Obesity

FAIRFAX, VIRGINIA — The lack of data on optimal timing of delivery for pregnancies complicated by diabetes remains a major challenge in obstetrics — one with considerable implications given the high and rising prevalence of pregestational and gestational diabetes, Katherine Laughon Grantz, MD, MS, of the National Institute of Child Health and Human Development, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

“While 39-40 weeks might be ideal for low-risk pregnancies, the optimal timing for pregnancies with complications [like diabetes] is unknown,” said Dr. Grantz, a senior investigator in the NICHD’s epidemiology branch.

The percentage of mothers with gestational diabetes mellitus (GDM) increased from 6% in 2016 to 8% in 2021, according to the most recent data from the National Vital Statistics System of the Centers for Disease Control and Prevention (MMWR Morb Mortal Wkly Rep. 2023;72:16). Meanwhile, the prevalence of prepregnancy obesity, which raises the risk of gestational and type 2 diabetes, was 29% in 2019; this represents an 11% increase from 2015 (NCHS Data Brief. 2020;392:1-8) and has occurred across all maternal ages, races, ethnic groups, and educational levels, she said.

“The reason clinicians deliver pregnancies with diabetes earlier is because there’s a decreased risk of macrosomia, shoulder dystocia, and stillbirth. And these risks need to be balanced with the increased risk of neonatal morbidity and mortality associated with earlier delivery,” said Dr. Grantz, who noted during her talk that delivery timing also appears to influence long-term neurodevelopmental outcomes. “Yet despite [diabetes in pregnancy] being so common, there is complete uncertainty about when to deliver.”
 

ACOG Recommendations, Randomized Trials (New And Old)

The American College of Obstetricians and Gynecologists, in a Committee Opinion on Medically Indicated Late-Preterm and Early-Term Deliveries, published in collaboration with the Society of Maternal-Fetal Medicine, offers recommendations based on the type of diabetes and the level of control. For instance, the suggested delivery timing for well-controlled GDM is full term (39 0/7 to 40 6/7 weeks of gestation), while the recommendation for poorly controlled diabetes is individualized late preterm/early term management (Obstet Gynecol. 2021;138:e35-9).

In defining and evaluating control, she noted, “the clinical focus is on glucose, but there are likely other important parameters that are not taken into account ... which [could be] important when considering the timing of delivery.” Potentially important factors include estimated fetal weight, fetal growth velocity, lipids, and amino acids, she said.

ACOG’s recommendations are based mainly on retrospective data, Dr. Grantz said. Only two randomized controlled trials have investigated the timing of delivery in the context of diabetes, and both focused on cesarean section and were “generally underpowered to study neonatal outcomes,” she said.

The first RCT, published in 1993, enrolled 200 women with uncomplicated insulin-requiring diabetes (187 with GDM and 13 with pregestational diabetes) at 38 weeks of gestation, and compared active induction of labor within 5 days to expectant management. There was no significant difference in the cesarean delivery rate (the primary outcome), but rates of macrosomia and large for gestational age were higher in the expectant management group (27% vs. 15%, P = .05, and 23% vs. 10%, P = .02, respectively). Shoulder dystocia occurred in three deliveries, each of which was expectantly managed (Am J Obstet Gynecol. 1993;169[3]:611-5). Notably, the study included “only women with excellent glucose control,” Dr. Grantz said.

The second RCT, published in 2017 by a group in Italy, enrolled 425 patients with GDM (diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria) between week 38 and week 39 of gestation and similarly randomized them to induction of labor or expectant management. No difference in cesarean delivery was found (BJOG. 2017;124[4]:669-77). Induction of labor was associated with a higher risk of hyperbilirubinemia, and there was a trend toward a decreased risk of macrosomia, but again, the study was underpowered to detect differences in most outcomes, she said. (The study also was stopped early because of an inability to recruit, she noted.)

Dr. Grantz is currently recruiting for a randomized trial aimed at determining the optimal time between 37 and 39 weeks to initiate delivery — the time when neonatal morbidity and perinatal mortality risk is the lowest – for uncontrolled GDM-complicated pregnancies. The trial is designed to recruit up to 3,450 pregnant women with uncontrolled GDM and randomize the timing of their delivery (NCT05515744).

Those who are eligible for the study but do not consent to participate in randomization for delivery will be asked about chart review only (an estimated additional 3,000). The SPAN TIME study will also assess newborn development and behavior outcomes, as well as anthropometric measures, as secondary outcomes. An exploratory analysis will look for clinical, nonclinical or biochemical factors that could be helpful in optimizing delivery timing.

What Retrospective Studies Reveal

Factors that may influence the timing of delivery include the duration of neonatal exposure to hyperglycemia/hyperinsulinemia (pregestational vs. gestational diabetes), the level of diabetes control, and comorbidities (e.g. maternal renal disease or chronic hypertension). However, research “investigating how these factors influence morbidity and the timing of delivery is limited,” said Dr. Grantz.

Overall, it has been difficult through retrospective studies, she said, to investigate neonatal morbidity in diabetic pregnancies and tease apart the relative effects of diabetes as a precursor for early delivery and prematurity itself. Among the studies suggesting an independent risk of diabetes is a retrospective study focusing on neonatal respiratory morbidity — “one of the most common adverse outcomes associated with diabetes.”

The study, an analysis of the Consortium on Safe Labor study (an electronic medical record study of more than 220,000 singleton pregnancies), stratified morbidity by the probability of delivering at term (≥ 37 weeks). GDM and pregestational diabetes complicated 5.1% and 1.5% of the pregnancies, respectively, and were found to be associated with increased risks of neonatal respiratory morbidity compared to women without diabetes — regardless of the probability of delivering at term.

However, these associations were stronger with a higher probability of delivering at term, which suggests that the neonatal respiratory morbidity associated with diabetes is not fully explained by a greater propensity for prematurity (Am J Perinatol. 2017;34[11]:1160-8).

In addition, the rates of all neonatal respiratory morbidities and mortality were higher for pregestational diabetes compared with gestational diabetes, said Dr. Grantz, a senior author of the study. (Morbidities included neonatal intensive care unit admission, transient tachypnea of newborn, apnea, respiratory distress syndrome, mechanical ventilation, and stillbirth.)

The pathophysiology of diabetes and neonatal respiratory morbidity is “not fully known,” she said. It is believed that fetal hyperinsulinemia may cause delayed pulmonary maturation and there is evidence from animal studies that insulin decreases the incorporation of glucose and fatty acids into phospholipid phosphatidylglycerol. Indirect effects stem from the physiologic immaturity of earlier delivery and a higher cesarean delivery rate in pregnancies complicated by diabetes, Dr. Grantz said.

Among other retrospective studies was a population-based study from Canada (2004-2014), published in 2020, of large numbers of women with all types of diabetes and a comparison group of over 2.5 million without diabetes. For maternal morbidity/mortality, there were no significant differences by gestational age between iatrogenic delivery and expectant management among any form of diabetes. But for neonatal morbidity and mortality, the study found differences.

In women with gestational diabetes, iatrogenic delivery was associated with increased risk of neonatal morbidity/mortality at 36 and 37 weeks’ gestation and with decreased risk at weeks 38-40. Increased risk with iatrogenic delivery was also found for women with type 1 and type 2 diabetes at weeks 36 and 37 (Acta Obstet Gynecol Scand. 2020;99[3]:341-9).

Another retrospective study using California vital statistics (1997-2006) examined rates of stillbirth and infant death in women with GDM by gestational age at delivery (Am J Obstet Gynecol. 2012;206[4]:309.e1-e7). The 190,000-plus women with GDM had elevated risk of stillbirth at each gestational age compared to those without GDM, but “the [excess] risk for GDM was lowest at 38 weeks and again at 40 weeks,” Dr. Grantz said. The investigators concluded, she said, “that the risk of expectant management exceeded that of delivery at 38 weeks and beyond.”

Dr. Grantz reported no disclosures.

FAIRFAX, VIRGINIA — The lack of data on optimal timing of delivery for pregnancies complicated by diabetes remains a major challenge in obstetrics — one with considerable implications given the high and rising prevalence of pregestational and gestational diabetes, Katherine Laughon Grantz, MD, MS, of the National Institute of Child Health and Human Development, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

“While 39-40 weeks might be ideal for low-risk pregnancies, the optimal timing for pregnancies with complications [like diabetes] is unknown,” said Dr. Grantz, a senior investigator in the NICHD’s epidemiology branch.

The percentage of mothers with gestational diabetes mellitus (GDM) increased from 6% in 2016 to 8% in 2021, according to the most recent data from the National Vital Statistics System of the Centers for Disease Control and Prevention (MMWR Morb Mortal Wkly Rep. 2023;72:16). Meanwhile, the prevalence of prepregnancy obesity, which raises the risk of gestational and type 2 diabetes, was 29% in 2019; this represents an 11% increase from 2015 (NCHS Data Brief. 2020;392:1-8) and has occurred across all maternal ages, races, ethnic groups, and educational levels, she said.

“The reason clinicians deliver pregnancies with diabetes earlier is because there’s a decreased risk of macrosomia, shoulder dystocia, and stillbirth. And these risks need to be balanced with the increased risk of neonatal morbidity and mortality associated with earlier delivery,” said Dr. Grantz, who noted during her talk that delivery timing also appears to influence long-term neurodevelopmental outcomes. “Yet despite [diabetes in pregnancy] being so common, there is complete uncertainty about when to deliver.”
 

ACOG Recommendations, Randomized Trials (New And Old)

The American College of Obstetricians and Gynecologists, in a Committee Opinion on Medically Indicated Late-Preterm and Early-Term Deliveries, published in collaboration with the Society of Maternal-Fetal Medicine, offers recommendations based on the type of diabetes and the level of control. For instance, the suggested delivery timing for well-controlled GDM is full term (39 0/7 to 40 6/7 weeks of gestation), while the recommendation for poorly controlled diabetes is individualized late preterm/early term management (Obstet Gynecol. 2021;138:e35-9).

In defining and evaluating control, she noted, “the clinical focus is on glucose, but there are likely other important parameters that are not taken into account ... which [could be] important when considering the timing of delivery.” Potentially important factors include estimated fetal weight, fetal growth velocity, lipids, and amino acids, she said.

ACOG’s recommendations are based mainly on retrospective data, Dr. Grantz said. Only two randomized controlled trials have investigated the timing of delivery in the context of diabetes, and both focused on cesarean section and were “generally underpowered to study neonatal outcomes,” she said.

The first RCT, published in 1993, enrolled 200 women with uncomplicated insulin-requiring diabetes (187 with GDM and 13 with pregestational diabetes) at 38 weeks of gestation, and compared active induction of labor within 5 days to expectant management. There was no significant difference in the cesarean delivery rate (the primary outcome), but rates of macrosomia and large for gestational age were higher in the expectant management group (27% vs. 15%, P = .05, and 23% vs. 10%, P = .02, respectively). Shoulder dystocia occurred in three deliveries, each of which was expectantly managed (Am J Obstet Gynecol. 1993;169[3]:611-5). Notably, the study included “only women with excellent glucose control,” Dr. Grantz said.

The second RCT, published in 2017 by a group in Italy, enrolled 425 patients with GDM (diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria) between week 38 and week 39 of gestation and similarly randomized them to induction of labor or expectant management. No difference in cesarean delivery was found (BJOG. 2017;124[4]:669-77). Induction of labor was associated with a higher risk of hyperbilirubinemia, and there was a trend toward a decreased risk of macrosomia, but again, the study was underpowered to detect differences in most outcomes, she said. (The study also was stopped early because of an inability to recruit, she noted.)

Dr. Grantz is currently recruiting for a randomized trial aimed at determining the optimal time between 37 and 39 weeks to initiate delivery — the time when neonatal morbidity and perinatal mortality risk is the lowest – for uncontrolled GDM-complicated pregnancies. The trial is designed to recruit up to 3,450 pregnant women with uncontrolled GDM and randomize the timing of their delivery (NCT05515744).

Those who are eligible for the study but do not consent to participate in randomization for delivery will be asked about chart review only (an estimated additional 3,000). The SPAN TIME study will also assess newborn development and behavior outcomes, as well as anthropometric measures, as secondary outcomes. An exploratory analysis will look for clinical, nonclinical or biochemical factors that could be helpful in optimizing delivery timing.

What Retrospective Studies Reveal

Factors that may influence the timing of delivery include the duration of neonatal exposure to hyperglycemia/hyperinsulinemia (pregestational vs. gestational diabetes), the level of diabetes control, and comorbidities (e.g. maternal renal disease or chronic hypertension). However, research “investigating how these factors influence morbidity and the timing of delivery is limited,” said Dr. Grantz.

Overall, it has been difficult through retrospective studies, she said, to investigate neonatal morbidity in diabetic pregnancies and tease apart the relative effects of diabetes as a precursor for early delivery and prematurity itself. Among the studies suggesting an independent risk of diabetes is a retrospective study focusing on neonatal respiratory morbidity — “one of the most common adverse outcomes associated with diabetes.”

The study, an analysis of the Consortium on Safe Labor study (an electronic medical record study of more than 220,000 singleton pregnancies), stratified morbidity by the probability of delivering at term (≥ 37 weeks). GDM and pregestational diabetes complicated 5.1% and 1.5% of the pregnancies, respectively, and were found to be associated with increased risks of neonatal respiratory morbidity compared to women without diabetes — regardless of the probability of delivering at term.

However, these associations were stronger with a higher probability of delivering at term, which suggests that the neonatal respiratory morbidity associated with diabetes is not fully explained by a greater propensity for prematurity (Am J Perinatol. 2017;34[11]:1160-8).

In addition, the rates of all neonatal respiratory morbidities and mortality were higher for pregestational diabetes compared with gestational diabetes, said Dr. Grantz, a senior author of the study. (Morbidities included neonatal intensive care unit admission, transient tachypnea of newborn, apnea, respiratory distress syndrome, mechanical ventilation, and stillbirth.)

The pathophysiology of diabetes and neonatal respiratory morbidity is “not fully known,” she said. It is believed that fetal hyperinsulinemia may cause delayed pulmonary maturation and there is evidence from animal studies that insulin decreases the incorporation of glucose and fatty acids into phospholipid phosphatidylglycerol. Indirect effects stem from the physiologic immaturity of earlier delivery and a higher cesarean delivery rate in pregnancies complicated by diabetes, Dr. Grantz said.

Among other retrospective studies was a population-based study from Canada (2004-2014), published in 2020, of large numbers of women with all types of diabetes and a comparison group of over 2.5 million without diabetes. For maternal morbidity/mortality, there were no significant differences by gestational age between iatrogenic delivery and expectant management among any form of diabetes. But for neonatal morbidity and mortality, the study found differences.

In women with gestational diabetes, iatrogenic delivery was associated with increased risk of neonatal morbidity/mortality at 36 and 37 weeks’ gestation and with decreased risk at weeks 38-40. Increased risk with iatrogenic delivery was also found for women with type 1 and type 2 diabetes at weeks 36 and 37 (Acta Obstet Gynecol Scand. 2020;99[3]:341-9).

Another retrospective study using California vital statistics (1997-2006) examined rates of stillbirth and infant death in women with GDM by gestational age at delivery (Am J Obstet Gynecol. 2012;206[4]:309.e1-e7). The 190,000-plus women with GDM had elevated risk of stillbirth at each gestational age compared to those without GDM, but “the [excess] risk for GDM was lowest at 38 weeks and again at 40 weeks,” Dr. Grantz said. The investigators concluded, she said, “that the risk of expectant management exceeded that of delivery at 38 weeks and beyond.”

Dr. Grantz reported no disclosures.

FAIRFAX, VIRGINIA — The lack of data on optimal timing of delivery for pregnancies complicated by diabetes remains a major challenge in obstetrics — one with considerable implications given the high and rising prevalence of pregestational and gestational diabetes, Katherine Laughon Grantz, MD, MS, of the National Institute of Child Health and Human Development, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

“While 39-40 weeks might be ideal for low-risk pregnancies, the optimal timing for pregnancies with complications [like diabetes] is unknown,” said Dr. Grantz, a senior investigator in the NICHD’s epidemiology branch.

The percentage of mothers with gestational diabetes mellitus (GDM) increased from 6% in 2016 to 8% in 2021, according to the most recent data from the National Vital Statistics System of the Centers for Disease Control and Prevention (MMWR Morb Mortal Wkly Rep. 2023;72:16). Meanwhile, the prevalence of prepregnancy obesity, which raises the risk of gestational and type 2 diabetes, was 29% in 2019; this represents an 11% increase from 2015 (NCHS Data Brief. 2020;392:1-8) and has occurred across all maternal ages, races, ethnic groups, and educational levels, she said.

“The reason clinicians deliver pregnancies with diabetes earlier is because there’s a decreased risk of macrosomia, shoulder dystocia, and stillbirth. And these risks need to be balanced with the increased risk of neonatal morbidity and mortality associated with earlier delivery,” said Dr. Grantz, who noted during her talk that delivery timing also appears to influence long-term neurodevelopmental outcomes. “Yet despite [diabetes in pregnancy] being so common, there is complete uncertainty about when to deliver.”
 

ACOG Recommendations, Randomized Trials (New And Old)

The American College of Obstetricians and Gynecologists, in a Committee Opinion on Medically Indicated Late-Preterm and Early-Term Deliveries, published in collaboration with the Society of Maternal-Fetal Medicine, offers recommendations based on the type of diabetes and the level of control. For instance, the suggested delivery timing for well-controlled GDM is full term (39 0/7 to 40 6/7 weeks of gestation), while the recommendation for poorly controlled diabetes is individualized late preterm/early term management (Obstet Gynecol. 2021;138:e35-9).

In defining and evaluating control, she noted, “the clinical focus is on glucose, but there are likely other important parameters that are not taken into account ... which [could be] important when considering the timing of delivery.” Potentially important factors include estimated fetal weight, fetal growth velocity, lipids, and amino acids, she said.

ACOG’s recommendations are based mainly on retrospective data, Dr. Grantz said. Only two randomized controlled trials have investigated the timing of delivery in the context of diabetes, and both focused on cesarean section and were “generally underpowered to study neonatal outcomes,” she said.

The first RCT, published in 1993, enrolled 200 women with uncomplicated insulin-requiring diabetes (187 with GDM and 13 with pregestational diabetes) at 38 weeks of gestation, and compared active induction of labor within 5 days to expectant management. There was no significant difference in the cesarean delivery rate (the primary outcome), but rates of macrosomia and large for gestational age were higher in the expectant management group (27% vs. 15%, P = .05, and 23% vs. 10%, P = .02, respectively). Shoulder dystocia occurred in three deliveries, each of which was expectantly managed (Am J Obstet Gynecol. 1993;169[3]:611-5). Notably, the study included “only women with excellent glucose control,” Dr. Grantz said.

The second RCT, published in 2017 by a group in Italy, enrolled 425 patients with GDM (diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria) between week 38 and week 39 of gestation and similarly randomized them to induction of labor or expectant management. No difference in cesarean delivery was found (BJOG. 2017;124[4]:669-77). Induction of labor was associated with a higher risk of hyperbilirubinemia, and there was a trend toward a decreased risk of macrosomia, but again, the study was underpowered to detect differences in most outcomes, she said. (The study also was stopped early because of an inability to recruit, she noted.)

Dr. Grantz is currently recruiting for a randomized trial aimed at determining the optimal time between 37 and 39 weeks to initiate delivery — the time when neonatal morbidity and perinatal mortality risk is the lowest – for uncontrolled GDM-complicated pregnancies. The trial is designed to recruit up to 3,450 pregnant women with uncontrolled GDM and randomize the timing of their delivery (NCT05515744).

Those who are eligible for the study but do not consent to participate in randomization for delivery will be asked about chart review only (an estimated additional 3,000). The SPAN TIME study will also assess newborn development and behavior outcomes, as well as anthropometric measures, as secondary outcomes. An exploratory analysis will look for clinical, nonclinical or biochemical factors that could be helpful in optimizing delivery timing.

What Retrospective Studies Reveal

Factors that may influence the timing of delivery include the duration of neonatal exposure to hyperglycemia/hyperinsulinemia (pregestational vs. gestational diabetes), the level of diabetes control, and comorbidities (e.g. maternal renal disease or chronic hypertension). However, research “investigating how these factors influence morbidity and the timing of delivery is limited,” said Dr. Grantz.

Overall, it has been difficult through retrospective studies, she said, to investigate neonatal morbidity in diabetic pregnancies and tease apart the relative effects of diabetes as a precursor for early delivery and prematurity itself. Among the studies suggesting an independent risk of diabetes is a retrospective study focusing on neonatal respiratory morbidity — “one of the most common adverse outcomes associated with diabetes.”

The study, an analysis of the Consortium on Safe Labor study (an electronic medical record study of more than 220,000 singleton pregnancies), stratified morbidity by the probability of delivering at term (≥ 37 weeks). GDM and pregestational diabetes complicated 5.1% and 1.5% of the pregnancies, respectively, and were found to be associated with increased risks of neonatal respiratory morbidity compared to women without diabetes — regardless of the probability of delivering at term.

However, these associations were stronger with a higher probability of delivering at term, which suggests that the neonatal respiratory morbidity associated with diabetes is not fully explained by a greater propensity for prematurity (Am J Perinatol. 2017;34[11]:1160-8).

In addition, the rates of all neonatal respiratory morbidities and mortality were higher for pregestational diabetes compared with gestational diabetes, said Dr. Grantz, a senior author of the study. (Morbidities included neonatal intensive care unit admission, transient tachypnea of newborn, apnea, respiratory distress syndrome, mechanical ventilation, and stillbirth.)

The pathophysiology of diabetes and neonatal respiratory morbidity is “not fully known,” she said. It is believed that fetal hyperinsulinemia may cause delayed pulmonary maturation and there is evidence from animal studies that insulin decreases the incorporation of glucose and fatty acids into phospholipid phosphatidylglycerol. Indirect effects stem from the physiologic immaturity of earlier delivery and a higher cesarean delivery rate in pregnancies complicated by diabetes, Dr. Grantz said.

Among other retrospective studies was a population-based study from Canada (2004-2014), published in 2020, of large numbers of women with all types of diabetes and a comparison group of over 2.5 million without diabetes. For maternal morbidity/mortality, there were no significant differences by gestational age between iatrogenic delivery and expectant management among any form of diabetes. But for neonatal morbidity and mortality, the study found differences.

In women with gestational diabetes, iatrogenic delivery was associated with increased risk of neonatal morbidity/mortality at 36 and 37 weeks’ gestation and with decreased risk at weeks 38-40. Increased risk with iatrogenic delivery was also found for women with type 1 and type 2 diabetes at weeks 36 and 37 (Acta Obstet Gynecol Scand. 2020;99[3]:341-9).

Another retrospective study using California vital statistics (1997-2006) examined rates of stillbirth and infant death in women with GDM by gestational age at delivery (Am J Obstet Gynecol. 2012;206[4]:309.e1-e7). The 190,000-plus women with GDM had elevated risk of stillbirth at each gestational age compared to those without GDM, but “the [excess] risk for GDM was lowest at 38 weeks and again at 40 weeks,” Dr. Grantz said. The investigators concluded, she said, “that the risk of expectant management exceeded that of delivery at 38 weeks and beyond.”

Dr. Grantz reported no disclosures.

TOPLINE:

In people with obesity, weight loss by intermittent energy restriction (IER) has multiple, dynamic effects on the brain-gut-microbiome (BGM) axis, including reduced activity in brain regions affecting eating behavior and increased microbial diversity in the gut, over the short term, new research suggested.

METHODOLOGY:

• Researchers studied 25 individuals with obesity in China who successfully lost weight during a three-phase IER intervention. In the first phase, participants were on a normal diet without restriction for 4 days. In the second, they were on a tightly controlled diet of clinically formulated IER meals every other day that decreased stepwise in caloric value to one quarter of their basic energy intake over 32 days. The last phase was a 30-day low-controlled fasting period.
• Blood and stool samples were collected at baseline, at the midpoint and endpoint of the tightly controlled fasting phase, and at the endpoint of the low-controlled fasting phase.
• A functional MRI was used to determine the activity of specific brain regions, and metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways from stool samples.

TAKEAWAY:

• Patients lost weight (7.6 kg on average) and showed sustained, significant reductions on several measures, including body mass index, body fat, systolic blood pressure, and serum levels of glycosylated hemoglobin during the IER. Diastolic blood pressure, serum levels of fasting plasma glucose, total cholesterol, various lipids, and levels of several key liver enzymes were significantly decreased at at least one timepoint during the IER.
• IER reduced the activity of obesity-related brain regions (ie, the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit) at different timepoints during the intervention. No significant changes were observed in brain activity in the reward circuit.
• Gut microbial diversity increased during the tightly controlled fasting phase. The abundance of the probiotic Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis was elevated during this phase. The abundance of pathogenic Escherichia coli was reduced across multiple timepoints. A correlation analysis revealed longitudinal correlations between gut bacteria abundance alterations and brain activity changes.
• Overall, there was a dynamical alteration of the BGM axis during weight loss using IER, although whether changes in the gut microbiome drive changes in the brain, or vice versa, is still unknown.

IN PRACTICE:

“IER induced constant, significant reductions in the activity of eating behavior-related brain regions…[and] significant, dynamic changes in the abundance of some gut bacteria. Importantly, gut microbiota alterations correlated with brain activity changes across different timepoints in IER intervention. These data suggest that the dynamic interplay between the brain and gut microbiota plays an important role in weight loss,” the authors wrote.

SOURCE:

Jing Zhou, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, China, led the study, which was published online on December 30, 2023, in Frontiers in Cellular and Infection Microbiology.

LIMITATIONS:

The study examines BGM axis changes during weight loss only in the short term and does not establish causation. Longer follow-up is needed to establish the BGM axis changes that may influence long-term weight loss.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, the National Key R&D Program of China, Young and Middle-Aged Health Science and Technology Innovative Talent Cultivation Project of Henan Provincial Leading Talents, and the Medical Science and Technology Research Program of Henan Province. One coauthor was employed by a supplement company and another by a biotech company. No other disclosures were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

In people with obesity, weight loss by intermittent energy restriction (IER) has multiple, dynamic effects on the brain-gut-microbiome (BGM) axis, including reduced activity in brain regions affecting eating behavior and increased microbial diversity in the gut, over the short term, new research suggested.

METHODOLOGY:

• Researchers studied 25 individuals with obesity in China who successfully lost weight during a three-phase IER intervention. In the first phase, participants were on a normal diet without restriction for 4 days. In the second, they were on a tightly controlled diet of clinically formulated IER meals every other day that decreased stepwise in caloric value to one quarter of their basic energy intake over 32 days. The last phase was a 30-day low-controlled fasting period.
• Blood and stool samples were collected at baseline, at the midpoint and endpoint of the tightly controlled fasting phase, and at the endpoint of the low-controlled fasting phase.
• A functional MRI was used to determine the activity of specific brain regions, and metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways from stool samples.

TAKEAWAY:

• Patients lost weight (7.6 kg on average) and showed sustained, significant reductions on several measures, including body mass index, body fat, systolic blood pressure, and serum levels of glycosylated hemoglobin during the IER. Diastolic blood pressure, serum levels of fasting plasma glucose, total cholesterol, various lipids, and levels of several key liver enzymes were significantly decreased at at least one timepoint during the IER.
• IER reduced the activity of obesity-related brain regions (ie, the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit) at different timepoints during the intervention. No significant changes were observed in brain activity in the reward circuit.
• Gut microbial diversity increased during the tightly controlled fasting phase. The abundance of the probiotic Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis was elevated during this phase. The abundance of pathogenic Escherichia coli was reduced across multiple timepoints. A correlation analysis revealed longitudinal correlations between gut bacteria abundance alterations and brain activity changes.
• Overall, there was a dynamical alteration of the BGM axis during weight loss using IER, although whether changes in the gut microbiome drive changes in the brain, or vice versa, is still unknown.

IN PRACTICE:

“IER induced constant, significant reductions in the activity of eating behavior-related brain regions…[and] significant, dynamic changes in the abundance of some gut bacteria. Importantly, gut microbiota alterations correlated with brain activity changes across different timepoints in IER intervention. These data suggest that the dynamic interplay between the brain and gut microbiota plays an important role in weight loss,” the authors wrote.

SOURCE:

Jing Zhou, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, China, led the study, which was published online on December 30, 2023, in Frontiers in Cellular and Infection Microbiology.

LIMITATIONS:

The study examines BGM axis changes during weight loss only in the short term and does not establish causation. Longer follow-up is needed to establish the BGM axis changes that may influence long-term weight loss.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, the National Key R&D Program of China, Young and Middle-Aged Health Science and Technology Innovative Talent Cultivation Project of Henan Provincial Leading Talents, and the Medical Science and Technology Research Program of Henan Province. One coauthor was employed by a supplement company and another by a biotech company. No other disclosures were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

In people with obesity, weight loss by intermittent energy restriction (IER) has multiple, dynamic effects on the brain-gut-microbiome (BGM) axis, including reduced activity in brain regions affecting eating behavior and increased microbial diversity in the gut, over the short term, new research suggested.

METHODOLOGY:

• Researchers studied 25 individuals with obesity in China who successfully lost weight during a three-phase IER intervention. In the first phase, participants were on a normal diet without restriction for 4 days. In the second, they were on a tightly controlled diet of clinically formulated IER meals every other day that decreased stepwise in caloric value to one quarter of their basic energy intake over 32 days. The last phase was a 30-day low-controlled fasting period.
• Blood and stool samples were collected at baseline, at the midpoint and endpoint of the tightly controlled fasting phase, and at the endpoint of the low-controlled fasting phase.
• A functional MRI was used to determine the activity of specific brain regions, and metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways from stool samples.

TAKEAWAY:

• Patients lost weight (7.6 kg on average) and showed sustained, significant reductions on several measures, including body mass index, body fat, systolic blood pressure, and serum levels of glycosylated hemoglobin during the IER. Diastolic blood pressure, serum levels of fasting plasma glucose, total cholesterol, various lipids, and levels of several key liver enzymes were significantly decreased at at least one timepoint during the IER.
• IER reduced the activity of obesity-related brain regions (ie, the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit) at different timepoints during the intervention. No significant changes were observed in brain activity in the reward circuit.
• Gut microbial diversity increased during the tightly controlled fasting phase. The abundance of the probiotic Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis was elevated during this phase. The abundance of pathogenic Escherichia coli was reduced across multiple timepoints. A correlation analysis revealed longitudinal correlations between gut bacteria abundance alterations and brain activity changes.
• Overall, there was a dynamical alteration of the BGM axis during weight loss using IER, although whether changes in the gut microbiome drive changes in the brain, or vice versa, is still unknown.

IN PRACTICE:

“IER induced constant, significant reductions in the activity of eating behavior-related brain regions…[and] significant, dynamic changes in the abundance of some gut bacteria. Importantly, gut microbiota alterations correlated with brain activity changes across different timepoints in IER intervention. These data suggest that the dynamic interplay between the brain and gut microbiota plays an important role in weight loss,” the authors wrote.

SOURCE:

Jing Zhou, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, China, led the study, which was published online on December 30, 2023, in Frontiers in Cellular and Infection Microbiology.

LIMITATIONS:

The study examines BGM axis changes during weight loss only in the short term and does not establish causation. Longer follow-up is needed to establish the BGM axis changes that may influence long-term weight loss.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, the National Key R&D Program of China, Young and Middle-Aged Health Science and Technology Innovative Talent Cultivation Project of Henan Provincial Leading Talents, and the Medical Science and Technology Research Program of Henan Province. One coauthor was employed by a supplement company and another by a biotech company. No other disclosures were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

An intensive weight loss program is safe for individuals with gout and obesity but does not ease gout symptoms compared with a “control diet” with basic nutritional counseling.

METHODOLOGY:

• Weight loss is recommended as a gout management strategy, despite little clinical evidence.
• Researchers recruited 61 patients with gout and obesity to participate in a 16-week, randomized, nonblinded, parallel-group trial in Denmark.
• A total of 29 participants were assigned to an intensive, low-calorie diet with provided meal replacements.
• Another 32 participants were assigned to the “control diet” with basic nutritional counseling.

TAKEAWAY:

• Patients in the intensive group lost more weight (−15.4 kg/34 lbs) than those the control group (−7.7 kg/17 lbs).
• There were no differences in pain, fatigue, or gout flares between the two groups.
• Weight loss was associated with reduction in serum urate (SU).
• Patients in the intervention group had a numerically larger mean SU change (−0.6 mg/dL) than the control group (−0.3 mg/dL), but this difference was not statistically significant.

IN PRACTICE:

Weight loss can lower SU levels, but this did not translate to improved gout symptoms.

SOURCE:

Robin Christensen, PhD, and Kristian Zobbe, MD, PhD, of the Parker Institute at Bispebjerg and Frederiksberg Hospital in Copenhagen, Denmark, were co-first authors of the study, published on January 2, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

The study had a relatively small sample size and short-term intervention period, which may have made it difficult to detect differences between the intervention and control groups. Patients in the control group lost a significant amount of weight, which also affected comparisons between the two groups.

DISCLOSURES:

Several of the authors disclosed financial relationships with pharmaceutical companies. The Parker Institute, which funded the study, is supported by grants from the Oak Foundation and the Danish Rheumatism Association.

A version of this article appeared on Medscape.com.

TOPLINE:

An intensive weight loss program is safe for individuals with gout and obesity but does not ease gout symptoms compared with a “control diet” with basic nutritional counseling.

METHODOLOGY:

• Weight loss is recommended as a gout management strategy, despite little clinical evidence.
• Researchers recruited 61 patients with gout and obesity to participate in a 16-week, randomized, nonblinded, parallel-group trial in Denmark.
• A total of 29 participants were assigned to an intensive, low-calorie diet with provided meal replacements.
• Another 32 participants were assigned to the “control diet” with basic nutritional counseling.

TAKEAWAY:

• Patients in the intensive group lost more weight (−15.4 kg/34 lbs) than those the control group (−7.7 kg/17 lbs).
• There were no differences in pain, fatigue, or gout flares between the two groups.
• Weight loss was associated with reduction in serum urate (SU).
• Patients in the intervention group had a numerically larger mean SU change (−0.6 mg/dL) than the control group (−0.3 mg/dL), but this difference was not statistically significant.

IN PRACTICE:

Weight loss can lower SU levels, but this did not translate to improved gout symptoms.

SOURCE:

Robin Christensen, PhD, and Kristian Zobbe, MD, PhD, of the Parker Institute at Bispebjerg and Frederiksberg Hospital in Copenhagen, Denmark, were co-first authors of the study, published on January 2, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

The study had a relatively small sample size and short-term intervention period, which may have made it difficult to detect differences between the intervention and control groups. Patients in the control group lost a significant amount of weight, which also affected comparisons between the two groups.

DISCLOSURES:

Several of the authors disclosed financial relationships with pharmaceutical companies. The Parker Institute, which funded the study, is supported by grants from the Oak Foundation and the Danish Rheumatism Association.

A version of this article appeared on Medscape.com.

TOPLINE:

An intensive weight loss program is safe for individuals with gout and obesity but does not ease gout symptoms compared with a “control diet” with basic nutritional counseling.

METHODOLOGY:

• Weight loss is recommended as a gout management strategy, despite little clinical evidence.
• Researchers recruited 61 patients with gout and obesity to participate in a 16-week, randomized, nonblinded, parallel-group trial in Denmark.
• A total of 29 participants were assigned to an intensive, low-calorie diet with provided meal replacements.
• Another 32 participants were assigned to the “control diet” with basic nutritional counseling.

TAKEAWAY:

• Patients in the intensive group lost more weight (−15.4 kg/34 lbs) than those the control group (−7.7 kg/17 lbs).
• There were no differences in pain, fatigue, or gout flares between the two groups.
• Weight loss was associated with reduction in serum urate (SU).
• Patients in the intervention group had a numerically larger mean SU change (−0.6 mg/dL) than the control group (−0.3 mg/dL), but this difference was not statistically significant.

IN PRACTICE:

Weight loss can lower SU levels, but this did not translate to improved gout symptoms.

SOURCE:

Robin Christensen, PhD, and Kristian Zobbe, MD, PhD, of the Parker Institute at Bispebjerg and Frederiksberg Hospital in Copenhagen, Denmark, were co-first authors of the study, published on January 2, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

The study had a relatively small sample size and short-term intervention period, which may have made it difficult to detect differences between the intervention and control groups. Patients in the control group lost a significant amount of weight, which also affected comparisons between the two groups.

DISCLOSURES:

Several of the authors disclosed financial relationships with pharmaceutical companies. The Parker Institute, which funded the study, is supported by grants from the Oak Foundation and the Danish Rheumatism Association.

A version of this article appeared on Medscape.com.

With the flip of the calendar a few short weeks ago, gyms and fitness centers began ramping up their advertising campaigns in hopes of attracting the horde of resolution makers searching for a place where they can inject some exercise into their sedentary lives. A recent survey by C.S. Mott’s Children’s Hospital found that even young people are setting health-related goals with more than half of the parents of 11- to 18-year-olds reporting their children were setting personal goals for themselves. More than 40% of the young people listed more exercise as a target.

However, our personal and professional experiences have taught us that achieving goals, particularly when it comes to exercise, is far more difficult than setting the target. Finding an exercise buddy can be an important motivator on the days when just lacing up one’s sneakers is a stumbling block. Investing in a gym membership and sweating with a peer group can help. However, it is an investment that rarely pays a dividend. Exercise isn’t fun for everyone. For adults, showing up at a gym may be just one more reminder of how they have already lost their competitive edge over their leaner and fitter peers. If they aren’t lucky enough to find a sport or activity that they enjoy, the loneliness of the long-distance runner has little appeal.

A recent study on children in the United Kingdom suggests that at least when it comes to teens and young adults we as physicians may actually have been making things worse for our obese patients by urging them to accept unrealistic activity goals. While it is already known that sedentary time is responsible for 70% of the total increase in cholesterol as children advance to young adulthood an unqualified recommendation for more exercise may not be the best advice.

In an interview with the study author, Andre O. Agbaje MD, MPH, said that in his large study population “light physical activity outperforms moderate to vigorous physical activity by five to eight times in lowering lipids”. While we may be surprised by this counterintuitive finding, Dr. Agbaje points out that an increase in sedentariness from 6 to 9 hours per day translates into a loss of 3 hours of light physical activity. In other words if you’re not sedentary you must be standing at attention or engaged in some light activity.

In my experience, and I suspect yours, it is difficult to get adults to do something, particularly if that something involves exerting energy, even a small amount of energy. The general admonishment of “be more active” is often met with a blank stare and the sometimes unspoken question “Like what?”

You could fall into a bottomless trap with them by suggesting a long list of activities, many of which are probably ones you do or would enjoy but don’t happen to fit with any of their interests or capabilities. Your chances of hitting on a perfect activity that the patient will attempt, let alone adopt, is very slim. Those of you with more patience than I have may choose to persist with this strategy. You could argue that even if the patient only dabbles briefly in one of your recommended activities, this is a minor victory worth celebrating. Who knows? The brief jolt of energy they received from this activity may prompt them to seek and find something else that works.

My interpretation of Dr. Agbaje’s findings is this: If we are going to suggest more activity, aim low. Don’t even mention the heavily weighted words “sport” or “exercise,” which are likely to dredge up bad memories. For adults, “Go shopping” or “Visit a friend” may be sufficient to at least get the person off the couch and on their feet and moving, even if very briefly.

The second message from this study applies more to children and adolescents and is one of those unusual instances in which a negative intervention may be more effective than a positive approach. Acknowledging that we are likely to have difficulty finding even a light activity that the child enjoys, why not pivot to the other side of the equation? Make a list of the child’s primary sedentary “activities.” Then suggest the parents put the child on a couch potato diet by immediately cutting in half the time he or she spends being sedentary. By definition, this will automatically increase his or her light physical activity by 50%. According to Dr. Agbaje’s data, this should be more effective in lowering lipids than in the unlikely event of finding a moderate activity the child accepts.

You can argue that the child will hound his or her parents unmercifully asking to be entertained. This may be true and this persistent complaining will be more likely to come from the older the child and the longer that the child has been allowed to be sedentary. Although the child may appear to have lost the ability to self amuse, I contend this isn’t a permanent loss and, with parental help, self-generated activity is a skill that can be regained if sedentary behavior is curtailed. This is another example of how saying “No!” in the right circumstances is often the most effective remedy for an unhealthy situation. I would never claim saying “No” is easy and helping parents to learn how to say “No” is one of our most difficult challenges. But, nothing else seems to be working.
 

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].

With the flip of the calendar a few short weeks ago, gyms and fitness centers began ramping up their advertising campaigns in hopes of attracting the horde of resolution makers searching for a place where they can inject some exercise into their sedentary lives. A recent survey by C.S. Mott’s Children’s Hospital found that even young people are setting health-related goals with more than half of the parents of 11- to 18-year-olds reporting their children were setting personal goals for themselves. More than 40% of the young people listed more exercise as a target.

However, our personal and professional experiences have taught us that achieving goals, particularly when it comes to exercise, is far more difficult than setting the target. Finding an exercise buddy can be an important motivator on the days when just lacing up one’s sneakers is a stumbling block. Investing in a gym membership and sweating with a peer group can help. However, it is an investment that rarely pays a dividend. Exercise isn’t fun for everyone. For adults, showing up at a gym may be just one more reminder of how they have already lost their competitive edge over their leaner and fitter peers. If they aren’t lucky enough to find a sport or activity that they enjoy, the loneliness of the long-distance runner has little appeal.

A recent study on children in the United Kingdom suggests that at least when it comes to teens and young adults we as physicians may actually have been making things worse for our obese patients by urging them to accept unrealistic activity goals. While it is already known that sedentary time is responsible for 70% of the total increase in cholesterol as children advance to young adulthood an unqualified recommendation for more exercise may not be the best advice.

In an interview with the study author, Andre O. Agbaje MD, MPH, said that in his large study population “light physical activity outperforms moderate to vigorous physical activity by five to eight times in lowering lipids”. While we may be surprised by this counterintuitive finding, Dr. Agbaje points out that an increase in sedentariness from 6 to 9 hours per day translates into a loss of 3 hours of light physical activity. In other words if you’re not sedentary you must be standing at attention or engaged in some light activity.

In my experience, and I suspect yours, it is difficult to get adults to do something, particularly if that something involves exerting energy, even a small amount of energy. The general admonishment of “be more active” is often met with a blank stare and the sometimes unspoken question “Like what?”

You could fall into a bottomless trap with them by suggesting a long list of activities, many of which are probably ones you do or would enjoy but don’t happen to fit with any of their interests or capabilities. Your chances of hitting on a perfect activity that the patient will attempt, let alone adopt, is very slim. Those of you with more patience than I have may choose to persist with this strategy. You could argue that even if the patient only dabbles briefly in one of your recommended activities, this is a minor victory worth celebrating. Who knows? The brief jolt of energy they received from this activity may prompt them to seek and find something else that works.

My interpretation of Dr. Agbaje’s findings is this: If we are going to suggest more activity, aim low. Don’t even mention the heavily weighted words “sport” or “exercise,” which are likely to dredge up bad memories. For adults, “Go shopping” or “Visit a friend” may be sufficient to at least get the person off the couch and on their feet and moving, even if very briefly.

The second message from this study applies more to children and adolescents and is one of those unusual instances in which a negative intervention may be more effective than a positive approach. Acknowledging that we are likely to have difficulty finding even a light activity that the child enjoys, why not pivot to the other side of the equation? Make a list of the child’s primary sedentary “activities.” Then suggest the parents put the child on a couch potato diet by immediately cutting in half the time he or she spends being sedentary. By definition, this will automatically increase his or her light physical activity by 50%. According to Dr. Agbaje’s data, this should be more effective in lowering lipids than in the unlikely event of finding a moderate activity the child accepts.

You can argue that the child will hound his or her parents unmercifully asking to be entertained. This may be true and this persistent complaining will be more likely to come from the older the child and the longer that the child has been allowed to be sedentary. Although the child may appear to have lost the ability to self amuse, I contend this isn’t a permanent loss and, with parental help, self-generated activity is a skill that can be regained if sedentary behavior is curtailed. This is another example of how saying “No!” in the right circumstances is often the most effective remedy for an unhealthy situation. I would never claim saying “No” is easy and helping parents to learn how to say “No” is one of our most difficult challenges. But, nothing else seems to be working.
 

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].

With the flip of the calendar a few short weeks ago, gyms and fitness centers began ramping up their advertising campaigns in hopes of attracting the horde of resolution makers searching for a place where they can inject some exercise into their sedentary lives. A recent survey by C.S. Mott’s Children’s Hospital found that even young people are setting health-related goals with more than half of the parents of 11- to 18-year-olds reporting their children were setting personal goals for themselves. More than 40% of the young people listed more exercise as a target.

However, our personal and professional experiences have taught us that achieving goals, particularly when it comes to exercise, is far more difficult than setting the target. Finding an exercise buddy can be an important motivator on the days when just lacing up one’s sneakers is a stumbling block. Investing in a gym membership and sweating with a peer group can help. However, it is an investment that rarely pays a dividend. Exercise isn’t fun for everyone. For adults, showing up at a gym may be just one more reminder of how they have already lost their competitive edge over their leaner and fitter peers. If they aren’t lucky enough to find a sport or activity that they enjoy, the loneliness of the long-distance runner has little appeal.

A recent study on children in the United Kingdom suggests that at least when it comes to teens and young adults we as physicians may actually have been making things worse for our obese patients by urging them to accept unrealistic activity goals. While it is already known that sedentary time is responsible for 70% of the total increase in cholesterol as children advance to young adulthood an unqualified recommendation for more exercise may not be the best advice.

In an interview with the study author, Andre O. Agbaje MD, MPH, said that in his large study population “light physical activity outperforms moderate to vigorous physical activity by five to eight times in lowering lipids”. While we may be surprised by this counterintuitive finding, Dr. Agbaje points out that an increase in sedentariness from 6 to 9 hours per day translates into a loss of 3 hours of light physical activity. In other words if you’re not sedentary you must be standing at attention or engaged in some light activity.

In my experience, and I suspect yours, it is difficult to get adults to do something, particularly if that something involves exerting energy, even a small amount of energy. The general admonishment of “be more active” is often met with a blank stare and the sometimes unspoken question “Like what?”

You could fall into a bottomless trap with them by suggesting a long list of activities, many of which are probably ones you do or would enjoy but don’t happen to fit with any of their interests or capabilities. Your chances of hitting on a perfect activity that the patient will attempt, let alone adopt, is very slim. Those of you with more patience than I have may choose to persist with this strategy. You could argue that even if the patient only dabbles briefly in one of your recommended activities, this is a minor victory worth celebrating. Who knows? The brief jolt of energy they received from this activity may prompt them to seek and find something else that works.

My interpretation of Dr. Agbaje’s findings is this: If we are going to suggest more activity, aim low. Don’t even mention the heavily weighted words “sport” or “exercise,” which are likely to dredge up bad memories. For adults, “Go shopping” or “Visit a friend” may be sufficient to at least get the person off the couch and on their feet and moving, even if very briefly.

The second message from this study applies more to children and adolescents and is one of those unusual instances in which a negative intervention may be more effective than a positive approach. Acknowledging that we are likely to have difficulty finding even a light activity that the child enjoys, why not pivot to the other side of the equation? Make a list of the child’s primary sedentary “activities.” Then suggest the parents put the child on a couch potato diet by immediately cutting in half the time he or she spends being sedentary. By definition, this will automatically increase his or her light physical activity by 50%. According to Dr. Agbaje’s data, this should be more effective in lowering lipids than in the unlikely event of finding a moderate activity the child accepts.

You can argue that the child will hound his or her parents unmercifully asking to be entertained. This may be true and this persistent complaining will be more likely to come from the older the child and the longer that the child has been allowed to be sedentary. Although the child may appear to have lost the ability to self amuse, I contend this isn’t a permanent loss and, with parental help, self-generated activity is a skill that can be regained if sedentary behavior is curtailed. This is another example of how saying “No!” in the right circumstances is often the most effective remedy for an unhealthy situation. I would never claim saying “No” is easy and helping parents to learn how to say “No” is one of our most difficult challenges. But, nothing else seems to be working.
 

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].

The FDA is formally looking into reports that some people who took popular diabetes and weight loss drugs had suicidal thoughts or two other health problems.

A new FDA report listed potential links between the medications and alopecia, aspiration, or suicidal ideation, CBS News reported. The investigation centers on reports of the health problems among people taking GLP-1 receptor agonists, some of which are Ozempic, Wegovy, Mounjaro, and Zepbound. The drugs are used to treat diabetes and overweight or obesity.

An investigation by the FDA doesn’t mean that the FDA has concluded a risk exists, the FDA’s webpage for risk evaluation cautions.

“It means that FDA has identified a potential safety issue, but it does not mean that FDA has identified a causal relationship between the drug and the listed risk,” the FDA site states.

Possible next steps after an investigation could include updating drug labels with new information, putting a risk management plan in place to prevent or manage the health risks, or gathering more information.

“The FDA monitors the safety of drugs throughout their life cycle,” even after the drugs are approved. In addition, the FDA uses “surveillance and risk assessment programs to identify and evaluate adverse events that did not appear during the drug development process,” FDA spokesperson Chanapa Tantibanchachai said in an email published by multiple news outlets.

Although an investigation may lead to no changes in how a drug is regulated by the FDA, this isn’t the first time that the popular medicines have landed on the FDA’s radar for safety reevaluation. Last year, the label for the drug Ozempic was updated to acknowledge reports of intestinal obstructions, CBS News reported.

European regulators are also looking into reports of suicidal thoughts among people taking GLP-1 receptor agonists, although no link has been established.

Concerns about aspiration during surgery resulted in the American Society of Anesthesiologists advising in June that people should stop taking GLP-1 receptor agonists before they have elective surgeries.

“While there is currently a lack of scientific data on how GLP-1 receptor agonists affect patients having surgery and interact with anesthesia, we’ve received anecdotal reports that the delay in stomach emptying could be associated with an increased risk of regurgitation and aspiration of food into the airways and lungs during general anesthesia and deep sedation,” the society’s president, Michael W. Champeau, MD, said in a statement at the time.

According to CBS News, the FDA’s drug reporting system links the medications to 201 reports of suicide or suicidal ideation, 18 reports that mention aspiration, and 422 reports that mention alopecia.

Novo Nordisk, whose portfolio includes Wegovy and Ozempic, told CNN that it works with the FDA to monitor safety and is aware of the reports of side effects.

“Novo Nordisk stands behind the safety and efficacy of all of our GLP-1RA medicines when they are used as indicated and when they are taken under the care of a licensed healthcare professional,” the company said in a statement to CNN.

A spokesperson for Eli Lilly, which makes Mounjaro and Zepbound, told CBS News in a statement, “Currently, the FDA is reviewing data on certain potential risks for GLP-1 receptor agonist medicines. Patient safety is our priority, and we are collaborating with the FDA on these potential signals.”
 

A version of this article appeared on WebMD.com .

The FDA is formally looking into reports that some people who took popular diabetes and weight loss drugs had suicidal thoughts or two other health problems.

A new FDA report listed potential links between the medications and alopecia, aspiration, or suicidal ideation, CBS News reported. The investigation centers on reports of the health problems among people taking GLP-1 receptor agonists, some of which are Ozempic, Wegovy, Mounjaro, and Zepbound. The drugs are used to treat diabetes and overweight or obesity.

An investigation by the FDA doesn’t mean that the FDA has concluded a risk exists, the FDA’s webpage for risk evaluation cautions.

“It means that FDA has identified a potential safety issue, but it does not mean that FDA has identified a causal relationship between the drug and the listed risk,” the FDA site states.

Possible next steps after an investigation could include updating drug labels with new information, putting a risk management plan in place to prevent or manage the health risks, or gathering more information.

“The FDA monitors the safety of drugs throughout their life cycle,” even after the drugs are approved. In addition, the FDA uses “surveillance and risk assessment programs to identify and evaluate adverse events that did not appear during the drug development process,” FDA spokesperson Chanapa Tantibanchachai said in an email published by multiple news outlets.

Although an investigation may lead to no changes in how a drug is regulated by the FDA, this isn’t the first time that the popular medicines have landed on the FDA’s radar for safety reevaluation. Last year, the label for the drug Ozempic was updated to acknowledge reports of intestinal obstructions, CBS News reported.

European regulators are also looking into reports of suicidal thoughts among people taking GLP-1 receptor agonists, although no link has been established.

Concerns about aspiration during surgery resulted in the American Society of Anesthesiologists advising in June that people should stop taking GLP-1 receptor agonists before they have elective surgeries.

“While there is currently a lack of scientific data on how GLP-1 receptor agonists affect patients having surgery and interact with anesthesia, we’ve received anecdotal reports that the delay in stomach emptying could be associated with an increased risk of regurgitation and aspiration of food into the airways and lungs during general anesthesia and deep sedation,” the society’s president, Michael W. Champeau, MD, said in a statement at the time.

According to CBS News, the FDA’s drug reporting system links the medications to 201 reports of suicide or suicidal ideation, 18 reports that mention aspiration, and 422 reports that mention alopecia.

Novo Nordisk, whose portfolio includes Wegovy and Ozempic, told CNN that it works with the FDA to monitor safety and is aware of the reports of side effects.

“Novo Nordisk stands behind the safety and efficacy of all of our GLP-1RA medicines when they are used as indicated and when they are taken under the care of a licensed healthcare professional,” the company said in a statement to CNN.

A spokesperson for Eli Lilly, which makes Mounjaro and Zepbound, told CBS News in a statement, “Currently, the FDA is reviewing data on certain potential risks for GLP-1 receptor agonist medicines. Patient safety is our priority, and we are collaborating with the FDA on these potential signals.”
 

A version of this article appeared on WebMD.com .

The FDA is formally looking into reports that some people who took popular diabetes and weight loss drugs had suicidal thoughts or two other health problems.

A new FDA report listed potential links between the medications and alopecia, aspiration, or suicidal ideation, CBS News reported. The investigation centers on reports of the health problems among people taking GLP-1 receptor agonists, some of which are Ozempic, Wegovy, Mounjaro, and Zepbound. The drugs are used to treat diabetes and overweight or obesity.

An investigation by the FDA doesn’t mean that the FDA has concluded a risk exists, the FDA’s webpage for risk evaluation cautions.

“It means that FDA has identified a potential safety issue, but it does not mean that FDA has identified a causal relationship between the drug and the listed risk,” the FDA site states.

Possible next steps after an investigation could include updating drug labels with new information, putting a risk management plan in place to prevent or manage the health risks, or gathering more information.

“The FDA monitors the safety of drugs throughout their life cycle,” even after the drugs are approved. In addition, the FDA uses “surveillance and risk assessment programs to identify and evaluate adverse events that did not appear during the drug development process,” FDA spokesperson Chanapa Tantibanchachai said in an email published by multiple news outlets.

Although an investigation may lead to no changes in how a drug is regulated by the FDA, this isn’t the first time that the popular medicines have landed on the FDA’s radar for safety reevaluation. Last year, the label for the drug Ozempic was updated to acknowledge reports of intestinal obstructions, CBS News reported.

European regulators are also looking into reports of suicidal thoughts among people taking GLP-1 receptor agonists, although no link has been established.

Concerns about aspiration during surgery resulted in the American Society of Anesthesiologists advising in June that people should stop taking GLP-1 receptor agonists before they have elective surgeries.

“While there is currently a lack of scientific data on how GLP-1 receptor agonists affect patients having surgery and interact with anesthesia, we’ve received anecdotal reports that the delay in stomach emptying could be associated with an increased risk of regurgitation and aspiration of food into the airways and lungs during general anesthesia and deep sedation,” the society’s president, Michael W. Champeau, MD, said in a statement at the time.

According to CBS News, the FDA’s drug reporting system links the medications to 201 reports of suicide or suicidal ideation, 18 reports that mention aspiration, and 422 reports that mention alopecia.

Novo Nordisk, whose portfolio includes Wegovy and Ozempic, told CNN that it works with the FDA to monitor safety and is aware of the reports of side effects.

“Novo Nordisk stands behind the safety and efficacy of all of our GLP-1RA medicines when they are used as indicated and when they are taken under the care of a licensed healthcare professional,” the company said in a statement to CNN.

A spokesperson for Eli Lilly, which makes Mounjaro and Zepbound, told CBS News in a statement, “Currently, the FDA is reviewing data on certain potential risks for GLP-1 receptor agonist medicines. Patient safety is our priority, and we are collaborating with the FDA on these potential signals.”
 

A version of this article appeared on WebMD.com .

TOPLINE:

Light physical activity during childhood may lower blood cholesterol levels more effectively than moderate to vigorous physical activity, regardless of body fat mass.

METHODOLOGY:

• Researchers analyzed the data of 792 children (58% females) from the Avon Longitudinal Study of Parents and Children (ALSPAC) UK birth cohort.
• The measures included accelerometer-based sedentary time, light physical activity, and moderate to vigorous physical activity at ages 11, 15, and 24 years.
• The children had complete measurements of fasting high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and total cholesterol levels at ages 15 , 17, and 24 years.
• Data also included measures of body mass, composition (fat and lean mass), insulin resistance, inflammation, and other cardiometabolic, socioeconomic, and lifestyle factors.
• The researchers conducted two types of analyses: Mediation path, to examine how fat and lean body mass affected longitudinal associations of activity level with blood lipids over 13 years, and temporal path, to look at temporal relationships between activity and lipid levels at ages 15 and 24 years only.

TAKEAWAY:

• Higher cumulative light physical activity from childhood through young adulthood was associated with a fivefold to eightfold decrease in total cholesterol, while total body fat mass decreased the impact of light physical activity on total cholesterol by 6%.
• Higher cumulative moderate to vigorous physical activity over 13 years led to a modest decrease in total cholesterol, an effect reduced to nonsignificance by the presence of higher fat mass.
• More cumulative sedentary time was associated with increasing total cholesterol.

IN PRACTICE:

“Light physical activity provides an opportunity for persons with obesity to follow a path to potentially benefit from the lipid-lowering effect of mild exercise,» wrote the author.

SOURCE:

Andrew O. Agbaje, from the Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Kuopio, Finland, conducted this study. It was published online December 14, 2023, in the Journal of Clinical Endocrinology and Metabolism.

LIMITATIONS:

The study included mostly White participants, so the findings might not apply to diverse racial and ethnic groups. The accelerometer data were gathered using a 60-second epoch, a duration known to underestimate moderate to vigorous physical activity in pediatric populations. There were no measures of fasting plasma lipids at age 11 years. The study also lacked data on participants’ dietary habits, alcohol intake, and menstrual cycle.

DISCLOSURES:

The ALSPAC UK birth cohort is funded by the UK Medical Research Council, the Wellcome Trust, and the University of Bristol. The author is funded by multiple foundations. No conflicts of interest were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Light physical activity during childhood may lower blood cholesterol levels more effectively than moderate to vigorous physical activity, regardless of body fat mass.

METHODOLOGY:

• Researchers analyzed the data of 792 children (58% females) from the Avon Longitudinal Study of Parents and Children (ALSPAC) UK birth cohort.
• The measures included accelerometer-based sedentary time, light physical activity, and moderate to vigorous physical activity at ages 11, 15, and 24 years.
• The children had complete measurements of fasting high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and total cholesterol levels at ages 15 , 17, and 24 years.
• Data also included measures of body mass, composition (fat and lean mass), insulin resistance, inflammation, and other cardiometabolic, socioeconomic, and lifestyle factors.
• The researchers conducted two types of analyses: Mediation path, to examine how fat and lean body mass affected longitudinal associations of activity level with blood lipids over 13 years, and temporal path, to look at temporal relationships between activity and lipid levels at ages 15 and 24 years only.

TAKEAWAY:

• Higher cumulative light physical activity from childhood through young adulthood was associated with a fivefold to eightfold decrease in total cholesterol, while total body fat mass decreased the impact of light physical activity on total cholesterol by 6%.
• Higher cumulative moderate to vigorous physical activity over 13 years led to a modest decrease in total cholesterol, an effect reduced to nonsignificance by the presence of higher fat mass.
• More cumulative sedentary time was associated with increasing total cholesterol.

IN PRACTICE:

“Light physical activity provides an opportunity for persons with obesity to follow a path to potentially benefit from the lipid-lowering effect of mild exercise,» wrote the author.

SOURCE:

Andrew O. Agbaje, from the Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Kuopio, Finland, conducted this study. It was published online December 14, 2023, in the Journal of Clinical Endocrinology and Metabolism.

LIMITATIONS:

The study included mostly White participants, so the findings might not apply to diverse racial and ethnic groups. The accelerometer data were gathered using a 60-second epoch, a duration known to underestimate moderate to vigorous physical activity in pediatric populations. There were no measures of fasting plasma lipids at age 11 years. The study also lacked data on participants’ dietary habits, alcohol intake, and menstrual cycle.

DISCLOSURES:

The ALSPAC UK birth cohort is funded by the UK Medical Research Council, the Wellcome Trust, and the University of Bristol. The author is funded by multiple foundations. No conflicts of interest were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Light physical activity during childhood may lower blood cholesterol levels more effectively than moderate to vigorous physical activity, regardless of body fat mass.

METHODOLOGY:

• Researchers analyzed the data of 792 children (58% females) from the Avon Longitudinal Study of Parents and Children (ALSPAC) UK birth cohort.
• The measures included accelerometer-based sedentary time, light physical activity, and moderate to vigorous physical activity at ages 11, 15, and 24 years.
• The children had complete measurements of fasting high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and total cholesterol levels at ages 15 , 17, and 24 years.
• Data also included measures of body mass, composition (fat and lean mass), insulin resistance, inflammation, and other cardiometabolic, socioeconomic, and lifestyle factors.
• The researchers conducted two types of analyses: Mediation path, to examine how fat and lean body mass affected longitudinal associations of activity level with blood lipids over 13 years, and temporal path, to look at temporal relationships between activity and lipid levels at ages 15 and 24 years only.

TAKEAWAY:

• Higher cumulative light physical activity from childhood through young adulthood was associated with a fivefold to eightfold decrease in total cholesterol, while total body fat mass decreased the impact of light physical activity on total cholesterol by 6%.
• Higher cumulative moderate to vigorous physical activity over 13 years led to a modest decrease in total cholesterol, an effect reduced to nonsignificance by the presence of higher fat mass.
• More cumulative sedentary time was associated with increasing total cholesterol.

IN PRACTICE:

“Light physical activity provides an opportunity for persons with obesity to follow a path to potentially benefit from the lipid-lowering effect of mild exercise,» wrote the author.

SOURCE:

Andrew O. Agbaje, from the Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Kuopio, Finland, conducted this study. It was published online December 14, 2023, in the Journal of Clinical Endocrinology and Metabolism.

LIMITATIONS:

The study included mostly White participants, so the findings might not apply to diverse racial and ethnic groups. The accelerometer data were gathered using a 60-second epoch, a duration known to underestimate moderate to vigorous physical activity in pediatric populations. There were no measures of fasting plasma lipids at age 11 years. The study also lacked data on participants’ dietary habits, alcohol intake, and menstrual cycle.

DISCLOSURES:

The ALSPAC UK birth cohort is funded by the UK Medical Research Council, the Wellcome Trust, and the University of Bristol. The author is funded by multiple foundations. No conflicts of interest were reported.

A version of this article appeared on Medscape.com.

While adults, many of whom don’t meet the clinical definition of obesity, scramble to procure glucagon-like peptide 1 (GLP-1) agonists for weight loss, pediatric obesity specialists said their young patients who could benefit more over the long term often are unable to access the potentially life-altering medications.

The US Food and Drug Administration (FDA) approved two GLP-1 agonists — both marketed by Novo Nordisk — for use in adolescents aged ≥ 12 years: Wegovy (semaglutide) in December 2022 and Saxenda (liraglutide) in December 2020. Novo Nordisk and Eli Lilly — which makes the dual glucose-dependent insulinotropic polypetide/GLP-1 agonist tirzepatide (Zepbound) — are also investigating the drugs for obesity in children as young as age 6 years. The crushing demand for semaglutide in the last year — driving a thriving market in compounded versions and online prescriptions — has made it increasingly difficult to find pharmacies that can fill prescriptions, pediatricians told this news organization.

“It’s been more difficult to get people initiated now than it was a year ago,” said Brooke Sweeney, MD, medical director of weight management services at Children’s Mercy in Kansas City, Missouri. “Because of the supply issues, for the most part we›re not starting anyone new because I don›t have enough medication to keep my patients on it who are already on it,” she said.

Sarah Raatz, MD, a pediatrician at the University of Minnesota’s Center for Pediatric Obesity Medicine, said, “I actually haven’t really been prescribing many of these medications as of late.” Both liraglutide and semaglutide “are largely unavailable or quite hard to get a hold of,” Dr. Raatz told this news organization.

Susma Shanti Vaidya, MPH, MD, associate medical director of the IDEAL pediatric obesity clinic at Children›s National Hospital in Washington, DC, said that patients taking GLP-1 agonists in her practice have reduced their body mass index and have seen resolution of prediabetes, diabetes, and fatty liver disease. «I had one patient who had severe obstructive sleep apnea which resolved with semaglutide.»

But when they can’t find the medications, it can lead to a plateauing of weight loss and a reversal of hard-won victories, Dr. Vaidya said.

Insurance Denials Also Growing

In January 2023, the American Academy of Pediatrics urged aggressive treatment of childhood obesity, including using FDA-approved medications such as GLP-1 agonists combined with lifestyle and dietary modifications.

The US Preventive Services Task Force, however, has issued a draft proposal that recommends a variety of lifestyle and behavior modification interventions for children and adolescents but says the evidence does not yet support recommending bariatric surgery or medications.

Insurance coverage for children — even for FDA-approved indications and the age 12-and-over population — has become increasingly difficult, said the pediatric obesity specialists. Insurers are also creating hurdles that make getting coverage more difficult, they said.

Some insurers track an adolescent’s weight trajectory, “and if they’re not meeting a certain response threshold set by the insurance company, then they can pull coverage and then we have to try to advocate for why continued coverage might be beneficial and necessary,” Dr. Raatz said.

Insurers in the region around Children’s Mercy are erecting similar barriers, said Sweeney. Interim weight loss goals are challenging in pediatrics — given that adolescents are constantly changing and growing, she said.

Dr. Vaidya said she’s had success with commercial insurers but that the Washington, DC, and Maryland Medicaid programs have been stingier.

All the pediatricians said they expect greater restrictions in 2024.

Dr. Vaidya said some patients told her they had been notified that prior authorization will be required for new prescriptions for a GLP-1 agonist.

“We will just kind of be forced to see what happens when these medications are taken away from patients who have benefited from them,” Dr. Raatz said.
 

Some Parents Asking for GLP-1 Agonists

Pediatric obesity specialists said more parents are asking if a GLP-1 agonist might be appropriate for their children this year than in 2022.

Dr. Sweeney said parents ask for the medications when they feel they have exhausted all other options for their children. “These parents are not coming because they are concerned about the cosmetic effects of the weight,” she said. In most cases, children she sees have been struggling for years with extreme hunger and lack of satiety and may have prediabetes or diabetes. Many are being bullied in school because of their weight. They have only marginally been helped by interventions suggested by primary care or dietitians or other specialists, Dr. Sweeney said.

“Starting semaglutide really is life-changing for some of these patients,” Dr. Vaidya said. One patient said, “it just stopped the food chatter,” she added, noting that the adolescent no longer felt ruled by cravings.

In a recent poll by Morning Consult, 65% of parents of children with weight-related issues said they would be interested in GLP-1 agonists for their kids. A third of all parents said they would be interested in having their children use the drugs if they were available.
 

Lifelong Medication?

Parents — and adolescents — are generally counseled that obesity is a chronic disease and GLP-1 agonists are likely a lifelong treatment.

With the medications, “our first step is to get induction of weight loss and get your set point decreased enough that we can get you to a healthier weight for your body,” Dr. Sweeney said.

She tells patients and families, “I can’t tell you that you’re necessarily going to be on this medication at this dose for the rest of your life, but you will need treatment for life.”

Based on current knowledge, the risks for lifelong obesity outweigh the risk for the medications. Dr. Sweeney said she would like to see more data. “There absolutely is an evidence gap, and we need more information on the long-term effectiveness and safety.”

“When we start kids on this medication, I’m very clear that we are going to try to get to the lowest effective dose,” Dr. Vaidya said. She also emphasizes to parents that the medications must be used in conjunction with continued lifestyle modifications. She expressed hope that as clinicians gain more experience, and patients’ comorbidities resolve, perhaps it will be possible in some cases to take individuals “off for a period of time, with the understanding that they might have to go back on in a few months.”

“We’re weighing the pros and cons of being on a medication long term but we’re also weighing the pros and cons of weight-related health complications long term,” Dr. Raatz said.

Dr. Raatz also said clinicians have much to learn about the long-term safety of GLP-1 agonists in their pediatric patients.

She tells parents and families, “we expect that this is going to be a long-term medication, and this is going to be something that we’re going to continue to monitor.”

Dr. Sweeney reports that she is a speaker and unpaid consultant on Rhythm Pharmaceuticals’ Imcivree (setmelanotide) medication and that she consults for Eli Lilly. Dr. Raatz is a coprincipal investigator for a Novo Nordisk trial of semaglutide in young children and will be a co-PI for a similar trial for Eli Lilly’s tirzepatide but receives no consulting fees or honoraria. Dr. Vaidya reported no conflicts.

A version of this article appeared on Medscape.com.

While adults, many of whom don’t meet the clinical definition of obesity, scramble to procure glucagon-like peptide 1 (GLP-1) agonists for weight loss, pediatric obesity specialists said their young patients who could benefit more over the long term often are unable to access the potentially life-altering medications.

The US Food and Drug Administration (FDA) approved two GLP-1 agonists — both marketed by Novo Nordisk — for use in adolescents aged ≥ 12 years: Wegovy (semaglutide) in December 2022 and Saxenda (liraglutide) in December 2020. Novo Nordisk and Eli Lilly — which makes the dual glucose-dependent insulinotropic polypetide/GLP-1 agonist tirzepatide (Zepbound) — are also investigating the drugs for obesity in children as young as age 6 years. The crushing demand for semaglutide in the last year — driving a thriving market in compounded versions and online prescriptions — has made it increasingly difficult to find pharmacies that can fill prescriptions, pediatricians told this news organization.

“It’s been more difficult to get people initiated now than it was a year ago,” said Brooke Sweeney, MD, medical director of weight management services at Children’s Mercy in Kansas City, Missouri. “Because of the supply issues, for the most part we›re not starting anyone new because I don›t have enough medication to keep my patients on it who are already on it,” she said.

Sarah Raatz, MD, a pediatrician at the University of Minnesota’s Center for Pediatric Obesity Medicine, said, “I actually haven’t really been prescribing many of these medications as of late.” Both liraglutide and semaglutide “are largely unavailable or quite hard to get a hold of,” Dr. Raatz told this news organization.

Susma Shanti Vaidya, MPH, MD, associate medical director of the IDEAL pediatric obesity clinic at Children›s National Hospital in Washington, DC, said that patients taking GLP-1 agonists in her practice have reduced their body mass index and have seen resolution of prediabetes, diabetes, and fatty liver disease. «I had one patient who had severe obstructive sleep apnea which resolved with semaglutide.»

But when they can’t find the medications, it can lead to a plateauing of weight loss and a reversal of hard-won victories, Dr. Vaidya said.

Insurance Denials Also Growing

In January 2023, the American Academy of Pediatrics urged aggressive treatment of childhood obesity, including using FDA-approved medications such as GLP-1 agonists combined with lifestyle and dietary modifications.

The US Preventive Services Task Force, however, has issued a draft proposal that recommends a variety of lifestyle and behavior modification interventions for children and adolescents but says the evidence does not yet support recommending bariatric surgery or medications.

Insurance coverage for children — even for FDA-approved indications and the age 12-and-over population — has become increasingly difficult, said the pediatric obesity specialists. Insurers are also creating hurdles that make getting coverage more difficult, they said.

Some insurers track an adolescent’s weight trajectory, “and if they’re not meeting a certain response threshold set by the insurance company, then they can pull coverage and then we have to try to advocate for why continued coverage might be beneficial and necessary,” Dr. Raatz said.

Insurers in the region around Children’s Mercy are erecting similar barriers, said Sweeney. Interim weight loss goals are challenging in pediatrics — given that adolescents are constantly changing and growing, she said.

Dr. Vaidya said she’s had success with commercial insurers but that the Washington, DC, and Maryland Medicaid programs have been stingier.

All the pediatricians said they expect greater restrictions in 2024.

Dr. Vaidya said some patients told her they had been notified that prior authorization will be required for new prescriptions for a GLP-1 agonist.

“We will just kind of be forced to see what happens when these medications are taken away from patients who have benefited from them,” Dr. Raatz said.
 

Some Parents Asking for GLP-1 Agonists

Pediatric obesity specialists said more parents are asking if a GLP-1 agonist might be appropriate for their children this year than in 2022.

Dr. Sweeney said parents ask for the medications when they feel they have exhausted all other options for their children. “These parents are not coming because they are concerned about the cosmetic effects of the weight,” she said. In most cases, children she sees have been struggling for years with extreme hunger and lack of satiety and may have prediabetes or diabetes. Many are being bullied in school because of their weight. They have only marginally been helped by interventions suggested by primary care or dietitians or other specialists, Dr. Sweeney said.

“Starting semaglutide really is life-changing for some of these patients,” Dr. Vaidya said. One patient said, “it just stopped the food chatter,” she added, noting that the adolescent no longer felt ruled by cravings.

In a recent poll by Morning Consult, 65% of parents of children with weight-related issues said they would be interested in GLP-1 agonists for their kids. A third of all parents said they would be interested in having their children use the drugs if they were available.
 

Lifelong Medication?

Parents — and adolescents — are generally counseled that obesity is a chronic disease and GLP-1 agonists are likely a lifelong treatment.

With the medications, “our first step is to get induction of weight loss and get your set point decreased enough that we can get you to a healthier weight for your body,” Dr. Sweeney said.

She tells patients and families, “I can’t tell you that you’re necessarily going to be on this medication at this dose for the rest of your life, but you will need treatment for life.”

Based on current knowledge, the risks for lifelong obesity outweigh the risk for the medications. Dr. Sweeney said she would like to see more data. “There absolutely is an evidence gap, and we need more information on the long-term effectiveness and safety.”

“When we start kids on this medication, I’m very clear that we are going to try to get to the lowest effective dose,” Dr. Vaidya said. She also emphasizes to parents that the medications must be used in conjunction with continued lifestyle modifications. She expressed hope that as clinicians gain more experience, and patients’ comorbidities resolve, perhaps it will be possible in some cases to take individuals “off for a period of time, with the understanding that they might have to go back on in a few months.”

“We’re weighing the pros and cons of being on a medication long term but we’re also weighing the pros and cons of weight-related health complications long term,” Dr. Raatz said.

Dr. Raatz also said clinicians have much to learn about the long-term safety of GLP-1 agonists in their pediatric patients.

She tells parents and families, “we expect that this is going to be a long-term medication, and this is going to be something that we’re going to continue to monitor.”

Dr. Sweeney reports that she is a speaker and unpaid consultant on Rhythm Pharmaceuticals’ Imcivree (setmelanotide) medication and that she consults for Eli Lilly. Dr. Raatz is a coprincipal investigator for a Novo Nordisk trial of semaglutide in young children and will be a co-PI for a similar trial for Eli Lilly’s tirzepatide but receives no consulting fees or honoraria. Dr. Vaidya reported no conflicts.

A version of this article appeared on Medscape.com.

While adults, many of whom don’t meet the clinical definition of obesity, scramble to procure glucagon-like peptide 1 (GLP-1) agonists for weight loss, pediatric obesity specialists said their young patients who could benefit more over the long term often are unable to access the potentially life-altering medications.

The US Food and Drug Administration (FDA) approved two GLP-1 agonists — both marketed by Novo Nordisk — for use in adolescents aged ≥ 12 years: Wegovy (semaglutide) in December 2022 and Saxenda (liraglutide) in December 2020. Novo Nordisk and Eli Lilly — which makes the dual glucose-dependent insulinotropic polypetide/GLP-1 agonist tirzepatide (Zepbound) — are also investigating the drugs for obesity in children as young as age 6 years. The crushing demand for semaglutide in the last year — driving a thriving market in compounded versions and online prescriptions — has made it increasingly difficult to find pharmacies that can fill prescriptions, pediatricians told this news organization.

“It’s been more difficult to get people initiated now than it was a year ago,” said Brooke Sweeney, MD, medical director of weight management services at Children’s Mercy in Kansas City, Missouri. “Because of the supply issues, for the most part we›re not starting anyone new because I don›t have enough medication to keep my patients on it who are already on it,” she said.

Sarah Raatz, MD, a pediatrician at the University of Minnesota’s Center for Pediatric Obesity Medicine, said, “I actually haven’t really been prescribing many of these medications as of late.” Both liraglutide and semaglutide “are largely unavailable or quite hard to get a hold of,” Dr. Raatz told this news organization.

Susma Shanti Vaidya, MPH, MD, associate medical director of the IDEAL pediatric obesity clinic at Children›s National Hospital in Washington, DC, said that patients taking GLP-1 agonists in her practice have reduced their body mass index and have seen resolution of prediabetes, diabetes, and fatty liver disease. «I had one patient who had severe obstructive sleep apnea which resolved with semaglutide.»

But when they can’t find the medications, it can lead to a plateauing of weight loss and a reversal of hard-won victories, Dr. Vaidya said.

Insurance Denials Also Growing

In January 2023, the American Academy of Pediatrics urged aggressive treatment of childhood obesity, including using FDA-approved medications such as GLP-1 agonists combined with lifestyle and dietary modifications.

The US Preventive Services Task Force, however, has issued a draft proposal that recommends a variety of lifestyle and behavior modification interventions for children and adolescents but says the evidence does not yet support recommending bariatric surgery or medications.

Insurance coverage for children — even for FDA-approved indications and the age 12-and-over population — has become increasingly difficult, said the pediatric obesity specialists. Insurers are also creating hurdles that make getting coverage more difficult, they said.

Some insurers track an adolescent’s weight trajectory, “and if they’re not meeting a certain response threshold set by the insurance company, then they can pull coverage and then we have to try to advocate for why continued coverage might be beneficial and necessary,” Dr. Raatz said.

Insurers in the region around Children’s Mercy are erecting similar barriers, said Sweeney. Interim weight loss goals are challenging in pediatrics — given that adolescents are constantly changing and growing, she said.

Dr. Vaidya said she’s had success with commercial insurers but that the Washington, DC, and Maryland Medicaid programs have been stingier.

All the pediatricians said they expect greater restrictions in 2024.

Dr. Vaidya said some patients told her they had been notified that prior authorization will be required for new prescriptions for a GLP-1 agonist.

“We will just kind of be forced to see what happens when these medications are taken away from patients who have benefited from them,” Dr. Raatz said.
 

Some Parents Asking for GLP-1 Agonists

Pediatric obesity specialists said more parents are asking if a GLP-1 agonist might be appropriate for their children this year than in 2022.

Dr. Sweeney said parents ask for the medications when they feel they have exhausted all other options for their children. “These parents are not coming because they are concerned about the cosmetic effects of the weight,” she said. In most cases, children she sees have been struggling for years with extreme hunger and lack of satiety and may have prediabetes or diabetes. Many are being bullied in school because of their weight. They have only marginally been helped by interventions suggested by primary care or dietitians or other specialists, Dr. Sweeney said.

“Starting semaglutide really is life-changing for some of these patients,” Dr. Vaidya said. One patient said, “it just stopped the food chatter,” she added, noting that the adolescent no longer felt ruled by cravings.

In a recent poll by Morning Consult, 65% of parents of children with weight-related issues said they would be interested in GLP-1 agonists for their kids. A third of all parents said they would be interested in having their children use the drugs if they were available.
 

Lifelong Medication?

Parents — and adolescents — are generally counseled that obesity is a chronic disease and GLP-1 agonists are likely a lifelong treatment.

With the medications, “our first step is to get induction of weight loss and get your set point decreased enough that we can get you to a healthier weight for your body,” Dr. Sweeney said.

She tells patients and families, “I can’t tell you that you’re necessarily going to be on this medication at this dose for the rest of your life, but you will need treatment for life.”

Based on current knowledge, the risks for lifelong obesity outweigh the risk for the medications. Dr. Sweeney said she would like to see more data. “There absolutely is an evidence gap, and we need more information on the long-term effectiveness and safety.”

“When we start kids on this medication, I’m very clear that we are going to try to get to the lowest effective dose,” Dr. Vaidya said. She also emphasizes to parents that the medications must be used in conjunction with continued lifestyle modifications. She expressed hope that as clinicians gain more experience, and patients’ comorbidities resolve, perhaps it will be possible in some cases to take individuals “off for a period of time, with the understanding that they might have to go back on in a few months.”

“We’re weighing the pros and cons of being on a medication long term but we’re also weighing the pros and cons of weight-related health complications long term,” Dr. Raatz said.

Dr. Raatz also said clinicians have much to learn about the long-term safety of GLP-1 agonists in their pediatric patients.

She tells parents and families, “we expect that this is going to be a long-term medication, and this is going to be something that we’re going to continue to monitor.”

Dr. Sweeney reports that she is a speaker and unpaid consultant on Rhythm Pharmaceuticals’ Imcivree (setmelanotide) medication and that she consults for Eli Lilly. Dr. Raatz is a coprincipal investigator for a Novo Nordisk trial of semaglutide in young children and will be a co-PI for a similar trial for Eli Lilly’s tirzepatide but receives no consulting fees or honoraria. Dr. Vaidya reported no conflicts.

A version of this article appeared on Medscape.com.

Weight-loss drugs should be covered by Medicare and by other health insurance, according to a poll of US adults aged 50-80 years.

Among more than 2600 polled, 83% say that health insurance should cover prescription weight-loss drugs that have been approved by the US Food and Drug Administration (FDA), and 76% say Medicare should cover such drugs. However, only 30% would be willing to pay higher Medicare premiums to have these medications covered.

Among the 27% of respondents who say they are overweight, 63% are interested in taking such medications, as are 45% of those with diabetes, regardless of weight.

The University of Michigan (U-M) National Poll on Healthy Aging was  published online  on December 13, 2023.

High Awareness

The findings come at a time when injectable glucagon-like peptide 1 receptor agonists (GLP-1 RAs), such as Ozempic, Wegovy, Zepbound, and Mounjaro, are receiving a lot of public attention, the university noted.

Overall, 64% of survey respondents had heard of at least one prescription medication used for weight management. 

By brand name, 61% had heard of Ozempic, approved for the treatment of  type 2 diabetes  but prescribed off label for weight loss; 18% had heard of Wegovy; and 13% had heard of the anorexiant drug  phentermine .

Very few respondents (3% for each) had heard of the GLP-1 RA Saxenda, Qsymia (phentermine plus the anticonvulsant  topiramate ), and the opiate antagonist Contrave. 

Zepbound, the  obesity -specific form of the diabetes drug Mounjaro, received FDA approval after the poll was taken and was not included in survey questions.

Among respondents who had heard of at least one prescription medication used for weight management, 58% had heard about them through the news (eg, TV, magazines, newspapers) and 53% had heard about them from an advertisement on TV, the Internet, or radio. Only 11% heard about them from their healthcare providers.

Respondents more likely to be interested in taking a prescription medication for weight management included women, those aged 50-64 years, Black persons, Hispanic persons, those with household incomes of less than $60,000 annually, those with lower levels of education, those in fair or poor physical or mental health, and those with a health problem or disability limiting their daily activities.

Spotty Coverage

The GLP-1 RAs can cost more than $12,000 a year for people who pay out of pocket, the university noted. 

A  Medicare Part D law  passed in 2003 prohibits Medicare from covering medications for weight loss, although currently it can cover such drugs to help people with type 2 diabetes manage their weight. 

Medicaid covers the cost of antiobesity drugs in some states. 

Most private plans and the  Veterans Health Administration  cover them, but with restrictions due to high monthly costs for the newer medications.

The American Medical Association recently  called on insurers  to cover evidence-based weight-loss medications.

The strong demand for these medications, including for off-label purposes by people willing to pay full price, has created major shortages, the university noted. 

“As these medications grow in awareness and use, and insurers make decisions about coverage, it’s crucial for patients who have obesity or diabetes, or who are overweight with other health problems, to talk with their healthcare providers about their options,” said poll director Jeffrey Kullgren, MD, MPH, MS, a primary care physician at the VA Ann Arbor Healthcare System and associate professor of internal medicine at U-M.

Other weight-management strategies that respondents think should be covered by health insurance include sessions with a registered dietitian or nutritionist (85%);  weight-loss surgery  (73%); gym or fitness facility memberships (65%); apps or online programs to track diet, exercise, and/or behavior change (58%); and sessions with a personal trainer (53%).

The randomly selected nationally representative household survey of 2657 adults was conducted from July 17 to August 7, 2023, by NORC at the University of Chicago for the U-M Institute for Healthcare Policy and Innovation. The sample was subsequently weighted to reflect population figures from the US Census Bureau. The completion rate was 50% among those contacted to participate. The margin of error is ±1 to 5 percentage points for questions asked of the full sample and higher among subgroups.

The poll is based at the U-M Institute for Healthcare Policy and Innovation and supported by AARP and Michigan Medicine, the University of Michigan’s academic medical center.
 

A version of this article appeared on Medscape.com.

Weight-loss drugs should be covered by Medicare and by other health insurance, according to a poll of US adults aged 50-80 years.

Among more than 2600 polled, 83% say that health insurance should cover prescription weight-loss drugs that have been approved by the US Food and Drug Administration (FDA), and 76% say Medicare should cover such drugs. However, only 30% would be willing to pay higher Medicare premiums to have these medications covered.

Among the 27% of respondents who say they are overweight, 63% are interested in taking such medications, as are 45% of those with diabetes, regardless of weight.

The University of Michigan (U-M) National Poll on Healthy Aging was  published online  on December 13, 2023.

High Awareness

The findings come at a time when injectable glucagon-like peptide 1 receptor agonists (GLP-1 RAs), such as Ozempic, Wegovy, Zepbound, and Mounjaro, are receiving a lot of public attention, the university noted.

Overall, 64% of survey respondents had heard of at least one prescription medication used for weight management. 

By brand name, 61% had heard of Ozempic, approved for the treatment of  type 2 diabetes  but prescribed off label for weight loss; 18% had heard of Wegovy; and 13% had heard of the anorexiant drug  phentermine .

Very few respondents (3% for each) had heard of the GLP-1 RA Saxenda, Qsymia (phentermine plus the anticonvulsant  topiramate ), and the opiate antagonist Contrave. 

Zepbound, the  obesity -specific form of the diabetes drug Mounjaro, received FDA approval after the poll was taken and was not included in survey questions.

Among respondents who had heard of at least one prescription medication used for weight management, 58% had heard about them through the news (eg, TV, magazines, newspapers) and 53% had heard about them from an advertisement on TV, the Internet, or radio. Only 11% heard about them from their healthcare providers.

Respondents more likely to be interested in taking a prescription medication for weight management included women, those aged 50-64 years, Black persons, Hispanic persons, those with household incomes of less than $60,000 annually, those with lower levels of education, those in fair or poor physical or mental health, and those with a health problem or disability limiting their daily activities.

Spotty Coverage

The GLP-1 RAs can cost more than $12,000 a year for people who pay out of pocket, the university noted. 

A  Medicare Part D law  passed in 2003 prohibits Medicare from covering medications for weight loss, although currently it can cover such drugs to help people with type 2 diabetes manage their weight. 

Medicaid covers the cost of antiobesity drugs in some states. 

Most private plans and the  Veterans Health Administration  cover them, but with restrictions due to high monthly costs for the newer medications.

The American Medical Association recently  called on insurers  to cover evidence-based weight-loss medications.

The strong demand for these medications, including for off-label purposes by people willing to pay full price, has created major shortages, the university noted. 

“As these medications grow in awareness and use, and insurers make decisions about coverage, it’s crucial for patients who have obesity or diabetes, or who are overweight with other health problems, to talk with their healthcare providers about their options,” said poll director Jeffrey Kullgren, MD, MPH, MS, a primary care physician at the VA Ann Arbor Healthcare System and associate professor of internal medicine at U-M.

Other weight-management strategies that respondents think should be covered by health insurance include sessions with a registered dietitian or nutritionist (85%);  weight-loss surgery  (73%); gym or fitness facility memberships (65%); apps or online programs to track diet, exercise, and/or behavior change (58%); and sessions with a personal trainer (53%).

The randomly selected nationally representative household survey of 2657 adults was conducted from July 17 to August 7, 2023, by NORC at the University of Chicago for the U-M Institute for Healthcare Policy and Innovation. The sample was subsequently weighted to reflect population figures from the US Census Bureau. The completion rate was 50% among those contacted to participate. The margin of error is ±1 to 5 percentage points for questions asked of the full sample and higher among subgroups.

The poll is based at the U-M Institute for Healthcare Policy and Innovation and supported by AARP and Michigan Medicine, the University of Michigan’s academic medical center.
 

A version of this article appeared on Medscape.com.

Weight-loss drugs should be covered by Medicare and by other health insurance, according to a poll of US adults aged 50-80 years.

Among more than 2600 polled, 83% say that health insurance should cover prescription weight-loss drugs that have been approved by the US Food and Drug Administration (FDA), and 76% say Medicare should cover such drugs. However, only 30% would be willing to pay higher Medicare premiums to have these medications covered.

Among the 27% of respondents who say they are overweight, 63% are interested in taking such medications, as are 45% of those with diabetes, regardless of weight.

The University of Michigan (U-M) National Poll on Healthy Aging was  published online  on December 13, 2023.

High Awareness

The findings come at a time when injectable glucagon-like peptide 1 receptor agonists (GLP-1 RAs), such as Ozempic, Wegovy, Zepbound, and Mounjaro, are receiving a lot of public attention, the university noted.

Overall, 64% of survey respondents had heard of at least one prescription medication used for weight management. 

By brand name, 61% had heard of Ozempic, approved for the treatment of  type 2 diabetes  but prescribed off label for weight loss; 18% had heard of Wegovy; and 13% had heard of the anorexiant drug  phentermine .

Very few respondents (3% for each) had heard of the GLP-1 RA Saxenda, Qsymia (phentermine plus the anticonvulsant  topiramate ), and the opiate antagonist Contrave. 

Zepbound, the  obesity -specific form of the diabetes drug Mounjaro, received FDA approval after the poll was taken and was not included in survey questions.

Among respondents who had heard of at least one prescription medication used for weight management, 58% had heard about them through the news (eg, TV, magazines, newspapers) and 53% had heard about them from an advertisement on TV, the Internet, or radio. Only 11% heard about them from their healthcare providers.

Respondents more likely to be interested in taking a prescription medication for weight management included women, those aged 50-64 years, Black persons, Hispanic persons, those with household incomes of less than $60,000 annually, those with lower levels of education, those in fair or poor physical or mental health, and those with a health problem or disability limiting their daily activities.

Spotty Coverage

The GLP-1 RAs can cost more than $12,000 a year for people who pay out of pocket, the university noted. 

A  Medicare Part D law  passed in 2003 prohibits Medicare from covering medications for weight loss, although currently it can cover such drugs to help people with type 2 diabetes manage their weight. 

Medicaid covers the cost of antiobesity drugs in some states. 

Most private plans and the  Veterans Health Administration  cover them, but with restrictions due to high monthly costs for the newer medications.

The American Medical Association recently  called on insurers  to cover evidence-based weight-loss medications.

The strong demand for these medications, including for off-label purposes by people willing to pay full price, has created major shortages, the university noted. 

“As these medications grow in awareness and use, and insurers make decisions about coverage, it’s crucial for patients who have obesity or diabetes, or who are overweight with other health problems, to talk with their healthcare providers about their options,” said poll director Jeffrey Kullgren, MD, MPH, MS, a primary care physician at the VA Ann Arbor Healthcare System and associate professor of internal medicine at U-M.

Other weight-management strategies that respondents think should be covered by health insurance include sessions with a registered dietitian or nutritionist (85%);  weight-loss surgery  (73%); gym or fitness facility memberships (65%); apps or online programs to track diet, exercise, and/or behavior change (58%); and sessions with a personal trainer (53%).

The randomly selected nationally representative household survey of 2657 adults was conducted from July 17 to August 7, 2023, by NORC at the University of Chicago for the U-M Institute for Healthcare Policy and Innovation. The sample was subsequently weighted to reflect population figures from the US Census Bureau. The completion rate was 50% among those contacted to participate. The margin of error is ±1 to 5 percentage points for questions asked of the full sample and higher among subgroups.

The poll is based at the U-M Institute for Healthcare Policy and Innovation and supported by AARP and Michigan Medicine, the University of Michigan’s academic medical center.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A high-quality, low-carbohydrate diet (LCD), rich in plant-based proteins and healthy fats, was associated with slower weight gain, while a lower-quality LCD was associated with the reverse.

METHODOLOGY:

• Prospective cohort study included 123,332 participants from the Nurses’ Health Studies (NHS, 1986-2010 and 1991-2015) and the Health Professionals Follow-up Study (HPFS, 1986-2018).
• Diets assessed by questionnaires were categorized as: (1) total LCD (TLCD), emphasizing overall lower carbohydrate intake; (2) animal-based LCD (ALCD), emphasizing animal-sourced protein and fat; (3) vegetable-based LCD (VLCD), emphasizing plant-sourced protein and fat; (4) a healthy LCD (HLCD), emphasizing less refined carbohydrates, more plant protein, and healthy fat; and (5) unhealthy LCD (ULCD), emphasizing less healthful carbohydrates, more animal protein, and unhealthy fat.
• The primary outcome was 4-year reported changes in body weight, divided into quintiles, with Q3 = no change, Q1 = largest decrease, and Q5 = largest increase.

TAKEAWAY:

• Participants gained a mean of 1.3 kg over each 4-year interval, with gains of 0.8, 1.8, and 0.5 kg for NHS, NHSII, and HPFS, respectively.
• After adjustment for baseline and concomitant changes in lifestyle and demographic factors, compared with participants with no change in the TLCD score over 4-year intervals, those with the largest increase (Q5) in the TLCD score did not have significant weight change (0.03 kg), while those with the largest decrease (Q1) in the TLCD score had significantly less weight gain (−0.20 kg).
• Similarly, those following a VLCD with Q5 change, compared with those with stable Q3 adherence, experienced 0.21 kg less weight gain, and those with Q1 change experienced 0.17 kg less weight gain, both significant.
• Adhering to an ALCD was associated with more weight gain over time, with each 1 standard deviation (SD) increase in ALCD associated with a significant 0.13 kg more weight gain over 4-year intervals.
• Opposite results were seen for ULCD and HLCD scores, where a 1-SD increase in HLCD and ULCD was associated with a significant 0.36 kg weight loss and 0.39 kg weight gain, respectively, over 4-year intervals.
• The associations were stronger among individuals with baseline body mass index ≥ 30 kg/m².

IN PRACTICE:

“The findings of this cohort study underscore the importance of diet quality within LCD patterns for weight management… Overall, the study findings argue against the sole focus of macronutrient quantity for weight management and suggest the crucial role of nutrient quality in maintaining a healthy body weight.”

SOURCE:

This study was conducted by Binkai Liu, MS, of the department of nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, and colleagues. 

The findings were published online in  JAMA Network Open .

LIMITATIONS:

• Self-reported data.
• Observational study, potential for residual confounding.
• No body composition measurement.
• Study population was mainly White health professionals.

DISCLOSURES:

This study was funded by research grants from the National Institutes of Health, and one coauthor is supported by a postdoctoral fellowship award from the Canadian Institutes of Health Research.

A version of this article appeared on Medscape.com.

TOPLINE:

A high-quality, low-carbohydrate diet (LCD), rich in plant-based proteins and healthy fats, was associated with slower weight gain, while a lower-quality LCD was associated with the reverse.

METHODOLOGY:

• Prospective cohort study included 123,332 participants from the Nurses’ Health Studies (NHS, 1986-2010 and 1991-2015) and the Health Professionals Follow-up Study (HPFS, 1986-2018).
• Diets assessed by questionnaires were categorized as: (1) total LCD (TLCD), emphasizing overall lower carbohydrate intake; (2) animal-based LCD (ALCD), emphasizing animal-sourced protein and fat; (3) vegetable-based LCD (VLCD), emphasizing plant-sourced protein and fat; (4) a healthy LCD (HLCD), emphasizing less refined carbohydrates, more plant protein, and healthy fat; and (5) unhealthy LCD (ULCD), emphasizing less healthful carbohydrates, more animal protein, and unhealthy fat.
• The primary outcome was 4-year reported changes in body weight, divided into quintiles, with Q3 = no change, Q1 = largest decrease, and Q5 = largest increase.

TAKEAWAY:

• Participants gained a mean of 1.3 kg over each 4-year interval, with gains of 0.8, 1.8, and 0.5 kg for NHS, NHSII, and HPFS, respectively.
• After adjustment for baseline and concomitant changes in lifestyle and demographic factors, compared with participants with no change in the TLCD score over 4-year intervals, those with the largest increase (Q5) in the TLCD score did not have significant weight change (0.03 kg), while those with the largest decrease (Q1) in the TLCD score had significantly less weight gain (−0.20 kg).
• Similarly, those following a VLCD with Q5 change, compared with those with stable Q3 adherence, experienced 0.21 kg less weight gain, and those with Q1 change experienced 0.17 kg less weight gain, both significant.
• Adhering to an ALCD was associated with more weight gain over time, with each 1 standard deviation (SD) increase in ALCD associated with a significant 0.13 kg more weight gain over 4-year intervals.
• Opposite results were seen for ULCD and HLCD scores, where a 1-SD increase in HLCD and ULCD was associated with a significant 0.36 kg weight loss and 0.39 kg weight gain, respectively, over 4-year intervals.
• The associations were stronger among individuals with baseline body mass index ≥ 30 kg/m².

IN PRACTICE:

“The findings of this cohort study underscore the importance of diet quality within LCD patterns for weight management… Overall, the study findings argue against the sole focus of macronutrient quantity for weight management and suggest the crucial role of nutrient quality in maintaining a healthy body weight.”

SOURCE:

This study was conducted by Binkai Liu, MS, of the department of nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, and colleagues. 

The findings were published online in  JAMA Network Open .

LIMITATIONS:

• Self-reported data.
• Observational study, potential for residual confounding.
• No body composition measurement.
• Study population was mainly White health professionals.

DISCLOSURES:

This study was funded by research grants from the National Institutes of Health, and one coauthor is supported by a postdoctoral fellowship award from the Canadian Institutes of Health Research.

A version of this article appeared on Medscape.com.

TOPLINE:

A high-quality, low-carbohydrate diet (LCD), rich in plant-based proteins and healthy fats, was associated with slower weight gain, while a lower-quality LCD was associated with the reverse.

METHODOLOGY:

• Prospective cohort study included 123,332 participants from the Nurses’ Health Studies (NHS, 1986-2010 and 1991-2015) and the Health Professionals Follow-up Study (HPFS, 1986-2018).
• Diets assessed by questionnaires were categorized as: (1) total LCD (TLCD), emphasizing overall lower carbohydrate intake; (2) animal-based LCD (ALCD), emphasizing animal-sourced protein and fat; (3) vegetable-based LCD (VLCD), emphasizing plant-sourced protein and fat; (4) a healthy LCD (HLCD), emphasizing less refined carbohydrates, more plant protein, and healthy fat; and (5) unhealthy LCD (ULCD), emphasizing less healthful carbohydrates, more animal protein, and unhealthy fat.
• The primary outcome was 4-year reported changes in body weight, divided into quintiles, with Q3 = no change, Q1 = largest decrease, and Q5 = largest increase.

TAKEAWAY:

• Participants gained a mean of 1.3 kg over each 4-year interval, with gains of 0.8, 1.8, and 0.5 kg for NHS, NHSII, and HPFS, respectively.
• After adjustment for baseline and concomitant changes in lifestyle and demographic factors, compared with participants with no change in the TLCD score over 4-year intervals, those with the largest increase (Q5) in the TLCD score did not have significant weight change (0.03 kg), while those with the largest decrease (Q1) in the TLCD score had significantly less weight gain (−0.20 kg).
• Similarly, those following a VLCD with Q5 change, compared with those with stable Q3 adherence, experienced 0.21 kg less weight gain, and those with Q1 change experienced 0.17 kg less weight gain, both significant.
• Adhering to an ALCD was associated with more weight gain over time, with each 1 standard deviation (SD) increase in ALCD associated with a significant 0.13 kg more weight gain over 4-year intervals.
• Opposite results were seen for ULCD and HLCD scores, where a 1-SD increase in HLCD and ULCD was associated with a significant 0.36 kg weight loss and 0.39 kg weight gain, respectively, over 4-year intervals.
• The associations were stronger among individuals with baseline body mass index ≥ 30 kg/m².

IN PRACTICE:

“The findings of this cohort study underscore the importance of diet quality within LCD patterns for weight management… Overall, the study findings argue against the sole focus of macronutrient quantity for weight management and suggest the crucial role of nutrient quality in maintaining a healthy body weight.”

SOURCE:

This study was conducted by Binkai Liu, MS, of the department of nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, and colleagues. 

The findings were published online in  JAMA Network Open .

LIMITATIONS:

• Self-reported data.
• Observational study, potential for residual confounding.
• No body composition measurement.
• Study population was mainly White health professionals.

DISCLOSURES:

This study was funded by research grants from the National Institutes of Health, and one coauthor is supported by a postdoctoral fellowship award from the Canadian Institutes of Health Research.

A version of this article appeared on Medscape.com.

The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide has made headlines as a US Food and Drug Administration (FDA)–approved treatment for type 2 diabetes (Ozempic) and obesity (Wegovy). 

Recently, attention has turned to the possibility that semaglutide may have broader applications, including its potential positive impact on addictive behaviors such as reducing drug craving and alcohol consumption. 

“There is some really interesting preclinical research in rodents and monkeys that shows that GLP-1 agonist molecules, like semaglutide, have the effect of reducing the consumption of not just food, but also alcohol, nicotine, cocaine and amphetamines,” Kyle Simmons, PhD, professor of pharmacology and physiology at Oklahoma State University Center for Health Sciences in Tulsa, said in an interview. 

Some of that early research was conducted by Elisabet Jerlhag Holm, PhD, and colleagues at University of Gothenburg, Sweden.

“We have worked on GLP-1 and alcohol since 2012, and observe promising effects,” Holm told this news organization. 

Her team published two studies earlier this year — one in one in Frontiers in Pharmacology and the other in eBioMedicine — demonstrating that semaglutide, in low doses, reduces alcohol intake in male and female rats.

“We have shown that semaglutide binds to the nucleus accumbens — an area of the brain associated with reward. We have also shown that semaglutide alters the dopamine metabolism when alcohol is on board. This provides a tentative mechanism,” Dr. Holm said. 

First Human Data 

The preclinical data fueled interest in testing the value of the GLP-1 agonist in patient populations with addiction.

Dr. Simmons and colleagues have now published what is believed to be the first evidence in humans that semaglutide specifically reduces the symptoms of alcohol use disorder (AUD).

In a report published online on November 27 in The Journal of Clinical Psychiatry, they describe six patients (of whom five are female; mean age, 43 years) who received semaglutide treatment in the course of pharmacotherapy for weight loss.

All six screened positive for AUD on the Alcohol Use Disorders Identification Test (AUDIT), and all six showed significant improvement in their alcohol-related symptoms after starting semaglutide. 

An AUDIT score > 8 is considered positive. The mean AUDIT score at baseline was 14. It fell to 4.5 on average after semaglutide treatment. The mean 9.5-point decrease in AUDIT scores with semaglutide was statistically significant (P < .001). 

The patients were followed up from a few weeks to almost 9 months, and all of them had a reduction in AUD symptoms. At the various follow-up time points, all six patients had AUDIT scores consistent with “low-risk” drinking.

Strong Response at Low Doses 

“There was a very strong response, even at a very low dose,” lead author Jesse Richards, DO, director of obesity medicine and assistant professor of medicine University of Oklahoma School of Community Medicine, Tulsa, said in an interview. 

Three patients were treated with 0.5 mg of semaglutide weekly, two with 0.25 mg weekly, and one with 1 mg weekly. These doses are lower than those currently approved for treatment of type 2 diabetes and obesity. 

Dr. Holm is not surprised by the results in these six patients. “Based on our preclinical data, this outcome is expected. The data are promising and bigger studies needed,” she said.

Simmons is currently leading a randomized placebo-controlled trial to further test the impact of semaglutide on AUD. 

The STAR (Semaglutide Therapy for Alcohol Reduction) study is funded by the Hardesty Family Foundation and Oklahoma State University Center for Health Sciences.

A sister study is also currently underway in Baltimore, funded by the National Institute on Drug Abuse.

Hopefully, these studies will be able to “definitively tell us whether semaglutide is safe and effective for treatment” for AUD, Dr. Simmons said in a statement. 

Despite being a major cause of preventable death worldwide, AUD currently has only three FDA-approved pharmacotherapies. However, there has been limited uptake of these drugs. 

“There remains a significant treatment gap and need for new and novel or perhaps better tolerated or different mechanism treatment options for patients,” Dr. Richards said. 

The preclinical and early clinical data provide a “signal” of a treatment effect for semaglutide in AUD, Dr. Richards said. The randomized controlled trials now underway should be concluding in the next 1-2 years, “at which point we’ll have a much better sense of the safety and efficacy of this drug for AUD,” he said. 

The case series had no specific funding. Dr. Richards is on speakers bureaus for Rhythm Pharmaceuticals and Novo Nordisk and is on an advisory board for Rhythm Pharmaceuticals. Simmons is the recipient of a grant from the Hardesty Family Foundation to support an ongoing clinical trial of semaglutide in the treatment of AUD. Dr. Holm has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide has made headlines as a US Food and Drug Administration (FDA)–approved treatment for type 2 diabetes (Ozempic) and obesity (Wegovy). 

Recently, attention has turned to the possibility that semaglutide may have broader applications, including its potential positive impact on addictive behaviors such as reducing drug craving and alcohol consumption. 

“There is some really interesting preclinical research in rodents and monkeys that shows that GLP-1 agonist molecules, like semaglutide, have the effect of reducing the consumption of not just food, but also alcohol, nicotine, cocaine and amphetamines,” Kyle Simmons, PhD, professor of pharmacology and physiology at Oklahoma State University Center for Health Sciences in Tulsa, said in an interview. 

Some of that early research was conducted by Elisabet Jerlhag Holm, PhD, and colleagues at University of Gothenburg, Sweden.

“We have worked on GLP-1 and alcohol since 2012, and observe promising effects,” Holm told this news organization. 

Her team published two studies earlier this year — one in one in Frontiers in Pharmacology and the other in eBioMedicine — demonstrating that semaglutide, in low doses, reduces alcohol intake in male and female rats.

“We have shown that semaglutide binds to the nucleus accumbens — an area of the brain associated with reward. We have also shown that semaglutide alters the dopamine metabolism when alcohol is on board. This provides a tentative mechanism,” Dr. Holm said. 

First Human Data 

The preclinical data fueled interest in testing the value of the GLP-1 agonist in patient populations with addiction.

Dr. Simmons and colleagues have now published what is believed to be the first evidence in humans that semaglutide specifically reduces the symptoms of alcohol use disorder (AUD).

In a report published online on November 27 in The Journal of Clinical Psychiatry, they describe six patients (of whom five are female; mean age, 43 years) who received semaglutide treatment in the course of pharmacotherapy for weight loss.

All six screened positive for AUD on the Alcohol Use Disorders Identification Test (AUDIT), and all six showed significant improvement in their alcohol-related symptoms after starting semaglutide. 

An AUDIT score > 8 is considered positive. The mean AUDIT score at baseline was 14. It fell to 4.5 on average after semaglutide treatment. The mean 9.5-point decrease in AUDIT scores with semaglutide was statistically significant (P < .001). 

The patients were followed up from a few weeks to almost 9 months, and all of them had a reduction in AUD symptoms. At the various follow-up time points, all six patients had AUDIT scores consistent with “low-risk” drinking.

Strong Response at Low Doses 

“There was a very strong response, even at a very low dose,” lead author Jesse Richards, DO, director of obesity medicine and assistant professor of medicine University of Oklahoma School of Community Medicine, Tulsa, said in an interview. 

Three patients were treated with 0.5 mg of semaglutide weekly, two with 0.25 mg weekly, and one with 1 mg weekly. These doses are lower than those currently approved for treatment of type 2 diabetes and obesity. 

Dr. Holm is not surprised by the results in these six patients. “Based on our preclinical data, this outcome is expected. The data are promising and bigger studies needed,” she said.

Simmons is currently leading a randomized placebo-controlled trial to further test the impact of semaglutide on AUD. 

The STAR (Semaglutide Therapy for Alcohol Reduction) study is funded by the Hardesty Family Foundation and Oklahoma State University Center for Health Sciences.

A sister study is also currently underway in Baltimore, funded by the National Institute on Drug Abuse.

Hopefully, these studies will be able to “definitively tell us whether semaglutide is safe and effective for treatment” for AUD, Dr. Simmons said in a statement. 

Despite being a major cause of preventable death worldwide, AUD currently has only three FDA-approved pharmacotherapies. However, there has been limited uptake of these drugs. 

“There remains a significant treatment gap and need for new and novel or perhaps better tolerated or different mechanism treatment options for patients,” Dr. Richards said. 

The preclinical and early clinical data provide a “signal” of a treatment effect for semaglutide in AUD, Dr. Richards said. The randomized controlled trials now underway should be concluding in the next 1-2 years, “at which point we’ll have a much better sense of the safety and efficacy of this drug for AUD,” he said. 

The case series had no specific funding. Dr. Richards is on speakers bureaus for Rhythm Pharmaceuticals and Novo Nordisk and is on an advisory board for Rhythm Pharmaceuticals. Simmons is the recipient of a grant from the Hardesty Family Foundation to support an ongoing clinical trial of semaglutide in the treatment of AUD. Dr. Holm has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide has made headlines as a US Food and Drug Administration (FDA)–approved treatment for type 2 diabetes (Ozempic) and obesity (Wegovy). 

Recently, attention has turned to the possibility that semaglutide may have broader applications, including its potential positive impact on addictive behaviors such as reducing drug craving and alcohol consumption. 

“There is some really interesting preclinical research in rodents and monkeys that shows that GLP-1 agonist molecules, like semaglutide, have the effect of reducing the consumption of not just food, but also alcohol, nicotine, cocaine and amphetamines,” Kyle Simmons, PhD, professor of pharmacology and physiology at Oklahoma State University Center for Health Sciences in Tulsa, said in an interview. 

Some of that early research was conducted by Elisabet Jerlhag Holm, PhD, and colleagues at University of Gothenburg, Sweden.

“We have worked on GLP-1 and alcohol since 2012, and observe promising effects,” Holm told this news organization. 

Her team published two studies earlier this year — one in one in Frontiers in Pharmacology and the other in eBioMedicine — demonstrating that semaglutide, in low doses, reduces alcohol intake in male and female rats.

“We have shown that semaglutide binds to the nucleus accumbens — an area of the brain associated with reward. We have also shown that semaglutide alters the dopamine metabolism when alcohol is on board. This provides a tentative mechanism,” Dr. Holm said. 

First Human Data 

The preclinical data fueled interest in testing the value of the GLP-1 agonist in patient populations with addiction.

Dr. Simmons and colleagues have now published what is believed to be the first evidence in humans that semaglutide specifically reduces the symptoms of alcohol use disorder (AUD).

In a report published online on November 27 in The Journal of Clinical Psychiatry, they describe six patients (of whom five are female; mean age, 43 years) who received semaglutide treatment in the course of pharmacotherapy for weight loss.

All six screened positive for AUD on the Alcohol Use Disorders Identification Test (AUDIT), and all six showed significant improvement in their alcohol-related symptoms after starting semaglutide. 

An AUDIT score > 8 is considered positive. The mean AUDIT score at baseline was 14. It fell to 4.5 on average after semaglutide treatment. The mean 9.5-point decrease in AUDIT scores with semaglutide was statistically significant (P < .001). 

The patients were followed up from a few weeks to almost 9 months, and all of them had a reduction in AUD symptoms. At the various follow-up time points, all six patients had AUDIT scores consistent with “low-risk” drinking.

Strong Response at Low Doses 

“There was a very strong response, even at a very low dose,” lead author Jesse Richards, DO, director of obesity medicine and assistant professor of medicine University of Oklahoma School of Community Medicine, Tulsa, said in an interview. 

Three patients were treated with 0.5 mg of semaglutide weekly, two with 0.25 mg weekly, and one with 1 mg weekly. These doses are lower than those currently approved for treatment of type 2 diabetes and obesity. 

Dr. Holm is not surprised by the results in these six patients. “Based on our preclinical data, this outcome is expected. The data are promising and bigger studies needed,” she said.

Simmons is currently leading a randomized placebo-controlled trial to further test the impact of semaglutide on AUD. 

The STAR (Semaglutide Therapy for Alcohol Reduction) study is funded by the Hardesty Family Foundation and Oklahoma State University Center for Health Sciences.

A sister study is also currently underway in Baltimore, funded by the National Institute on Drug Abuse.

Hopefully, these studies will be able to “definitively tell us whether semaglutide is safe and effective for treatment” for AUD, Dr. Simmons said in a statement. 

Despite being a major cause of preventable death worldwide, AUD currently has only three FDA-approved pharmacotherapies. However, there has been limited uptake of these drugs. 

“There remains a significant treatment gap and need for new and novel or perhaps better tolerated or different mechanism treatment options for patients,” Dr. Richards said. 

The preclinical and early clinical data provide a “signal” of a treatment effect for semaglutide in AUD, Dr. Richards said. The randomized controlled trials now underway should be concluding in the next 1-2 years, “at which point we’ll have a much better sense of the safety and efficacy of this drug for AUD,” he said. 

The case series had no specific funding. Dr. Richards is on speakers bureaus for Rhythm Pharmaceuticals and Novo Nordisk and is on an advisory board for Rhythm Pharmaceuticals. Simmons is the recipient of a grant from the Hardesty Family Foundation to support an ongoing clinical trial of semaglutide in the treatment of AUD. Dr. Holm has no relevant disclosures.
 

A version of this article appeared on Medscape.com.