tirzepatide.

At 12 months, among those taking semaglutide, patients classified as APS+ achieved a mean 18% body weight loss compared with 10% in those classified as APS−. But the test didn’t find these kinds of differences for the tirzepatide group, with a mean 19.4% body weight loss in the APS+ group and a mean loss of 22.1% in the APS− group.

Further studies are warranted to assess the clinical utility of these biomarkers, Dr. Hurtado Andrade said. But these findings do support “the use of precision medicine for obesity based on an individual’s genetic background,” she said.

Dr. Hurtado Andrade’s presentation impressed fellow researchers who noted it as an early step toward the long-sought goal of more personalized medicine.

Daniel S. Hsia, MD, of Emory University, Atlanta, who led the ADA session at which Dr. Hurtado Andrade presented, said it was good to see new information being presented about using genetic risk scoring in obesity.

“The numbers were very small for the tirzepatide group as compared to the semaglutide group, so it’s a little hard to really come to any significant conclusions,” Dr. Hsia said in an interview.

At the ADA meeting, Ajay D. Rao, MD, MMSc, of Temple University, Philadelphia, said clinicians are excited about the idea of having biomarkers to aid in decisions about approaches to obesity.

In a follow-up interview with this news organization, Dr. Rao said he too is looking to see more testing of this approach to care, while describing Hurtado Andrade’s work as a “very well-done study.”

“We still need to see more large-scale studies of responsiveness to certain interventions,” he said. 

Dr. Hurtado Andrade noted that researchers at academic centers such as Mayo can try to hone in the combination of genetic and other factors that led to obesity, such as emotional eating patterns and abnormal postprandial satiety. 

But this approach is not widely scalable, as it demands resources of time and staffing that not all clinicians and patients enjoy.

“To overcome this challenge, our team has been working on developing biomarkers” such as the machine-learning gene risk score used to predict abnormal postprandial satiety, she said.

Findings for a related project were presented in May at Digestive Disease Week, as this news organization reported earlier. In that study, researchers calculated the genetic risk score for 84 adults undergoing weight loss interventions at Mayo Clinic who were prescribed the glucagon-like peptide 1 receptor agonist semaglutide.

This news organization separately asked Phenomix about the sales of MyPhenome Test kits. These cost $499, and about 500 tests have been sold since commercialization started last year, a spokesperson said.

The study was funded by Phenomix Sciences. Separately, Dr. Hurtado Andrade has worked as a consultant for Novo Nordisk and received research support from the National Institutes of Health. 

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

— An analysis of data from 137 patients suggested testing whether people have a trait known as abnormal postprandial satiety (APS), or hungry gut, can predict how well they may respond to the obesity drug semaglutide, although it failed to establish this link for the somewhat similar tirzepatide.

At the American Diabetes Association (ADA) Scientific Sessions, Maria Daniela Hurtado Andrade, MD, PhD, of the Mayo Clinic, Jacksonville, Florida, presented results of a study using the MyPhenome Hungry Gut test, which was developed through machine learning, a form of artificial intelligence. 

The test is part of the MyPhenome obesity phenotyping portfolio from Phenomix Sciences, a company founded by Mayo Clinic physicians, scientists, and researchers Andres Acosta, MD, PhD, and Michael Camilleri, MD, DSc. 

At the ADA meeting, Dr. Hurtado Andrade discussed a test of 137 adults: 91 were considered to have a positive biomarker for abnormal postprandial satiety (APS+), and 46 who did not have it were classified as APS−. These were patients of the Mayo Clinic who were already taking obesity drugs and agreed to phenotyping. Of this group, 113 were on semaglutide and 24 on tirzepatide.

At 12 months, among those taking semaglutide, patients classified as APS+ achieved a mean 18% body weight loss compared with 10% in those classified as APS−. But the test didn’t find these kinds of differences for the tirzepatide group, with a mean 19.4% body weight loss in the APS+ group and a mean loss of 22.1% in the APS− group.

Further studies are warranted to assess the clinical utility of these biomarkers, Dr. Hurtado Andrade said. But these findings do support “the use of precision medicine for obesity based on an individual’s genetic background,” she said.

Dr. Hurtado Andrade’s presentation impressed fellow researchers who noted it as an early step toward the long-sought goal of more personalized medicine.

Daniel S. Hsia, MD, of Emory University, Atlanta, who led the ADA session at which Dr. Hurtado Andrade presented, said it was good to see new information being presented about using genetic risk scoring in obesity.

“The numbers were very small for the tirzepatide group as compared to the semaglutide group, so it’s a little hard to really come to any significant conclusions,” Dr. Hsia said in an interview.

At the ADA meeting, Ajay D. Rao, MD, MMSc, of Temple University, Philadelphia, said clinicians are excited about the idea of having biomarkers to aid in decisions about approaches to obesity.

In a follow-up interview with this news organization, Dr. Rao said he too is looking to see more testing of this approach to care, while describing Hurtado Andrade’s work as a “very well-done study.”

“We still need to see more large-scale studies of responsiveness to certain interventions,” he said. 

Dr. Hurtado Andrade noted that researchers at academic centers such as Mayo can try to hone in the combination of genetic and other factors that led to obesity, such as emotional eating patterns and abnormal postprandial satiety. 

But this approach is not widely scalable, as it demands resources of time and staffing that not all clinicians and patients enjoy.

“To overcome this challenge, our team has been working on developing biomarkers” such as the machine-learning gene risk score used to predict abnormal postprandial satiety, she said.

Findings for a related project were presented in May at Digestive Disease Week, as this news organization reported earlier. In that study, researchers calculated the genetic risk score for 84 adults undergoing weight loss interventions at Mayo Clinic who were prescribed the glucagon-like peptide 1 receptor agonist semaglutide.

This news organization separately asked Phenomix about the sales of MyPhenome Test kits. These cost $499, and about 500 tests have been sold since commercialization started last year, a spokesperson said.

The study was funded by Phenomix Sciences. Separately, Dr. Hurtado Andrade has worked as a consultant for Novo Nordisk and received research support from the National Institutes of Health. 

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

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Should South Park: The End of Obesity Be Required Viewing in Medical School?

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Should South Park: The End of Obesity Be Required Viewing in Medical School?

Yes, there’s still much to find offensive, but South Park: The End of Obesity, in just 51 minutes, does more to explain some of obesity’s realities, its pharmacotherapy, and weight bias than the mainstream media has done perhaps ever. 

The mini-movie follows the plight of Eric Cartman, the fictional South Parkian child with severe obesity. 

South Park got everything right. The movie starts in a medical center where discussions with Cartman, his mother, and his doctor make it clear that obesity isn’t something that Cartman chose and is perhaps the most distressing aspect of his life. This certainly echoes study findings which report that quality-of-life scores in children with severe obesity are lower than those of children with newly diagnosed on-treatment cancers. As to how obesity erodes a child’s quality of life, no doubt part of its impact stems from obesity being a top source of schoolyard bullying, which is reflected by Cartman as he imagines his life without it. 

Cartman’s mother explains that of course they’ve tried diet and exercise, but that intentional behavior change alone hasn’t been sufficient to sustainably move the scale’s needle — a truth for the vast majority of people with obesity. But here, unlike in many actual doctors’ offices, Cartman’s doctor doesn’t spend time doubting or cajoling; instead, he does his job — which is to inform his patient, without judgment, about a pharmaceutical option that has proved to be beneficial. He accurately describes these medications as ushering in “a whole new era of medicine, a miracle really” that can “help people lose vast amounts of weight.”

The kicker, though, comes next. The doctor explains that insurance companies cover the medications only for patients with diabetes, “so if you can’t afford them, you’re just kind of out of luck.” This is changing somewhat now, at least here in Canada, where two of our main private insurers have changed their base coverages to make antiobesity medications something employers need to opt out of rather than opt into, but certainly they’re not covered by US Medicare for weight management, nor by our version of the same here in Canada.

But even for those who have coverage, there are hoops to jump through, which is highlighted by the incredible efforts made by Cartman and his friends to get his insurance plan to cover the medications. Thwarted at every turn, despite the undeniable benefits of these medications to health and quality of life, they are forced to turn to compounding — a phenomenon certainly pervasive here in North America whereby compounding pharmacies claim to be able to provide glucagon-like peptide-1 (GLP-1) analogs with comparable efficacy at a fraction of the price, but without the same rigor of proof of purity or efficacy. 

Also covered by South Park is that the GLP-1 analog supply is impacted by use by people who don’t meet approved medical criteria and are using the medications for aesthetic purposes. This speaks to the incredible societal pressure to be thin and to the comfort of some physicians to inappropriately prescribe these medications. This is covered by the subplot of South Park’s weed farmer, Randy, who in turn delivers an important insight into how it feels to use a GLP-1 analog: “I think there’s something wrong with these drugs ... I feel satisfied. With any drugs I want to do more and more, but with these drugs I feel like I want things less. With these drugs you don’t really crave anything.” The sentiment is echoed by Cartman, who exclaims, “I think I’m full. I’ve never known that feeling before in my life, but I’m full.”

It’s remarkable that South Park, a show built on serving up politically incorrect offense, covers obesity and its treatment with more accuracy, nuance, and compassion than does society as a whole. The show notes that obesity is a biological condition (it is), that when it comes to health (in America) “you have to have some f-ing willpower.” But where they explicitly mean having willpower in terms of filing and pursing insurance claims (you do), explains that drug companies are making antiobesity medications more expensive in America than anywhere else in the world (they are), and finally delivers this quote, which, while missing the biological basis of behavior and hunger with respect to obesity, certainly sums up why blame has no place in the discourse:

“We have sugar companies, pharmaceutical companies, and insurance companies all just trying to figure out how to make money off our health. It isn’t fair to put the blame on anyone for their weight.”

No, it’s not.

This movie should be required viewing in medical schools.
 

Dr. Freedhoff is associate professor, department of family medicine, University of Ottawa, and medical director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He disclosed ties with Bariatric Medical Institute, Constant Health, Novo Nordisk, and Weighty Matters.

A version of this article appeared on Medscape.com.

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Yes, there’s still much to find offensive, but South Park: The End of Obesity, in just 51 minutes, does more to explain some of obesity’s realities, its pharmacotherapy, and weight bias than the mainstream media has done perhaps ever. 

The mini-movie follows the plight of Eric Cartman, the fictional South Parkian child with severe obesity. 

South Park got everything right. The movie starts in a medical center where discussions with Cartman, his mother, and his doctor make it clear that obesity isn’t something that Cartman chose and is perhaps the most distressing aspect of his life. This certainly echoes study findings which report that quality-of-life scores in children with severe obesity are lower than those of children with newly diagnosed on-treatment cancers. As to how obesity erodes a child’s quality of life, no doubt part of its impact stems from obesity being a top source of schoolyard bullying, which is reflected by Cartman as he imagines his life without it. 

Cartman’s mother explains that of course they’ve tried diet and exercise, but that intentional behavior change alone hasn’t been sufficient to sustainably move the scale’s needle — a truth for the vast majority of people with obesity. But here, unlike in many actual doctors’ offices, Cartman’s doctor doesn’t spend time doubting or cajoling; instead, he does his job — which is to inform his patient, without judgment, about a pharmaceutical option that has proved to be beneficial. He accurately describes these medications as ushering in “a whole new era of medicine, a miracle really” that can “help people lose vast amounts of weight.”

The kicker, though, comes next. The doctor explains that insurance companies cover the medications only for patients with diabetes, “so if you can’t afford them, you’re just kind of out of luck.” This is changing somewhat now, at least here in Canada, where two of our main private insurers have changed their base coverages to make antiobesity medications something employers need to opt out of rather than opt into, but certainly they’re not covered by US Medicare for weight management, nor by our version of the same here in Canada.

But even for those who have coverage, there are hoops to jump through, which is highlighted by the incredible efforts made by Cartman and his friends to get his insurance plan to cover the medications. Thwarted at every turn, despite the undeniable benefits of these medications to health and quality of life, they are forced to turn to compounding — a phenomenon certainly pervasive here in North America whereby compounding pharmacies claim to be able to provide glucagon-like peptide-1 (GLP-1) analogs with comparable efficacy at a fraction of the price, but without the same rigor of proof of purity or efficacy. 

Also covered by South Park is that the GLP-1 analog supply is impacted by use by people who don’t meet approved medical criteria and are using the medications for aesthetic purposes. This speaks to the incredible societal pressure to be thin and to the comfort of some physicians to inappropriately prescribe these medications. This is covered by the subplot of South Park’s weed farmer, Randy, who in turn delivers an important insight into how it feels to use a GLP-1 analog: “I think there’s something wrong with these drugs ... I feel satisfied. With any drugs I want to do more and more, but with these drugs I feel like I want things less. With these drugs you don’t really crave anything.” The sentiment is echoed by Cartman, who exclaims, “I think I’m full. I’ve never known that feeling before in my life, but I’m full.”

It’s remarkable that South Park, a show built on serving up politically incorrect offense, covers obesity and its treatment with more accuracy, nuance, and compassion than does society as a whole. The show notes that obesity is a biological condition (it is), that when it comes to health (in America) “you have to have some f-ing willpower.” But where they explicitly mean having willpower in terms of filing and pursing insurance claims (you do), explains that drug companies are making antiobesity medications more expensive in America than anywhere else in the world (they are), and finally delivers this quote, which, while missing the biological basis of behavior and hunger with respect to obesity, certainly sums up why blame has no place in the discourse:

“We have sugar companies, pharmaceutical companies, and insurance companies all just trying to figure out how to make money off our health. It isn’t fair to put the blame on anyone for their weight.”

No, it’s not.

This movie should be required viewing in medical schools.
 

Dr. Freedhoff is associate professor, department of family medicine, University of Ottawa, and medical director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He disclosed ties with Bariatric Medical Institute, Constant Health, Novo Nordisk, and Weighty Matters.

A version of this article appeared on Medscape.com.

Yes, there’s still much to find offensive, but South Park: The End of Obesity, in just 51 minutes, does more to explain some of obesity’s realities, its pharmacotherapy, and weight bias than the mainstream media has done perhaps ever. 

The mini-movie follows the plight of Eric Cartman, the fictional South Parkian child with severe obesity. 

South Park got everything right. The movie starts in a medical center where discussions with Cartman, his mother, and his doctor make it clear that obesity isn’t something that Cartman chose and is perhaps the most distressing aspect of his life. This certainly echoes study findings which report that quality-of-life scores in children with severe obesity are lower than those of children with newly diagnosed on-treatment cancers. As to how obesity erodes a child’s quality of life, no doubt part of its impact stems from obesity being a top source of schoolyard bullying, which is reflected by Cartman as he imagines his life without it. 

Cartman’s mother explains that of course they’ve tried diet and exercise, but that intentional behavior change alone hasn’t been sufficient to sustainably move the scale’s needle — a truth for the vast majority of people with obesity. But here, unlike in many actual doctors’ offices, Cartman’s doctor doesn’t spend time doubting or cajoling; instead, he does his job — which is to inform his patient, without judgment, about a pharmaceutical option that has proved to be beneficial. He accurately describes these medications as ushering in “a whole new era of medicine, a miracle really” that can “help people lose vast amounts of weight.”

The kicker, though, comes next. The doctor explains that insurance companies cover the medications only for patients with diabetes, “so if you can’t afford them, you’re just kind of out of luck.” This is changing somewhat now, at least here in Canada, where two of our main private insurers have changed their base coverages to make antiobesity medications something employers need to opt out of rather than opt into, but certainly they’re not covered by US Medicare for weight management, nor by our version of the same here in Canada.

But even for those who have coverage, there are hoops to jump through, which is highlighted by the incredible efforts made by Cartman and his friends to get his insurance plan to cover the medications. Thwarted at every turn, despite the undeniable benefits of these medications to health and quality of life, they are forced to turn to compounding — a phenomenon certainly pervasive here in North America whereby compounding pharmacies claim to be able to provide glucagon-like peptide-1 (GLP-1) analogs with comparable efficacy at a fraction of the price, but without the same rigor of proof of purity or efficacy. 

Also covered by South Park is that the GLP-1 analog supply is impacted by use by people who don’t meet approved medical criteria and are using the medications for aesthetic purposes. This speaks to the incredible societal pressure to be thin and to the comfort of some physicians to inappropriately prescribe these medications. This is covered by the subplot of South Park’s weed farmer, Randy, who in turn delivers an important insight into how it feels to use a GLP-1 analog: “I think there’s something wrong with these drugs ... I feel satisfied. With any drugs I want to do more and more, but with these drugs I feel like I want things less. With these drugs you don’t really crave anything.” The sentiment is echoed by Cartman, who exclaims, “I think I’m full. I’ve never known that feeling before in my life, but I’m full.”

It’s remarkable that South Park, a show built on serving up politically incorrect offense, covers obesity and its treatment with more accuracy, nuance, and compassion than does society as a whole. The show notes that obesity is a biological condition (it is), that when it comes to health (in America) “you have to have some f-ing willpower.” But where they explicitly mean having willpower in terms of filing and pursing insurance claims (you do), explains that drug companies are making antiobesity medications more expensive in America than anywhere else in the world (they are), and finally delivers this quote, which, while missing the biological basis of behavior and hunger with respect to obesity, certainly sums up why blame has no place in the discourse:

“We have sugar companies, pharmaceutical companies, and insurance companies all just trying to figure out how to make money off our health. It isn’t fair to put the blame on anyone for their weight.”

No, it’s not.

This movie should be required viewing in medical schools.
 

Dr. Freedhoff is associate professor, department of family medicine, University of Ottawa, and medical director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He disclosed ties with Bariatric Medical Institute, Constant Health, Novo Nordisk, and Weighty Matters.

A version of this article appeared on Medscape.com.

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What Should Be Prioritized in Managing Early Diabetes?

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— What to prioritize first in managing early diabetes? That was the question debated on an expert panel at the American Diabetes Association (ADA) 84th Scientific Sessions, with impassioned responses ranging from a plea to “treat obesity first,” to a James Carville–inspired counterpoint of “it’s the glucose, stupid.” 

With a focus on preventing complications and inducing remission rounding out the four positions argued, Session Moderator Ravi Retnakaran, MD, of the University of Toronto, noted that the options reflect the tricky choices clinicians treating patients with diabetes are pressed to make on a daily basis.

“In clinical decision-making [for early diabetes], we are faced with weighing each of these variables for the individual patient, and while all are good options, strong arguments can be made for prioritizing each — with the potential of each choice to influence or improve all of the others,” Dr. Retnakaran told this news organization.
 

Which to Prioritize First?

Making the obesity first argument, Ania M. Jastreboff, MD, PhD, associate professor and director of the Yale Obesity Research Center at Yale School of Medicine, New Haven, Connecticut, noted the striking statistic that nearly 90% of people with type 2 diabetes have overweight or obesity and discussed the ever-expanding data showing the benefits of drugs including glucagon-like peptide 1 (GLP-1) receptor agonists not just in weight loss but also in kidney, cardiovascular, and, as presented at the meeting, sleep apnea improvement.

She contrasted the experiences of two patients with obesity: One treated for the obesity upon type 2 diagnosis — who had a quick normalization of lipids and hypertension soon after the obesity treatment — and the other presenting after 10 years with type 2 diabetes — who was on therapy for hypertension and hyperlipidemia but not for obesity and whose diseases were not as easily treated by that point.

“Why are we treating all the downstream effects and we’re not treating the disease that is potentially the root cause of all these other diseases?” Dr. Jastreboff said.
 

Complications?

Arguing in favor of focusing on complications, Roopa Mehta, MD, PhD, with the department of endocrinology and metabolism at Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico City, made the case that stakes don’t get any higher in diabetes than when it comes the looming threat of potentially fatal complications.

Acute myocardial infarction, stroke, amputation, and end-stage renal disease are all on the list of unwanted outcomes and need to be considered even in the earliest stages, as data show early onset type 2 diabetes is linked to life expectancy.

“The main goal of management has always been to prevent complications,” she noted. Citing ADA guidelines, Dr. Mehta underscored the benefits of first- and second-line therapy of metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and GLP-1 receptor agonists for most patients.
 

Remission?

Discussing the priority of putting patients into disease remission, Roy Taylor, MD, professor of medicine and metabolism at Newcastle University and Newcastle Hospitals NHS in Newcastle upon Tyne, England, and author of the book Life Without Diabetes, focused on an evidence-based alternative to achieving remission — a nonpharmacologic approach that avoids costly and sometimes inaccessible drugs.

In the intervention, described in the DiRECT randomized trial and subsequently in the UK National Health Service Type 2 Diabetes Path to Remission Program, patients with overweight or obesity were placed on a highly restrictive diet of just 800-900 calories a day for 12-20 weeks, followed by maintenance for 12 months, and they not only achieved weight loss but also achieved diabetes remission, in some cases long term.

Acknowledging that “this is not for everyone,” Dr. Taylor asserted that “we have to realize there is a substantial minority of people who want to be healthy but who don’t want to be medicalized,” he said.

“They want their health, and they can do extremely well.”
 

Glucose?

In taking his self-titled “it’s the glucose, stupid” stand, David M. Nathan, MD, of the Diabetes Center, Massachusetts General Hospital, Harvard Medical School, in Boston, cited extensive evidence showing that early intensive blood glucose control with treatment including sulfonylureas, insulin, or metformin significantly reduced the risk for complications in type 2 diabetes 15 or more years later, including renal failure, blindness, amputation, and myocardial infarctions, in addition to a reduction in diabetes-related death.

“In many of these studies, you saw the benefit even in the setting of weight-gain,” Dr. Nathan underscored.

He further noted the “sobering” findings of the Look AHEAD study, which had to be stopped due to futility when an intensive lifestyle/weight loss intervention showed no significant benefits in terms of cardiovascular disease in people with type 2 diabetes at a median follow-up of 9.6 years.

Ultimately, “diabetes, type 1 and type 2, remains a gluco-centric disease,” Dr. Nathan asserted. “Hyperglycemia is the only universal link between all forms of diabetes and mortality, and the long-term complications of diabetes are intimately associated with hyperglycemia.”
 

Tackling the Caveats

The ensuing panel discussion did not fail to deliver in delving into key areas of contention, particularly in terms of GLP-1 treatment.

Regarding a lack of data on the potential long-term effects of GLP-1s: “Yes, there are a huge number of studies [on GLP-1 receptor agonists], but they are, in general, over short periods of time and driven by pharma, who get in and get out as quickly as they can and have little in the way of interest to do comparative effectiveness studies,” Dr. Nathan argued.

“Meanwhile, this is like the crack cocaine of medications — patients have to stay on it for a lifetime or they will regain the weight — are you concerned at all about a lifetime of exposure to GLP-1 [drugs]?” he asked the panel.

Dr. Jastreboff responded that the first GLP-1 receptor agonist medications were approved in 2005, nearly 20 years ago, by the US Food and Drug Administration.

“Do I think we need long-term lifetime data? Absolutely,” she said. “We need to do our due diligence, we need to be careful, we need to monitor patients, and when and if there are signals, we need to follow them.”

What about the notorious gastrointestinal side effects of the drugs? “A majority of them are mitigated by slow up-titration,” Dr. Jastreboff noted.

“If patients have nausea, I do not go up [in dose]. I invite patients to tell me if they’re having vomiting because I don’t want anybody to have it, and I can count on one hand how many of my patients do.”

Dr. Mehta added the concern that as the drugs’ popularity soars, “a lot of doctors don’t know when they need to put the brakes on [weight coming off too quickly].”

She underscored that “we are not treating obesity for weight loss or for cosmetic reasons — this is about optimizing health.”

Dr. Jastreboff noted that in her practice, “I down-titrate if they’re losing weight too quickly.”

“If the patient is losing more than 1% per week of their body weight, then I slow down to make sure they’re getting the nutrients that they need, that they have enough energy to exercise, and that they’re prioritizing protein and fruits and vegetables in their diet.

“We just need to go slow, and yes, we need to follow them long term,” she said.

Chiming in from the audience, Julio Rosenstock, MD, a recognized thought leader in type 2 diabetes, offered his own take on the issues, describing Dr. Taylor’s very low–calorie diet suggestion as “not realistic” and Dr. Nathan’s glucose-first argument to be “stuck in the past.”

Based on modern-day evidence, “there is no reason on earth to start [diabetes treatment] with only metformin,” asserted Dr. Rosenstock, director of the Velocity Clinical Research center at Medical City and clinical professor of medicine at the University of Texas Southwestern Medical Center, Dallas.

“We need to start at the very least with metformin and a sodium-glucose cotransporter 2 (SGLT2) inhibitor from day 1, and then, if it’s affordable and there is access, with a GLP-1 receptor agonist,” he said.

“There is nothing better these days than those agents that consistently have shown a reduction of cardiovascular events and slowing of kidney disease progression.”

Overall, however, “I think you are all right,” he added, a sentiment shared by most.

Noting that the discussion as a whole represents a virtual sea change from the evidence-based options that would have been discussed only a decade ago, Dr. Retnakaran summed up his take-home message: “Stay tuned.

“You could easily see things changing in the next decade to come as we get more data and evidence to support what we ultimately should prioritize an early type 2 diabetes, so this is an exciting time.”

Dr. Retnakaran disclosed ties with Novo Nordisk, Boehringer Ingelheim, Novartis, Sanofi, and Eli Lilly. Dr. Jastreboff disclosed ties with Amgen, AstraZeneca, Boehringer Ingelheim, Biohaven, Eli Lilly, Intellihealth, Novo Nordisk, Pfizer, Regeneron, Scholar Rock, Structure Therapeutics, Terms Pharmaceutical, Weight Watchers, and Zealand Pharmaceuticals. Dr. Roopa had relationships with Novo Nordisk, Boehringer Ingelheim, Amgen, AstraZeneca, Eli Lilly, Silanes, and Sanofi. Dr. Taylor received lecture fees from Novartis, Lilly, Abbott, and Nestle Health and research funding from Diabetes UK and is an advisor to Fast800. Dr. Rosenstock reported relationships with Applied Therapeutics, AstraZeneca, Biomea Fusion, Boehringer Ingelheim, Eli Lilly and Company, Hanmi, Merck, Oramed, Structure Therapeutics, Novartis, Novo Nordisk, Pfizer, Ragor, and Sanofi. Dr. Nathan had no disclosures to report.
 

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

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— What to prioritize first in managing early diabetes? That was the question debated on an expert panel at the American Diabetes Association (ADA) 84th Scientific Sessions, with impassioned responses ranging from a plea to “treat obesity first,” to a James Carville–inspired counterpoint of “it’s the glucose, stupid.” 

With a focus on preventing complications and inducing remission rounding out the four positions argued, Session Moderator Ravi Retnakaran, MD, of the University of Toronto, noted that the options reflect the tricky choices clinicians treating patients with diabetes are pressed to make on a daily basis.

“In clinical decision-making [for early diabetes], we are faced with weighing each of these variables for the individual patient, and while all are good options, strong arguments can be made for prioritizing each — with the potential of each choice to influence or improve all of the others,” Dr. Retnakaran told this news organization.
 

Which to Prioritize First?

Making the obesity first argument, Ania M. Jastreboff, MD, PhD, associate professor and director of the Yale Obesity Research Center at Yale School of Medicine, New Haven, Connecticut, noted the striking statistic that nearly 90% of people with type 2 diabetes have overweight or obesity and discussed the ever-expanding data showing the benefits of drugs including glucagon-like peptide 1 (GLP-1) receptor agonists not just in weight loss but also in kidney, cardiovascular, and, as presented at the meeting, sleep apnea improvement.

She contrasted the experiences of two patients with obesity: One treated for the obesity upon type 2 diagnosis — who had a quick normalization of lipids and hypertension soon after the obesity treatment — and the other presenting after 10 years with type 2 diabetes — who was on therapy for hypertension and hyperlipidemia but not for obesity and whose diseases were not as easily treated by that point.

“Why are we treating all the downstream effects and we’re not treating the disease that is potentially the root cause of all these other diseases?” Dr. Jastreboff said.
 

Complications?

Arguing in favor of focusing on complications, Roopa Mehta, MD, PhD, with the department of endocrinology and metabolism at Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico City, made the case that stakes don’t get any higher in diabetes than when it comes the looming threat of potentially fatal complications.

Acute myocardial infarction, stroke, amputation, and end-stage renal disease are all on the list of unwanted outcomes and need to be considered even in the earliest stages, as data show early onset type 2 diabetes is linked to life expectancy.

“The main goal of management has always been to prevent complications,” she noted. Citing ADA guidelines, Dr. Mehta underscored the benefits of first- and second-line therapy of metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and GLP-1 receptor agonists for most patients.
 

Remission?

Discussing the priority of putting patients into disease remission, Roy Taylor, MD, professor of medicine and metabolism at Newcastle University and Newcastle Hospitals NHS in Newcastle upon Tyne, England, and author of the book Life Without Diabetes, focused on an evidence-based alternative to achieving remission — a nonpharmacologic approach that avoids costly and sometimes inaccessible drugs.

In the intervention, described in the DiRECT randomized trial and subsequently in the UK National Health Service Type 2 Diabetes Path to Remission Program, patients with overweight or obesity were placed on a highly restrictive diet of just 800-900 calories a day for 12-20 weeks, followed by maintenance for 12 months, and they not only achieved weight loss but also achieved diabetes remission, in some cases long term.

Acknowledging that “this is not for everyone,” Dr. Taylor asserted that “we have to realize there is a substantial minority of people who want to be healthy but who don’t want to be medicalized,” he said.

“They want their health, and they can do extremely well.”
 

Glucose?

In taking his self-titled “it’s the glucose, stupid” stand, David M. Nathan, MD, of the Diabetes Center, Massachusetts General Hospital, Harvard Medical School, in Boston, cited extensive evidence showing that early intensive blood glucose control with treatment including sulfonylureas, insulin, or metformin significantly reduced the risk for complications in type 2 diabetes 15 or more years later, including renal failure, blindness, amputation, and myocardial infarctions, in addition to a reduction in diabetes-related death.

“In many of these studies, you saw the benefit even in the setting of weight-gain,” Dr. Nathan underscored.

He further noted the “sobering” findings of the Look AHEAD study, which had to be stopped due to futility when an intensive lifestyle/weight loss intervention showed no significant benefits in terms of cardiovascular disease in people with type 2 diabetes at a median follow-up of 9.6 years.

Ultimately, “diabetes, type 1 and type 2, remains a gluco-centric disease,” Dr. Nathan asserted. “Hyperglycemia is the only universal link between all forms of diabetes and mortality, and the long-term complications of diabetes are intimately associated with hyperglycemia.”
 

Tackling the Caveats

The ensuing panel discussion did not fail to deliver in delving into key areas of contention, particularly in terms of GLP-1 treatment.

Regarding a lack of data on the potential long-term effects of GLP-1s: “Yes, there are a huge number of studies [on GLP-1 receptor agonists], but they are, in general, over short periods of time and driven by pharma, who get in and get out as quickly as they can and have little in the way of interest to do comparative effectiveness studies,” Dr. Nathan argued.

“Meanwhile, this is like the crack cocaine of medications — patients have to stay on it for a lifetime or they will regain the weight — are you concerned at all about a lifetime of exposure to GLP-1 [drugs]?” he asked the panel.

Dr. Jastreboff responded that the first GLP-1 receptor agonist medications were approved in 2005, nearly 20 years ago, by the US Food and Drug Administration.

“Do I think we need long-term lifetime data? Absolutely,” she said. “We need to do our due diligence, we need to be careful, we need to monitor patients, and when and if there are signals, we need to follow them.”

What about the notorious gastrointestinal side effects of the drugs? “A majority of them are mitigated by slow up-titration,” Dr. Jastreboff noted.

“If patients have nausea, I do not go up [in dose]. I invite patients to tell me if they’re having vomiting because I don’t want anybody to have it, and I can count on one hand how many of my patients do.”

Dr. Mehta added the concern that as the drugs’ popularity soars, “a lot of doctors don’t know when they need to put the brakes on [weight coming off too quickly].”

She underscored that “we are not treating obesity for weight loss or for cosmetic reasons — this is about optimizing health.”

Dr. Jastreboff noted that in her practice, “I down-titrate if they’re losing weight too quickly.”

“If the patient is losing more than 1% per week of their body weight, then I slow down to make sure they’re getting the nutrients that they need, that they have enough energy to exercise, and that they’re prioritizing protein and fruits and vegetables in their diet.

“We just need to go slow, and yes, we need to follow them long term,” she said.

Chiming in from the audience, Julio Rosenstock, MD, a recognized thought leader in type 2 diabetes, offered his own take on the issues, describing Dr. Taylor’s very low–calorie diet suggestion as “not realistic” and Dr. Nathan’s glucose-first argument to be “stuck in the past.”

Based on modern-day evidence, “there is no reason on earth to start [diabetes treatment] with only metformin,” asserted Dr. Rosenstock, director of the Velocity Clinical Research center at Medical City and clinical professor of medicine at the University of Texas Southwestern Medical Center, Dallas.

“We need to start at the very least with metformin and a sodium-glucose cotransporter 2 (SGLT2) inhibitor from day 1, and then, if it’s affordable and there is access, with a GLP-1 receptor agonist,” he said.

“There is nothing better these days than those agents that consistently have shown a reduction of cardiovascular events and slowing of kidney disease progression.”

Overall, however, “I think you are all right,” he added, a sentiment shared by most.

Noting that the discussion as a whole represents a virtual sea change from the evidence-based options that would have been discussed only a decade ago, Dr. Retnakaran summed up his take-home message: “Stay tuned.

“You could easily see things changing in the next decade to come as we get more data and evidence to support what we ultimately should prioritize an early type 2 diabetes, so this is an exciting time.”

Dr. Retnakaran disclosed ties with Novo Nordisk, Boehringer Ingelheim, Novartis, Sanofi, and Eli Lilly. Dr. Jastreboff disclosed ties with Amgen, AstraZeneca, Boehringer Ingelheim, Biohaven, Eli Lilly, Intellihealth, Novo Nordisk, Pfizer, Regeneron, Scholar Rock, Structure Therapeutics, Terms Pharmaceutical, Weight Watchers, and Zealand Pharmaceuticals. Dr. Roopa had relationships with Novo Nordisk, Boehringer Ingelheim, Amgen, AstraZeneca, Eli Lilly, Silanes, and Sanofi. Dr. Taylor received lecture fees from Novartis, Lilly, Abbott, and Nestle Health and research funding from Diabetes UK and is an advisor to Fast800. Dr. Rosenstock reported relationships with Applied Therapeutics, AstraZeneca, Biomea Fusion, Boehringer Ingelheim, Eli Lilly and Company, Hanmi, Merck, Oramed, Structure Therapeutics, Novartis, Novo Nordisk, Pfizer, Ragor, and Sanofi. Dr. Nathan had no disclosures to report.
 

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

— What to prioritize first in managing early diabetes? That was the question debated on an expert panel at the American Diabetes Association (ADA) 84th Scientific Sessions, with impassioned responses ranging from a plea to “treat obesity first,” to a James Carville–inspired counterpoint of “it’s the glucose, stupid.” 

With a focus on preventing complications and inducing remission rounding out the four positions argued, Session Moderator Ravi Retnakaran, MD, of the University of Toronto, noted that the options reflect the tricky choices clinicians treating patients with diabetes are pressed to make on a daily basis.

“In clinical decision-making [for early diabetes], we are faced with weighing each of these variables for the individual patient, and while all are good options, strong arguments can be made for prioritizing each — with the potential of each choice to influence or improve all of the others,” Dr. Retnakaran told this news organization.
 

Which to Prioritize First?

Making the obesity first argument, Ania M. Jastreboff, MD, PhD, associate professor and director of the Yale Obesity Research Center at Yale School of Medicine, New Haven, Connecticut, noted the striking statistic that nearly 90% of people with type 2 diabetes have overweight or obesity and discussed the ever-expanding data showing the benefits of drugs including glucagon-like peptide 1 (GLP-1) receptor agonists not just in weight loss but also in kidney, cardiovascular, and, as presented at the meeting, sleep apnea improvement.

She contrasted the experiences of two patients with obesity: One treated for the obesity upon type 2 diagnosis — who had a quick normalization of lipids and hypertension soon after the obesity treatment — and the other presenting after 10 years with type 2 diabetes — who was on therapy for hypertension and hyperlipidemia but not for obesity and whose diseases were not as easily treated by that point.

“Why are we treating all the downstream effects and we’re not treating the disease that is potentially the root cause of all these other diseases?” Dr. Jastreboff said.
 

Complications?

Arguing in favor of focusing on complications, Roopa Mehta, MD, PhD, with the department of endocrinology and metabolism at Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico City, made the case that stakes don’t get any higher in diabetes than when it comes the looming threat of potentially fatal complications.

Acute myocardial infarction, stroke, amputation, and end-stage renal disease are all on the list of unwanted outcomes and need to be considered even in the earliest stages, as data show early onset type 2 diabetes is linked to life expectancy.

“The main goal of management has always been to prevent complications,” she noted. Citing ADA guidelines, Dr. Mehta underscored the benefits of first- and second-line therapy of metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and GLP-1 receptor agonists for most patients.
 

Remission?

Discussing the priority of putting patients into disease remission, Roy Taylor, MD, professor of medicine and metabolism at Newcastle University and Newcastle Hospitals NHS in Newcastle upon Tyne, England, and author of the book Life Without Diabetes, focused on an evidence-based alternative to achieving remission — a nonpharmacologic approach that avoids costly and sometimes inaccessible drugs.

In the intervention, described in the DiRECT randomized trial and subsequently in the UK National Health Service Type 2 Diabetes Path to Remission Program, patients with overweight or obesity were placed on a highly restrictive diet of just 800-900 calories a day for 12-20 weeks, followed by maintenance for 12 months, and they not only achieved weight loss but also achieved diabetes remission, in some cases long term.

Acknowledging that “this is not for everyone,” Dr. Taylor asserted that “we have to realize there is a substantial minority of people who want to be healthy but who don’t want to be medicalized,” he said.

“They want their health, and they can do extremely well.”
 

Glucose?

In taking his self-titled “it’s the glucose, stupid” stand, David M. Nathan, MD, of the Diabetes Center, Massachusetts General Hospital, Harvard Medical School, in Boston, cited extensive evidence showing that early intensive blood glucose control with treatment including sulfonylureas, insulin, or metformin significantly reduced the risk for complications in type 2 diabetes 15 or more years later, including renal failure, blindness, amputation, and myocardial infarctions, in addition to a reduction in diabetes-related death.

“In many of these studies, you saw the benefit even in the setting of weight-gain,” Dr. Nathan underscored.

He further noted the “sobering” findings of the Look AHEAD study, which had to be stopped due to futility when an intensive lifestyle/weight loss intervention showed no significant benefits in terms of cardiovascular disease in people with type 2 diabetes at a median follow-up of 9.6 years.

Ultimately, “diabetes, type 1 and type 2, remains a gluco-centric disease,” Dr. Nathan asserted. “Hyperglycemia is the only universal link between all forms of diabetes and mortality, and the long-term complications of diabetes are intimately associated with hyperglycemia.”
 

Tackling the Caveats

The ensuing panel discussion did not fail to deliver in delving into key areas of contention, particularly in terms of GLP-1 treatment.

Regarding a lack of data on the potential long-term effects of GLP-1s: “Yes, there are a huge number of studies [on GLP-1 receptor agonists], but they are, in general, over short periods of time and driven by pharma, who get in and get out as quickly as they can and have little in the way of interest to do comparative effectiveness studies,” Dr. Nathan argued.

“Meanwhile, this is like the crack cocaine of medications — patients have to stay on it for a lifetime or they will regain the weight — are you concerned at all about a lifetime of exposure to GLP-1 [drugs]?” he asked the panel.

Dr. Jastreboff responded that the first GLP-1 receptor agonist medications were approved in 2005, nearly 20 years ago, by the US Food and Drug Administration.

“Do I think we need long-term lifetime data? Absolutely,” she said. “We need to do our due diligence, we need to be careful, we need to monitor patients, and when and if there are signals, we need to follow them.”

What about the notorious gastrointestinal side effects of the drugs? “A majority of them are mitigated by slow up-titration,” Dr. Jastreboff noted.

“If patients have nausea, I do not go up [in dose]. I invite patients to tell me if they’re having vomiting because I don’t want anybody to have it, and I can count on one hand how many of my patients do.”

Dr. Mehta added the concern that as the drugs’ popularity soars, “a lot of doctors don’t know when they need to put the brakes on [weight coming off too quickly].”

She underscored that “we are not treating obesity for weight loss or for cosmetic reasons — this is about optimizing health.”

Dr. Jastreboff noted that in her practice, “I down-titrate if they’re losing weight too quickly.”

“If the patient is losing more than 1% per week of their body weight, then I slow down to make sure they’re getting the nutrients that they need, that they have enough energy to exercise, and that they’re prioritizing protein and fruits and vegetables in their diet.

“We just need to go slow, and yes, we need to follow them long term,” she said.

Chiming in from the audience, Julio Rosenstock, MD, a recognized thought leader in type 2 diabetes, offered his own take on the issues, describing Dr. Taylor’s very low–calorie diet suggestion as “not realistic” and Dr. Nathan’s glucose-first argument to be “stuck in the past.”

Based on modern-day evidence, “there is no reason on earth to start [diabetes treatment] with only metformin,” asserted Dr. Rosenstock, director of the Velocity Clinical Research center at Medical City and clinical professor of medicine at the University of Texas Southwestern Medical Center, Dallas.

“We need to start at the very least with metformin and a sodium-glucose cotransporter 2 (SGLT2) inhibitor from day 1, and then, if it’s affordable and there is access, with a GLP-1 receptor agonist,” he said.

“There is nothing better these days than those agents that consistently have shown a reduction of cardiovascular events and slowing of kidney disease progression.”

Overall, however, “I think you are all right,” he added, a sentiment shared by most.

Noting that the discussion as a whole represents a virtual sea change from the evidence-based options that would have been discussed only a decade ago, Dr. Retnakaran summed up his take-home message: “Stay tuned.

“You could easily see things changing in the next decade to come as we get more data and evidence to support what we ultimately should prioritize an early type 2 diabetes, so this is an exciting time.”

Dr. Retnakaran disclosed ties with Novo Nordisk, Boehringer Ingelheim, Novartis, Sanofi, and Eli Lilly. Dr. Jastreboff disclosed ties with Amgen, AstraZeneca, Boehringer Ingelheim, Biohaven, Eli Lilly, Intellihealth, Novo Nordisk, Pfizer, Regeneron, Scholar Rock, Structure Therapeutics, Terms Pharmaceutical, Weight Watchers, and Zealand Pharmaceuticals. Dr. Roopa had relationships with Novo Nordisk, Boehringer Ingelheim, Amgen, AstraZeneca, Eli Lilly, Silanes, and Sanofi. Dr. Taylor received lecture fees from Novartis, Lilly, Abbott, and Nestle Health and research funding from Diabetes UK and is an advisor to Fast800. Dr. Rosenstock reported relationships with Applied Therapeutics, AstraZeneca, Biomea Fusion, Boehringer Ingelheim, Eli Lilly and Company, Hanmi, Merck, Oramed, Structure Therapeutics, Novartis, Novo Nordisk, Pfizer, Ragor, and Sanofi. Dr. Nathan had no disclosures to report.
 

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

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Triple Therapy May Be Effective in Drug-Naive T2D

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Changed
Wed, 07/03/2024 - 10:12

 

TOPLINE:

A triple combination therapy (TCT) of metformindapagliflozin, and saxagliptin is an effective and safe treatment option for drug-naive patients with type 2 diabetes (T2D) compared with stepwise add-on therapy.

METHODOLOGY:

  • Current guidelines recommend early combination therapy to extend the time to treatment failure, reduce the risk for diabetic complications, and prevent clinical inertia in patients with T2D.
  • This randomized controlled open-label trial conducted at nine sites in South Korea included 105 drug-naive patients with T2D (mean age, 49.5 years; 32.4% women) who either received triple therapy (metformin, dapagliflozin, and saxagliptin) or stepwise add-on therapy (initiated with metformin, followed by glimepiride and sitagliptin for those with baseline hemoglobin A1c levels < 9.0% or with initial dual metformin and glimepiride in those with A1c levels ≥ 9.0% followed by sitagliptin).
  • The primary outcome was the proportion of patients who achieved A1c levels < 6.5% without hypoglycemia, weight gain ≥ 5%, or discontinuation of drugs because of adverse events at week 104.
  • The secondary outcomes were the proportion of patients whose A1c levels dropped to < 7.0% at weeks 56 and 104 and dropped to < 6.5% at week 56, all without hypoglycemia, weight gain, nor discontinuation due to adverse events.

TAKEAWAY:

  • At week 104, a higher proportion of patients in the triple therapy group achieved the primary outcome than those in the stepwise add-on therapy group (39.0% vs 17.1%; P = .027).
  • In both groups, a similar proportion of patients (46.3%) achieved A1c levels < 6.5% at week 104, but the proportion of patients without hypoglycemia, weight gain, or discontinuation because of adverse events was higher in the triple therapy group than those in the stepwise add-on therapy group (83.3% vs 38.0%; P < .001).

IN PRACTICE:

The authors wrote: “Although the glycemic efficacy of each drug in the TCT was modest, the combination of these drugs resulted in a 2-year durable glycemic efficacy, with greater than a 2.5% reduction in A1c levels from baseline. The overall results of this study suggest a novel strategy for initial combination therapy in newly diagnosed T2D patients.”

SOURCE:

The study was led by Nam Hoon Kim, MD, of the Department of Internal Medicine, Korea University College of Medicine, Seoul. It was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The study had a relatively small sample size as compared with previous clinical trials. More people in the standard therapy group had A1c levels ≥ 9.0%, which resulted in more than double the number of people receiving dual combination therapy over monotherapy in that group. The trial duration was insufficient to evaluate the cardiovascular outcomes.

DISCLOSURES:

The study was funded by AstraZeneca. Some authors reported financial ties with AstraZeneca and other pharmaceutical and medical device companies as members of advisory boards or recipients of grants, consulting fees, honoraria, or lecture fees.

A version of this article appeared on Medscape.com.

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TOPLINE:

A triple combination therapy (TCT) of metformindapagliflozin, and saxagliptin is an effective and safe treatment option for drug-naive patients with type 2 diabetes (T2D) compared with stepwise add-on therapy.

METHODOLOGY:

  • Current guidelines recommend early combination therapy to extend the time to treatment failure, reduce the risk for diabetic complications, and prevent clinical inertia in patients with T2D.
  • This randomized controlled open-label trial conducted at nine sites in South Korea included 105 drug-naive patients with T2D (mean age, 49.5 years; 32.4% women) who either received triple therapy (metformin, dapagliflozin, and saxagliptin) or stepwise add-on therapy (initiated with metformin, followed by glimepiride and sitagliptin for those with baseline hemoglobin A1c levels < 9.0% or with initial dual metformin and glimepiride in those with A1c levels ≥ 9.0% followed by sitagliptin).
  • The primary outcome was the proportion of patients who achieved A1c levels < 6.5% without hypoglycemia, weight gain ≥ 5%, or discontinuation of drugs because of adverse events at week 104.
  • The secondary outcomes were the proportion of patients whose A1c levels dropped to < 7.0% at weeks 56 and 104 and dropped to < 6.5% at week 56, all without hypoglycemia, weight gain, nor discontinuation due to adverse events.

TAKEAWAY:

  • At week 104, a higher proportion of patients in the triple therapy group achieved the primary outcome than those in the stepwise add-on therapy group (39.0% vs 17.1%; P = .027).
  • In both groups, a similar proportion of patients (46.3%) achieved A1c levels < 6.5% at week 104, but the proportion of patients without hypoglycemia, weight gain, or discontinuation because of adverse events was higher in the triple therapy group than those in the stepwise add-on therapy group (83.3% vs 38.0%; P < .001).

IN PRACTICE:

The authors wrote: “Although the glycemic efficacy of each drug in the TCT was modest, the combination of these drugs resulted in a 2-year durable glycemic efficacy, with greater than a 2.5% reduction in A1c levels from baseline. The overall results of this study suggest a novel strategy for initial combination therapy in newly diagnosed T2D patients.”

SOURCE:

The study was led by Nam Hoon Kim, MD, of the Department of Internal Medicine, Korea University College of Medicine, Seoul. It was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The study had a relatively small sample size as compared with previous clinical trials. More people in the standard therapy group had A1c levels ≥ 9.0%, which resulted in more than double the number of people receiving dual combination therapy over monotherapy in that group. The trial duration was insufficient to evaluate the cardiovascular outcomes.

DISCLOSURES:

The study was funded by AstraZeneca. Some authors reported financial ties with AstraZeneca and other pharmaceutical and medical device companies as members of advisory boards or recipients of grants, consulting fees, honoraria, or lecture fees.

A version of this article appeared on Medscape.com.

 

TOPLINE:

A triple combination therapy (TCT) of metformindapagliflozin, and saxagliptin is an effective and safe treatment option for drug-naive patients with type 2 diabetes (T2D) compared with stepwise add-on therapy.

METHODOLOGY:

  • Current guidelines recommend early combination therapy to extend the time to treatment failure, reduce the risk for diabetic complications, and prevent clinical inertia in patients with T2D.
  • This randomized controlled open-label trial conducted at nine sites in South Korea included 105 drug-naive patients with T2D (mean age, 49.5 years; 32.4% women) who either received triple therapy (metformin, dapagliflozin, and saxagliptin) or stepwise add-on therapy (initiated with metformin, followed by glimepiride and sitagliptin for those with baseline hemoglobin A1c levels < 9.0% or with initial dual metformin and glimepiride in those with A1c levels ≥ 9.0% followed by sitagliptin).
  • The primary outcome was the proportion of patients who achieved A1c levels < 6.5% without hypoglycemia, weight gain ≥ 5%, or discontinuation of drugs because of adverse events at week 104.
  • The secondary outcomes were the proportion of patients whose A1c levels dropped to < 7.0% at weeks 56 and 104 and dropped to < 6.5% at week 56, all without hypoglycemia, weight gain, nor discontinuation due to adverse events.

TAKEAWAY:

  • At week 104, a higher proportion of patients in the triple therapy group achieved the primary outcome than those in the stepwise add-on therapy group (39.0% vs 17.1%; P = .027).
  • In both groups, a similar proportion of patients (46.3%) achieved A1c levels < 6.5% at week 104, but the proportion of patients without hypoglycemia, weight gain, or discontinuation because of adverse events was higher in the triple therapy group than those in the stepwise add-on therapy group (83.3% vs 38.0%; P < .001).

IN PRACTICE:

The authors wrote: “Although the glycemic efficacy of each drug in the TCT was modest, the combination of these drugs resulted in a 2-year durable glycemic efficacy, with greater than a 2.5% reduction in A1c levels from baseline. The overall results of this study suggest a novel strategy for initial combination therapy in newly diagnosed T2D patients.”

SOURCE:

The study was led by Nam Hoon Kim, MD, of the Department of Internal Medicine, Korea University College of Medicine, Seoul. It was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The study had a relatively small sample size as compared with previous clinical trials. More people in the standard therapy group had A1c levels ≥ 9.0%, which resulted in more than double the number of people receiving dual combination therapy over monotherapy in that group. The trial duration was insufficient to evaluate the cardiovascular outcomes.

DISCLOSURES:

The study was funded by AstraZeneca. Some authors reported financial ties with AstraZeneca and other pharmaceutical and medical device companies as members of advisory boards or recipients of grants, consulting fees, honoraria, or lecture fees.

A version of this article appeared on Medscape.com.

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Trading TV Time for Physical Activity Boosts Healthy Aging

Article Type
Changed
Wed, 07/10/2024 - 13:54

 

TOPLINE:

Sedentary behavior, particularly sitting and watching television, is linked to lower odds of healthy aging, but substituting it with any physical activity — or even sleeping, in case of women with inadequate sleep — may lead to better overall health.

METHODOLOGY:

  • Previous studies have shown that replacing sedentary behavior with physical activity may improve mortality outcomes, but whether this increased lifespan is accompanied by better overall health remains an unanswered question.
  • To understand the impact of sedentary behavior and physical activity on healthy aging, researchers analyzed data from the prospective cohort Nurses’ Health Study.
  • They included 45,176 women aged > 50 years in 1992 (mean age, 59.2 years) who were free of major chronic diseases and were followed up for 20 years.
  • In 1992, validated questionnaires were used to record exposure to sedentary behavior, different levels of physical activity, and sleep. The time spent watching television was the primary exposure in the sedentary behavior category.
  • The main outcome was healthy aging, defined as survival to ≥ 70 years of age and maintenance of four domains of health — being free of 11 main chronic diseases and having no impairment of subjective memory, physical function, or mental health.

TAKEAWAY:

  • At 20 years of follow-up, 8.6% of the women achieved healthy aging, while 41.4% had none of the 11 chronic diseases, 16.1% had no physical function impairment, 44.1% had no mental health limitation, and 51.9% reported no memory impairment.
  • For each increase of 2 hours per day spent sitting and watching television, the odds of healthy aging dropped by 12% (95% confidence interval [CI], 7%-17%).
  • Conversely, every additional 2 hours per day of low-level physical activity at work upped the odds of healthy aging by 6% (95% CI, 3%-9%); furthermore, each extra hour per day of standardized moderate to vigorous physical activity (normal pace walking or the equivalent) was associated with 14% higher odds (95% CI, 11%-16%) of healthy aging.
  • In a theoretical modeling analysis, individuals could increase their odds of healthy aging by replacing 1 hour of television time per day with low levels of physical activity at home and work or with moderate to vigorous levels of physical activity — or even sleeping, for those who slept for ≤ 7 hours.

IN PRACTICE:

“These findings expand on the literature reporting that replacing sedentary behavior with light or moderate to vigorous physical activity is associated with decreased mortality by suggesting that this increased lifespan might be accompanied by better overall health,” the authors wrote.

SOURCE:

Hongying Shi, PhD, Department of Epidemiology and Health Statistics, School of Public Health, Wenzhou Medical University, Wenzhou, China, led this study, which was published online in JAMA Network Open.

LIMITATIONS:

The measures of different behaviors were self-reported and may, therefore, be less accurate than objective measurement methods. Measurement error may have attenuated the effect of low levels of physical activity. The single exposure assessment at baseline may not reflect the long-term pattern of these activities.

DISCLOSURES:

The lead author was supported by the National Social Science Foundation Project of China and the Zhejiang Provincial Philosophy and Social Sciences Planning Project. A co-author and the Nurses’ Health Study were supported by the US National Institutes of Health. The authors declared no conflicts of interest.

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

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TOPLINE:

Sedentary behavior, particularly sitting and watching television, is linked to lower odds of healthy aging, but substituting it with any physical activity — or even sleeping, in case of women with inadequate sleep — may lead to better overall health.

METHODOLOGY:

  • Previous studies have shown that replacing sedentary behavior with physical activity may improve mortality outcomes, but whether this increased lifespan is accompanied by better overall health remains an unanswered question.
  • To understand the impact of sedentary behavior and physical activity on healthy aging, researchers analyzed data from the prospective cohort Nurses’ Health Study.
  • They included 45,176 women aged > 50 years in 1992 (mean age, 59.2 years) who were free of major chronic diseases and were followed up for 20 years.
  • In 1992, validated questionnaires were used to record exposure to sedentary behavior, different levels of physical activity, and sleep. The time spent watching television was the primary exposure in the sedentary behavior category.
  • The main outcome was healthy aging, defined as survival to ≥ 70 years of age and maintenance of four domains of health — being free of 11 main chronic diseases and having no impairment of subjective memory, physical function, or mental health.

TAKEAWAY:

  • At 20 years of follow-up, 8.6% of the women achieved healthy aging, while 41.4% had none of the 11 chronic diseases, 16.1% had no physical function impairment, 44.1% had no mental health limitation, and 51.9% reported no memory impairment.
  • For each increase of 2 hours per day spent sitting and watching television, the odds of healthy aging dropped by 12% (95% confidence interval [CI], 7%-17%).
  • Conversely, every additional 2 hours per day of low-level physical activity at work upped the odds of healthy aging by 6% (95% CI, 3%-9%); furthermore, each extra hour per day of standardized moderate to vigorous physical activity (normal pace walking or the equivalent) was associated with 14% higher odds (95% CI, 11%-16%) of healthy aging.
  • In a theoretical modeling analysis, individuals could increase their odds of healthy aging by replacing 1 hour of television time per day with low levels of physical activity at home and work or with moderate to vigorous levels of physical activity — or even sleeping, for those who slept for ≤ 7 hours.

IN PRACTICE:

“These findings expand on the literature reporting that replacing sedentary behavior with light or moderate to vigorous physical activity is associated with decreased mortality by suggesting that this increased lifespan might be accompanied by better overall health,” the authors wrote.

SOURCE:

Hongying Shi, PhD, Department of Epidemiology and Health Statistics, School of Public Health, Wenzhou Medical University, Wenzhou, China, led this study, which was published online in JAMA Network Open.

LIMITATIONS:

The measures of different behaviors were self-reported and may, therefore, be less accurate than objective measurement methods. Measurement error may have attenuated the effect of low levels of physical activity. The single exposure assessment at baseline may not reflect the long-term pattern of these activities.

DISCLOSURES:

The lead author was supported by the National Social Science Foundation Project of China and the Zhejiang Provincial Philosophy and Social Sciences Planning Project. A co-author and the Nurses’ Health Study were supported by the US National Institutes of Health. The authors declared no conflicts of interest.

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

 

TOPLINE:

Sedentary behavior, particularly sitting and watching television, is linked to lower odds of healthy aging, but substituting it with any physical activity — or even sleeping, in case of women with inadequate sleep — may lead to better overall health.

METHODOLOGY:

  • Previous studies have shown that replacing sedentary behavior with physical activity may improve mortality outcomes, but whether this increased lifespan is accompanied by better overall health remains an unanswered question.
  • To understand the impact of sedentary behavior and physical activity on healthy aging, researchers analyzed data from the prospective cohort Nurses’ Health Study.
  • They included 45,176 women aged > 50 years in 1992 (mean age, 59.2 years) who were free of major chronic diseases and were followed up for 20 years.
  • In 1992, validated questionnaires were used to record exposure to sedentary behavior, different levels of physical activity, and sleep. The time spent watching television was the primary exposure in the sedentary behavior category.
  • The main outcome was healthy aging, defined as survival to ≥ 70 years of age and maintenance of four domains of health — being free of 11 main chronic diseases and having no impairment of subjective memory, physical function, or mental health.

TAKEAWAY:

  • At 20 years of follow-up, 8.6% of the women achieved healthy aging, while 41.4% had none of the 11 chronic diseases, 16.1% had no physical function impairment, 44.1% had no mental health limitation, and 51.9% reported no memory impairment.
  • For each increase of 2 hours per day spent sitting and watching television, the odds of healthy aging dropped by 12% (95% confidence interval [CI], 7%-17%).
  • Conversely, every additional 2 hours per day of low-level physical activity at work upped the odds of healthy aging by 6% (95% CI, 3%-9%); furthermore, each extra hour per day of standardized moderate to vigorous physical activity (normal pace walking or the equivalent) was associated with 14% higher odds (95% CI, 11%-16%) of healthy aging.
  • In a theoretical modeling analysis, individuals could increase their odds of healthy aging by replacing 1 hour of television time per day with low levels of physical activity at home and work or with moderate to vigorous levels of physical activity — or even sleeping, for those who slept for ≤ 7 hours.

IN PRACTICE:

“These findings expand on the literature reporting that replacing sedentary behavior with light or moderate to vigorous physical activity is associated with decreased mortality by suggesting that this increased lifespan might be accompanied by better overall health,” the authors wrote.

SOURCE:

Hongying Shi, PhD, Department of Epidemiology and Health Statistics, School of Public Health, Wenzhou Medical University, Wenzhou, China, led this study, which was published online in JAMA Network Open.

LIMITATIONS:

The measures of different behaviors were self-reported and may, therefore, be less accurate than objective measurement methods. Measurement error may have attenuated the effect of low levels of physical activity. The single exposure assessment at baseline may not reflect the long-term pattern of these activities.

DISCLOSURES:

The lead author was supported by the National Social Science Foundation Project of China and the Zhejiang Provincial Philosophy and Social Sciences Planning Project. A co-author and the Nurses’ Health Study were supported by the US National Institutes of Health. The authors declared no conflicts of interest.

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

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The Future of Obesity

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Changed
Tue, 07/02/2024 - 11:21

I am not planning on having a headstone on my grave, or even having a grave for that matter. However, if my heirs decide to ignore my wishes and opt for some pithy observation chiseled into a tastefully sized granite block, I suspect they might choose “He always knew which way the wind was blowing ... but wasn’t so sure about the tides.” Which aptly describes both my navigational deficiencies they have observed here over my six decades on the Maine coast as well as my general inability to predict the future. Nonetheless, I am going to throw caution to the wind and take this opportunity to ponder where obesity in this country will go over the next couple of decades.

In March of last year the London-based World Obesity Federation published its World Obesity Atlas. In the summary the authors predict that based on current trends “obesity will cost the global economy of US $4 trillion of potential income in 2035, nearly 3% of current global domestic product (GDP).” They envision the “rising prevalence of obesity to be steepest among children and adolescents rising from 10% to 20% of the world’s boys during the period 2029 to 2035, and rising fro 8% to 18% of the world’s girls.”

Dr. William G. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years.
Dr. William G. Wilkoff

These dire predictions assume no significant measures to reverse this trajectory such as universal health coverage. Nor do the authors attempt to predict the effect of the growing use of GLP-1 agonists. This omission is surprising and somewhat refreshing given the fact that the project was funded by an unrestricted grant from Novo Nordisk, a major producer of one of these drugs.

Unfortunately, I think it is unlikely that over the next couple of decades any large countries who do not already have a functioning universal health care system will find the political will to develop one capable of reversing the trend toward obesity. Certainly, I don’t see it in the cards for this country.

On the other hand, I can foresee the availability and ease of administration for GLP-1 agonists and similar drugs improving over the near term. However, the cost and availability will continue to widen the separation between the haves and the have-nots, both globally and within each country. This will mean that the countries and population subgroups that already experience the bulk of the economic and health consequences of obesity will continue to shoulder an outsized burden of this “disease.”

It is unclear how much this widening of the fat-getting-fatter dynamic will add to the global and national political unrest that already seems to be tracking the effects of climate change. However, I can’t imaging it is going to be a calming or uniting force.

Narrowing our focus from an international to an individual resource-rich country such as the United States, let’s consider what the significant growth in availability and affordability of GLP-1 agonist drugs will mean. There will certainly be short-term improvements in the morbidity and mortality of some of the obesity related diseases. However, for other conditions it may take longer than two decades for us to notice an effect. While it is tempting to consider these declines as a financial boon for the country that already spends a high percentage of its GDP on healthcare. However, as the well-known Saturday Night Live pundit Roseanne Roseannadanna often observed, ”it’s always something ... if it’s not one thing it’s another.” There may be other non-obesity conditions that surge to fill the gap, leaving us still with a substantial financial burden for healthcare.

Patients taking GLP-1 agonists lose weight because they feel full and eat less food. While currently the number of patients taking these drugs is relatively small, the effect on this country’s food consumption is too small to calculate. However, let’s assume that 20 years from now half of the obese patients are taking appetite blunting medication. Using today’s statistics this means that 50 million adults will be eating significantly less food. Will the agriculturists have gradually adjusted to produce less food? Will this mean there is more food for the those experiencing “food insecurity”? I doubt it. Most food insecurity seems to be a problem of distribution and inequality, not supply.

Physicians now caution patients taking GLP-1 agonists to eat a healthy and balanced diet. When the drugs are more commonly available, will this caution be heeded by the majority? Will we see a population that may no longer be obese but nonetheless malnourished because of bad choices?

And, finally, in a similar vein, will previously obese individuals suddenly or gradually begin to be more physically active once the appetite blunting medicines have helped them lose weight? Here, I have my doubts. Of course, some leaner individuals begin to take advantage of their new body morphology. But, I fear that old sedentary habits will die very slowly for most, and not at all for many. We have built a vehicle-centric society in which being physically active requires making a conscious effort. Electronic devices and sedentary entertainment options are not going to disappear just because a significant percentage of the population is no longer obese.

So there you have it. I suspect that I am correct about which way some of the winds are blowing as the obesity becomes moves into its treatable “disease” phase. But, as always, I haven’t a clue which way the tide is running.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

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I am not planning on having a headstone on my grave, or even having a grave for that matter. However, if my heirs decide to ignore my wishes and opt for some pithy observation chiseled into a tastefully sized granite block, I suspect they might choose “He always knew which way the wind was blowing ... but wasn’t so sure about the tides.” Which aptly describes both my navigational deficiencies they have observed here over my six decades on the Maine coast as well as my general inability to predict the future. Nonetheless, I am going to throw caution to the wind and take this opportunity to ponder where obesity in this country will go over the next couple of decades.

In March of last year the London-based World Obesity Federation published its World Obesity Atlas. In the summary the authors predict that based on current trends “obesity will cost the global economy of US $4 trillion of potential income in 2035, nearly 3% of current global domestic product (GDP).” They envision the “rising prevalence of obesity to be steepest among children and adolescents rising from 10% to 20% of the world’s boys during the period 2029 to 2035, and rising fro 8% to 18% of the world’s girls.”

Dr. William G. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years.
Dr. William G. Wilkoff

These dire predictions assume no significant measures to reverse this trajectory such as universal health coverage. Nor do the authors attempt to predict the effect of the growing use of GLP-1 agonists. This omission is surprising and somewhat refreshing given the fact that the project was funded by an unrestricted grant from Novo Nordisk, a major producer of one of these drugs.

Unfortunately, I think it is unlikely that over the next couple of decades any large countries who do not already have a functioning universal health care system will find the political will to develop one capable of reversing the trend toward obesity. Certainly, I don’t see it in the cards for this country.

On the other hand, I can foresee the availability and ease of administration for GLP-1 agonists and similar drugs improving over the near term. However, the cost and availability will continue to widen the separation between the haves and the have-nots, both globally and within each country. This will mean that the countries and population subgroups that already experience the bulk of the economic and health consequences of obesity will continue to shoulder an outsized burden of this “disease.”

It is unclear how much this widening of the fat-getting-fatter dynamic will add to the global and national political unrest that already seems to be tracking the effects of climate change. However, I can’t imaging it is going to be a calming or uniting force.

Narrowing our focus from an international to an individual resource-rich country such as the United States, let’s consider what the significant growth in availability and affordability of GLP-1 agonist drugs will mean. There will certainly be short-term improvements in the morbidity and mortality of some of the obesity related diseases. However, for other conditions it may take longer than two decades for us to notice an effect. While it is tempting to consider these declines as a financial boon for the country that already spends a high percentage of its GDP on healthcare. However, as the well-known Saturday Night Live pundit Roseanne Roseannadanna often observed, ”it’s always something ... if it’s not one thing it’s another.” There may be other non-obesity conditions that surge to fill the gap, leaving us still with a substantial financial burden for healthcare.

Patients taking GLP-1 agonists lose weight because they feel full and eat less food. While currently the number of patients taking these drugs is relatively small, the effect on this country’s food consumption is too small to calculate. However, let’s assume that 20 years from now half of the obese patients are taking appetite blunting medication. Using today’s statistics this means that 50 million adults will be eating significantly less food. Will the agriculturists have gradually adjusted to produce less food? Will this mean there is more food for the those experiencing “food insecurity”? I doubt it. Most food insecurity seems to be a problem of distribution and inequality, not supply.

Physicians now caution patients taking GLP-1 agonists to eat a healthy and balanced diet. When the drugs are more commonly available, will this caution be heeded by the majority? Will we see a population that may no longer be obese but nonetheless malnourished because of bad choices?

And, finally, in a similar vein, will previously obese individuals suddenly or gradually begin to be more physically active once the appetite blunting medicines have helped them lose weight? Here, I have my doubts. Of course, some leaner individuals begin to take advantage of their new body morphology. But, I fear that old sedentary habits will die very slowly for most, and not at all for many. We have built a vehicle-centric society in which being physically active requires making a conscious effort. Electronic devices and sedentary entertainment options are not going to disappear just because a significant percentage of the population is no longer obese.

So there you have it. I suspect that I am correct about which way some of the winds are blowing as the obesity becomes moves into its treatable “disease” phase. But, as always, I haven’t a clue which way the tide is running.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

I am not planning on having a headstone on my grave, or even having a grave for that matter. However, if my heirs decide to ignore my wishes and opt for some pithy observation chiseled into a tastefully sized granite block, I suspect they might choose “He always knew which way the wind was blowing ... but wasn’t so sure about the tides.” Which aptly describes both my navigational deficiencies they have observed here over my six decades on the Maine coast as well as my general inability to predict the future. Nonetheless, I am going to throw caution to the wind and take this opportunity to ponder where obesity in this country will go over the next couple of decades.

In March of last year the London-based World Obesity Federation published its World Obesity Atlas. In the summary the authors predict that based on current trends “obesity will cost the global economy of US $4 trillion of potential income in 2035, nearly 3% of current global domestic product (GDP).” They envision the “rising prevalence of obesity to be steepest among children and adolescents rising from 10% to 20% of the world’s boys during the period 2029 to 2035, and rising fro 8% to 18% of the world’s girls.”

Dr. William G. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years.
Dr. William G. Wilkoff

These dire predictions assume no significant measures to reverse this trajectory such as universal health coverage. Nor do the authors attempt to predict the effect of the growing use of GLP-1 agonists. This omission is surprising and somewhat refreshing given the fact that the project was funded by an unrestricted grant from Novo Nordisk, a major producer of one of these drugs.

Unfortunately, I think it is unlikely that over the next couple of decades any large countries who do not already have a functioning universal health care system will find the political will to develop one capable of reversing the trend toward obesity. Certainly, I don’t see it in the cards for this country.

On the other hand, I can foresee the availability and ease of administration for GLP-1 agonists and similar drugs improving over the near term. However, the cost and availability will continue to widen the separation between the haves and the have-nots, both globally and within each country. This will mean that the countries and population subgroups that already experience the bulk of the economic and health consequences of obesity will continue to shoulder an outsized burden of this “disease.”

It is unclear how much this widening of the fat-getting-fatter dynamic will add to the global and national political unrest that already seems to be tracking the effects of climate change. However, I can’t imaging it is going to be a calming or uniting force.

Narrowing our focus from an international to an individual resource-rich country such as the United States, let’s consider what the significant growth in availability and affordability of GLP-1 agonist drugs will mean. There will certainly be short-term improvements in the morbidity and mortality of some of the obesity related diseases. However, for other conditions it may take longer than two decades for us to notice an effect. While it is tempting to consider these declines as a financial boon for the country that already spends a high percentage of its GDP on healthcare. However, as the well-known Saturday Night Live pundit Roseanne Roseannadanna often observed, ”it’s always something ... if it’s not one thing it’s another.” There may be other non-obesity conditions that surge to fill the gap, leaving us still with a substantial financial burden for healthcare.

Patients taking GLP-1 agonists lose weight because they feel full and eat less food. While currently the number of patients taking these drugs is relatively small, the effect on this country’s food consumption is too small to calculate. However, let’s assume that 20 years from now half of the obese patients are taking appetite blunting medication. Using today’s statistics this means that 50 million adults will be eating significantly less food. Will the agriculturists have gradually adjusted to produce less food? Will this mean there is more food for the those experiencing “food insecurity”? I doubt it. Most food insecurity seems to be a problem of distribution and inequality, not supply.

Physicians now caution patients taking GLP-1 agonists to eat a healthy and balanced diet. When the drugs are more commonly available, will this caution be heeded by the majority? Will we see a population that may no longer be obese but nonetheless malnourished because of bad choices?

And, finally, in a similar vein, will previously obese individuals suddenly or gradually begin to be more physically active once the appetite blunting medicines have helped them lose weight? Here, I have my doubts. Of course, some leaner individuals begin to take advantage of their new body morphology. But, I fear that old sedentary habits will die very slowly for most, and not at all for many. We have built a vehicle-centric society in which being physically active requires making a conscious effort. Electronic devices and sedentary entertainment options are not going to disappear just because a significant percentage of the population is no longer obese.

So there you have it. I suspect that I am correct about which way some of the winds are blowing as the obesity becomes moves into its treatable “disease” phase. But, as always, I haven’t a clue which way the tide is running.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

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Exercise Plus GLP-1 RAs Upped Weight Loss, Bone Retention

Article Type
Changed
Tue, 07/02/2024 - 11:11

 

TOPLINE:

People with obesity who exercise while taking glucagon-like peptide 1 receptor agonists (GLP-1 RAs; liraglutide) showed increased weight loss and preserved bone health, according to a study published in JAMA Network Open.

METHODOLOGY:

  • Patients were placed on an initial diet that consisted of no more than 800 calories per day for 8 weeks. Those who lost at least 5% of their starting weight were then placed into a 1-year program.
  • Participants included 195 adults aged between 18 and 65 years with obesity and no diabetes, 64% of whom were women.
  • They were split into four groups of interventions: Exercise only (48 patients), liraglutide only (49 patients), a combination of both (49 participants), and placebo (49 participants), for a 1-year period.
  • Patients received liraglutide or volume-matched placebo as daily injections starting at 0.6 mg/d with a weekly increase until 3 mg/d was reached; exercise entailed 30-minute sessions for 4 days a week.
  • Researchers studied bone health at each patient’s hip, spine, and forearm after they lost weight, by measuring bone mineral density (BMD).

TAKEAWAY:

  • The overall average change in weight loss over the course of 52 weeks was 7.03 kg in the placebo group, 11.19 kg in the exercise group, 13.74 kg in the liraglutide group, and 16.88 kg in the combination group.
  • After the initial low-calorie diet-induced weight loss, the placebo group regained weight, the exercise and liraglutide groups maintained weight loss, and the combination group lost additional weight.
  • BMD did not change in the combination group in comparison to the placebo group at the hip (mean change, −0.006 g/cm2; 95% CI, −0.017 to 0.004 g/cm2; P = .24) or spine (−0.010 g/cm2; 95% CI, −0.025 to 0.005 g/cm2; P = .20).
  • BMD of the spine in the liraglutide group decreased in comparison to the exercise group (mean change, −0.016 g/cm2; 95% CI, −0.032 to −0.001 g/cm2; P = .04) and the placebo group, in addition to decreases in the hip.

IN PRACTICE:

“Our results show that the combination of exercise and GLP-1 RA was the most effective weight loss strategy while preserving bone health,” study authors wrote.

SOURCE:

The study was led by Simon Birk Kjær Jensen, PhD, of the Department of Biomedical Sciences and Faculty of Health and Medical Sciences at the University of Copenhagen in Denmark, and published on June 25 in JAMA Network Open.

LIMITATIONS:

The study only included adults aged between 18 and 65 years without other chronic diseases and may not apply to patients who are older or have diabetes. The study sample was diverse but was conducted in Denmark, with a population of generally similar ancestry.

DISCLOSURES:

One study author reported serving on advisory boards for AstraZeneca, Boehringer Ingelheim, Bayer, and Amgen, among others. Other authors reported various financial interests, including grants, personal fees, and salaries, from Amgen, Novo Nordisk, and Abbott Lab, among others.

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

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TOPLINE:

People with obesity who exercise while taking glucagon-like peptide 1 receptor agonists (GLP-1 RAs; liraglutide) showed increased weight loss and preserved bone health, according to a study published in JAMA Network Open.

METHODOLOGY:

  • Patients were placed on an initial diet that consisted of no more than 800 calories per day for 8 weeks. Those who lost at least 5% of their starting weight were then placed into a 1-year program.
  • Participants included 195 adults aged between 18 and 65 years with obesity and no diabetes, 64% of whom were women.
  • They were split into four groups of interventions: Exercise only (48 patients), liraglutide only (49 patients), a combination of both (49 participants), and placebo (49 participants), for a 1-year period.
  • Patients received liraglutide or volume-matched placebo as daily injections starting at 0.6 mg/d with a weekly increase until 3 mg/d was reached; exercise entailed 30-minute sessions for 4 days a week.
  • Researchers studied bone health at each patient’s hip, spine, and forearm after they lost weight, by measuring bone mineral density (BMD).

TAKEAWAY:

  • The overall average change in weight loss over the course of 52 weeks was 7.03 kg in the placebo group, 11.19 kg in the exercise group, 13.74 kg in the liraglutide group, and 16.88 kg in the combination group.
  • After the initial low-calorie diet-induced weight loss, the placebo group regained weight, the exercise and liraglutide groups maintained weight loss, and the combination group lost additional weight.
  • BMD did not change in the combination group in comparison to the placebo group at the hip (mean change, −0.006 g/cm2; 95% CI, −0.017 to 0.004 g/cm2; P = .24) or spine (−0.010 g/cm2; 95% CI, −0.025 to 0.005 g/cm2; P = .20).
  • BMD of the spine in the liraglutide group decreased in comparison to the exercise group (mean change, −0.016 g/cm2; 95% CI, −0.032 to −0.001 g/cm2; P = .04) and the placebo group, in addition to decreases in the hip.

IN PRACTICE:

“Our results show that the combination of exercise and GLP-1 RA was the most effective weight loss strategy while preserving bone health,” study authors wrote.

SOURCE:

The study was led by Simon Birk Kjær Jensen, PhD, of the Department of Biomedical Sciences and Faculty of Health and Medical Sciences at the University of Copenhagen in Denmark, and published on June 25 in JAMA Network Open.

LIMITATIONS:

The study only included adults aged between 18 and 65 years without other chronic diseases and may not apply to patients who are older or have diabetes. The study sample was diverse but was conducted in Denmark, with a population of generally similar ancestry.

DISCLOSURES:

One study author reported serving on advisory boards for AstraZeneca, Boehringer Ingelheim, Bayer, and Amgen, among others. Other authors reported various financial interests, including grants, personal fees, and salaries, from Amgen, Novo Nordisk, and Abbott Lab, among others.

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

 

TOPLINE:

People with obesity who exercise while taking glucagon-like peptide 1 receptor agonists (GLP-1 RAs; liraglutide) showed increased weight loss and preserved bone health, according to a study published in JAMA Network Open.

METHODOLOGY:

  • Patients were placed on an initial diet that consisted of no more than 800 calories per day for 8 weeks. Those who lost at least 5% of their starting weight were then placed into a 1-year program.
  • Participants included 195 adults aged between 18 and 65 years with obesity and no diabetes, 64% of whom were women.
  • They were split into four groups of interventions: Exercise only (48 patients), liraglutide only (49 patients), a combination of both (49 participants), and placebo (49 participants), for a 1-year period.
  • Patients received liraglutide or volume-matched placebo as daily injections starting at 0.6 mg/d with a weekly increase until 3 mg/d was reached; exercise entailed 30-minute sessions for 4 days a week.
  • Researchers studied bone health at each patient’s hip, spine, and forearm after they lost weight, by measuring bone mineral density (BMD).

TAKEAWAY:

  • The overall average change in weight loss over the course of 52 weeks was 7.03 kg in the placebo group, 11.19 kg in the exercise group, 13.74 kg in the liraglutide group, and 16.88 kg in the combination group.
  • After the initial low-calorie diet-induced weight loss, the placebo group regained weight, the exercise and liraglutide groups maintained weight loss, and the combination group lost additional weight.
  • BMD did not change in the combination group in comparison to the placebo group at the hip (mean change, −0.006 g/cm2; 95% CI, −0.017 to 0.004 g/cm2; P = .24) or spine (−0.010 g/cm2; 95% CI, −0.025 to 0.005 g/cm2; P = .20).
  • BMD of the spine in the liraglutide group decreased in comparison to the exercise group (mean change, −0.016 g/cm2; 95% CI, −0.032 to −0.001 g/cm2; P = .04) and the placebo group, in addition to decreases in the hip.

IN PRACTICE:

“Our results show that the combination of exercise and GLP-1 RA was the most effective weight loss strategy while preserving bone health,” study authors wrote.

SOURCE:

The study was led by Simon Birk Kjær Jensen, PhD, of the Department of Biomedical Sciences and Faculty of Health and Medical Sciences at the University of Copenhagen in Denmark, and published on June 25 in JAMA Network Open.

LIMITATIONS:

The study only included adults aged between 18 and 65 years without other chronic diseases and may not apply to patients who are older or have diabetes. The study sample was diverse but was conducted in Denmark, with a population of generally similar ancestry.

DISCLOSURES:

One study author reported serving on advisory boards for AstraZeneca, Boehringer Ingelheim, Bayer, and Amgen, among others. Other authors reported various financial interests, including grants, personal fees, and salaries, from Amgen, Novo Nordisk, and Abbott Lab, among others.

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

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