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Walking Fast May Help Prevent Type 2 Diabetes
Walking is a simple, cost-free form of exercise that benefits physical, social, and mental health in many ways. Several clinical trials have shown that walking regularly is associated with a lower risk for cardiovascular events and all-cause mortality, and having a higher daily step count is linked to a decreased risk for premature death.
Walking and Diabetes
In recent years, the link between walking speed and the risk for multiple health problems has sparked keen interest. Data suggest that a faster walking pace may have a greater physiological response and may be associated with more favorable health advantages than a slow walking pace. A previous meta-analysis of eight cohort studies suggested that individuals in the fastest walking-pace category (median = 5.6 km/h) had a 44% lower risk for stroke than those in the slowest walking-pace category (median = 1.6 km/h). The risk for the former decreased by 13% for every 1 km/h increment in baseline walking pace.
Type 2 diabetes (T2D) is one of the most common metabolic diseases in the world. People with this type of diabetes have an increased risk for microvascular and macrovascular complications and a shorter life expectancy. Approximately 537 million adults are estimated to be living with diabetes worldwide, and this number is expected to reach 783 million by 2045.
Physical activity is an essential component of T2D prevention programs and can favorably affect blood sugar control. A meta-analysis of cohort studies showed that being physically active was associated with a 35% reduction in the risk of acquiring T2D in the general population, and regular walking was associated with a 15% reduction in the risk of developing T2D.
However, no studies have investigated the link between different walking speeds and the risk for T2D. A team from the Research Center at the Semnan University of Medical Sciences in Iran carried out a systematic review of the association between walking speed and the risk of developing T2D in adults; this review was published in the British Journal of Sports Medicine.
10 Cohort Studies
This systematic review used publications (1999-2022) available in the usual data sources (PubMed, Scopus, CENTRAL, and Web of Science). Random-effects meta-analyses were used to calculate relative risk (RR) and risk difference (RD) based on different walking speeds. The researchers rated the credibility of subgroup differences and the certainty of evidence using the Instrument to assess the Credibility of Effect Modification ANalyses (ICEMAN) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tools, respectively.
Of the 508,121 potential participants, 18,410 adults from 10 prospective cohort studies conducted in the United States, Japan, and the United Kingdom were deemed eligible. The proportion of women was between 52% and 73%, depending on the cohort. Follow-up duration varied from 3 to 11.1 years (median, 8 years).
Five cohort studies measured walking speed using stopwatch testing, while the other five used self-assessed questionnaires. To define cases of T2D, seven studies used objective methods such as blood glucose measurement or linkage with medical records, and in three cohorts, self-assessment questionnaires were used (these were checked against patient records). All studies controlled age, sex, and tobacco consumption in the multivariate analyses, and some controlled just alcohol consumption, blood pressure, total physical activity volume, body mass index, time spent walking or daily step count, and a family history of diabetes.
The Right Speed
The authors first categorized walking speed into four prespecified levels: Easy or casual (< 2 mph or 3.2 km/h), average or normal (2-3 mph or 3.2-4.8 km/h), fairly brisk (3-4 mph or 4.8-6.4 km/h), and very brisk or brisk/striding (> 4 mph or > 6.4 km/h).
Four cohort studies with 6,520 cases of T2D among 160,321 participants reported information on average or normal walking. Participants with average or normal walking were at a 15% lower risk for T2D than those with easy or casual walking (RR = 0.85 [95% CI, 0.70-1.00]; RD = 0.86 [1.72-0]). Ten cohort studies with 18,410 cases among 508,121 participants reported information on fairly brisk walking. Those with fairly brisk walking were at a 24% lower risk for T2D than those with easy or casual walking (RR = 0.76 [0.65-0.87]; I2 = 90%; RD = 1.38 [2.01-0.75]).
There was no significant or credible subgroup difference by adjustment for the total physical activity or time spent walking per day. The dose-response analysis suggested that the risk for T2D decreased significantly at a walking speed of 4 km/h and above.
Study Limitations
This meta-analysis has strengths that may increase the generalizability of its results. The researchers included cohort studies, which allowed them to consider the temporal sequence of exposure and outcome. Cohort studies are less affected by recall and selection biases compared with retrospective case–control studies, which increase the likelihood of causality. The researchers also assessed the credibility of subgroup differences using the recently developed ICEMAN tool, calculated both relative and absolute risks, and rated the certainty of evidence using the GRADE approach.
Some shortcomings must be considered. Most of the studies included in the present review were rated as having a serious risk for bias, with the most important biases resulting from inadequate adjustment for potential confounders and the methods used for walking speed assessment and diagnosis of T2D. In addition, the findings could have been subject to reverse causality bias because participants with faster walking speed are more likely to perform more physical activity and have better cardiorespiratory fitness, greater muscle mass, and better health status. However, the subgroup analyses of fairly brisk and brisk/striding walking indicated that there were no significant subgroup differences by follow-up duration and that the significant inverse associations remained stable in the subgroup of cohort studies with a follow-up duration of > 10 years.
The authors concluded that While current strategies to increase total walking time are beneficial, it may also be reasonable to encourage people to walk at faster speeds to further increase the health benefits of walking.”
This article was translated from JIM, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.
Walking is a simple, cost-free form of exercise that benefits physical, social, and mental health in many ways. Several clinical trials have shown that walking regularly is associated with a lower risk for cardiovascular events and all-cause mortality, and having a higher daily step count is linked to a decreased risk for premature death.
Walking and Diabetes
In recent years, the link between walking speed and the risk for multiple health problems has sparked keen interest. Data suggest that a faster walking pace may have a greater physiological response and may be associated with more favorable health advantages than a slow walking pace. A previous meta-analysis of eight cohort studies suggested that individuals in the fastest walking-pace category (median = 5.6 km/h) had a 44% lower risk for stroke than those in the slowest walking-pace category (median = 1.6 km/h). The risk for the former decreased by 13% for every 1 km/h increment in baseline walking pace.
Type 2 diabetes (T2D) is one of the most common metabolic diseases in the world. People with this type of diabetes have an increased risk for microvascular and macrovascular complications and a shorter life expectancy. Approximately 537 million adults are estimated to be living with diabetes worldwide, and this number is expected to reach 783 million by 2045.
Physical activity is an essential component of T2D prevention programs and can favorably affect blood sugar control. A meta-analysis of cohort studies showed that being physically active was associated with a 35% reduction in the risk of acquiring T2D in the general population, and regular walking was associated with a 15% reduction in the risk of developing T2D.
However, no studies have investigated the link between different walking speeds and the risk for T2D. A team from the Research Center at the Semnan University of Medical Sciences in Iran carried out a systematic review of the association between walking speed and the risk of developing T2D in adults; this review was published in the British Journal of Sports Medicine.
10 Cohort Studies
This systematic review used publications (1999-2022) available in the usual data sources (PubMed, Scopus, CENTRAL, and Web of Science). Random-effects meta-analyses were used to calculate relative risk (RR) and risk difference (RD) based on different walking speeds. The researchers rated the credibility of subgroup differences and the certainty of evidence using the Instrument to assess the Credibility of Effect Modification ANalyses (ICEMAN) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tools, respectively.
Of the 508,121 potential participants, 18,410 adults from 10 prospective cohort studies conducted in the United States, Japan, and the United Kingdom were deemed eligible. The proportion of women was between 52% and 73%, depending on the cohort. Follow-up duration varied from 3 to 11.1 years (median, 8 years).
Five cohort studies measured walking speed using stopwatch testing, while the other five used self-assessed questionnaires. To define cases of T2D, seven studies used objective methods such as blood glucose measurement or linkage with medical records, and in three cohorts, self-assessment questionnaires were used (these were checked against patient records). All studies controlled age, sex, and tobacco consumption in the multivariate analyses, and some controlled just alcohol consumption, blood pressure, total physical activity volume, body mass index, time spent walking or daily step count, and a family history of diabetes.
The Right Speed
The authors first categorized walking speed into four prespecified levels: Easy or casual (< 2 mph or 3.2 km/h), average or normal (2-3 mph or 3.2-4.8 km/h), fairly brisk (3-4 mph or 4.8-6.4 km/h), and very brisk or brisk/striding (> 4 mph or > 6.4 km/h).
Four cohort studies with 6,520 cases of T2D among 160,321 participants reported information on average or normal walking. Participants with average or normal walking were at a 15% lower risk for T2D than those with easy or casual walking (RR = 0.85 [95% CI, 0.70-1.00]; RD = 0.86 [1.72-0]). Ten cohort studies with 18,410 cases among 508,121 participants reported information on fairly brisk walking. Those with fairly brisk walking were at a 24% lower risk for T2D than those with easy or casual walking (RR = 0.76 [0.65-0.87]; I2 = 90%; RD = 1.38 [2.01-0.75]).
There was no significant or credible subgroup difference by adjustment for the total physical activity or time spent walking per day. The dose-response analysis suggested that the risk for T2D decreased significantly at a walking speed of 4 km/h and above.
Study Limitations
This meta-analysis has strengths that may increase the generalizability of its results. The researchers included cohort studies, which allowed them to consider the temporal sequence of exposure and outcome. Cohort studies are less affected by recall and selection biases compared with retrospective case–control studies, which increase the likelihood of causality. The researchers also assessed the credibility of subgroup differences using the recently developed ICEMAN tool, calculated both relative and absolute risks, and rated the certainty of evidence using the GRADE approach.
Some shortcomings must be considered. Most of the studies included in the present review were rated as having a serious risk for bias, with the most important biases resulting from inadequate adjustment for potential confounders and the methods used for walking speed assessment and diagnosis of T2D. In addition, the findings could have been subject to reverse causality bias because participants with faster walking speed are more likely to perform more physical activity and have better cardiorespiratory fitness, greater muscle mass, and better health status. However, the subgroup analyses of fairly brisk and brisk/striding walking indicated that there were no significant subgroup differences by follow-up duration and that the significant inverse associations remained stable in the subgroup of cohort studies with a follow-up duration of > 10 years.
The authors concluded that While current strategies to increase total walking time are beneficial, it may also be reasonable to encourage people to walk at faster speeds to further increase the health benefits of walking.”
This article was translated from JIM, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.
Walking is a simple, cost-free form of exercise that benefits physical, social, and mental health in many ways. Several clinical trials have shown that walking regularly is associated with a lower risk for cardiovascular events and all-cause mortality, and having a higher daily step count is linked to a decreased risk for premature death.
Walking and Diabetes
In recent years, the link between walking speed and the risk for multiple health problems has sparked keen interest. Data suggest that a faster walking pace may have a greater physiological response and may be associated with more favorable health advantages than a slow walking pace. A previous meta-analysis of eight cohort studies suggested that individuals in the fastest walking-pace category (median = 5.6 km/h) had a 44% lower risk for stroke than those in the slowest walking-pace category (median = 1.6 km/h). The risk for the former decreased by 13% for every 1 km/h increment in baseline walking pace.
Type 2 diabetes (T2D) is one of the most common metabolic diseases in the world. People with this type of diabetes have an increased risk for microvascular and macrovascular complications and a shorter life expectancy. Approximately 537 million adults are estimated to be living with diabetes worldwide, and this number is expected to reach 783 million by 2045.
Physical activity is an essential component of T2D prevention programs and can favorably affect blood sugar control. A meta-analysis of cohort studies showed that being physically active was associated with a 35% reduction in the risk of acquiring T2D in the general population, and regular walking was associated with a 15% reduction in the risk of developing T2D.
However, no studies have investigated the link between different walking speeds and the risk for T2D. A team from the Research Center at the Semnan University of Medical Sciences in Iran carried out a systematic review of the association between walking speed and the risk of developing T2D in adults; this review was published in the British Journal of Sports Medicine.
10 Cohort Studies
This systematic review used publications (1999-2022) available in the usual data sources (PubMed, Scopus, CENTRAL, and Web of Science). Random-effects meta-analyses were used to calculate relative risk (RR) and risk difference (RD) based on different walking speeds. The researchers rated the credibility of subgroup differences and the certainty of evidence using the Instrument to assess the Credibility of Effect Modification ANalyses (ICEMAN) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tools, respectively.
Of the 508,121 potential participants, 18,410 adults from 10 prospective cohort studies conducted in the United States, Japan, and the United Kingdom were deemed eligible. The proportion of women was between 52% and 73%, depending on the cohort. Follow-up duration varied from 3 to 11.1 years (median, 8 years).
Five cohort studies measured walking speed using stopwatch testing, while the other five used self-assessed questionnaires. To define cases of T2D, seven studies used objective methods such as blood glucose measurement or linkage with medical records, and in three cohorts, self-assessment questionnaires were used (these were checked against patient records). All studies controlled age, sex, and tobacco consumption in the multivariate analyses, and some controlled just alcohol consumption, blood pressure, total physical activity volume, body mass index, time spent walking or daily step count, and a family history of diabetes.
The Right Speed
The authors first categorized walking speed into four prespecified levels: Easy or casual (< 2 mph or 3.2 km/h), average or normal (2-3 mph or 3.2-4.8 km/h), fairly brisk (3-4 mph or 4.8-6.4 km/h), and very brisk or brisk/striding (> 4 mph or > 6.4 km/h).
Four cohort studies with 6,520 cases of T2D among 160,321 participants reported information on average or normal walking. Participants with average or normal walking were at a 15% lower risk for T2D than those with easy or casual walking (RR = 0.85 [95% CI, 0.70-1.00]; RD = 0.86 [1.72-0]). Ten cohort studies with 18,410 cases among 508,121 participants reported information on fairly brisk walking. Those with fairly brisk walking were at a 24% lower risk for T2D than those with easy or casual walking (RR = 0.76 [0.65-0.87]; I2 = 90%; RD = 1.38 [2.01-0.75]).
There was no significant or credible subgroup difference by adjustment for the total physical activity or time spent walking per day. The dose-response analysis suggested that the risk for T2D decreased significantly at a walking speed of 4 km/h and above.
Study Limitations
This meta-analysis has strengths that may increase the generalizability of its results. The researchers included cohort studies, which allowed them to consider the temporal sequence of exposure and outcome. Cohort studies are less affected by recall and selection biases compared with retrospective case–control studies, which increase the likelihood of causality. The researchers also assessed the credibility of subgroup differences using the recently developed ICEMAN tool, calculated both relative and absolute risks, and rated the certainty of evidence using the GRADE approach.
Some shortcomings must be considered. Most of the studies included in the present review were rated as having a serious risk for bias, with the most important biases resulting from inadequate adjustment for potential confounders and the methods used for walking speed assessment and diagnosis of T2D. In addition, the findings could have been subject to reverse causality bias because participants with faster walking speed are more likely to perform more physical activity and have better cardiorespiratory fitness, greater muscle mass, and better health status. However, the subgroup analyses of fairly brisk and brisk/striding walking indicated that there were no significant subgroup differences by follow-up duration and that the significant inverse associations remained stable in the subgroup of cohort studies with a follow-up duration of > 10 years.
The authors concluded that While current strategies to increase total walking time are beneficial, it may also be reasonable to encourage people to walk at faster speeds to further increase the health benefits of walking.”
This article was translated from JIM, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.
FROM THE BRITISH JOURNAL OF SPORTS MEDICINE
FDA Issues Warning About Counterfeit Ozempic
Clinicians and patients are advised to check the product packages they have received and not to use those labeled with lot number NAR0074 and serial number 430834149057. Some of these counterfeit products may still be available for purchase, the FDA said in a statement.
Together with Ozempic manufacturer Novo Nordisk, the FDA is investigating “thousands of units” of the 1-mg injection product. Information is not yet available regarding the drugs’ identity, quality, or safety. However, the pen needles have been confirmed as fake — thereby raising the potential risk for infection — as have the pen labels, accompanying health care professional and patient label information, and carton.
“FDA takes reports of possible counterfeit products seriously and works closely with other federal agencies and the private sector to help protect the nation’s drug supply. FDA’s investigation is ongoing, and the agency is working with Novo Nordisk to identify, investigate, and remove further suspected counterfeit semaglutide injectable products found in the US,” the statement says.
Patients are advised to only obtain Ozempic with a valid prescription through state-licensed pharmacies and to check the product before using for any signs of counterfeiting. There are several differences between the genuine and counterfeit products in the way the pen needle is packaged. The most obvious is that the paper tab covering the fake needle says “Novofine®” whereas the genuine one says “Novofine® Plus.”
There have been at least five adverse events reported from this lot; none were serious and all were consistent with gastrointestinal issues known to occur with the genuine product.
Counterfeit products should be reported to the FDA ‘s consumer complaint coordinator or to the criminal activity division.
A version of this article first appeared on Medscape.com.
Clinicians and patients are advised to check the product packages they have received and not to use those labeled with lot number NAR0074 and serial number 430834149057. Some of these counterfeit products may still be available for purchase, the FDA said in a statement.
Together with Ozempic manufacturer Novo Nordisk, the FDA is investigating “thousands of units” of the 1-mg injection product. Information is not yet available regarding the drugs’ identity, quality, or safety. However, the pen needles have been confirmed as fake — thereby raising the potential risk for infection — as have the pen labels, accompanying health care professional and patient label information, and carton.
“FDA takes reports of possible counterfeit products seriously and works closely with other federal agencies and the private sector to help protect the nation’s drug supply. FDA’s investigation is ongoing, and the agency is working with Novo Nordisk to identify, investigate, and remove further suspected counterfeit semaglutide injectable products found in the US,” the statement says.
Patients are advised to only obtain Ozempic with a valid prescription through state-licensed pharmacies and to check the product before using for any signs of counterfeiting. There are several differences between the genuine and counterfeit products in the way the pen needle is packaged. The most obvious is that the paper tab covering the fake needle says “Novofine®” whereas the genuine one says “Novofine® Plus.”
There have been at least five adverse events reported from this lot; none were serious and all were consistent with gastrointestinal issues known to occur with the genuine product.
Counterfeit products should be reported to the FDA ‘s consumer complaint coordinator or to the criminal activity division.
A version of this article first appeared on Medscape.com.
Clinicians and patients are advised to check the product packages they have received and not to use those labeled with lot number NAR0074 and serial number 430834149057. Some of these counterfeit products may still be available for purchase, the FDA said in a statement.
Together with Ozempic manufacturer Novo Nordisk, the FDA is investigating “thousands of units” of the 1-mg injection product. Information is not yet available regarding the drugs’ identity, quality, or safety. However, the pen needles have been confirmed as fake — thereby raising the potential risk for infection — as have the pen labels, accompanying health care professional and patient label information, and carton.
“FDA takes reports of possible counterfeit products seriously and works closely with other federal agencies and the private sector to help protect the nation’s drug supply. FDA’s investigation is ongoing, and the agency is working with Novo Nordisk to identify, investigate, and remove further suspected counterfeit semaglutide injectable products found in the US,” the statement says.
Patients are advised to only obtain Ozempic with a valid prescription through state-licensed pharmacies and to check the product before using for any signs of counterfeiting. There are several differences between the genuine and counterfeit products in the way the pen needle is packaged. The most obvious is that the paper tab covering the fake needle says “Novofine®” whereas the genuine one says “Novofine® Plus.”
There have been at least five adverse events reported from this lot; none were serious and all were consistent with gastrointestinal issues known to occur with the genuine product.
Counterfeit products should be reported to the FDA ‘s consumer complaint coordinator or to the criminal activity division.
A version of this article first appeared on Medscape.com.
Spending the Holidays With GLP-1 Receptor Agonists: 5 Things to Know
As an endocrinologist, I treat many patients who have diabetes, obesity, or both. Antiobesity medications, particularly the class of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), are our first support tools when nutrition and physical activity aren’t enough.
1. Be mindful of fullness cues.
GLP-1 RAs increase satiety; they help patients feel fuller sooner within a meal and longer in between meals. This means consuming the “usual” at a holiday gathering makes them feel as if they ate too much, and often this will result in more side effects, such as nausea and reflux.
Patient tip: A good rule of thumb is to anticipate feeling full with half of your usual portion. Start with half a plate and reassess your hunger level after finishing.
2. Distinguish between hunger and “food noise.”
Ask your patients, “Do you ever find yourself eating even when you’re not hungry?” Many people eat because of emotions (eg, stress, anxiety, happiness), social situations, or cultural expectations. This type of food consumption is what scientists call “hedonic food intake” and may be driven by the “food noise” that patients describe as persistent thoughts about food in the absence of physiologic hunger. Semaglutide (Ozempic, Wegovy) has been found to reduce cravings, though other research has shown that emotional eating may blunt the effect of GLP-1 RAs.
Patient tip: Recognize when you might be seeking food for reasons other than hunger, and try a different way to address the cue (eg, chat with a friend or family member, go for a walk).
3. Be careful with alcohol.
GLP-1 RAs are being researched as potential treatments for alcohol use disorder. Many patients report less interest in alcohol and a lower tolerance to alcohol when they are taking a GLP-1 RA. Additionally, GLP-1 RAs may be a risk factor for pancreatitis, which can be caused by consuming too much alcohol.
Patient tip: The standard recommendation remains true: If drinking alcohol, limit to one to two servings per day, but also know that reduced intake or interest is normal when taking a GLP-1 RA.
4. Be aware of sickness vs side effects.
With holiday travel and the winter season, it is common for people to catch a cold or a stomach bug. Symptoms of common illnesses might include fatigue, loss of appetite, or diarrhea. These symptoms overlap with side effects of antiobesity medications like semaglutide and tirzepatide.
Patient tip: If you are experiencing constitutional or gastrointestinal symptoms due to illness, speak with your board-certified obesity medicine doctor, who may recommend a temporary medication adjustment to avoid excess side effects.
5. Stay strong against weight stigma.
The holiday season can be a stressful time, especially as patients are reconnecting with people who have not been a part of their health or weight loss journey. Unfortunately, weight bias and weight stigma remain rampant. Many people don’t understand the biology of obesity and refuse to accept the necessity of medical treatment. They may be surrounded by opinions, often louder and less informed.
Patient tip: Remember that obesity is a medical disease. Tell your nosy cousin that it’s a private health matter and that your decisions are your own.
Dr. Tchang is Assistant Professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine; Physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York, NY. She disclosed financial relationships with Gelesis and Novo Nordisk.
A version of this article appeared on Medscape.com.
As an endocrinologist, I treat many patients who have diabetes, obesity, or both. Antiobesity medications, particularly the class of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), are our first support tools when nutrition and physical activity aren’t enough.
1. Be mindful of fullness cues.
GLP-1 RAs increase satiety; they help patients feel fuller sooner within a meal and longer in between meals. This means consuming the “usual” at a holiday gathering makes them feel as if they ate too much, and often this will result in more side effects, such as nausea and reflux.
Patient tip: A good rule of thumb is to anticipate feeling full with half of your usual portion. Start with half a plate and reassess your hunger level after finishing.
2. Distinguish between hunger and “food noise.”
Ask your patients, “Do you ever find yourself eating even when you’re not hungry?” Many people eat because of emotions (eg, stress, anxiety, happiness), social situations, or cultural expectations. This type of food consumption is what scientists call “hedonic food intake” and may be driven by the “food noise” that patients describe as persistent thoughts about food in the absence of physiologic hunger. Semaglutide (Ozempic, Wegovy) has been found to reduce cravings, though other research has shown that emotional eating may blunt the effect of GLP-1 RAs.
Patient tip: Recognize when you might be seeking food for reasons other than hunger, and try a different way to address the cue (eg, chat with a friend or family member, go for a walk).
3. Be careful with alcohol.
GLP-1 RAs are being researched as potential treatments for alcohol use disorder. Many patients report less interest in alcohol and a lower tolerance to alcohol when they are taking a GLP-1 RA. Additionally, GLP-1 RAs may be a risk factor for pancreatitis, which can be caused by consuming too much alcohol.
Patient tip: The standard recommendation remains true: If drinking alcohol, limit to one to two servings per day, but also know that reduced intake or interest is normal when taking a GLP-1 RA.
4. Be aware of sickness vs side effects.
With holiday travel and the winter season, it is common for people to catch a cold or a stomach bug. Symptoms of common illnesses might include fatigue, loss of appetite, or diarrhea. These symptoms overlap with side effects of antiobesity medications like semaglutide and tirzepatide.
Patient tip: If you are experiencing constitutional or gastrointestinal symptoms due to illness, speak with your board-certified obesity medicine doctor, who may recommend a temporary medication adjustment to avoid excess side effects.
5. Stay strong against weight stigma.
The holiday season can be a stressful time, especially as patients are reconnecting with people who have not been a part of their health or weight loss journey. Unfortunately, weight bias and weight stigma remain rampant. Many people don’t understand the biology of obesity and refuse to accept the necessity of medical treatment. They may be surrounded by opinions, often louder and less informed.
Patient tip: Remember that obesity is a medical disease. Tell your nosy cousin that it’s a private health matter and that your decisions are your own.
Dr. Tchang is Assistant Professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine; Physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York, NY. She disclosed financial relationships with Gelesis and Novo Nordisk.
A version of this article appeared on Medscape.com.
As an endocrinologist, I treat many patients who have diabetes, obesity, or both. Antiobesity medications, particularly the class of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), are our first support tools when nutrition and physical activity aren’t enough.
1. Be mindful of fullness cues.
GLP-1 RAs increase satiety; they help patients feel fuller sooner within a meal and longer in between meals. This means consuming the “usual” at a holiday gathering makes them feel as if they ate too much, and often this will result in more side effects, such as nausea and reflux.
Patient tip: A good rule of thumb is to anticipate feeling full with half of your usual portion. Start with half a plate and reassess your hunger level after finishing.
2. Distinguish between hunger and “food noise.”
Ask your patients, “Do you ever find yourself eating even when you’re not hungry?” Many people eat because of emotions (eg, stress, anxiety, happiness), social situations, or cultural expectations. This type of food consumption is what scientists call “hedonic food intake” and may be driven by the “food noise” that patients describe as persistent thoughts about food in the absence of physiologic hunger. Semaglutide (Ozempic, Wegovy) has been found to reduce cravings, though other research has shown that emotional eating may blunt the effect of GLP-1 RAs.
Patient tip: Recognize when you might be seeking food for reasons other than hunger, and try a different way to address the cue (eg, chat with a friend or family member, go for a walk).
3. Be careful with alcohol.
GLP-1 RAs are being researched as potential treatments for alcohol use disorder. Many patients report less interest in alcohol and a lower tolerance to alcohol when they are taking a GLP-1 RA. Additionally, GLP-1 RAs may be a risk factor for pancreatitis, which can be caused by consuming too much alcohol.
Patient tip: The standard recommendation remains true: If drinking alcohol, limit to one to two servings per day, but also know that reduced intake or interest is normal when taking a GLP-1 RA.
4. Be aware of sickness vs side effects.
With holiday travel and the winter season, it is common for people to catch a cold or a stomach bug. Symptoms of common illnesses might include fatigue, loss of appetite, or diarrhea. These symptoms overlap with side effects of antiobesity medications like semaglutide and tirzepatide.
Patient tip: If you are experiencing constitutional or gastrointestinal symptoms due to illness, speak with your board-certified obesity medicine doctor, who may recommend a temporary medication adjustment to avoid excess side effects.
5. Stay strong against weight stigma.
The holiday season can be a stressful time, especially as patients are reconnecting with people who have not been a part of their health or weight loss journey. Unfortunately, weight bias and weight stigma remain rampant. Many people don’t understand the biology of obesity and refuse to accept the necessity of medical treatment. They may be surrounded by opinions, often louder and less informed.
Patient tip: Remember that obesity is a medical disease. Tell your nosy cousin that it’s a private health matter and that your decisions are your own.
Dr. Tchang is Assistant Professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine; Physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York, NY. She disclosed financial relationships with Gelesis and Novo Nordisk.
A version of this article appeared on Medscape.com.
ED Visits for Diabetes on the Rise in the US
Emergency department (ED) visits by adults with diabetes increased by more than 25% since 2012, with the highest rates among Blacks and those aged over 65 years, a new data brief from the Centers for Disease Control and Prevention’s National Center for Health Statistics shows.
In 2021, diabetes was the eighth leading cause of death in the United States, according to the brief, published online on December 19, 2023. Its frequency is increasing in young people, and increasing age is a risk factor for hospitalization.
The latest data show that in 2020-2021, the overall annual ED visit rate was 72.2 visits per 1000 adults with diabetes, with no significant difference in terms of sex (75.1 visits per 1000 women vs 69.1 visits per 1000 men). By race/ethnicity, Blacks had the highest rates, at 135.5 visits per 1000 adults, followed by Whites (69.9) and Hispanics (52.3). The rates increased with age for both women and men, and among the three race/ethnic groups.
Comorbidities Count
The most ED visits were made by patients with diabetes and two to four other chronic conditions (541.4 visits per 1000 visits). Rates for patients without other chronic conditions were the lowest (90.2).
Among individuals with diabetes aged 18-44 years, ED visit rates were the highest for those with two to four other chronic conditions (402.0) and lowest among those with five or more other conditions (93.8).
Among patients aged 45-64 years, ED visit rates were the highest for those with two to four other chronic conditions (526.4) and lowest for those without other conditions (87.7). In the 65 years and older group, rates were the highest for individuals with two to four other chronic conditions (605.2), followed by five or more conditions (217.7), one other condition (140.6), and no other conditions (36.5).
Notably, the ED visit rates for those with two to four or five or more other chronic conditions increased with age, whereas visits for those with no other chronic conditions or one other condition decreased with age.
Decade-Long Trend
ED visit rates among adults with diabetes increased throughout the past decade, from 48.6 visits per 1000 adults in 2012 to 74.9 per 1000 adults in 2021. Rates for those aged 65 and older were higher than all other age groups, increasing from 113.4 to 156.8. Increases were also seen among those aged 45-64 years (53.1 in 2012 to 89.2 in 2021) and 18-44 (20.9 in 2012 to 26.4 in 2016, then plateauing from 2016-2021).
Data are based on a sample of 4051 ED visits, representing about 18,238,000 average annual visits made by adults with diabetes to nonfederal, general, and short-stay hospitals during 2020-2021.
Taken together, these most recent estimates “show an increasing trend in rates by adults with diabetes in the ED setting,” the authors concluded.
A version of this article appeared on Medscape.com.
Emergency department (ED) visits by adults with diabetes increased by more than 25% since 2012, with the highest rates among Blacks and those aged over 65 years, a new data brief from the Centers for Disease Control and Prevention’s National Center for Health Statistics shows.
In 2021, diabetes was the eighth leading cause of death in the United States, according to the brief, published online on December 19, 2023. Its frequency is increasing in young people, and increasing age is a risk factor for hospitalization.
The latest data show that in 2020-2021, the overall annual ED visit rate was 72.2 visits per 1000 adults with diabetes, with no significant difference in terms of sex (75.1 visits per 1000 women vs 69.1 visits per 1000 men). By race/ethnicity, Blacks had the highest rates, at 135.5 visits per 1000 adults, followed by Whites (69.9) and Hispanics (52.3). The rates increased with age for both women and men, and among the three race/ethnic groups.
Comorbidities Count
The most ED visits were made by patients with diabetes and two to four other chronic conditions (541.4 visits per 1000 visits). Rates for patients without other chronic conditions were the lowest (90.2).
Among individuals with diabetes aged 18-44 years, ED visit rates were the highest for those with two to four other chronic conditions (402.0) and lowest among those with five or more other conditions (93.8).
Among patients aged 45-64 years, ED visit rates were the highest for those with two to four other chronic conditions (526.4) and lowest for those without other conditions (87.7). In the 65 years and older group, rates were the highest for individuals with two to four other chronic conditions (605.2), followed by five or more conditions (217.7), one other condition (140.6), and no other conditions (36.5).
Notably, the ED visit rates for those with two to four or five or more other chronic conditions increased with age, whereas visits for those with no other chronic conditions or one other condition decreased with age.
Decade-Long Trend
ED visit rates among adults with diabetes increased throughout the past decade, from 48.6 visits per 1000 adults in 2012 to 74.9 per 1000 adults in 2021. Rates for those aged 65 and older were higher than all other age groups, increasing from 113.4 to 156.8. Increases were also seen among those aged 45-64 years (53.1 in 2012 to 89.2 in 2021) and 18-44 (20.9 in 2012 to 26.4 in 2016, then plateauing from 2016-2021).
Data are based on a sample of 4051 ED visits, representing about 18,238,000 average annual visits made by adults with diabetes to nonfederal, general, and short-stay hospitals during 2020-2021.
Taken together, these most recent estimates “show an increasing trend in rates by adults with diabetes in the ED setting,” the authors concluded.
A version of this article appeared on Medscape.com.
Emergency department (ED) visits by adults with diabetes increased by more than 25% since 2012, with the highest rates among Blacks and those aged over 65 years, a new data brief from the Centers for Disease Control and Prevention’s National Center for Health Statistics shows.
In 2021, diabetes was the eighth leading cause of death in the United States, according to the brief, published online on December 19, 2023. Its frequency is increasing in young people, and increasing age is a risk factor for hospitalization.
The latest data show that in 2020-2021, the overall annual ED visit rate was 72.2 visits per 1000 adults with diabetes, with no significant difference in terms of sex (75.1 visits per 1000 women vs 69.1 visits per 1000 men). By race/ethnicity, Blacks had the highest rates, at 135.5 visits per 1000 adults, followed by Whites (69.9) and Hispanics (52.3). The rates increased with age for both women and men, and among the three race/ethnic groups.
Comorbidities Count
The most ED visits were made by patients with diabetes and two to four other chronic conditions (541.4 visits per 1000 visits). Rates for patients without other chronic conditions were the lowest (90.2).
Among individuals with diabetes aged 18-44 years, ED visit rates were the highest for those with two to four other chronic conditions (402.0) and lowest among those with five or more other conditions (93.8).
Among patients aged 45-64 years, ED visit rates were the highest for those with two to four other chronic conditions (526.4) and lowest for those without other conditions (87.7). In the 65 years and older group, rates were the highest for individuals with two to four other chronic conditions (605.2), followed by five or more conditions (217.7), one other condition (140.6), and no other conditions (36.5).
Notably, the ED visit rates for those with two to four or five or more other chronic conditions increased with age, whereas visits for those with no other chronic conditions or one other condition decreased with age.
Decade-Long Trend
ED visit rates among adults with diabetes increased throughout the past decade, from 48.6 visits per 1000 adults in 2012 to 74.9 per 1000 adults in 2021. Rates for those aged 65 and older were higher than all other age groups, increasing from 113.4 to 156.8. Increases were also seen among those aged 45-64 years (53.1 in 2012 to 89.2 in 2021) and 18-44 (20.9 in 2012 to 26.4 in 2016, then plateauing from 2016-2021).
Data are based on a sample of 4051 ED visits, representing about 18,238,000 average annual visits made by adults with diabetes to nonfederal, general, and short-stay hospitals during 2020-2021.
Taken together, these most recent estimates “show an increasing trend in rates by adults with diabetes in the ED setting,” the authors concluded.
A version of this article appeared on Medscape.com.
GLP-1 RAs Associated With Reduced Colorectal Cancer Risk in Patients With Type 2 Diabetes
according to a new analysis.
In particular, GLP-1 RAs were associated with decreased risk compared with other antidiabetic treatments, including insulin, metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, sulfonylureas, and thiazolidinediones.
More profound effects were seen in patients with overweight or obesity, “suggesting a potential protective effect against CRC partially mediated by weight loss and other mechanisms related to weight loss,” Lindsey Wang, an undergraduate student at Case Western Reserve University, Cleveland, Ohio, and colleagues wrote in JAMA Oncology.
Testing Treatments
GLP-1 RAs, usually given by injection, are approved by the US Food and Drug Administration to treat type 2 diabetes. They can lower blood sugar levels, improve insulin sensitivity, and help patients manage their weight.
Diabetes, overweight, and obesity are known risk factors for CRC and make prognosis worse. Ms. Wang and colleagues hypothesized that GLP-1 RAs might reduce CRC risk compared with other antidiabetics, including metformin and insulin, which have also been shown to reduce CRC risk.
Using a national database of more than 101 million electronic health records, Ms. Wang and colleagues conducted a population-based study of more than 1.2 million patients who had medical encounters for type 2 diabetes and were subsequently prescribed antidiabetic medications between 2005 and 2019. The patients had no prior antidiabetic medication use nor CRC diagnosis.
The researchers analyzed the effects of GLP-1 RAs on CRC incidence compared with the other prescribed antidiabetic drugs, matching for demographics, adverse socioeconomic determinants of health, preexisting medical conditions, family and personal history of cancers and colonic polyps, lifestyle factors, and procedures such as colonoscopy.
During a 15-year follow-up, GLP-1 RAs were associated with decreased risk for CRC compared with insulin (hazard ratio [HR], 0.56), metformin (HR, 0.75), SGLT2 inhibitors (HR, 0.77), sulfonylureas (HR, 0.82), and thiazolidinediones (HR, 0.82) in the overall study population.
For instance, among 22,572 patients who took insulin, 167 cases of CRC occurred, compared with 94 cases among the matched GLP-1 RA cohort. Among 18,518 patients who took metformin, 153 cases of CRC occurred compared with 96 cases among the matched GLP-1 RA cohort.
GLP-1 RAs also were associated with lower but not statistically significant risk than alpha-glucosidase inhibitors (HR, 0.59) and dipeptidyl-peptidase-4 (DPP-4) inhibitors (HR, 0.93).
In patients with overweight or obesity, GLP-1 RAs were associated with a lower risk for CRC than most of the other antidiabetics, including insulin (HR, 0.5), metformin (HR, 0.58), SGLT2 inhibitors (HR, 0.68), sulfonylureas (HR, 0.63), thiazolidinediones (HR, 0.73), and DPP-4 inhibitors (HR, 0.77).
Consistent findings were observed in women and men.
“Our results clearly demonstrate that GLP-1 RAs are significantly more effective than popular antidiabetic drugs, such as metformin or insulin, at preventing the development of CRC,” said Nathan Berger, MD, co-lead researcher, professor of experimental medicine, and member of the Case Comprehensive Cancer Center.
Targets for Future Research
Study limitations include potential unmeasured or uncontrolled confounders, self-selection, reverse causality, and other biases involved in observational studies, the research team noted.
Further research is warranted to investigate the effects in patients with prior antidiabetic treatments, underlying mechanisms, potential variation in effects among different GLP-1 RAs, and the potential of GLP-1 RAs to reduce the risks for other obesity-associated cancers, the researchers wrote.
“To our knowledge, this is the first indication this popular weight loss and antidiabetic class of drugs reduces incidence of CRC, relative to other antidiabetic agents,” said Rong Xu, PhD, co-lead researcher, professor of medicine, and member of the Case Comprehensive Cancer Center.
The study was supported by the National Cancer Institute Case Comprehensive Cancer Center, American Cancer Society, Landon Foundation-American Association for Cancer Research, National Institutes of Health Director’s New Innovator Award Program, National Institute on Aging, and National Institute on Alcohol Abuse and Alcoholism. Several authors reported grants from the National Institutes of Health during the conduct of the study.
A version of this article appeared on Medscape.com.
according to a new analysis.
In particular, GLP-1 RAs were associated with decreased risk compared with other antidiabetic treatments, including insulin, metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, sulfonylureas, and thiazolidinediones.
More profound effects were seen in patients with overweight or obesity, “suggesting a potential protective effect against CRC partially mediated by weight loss and other mechanisms related to weight loss,” Lindsey Wang, an undergraduate student at Case Western Reserve University, Cleveland, Ohio, and colleagues wrote in JAMA Oncology.
Testing Treatments
GLP-1 RAs, usually given by injection, are approved by the US Food and Drug Administration to treat type 2 diabetes. They can lower blood sugar levels, improve insulin sensitivity, and help patients manage their weight.
Diabetes, overweight, and obesity are known risk factors for CRC and make prognosis worse. Ms. Wang and colleagues hypothesized that GLP-1 RAs might reduce CRC risk compared with other antidiabetics, including metformin and insulin, which have also been shown to reduce CRC risk.
Using a national database of more than 101 million electronic health records, Ms. Wang and colleagues conducted a population-based study of more than 1.2 million patients who had medical encounters for type 2 diabetes and were subsequently prescribed antidiabetic medications between 2005 and 2019. The patients had no prior antidiabetic medication use nor CRC diagnosis.
The researchers analyzed the effects of GLP-1 RAs on CRC incidence compared with the other prescribed antidiabetic drugs, matching for demographics, adverse socioeconomic determinants of health, preexisting medical conditions, family and personal history of cancers and colonic polyps, lifestyle factors, and procedures such as colonoscopy.
During a 15-year follow-up, GLP-1 RAs were associated with decreased risk for CRC compared with insulin (hazard ratio [HR], 0.56), metformin (HR, 0.75), SGLT2 inhibitors (HR, 0.77), sulfonylureas (HR, 0.82), and thiazolidinediones (HR, 0.82) in the overall study population.
For instance, among 22,572 patients who took insulin, 167 cases of CRC occurred, compared with 94 cases among the matched GLP-1 RA cohort. Among 18,518 patients who took metformin, 153 cases of CRC occurred compared with 96 cases among the matched GLP-1 RA cohort.
GLP-1 RAs also were associated with lower but not statistically significant risk than alpha-glucosidase inhibitors (HR, 0.59) and dipeptidyl-peptidase-4 (DPP-4) inhibitors (HR, 0.93).
In patients with overweight or obesity, GLP-1 RAs were associated with a lower risk for CRC than most of the other antidiabetics, including insulin (HR, 0.5), metformin (HR, 0.58), SGLT2 inhibitors (HR, 0.68), sulfonylureas (HR, 0.63), thiazolidinediones (HR, 0.73), and DPP-4 inhibitors (HR, 0.77).
Consistent findings were observed in women and men.
“Our results clearly demonstrate that GLP-1 RAs are significantly more effective than popular antidiabetic drugs, such as metformin or insulin, at preventing the development of CRC,” said Nathan Berger, MD, co-lead researcher, professor of experimental medicine, and member of the Case Comprehensive Cancer Center.
Targets for Future Research
Study limitations include potential unmeasured or uncontrolled confounders, self-selection, reverse causality, and other biases involved in observational studies, the research team noted.
Further research is warranted to investigate the effects in patients with prior antidiabetic treatments, underlying mechanisms, potential variation in effects among different GLP-1 RAs, and the potential of GLP-1 RAs to reduce the risks for other obesity-associated cancers, the researchers wrote.
“To our knowledge, this is the first indication this popular weight loss and antidiabetic class of drugs reduces incidence of CRC, relative to other antidiabetic agents,” said Rong Xu, PhD, co-lead researcher, professor of medicine, and member of the Case Comprehensive Cancer Center.
The study was supported by the National Cancer Institute Case Comprehensive Cancer Center, American Cancer Society, Landon Foundation-American Association for Cancer Research, National Institutes of Health Director’s New Innovator Award Program, National Institute on Aging, and National Institute on Alcohol Abuse and Alcoholism. Several authors reported grants from the National Institutes of Health during the conduct of the study.
A version of this article appeared on Medscape.com.
according to a new analysis.
In particular, GLP-1 RAs were associated with decreased risk compared with other antidiabetic treatments, including insulin, metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, sulfonylureas, and thiazolidinediones.
More profound effects were seen in patients with overweight or obesity, “suggesting a potential protective effect against CRC partially mediated by weight loss and other mechanisms related to weight loss,” Lindsey Wang, an undergraduate student at Case Western Reserve University, Cleveland, Ohio, and colleagues wrote in JAMA Oncology.
Testing Treatments
GLP-1 RAs, usually given by injection, are approved by the US Food and Drug Administration to treat type 2 diabetes. They can lower blood sugar levels, improve insulin sensitivity, and help patients manage their weight.
Diabetes, overweight, and obesity are known risk factors for CRC and make prognosis worse. Ms. Wang and colleagues hypothesized that GLP-1 RAs might reduce CRC risk compared with other antidiabetics, including metformin and insulin, which have also been shown to reduce CRC risk.
Using a national database of more than 101 million electronic health records, Ms. Wang and colleagues conducted a population-based study of more than 1.2 million patients who had medical encounters for type 2 diabetes and were subsequently prescribed antidiabetic medications between 2005 and 2019. The patients had no prior antidiabetic medication use nor CRC diagnosis.
The researchers analyzed the effects of GLP-1 RAs on CRC incidence compared with the other prescribed antidiabetic drugs, matching for demographics, adverse socioeconomic determinants of health, preexisting medical conditions, family and personal history of cancers and colonic polyps, lifestyle factors, and procedures such as colonoscopy.
During a 15-year follow-up, GLP-1 RAs were associated with decreased risk for CRC compared with insulin (hazard ratio [HR], 0.56), metformin (HR, 0.75), SGLT2 inhibitors (HR, 0.77), sulfonylureas (HR, 0.82), and thiazolidinediones (HR, 0.82) in the overall study population.
For instance, among 22,572 patients who took insulin, 167 cases of CRC occurred, compared with 94 cases among the matched GLP-1 RA cohort. Among 18,518 patients who took metformin, 153 cases of CRC occurred compared with 96 cases among the matched GLP-1 RA cohort.
GLP-1 RAs also were associated with lower but not statistically significant risk than alpha-glucosidase inhibitors (HR, 0.59) and dipeptidyl-peptidase-4 (DPP-4) inhibitors (HR, 0.93).
In patients with overweight or obesity, GLP-1 RAs were associated with a lower risk for CRC than most of the other antidiabetics, including insulin (HR, 0.5), metformin (HR, 0.58), SGLT2 inhibitors (HR, 0.68), sulfonylureas (HR, 0.63), thiazolidinediones (HR, 0.73), and DPP-4 inhibitors (HR, 0.77).
Consistent findings were observed in women and men.
“Our results clearly demonstrate that GLP-1 RAs are significantly more effective than popular antidiabetic drugs, such as metformin or insulin, at preventing the development of CRC,” said Nathan Berger, MD, co-lead researcher, professor of experimental medicine, and member of the Case Comprehensive Cancer Center.
Targets for Future Research
Study limitations include potential unmeasured or uncontrolled confounders, self-selection, reverse causality, and other biases involved in observational studies, the research team noted.
Further research is warranted to investigate the effects in patients with prior antidiabetic treatments, underlying mechanisms, potential variation in effects among different GLP-1 RAs, and the potential of GLP-1 RAs to reduce the risks for other obesity-associated cancers, the researchers wrote.
“To our knowledge, this is the first indication this popular weight loss and antidiabetic class of drugs reduces incidence of CRC, relative to other antidiabetic agents,” said Rong Xu, PhD, co-lead researcher, professor of medicine, and member of the Case Comprehensive Cancer Center.
The study was supported by the National Cancer Institute Case Comprehensive Cancer Center, American Cancer Society, Landon Foundation-American Association for Cancer Research, National Institutes of Health Director’s New Innovator Award Program, National Institute on Aging, and National Institute on Alcohol Abuse and Alcoholism. Several authors reported grants from the National Institutes of Health during the conduct of the study.
A version of this article appeared on Medscape.com.
‘We Will Rock You’ Into Real-time Diabetes Control
, reveals a series of experiments.
The research was published in The Lancet Diabetes & Endocrinology.
After developing a cell line in which music-sensitive calcium channels triggered the release of insulin-containing vesicles, the researchers conducted a series of studies identifying the optimal frequency, pitch, and volume of sounds for triggering release.
After settling on low-bass heavy popular music, they tested their system on mice with type 1 diabetes that had the insulin-releasing cells implanted in their abdomen. Applying the music directly at 60 dB led to near wild-type levels of insulin in the blood within 15 minutes.
“With only 4 hours required for a full refill, [the system] can provide several therapeutic doses a day,” says Martin Fussenegger, PhD, professor of biotechnology and bioengineering, Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland, and colleagues.
“This would match the typical needs of people with type 2 diabetes consuming three meals a day, and for whom administration of prandial insulin is an established treatment option, as they do not have capability for early postprandial insulin secretion from preformed insulin.”
As the system requires nothing more than portable battery-powered commercially available loudspeakers, the multiple daily dosing of biopharmaceuticals becomes “straightforward in the absence of medical infrastructure or staff, simply by having the patient listen to the prescribed music.”
It therefore “could be an interesting option for cell-based therapies, especially where the need for frequent dosing raises compliance issues.”
It is a “very exciting piece of work, no doubt,” said Anandwardhan A. Hardikar, PhD, group leader, Diabetes and Islet Biology Group, Translational Health Research Institute, Western Sydney University, Penrith NSW, Australia.
He pointed out that the concept of using music to drive gene expression “is something we’ve known for the last 20 years,” but bringing the different strands of research together to generate cells that can be implanted into mice is “an amazing idea.”
Dr. Hardikar, who was not involved in the study, said, however, the publication of the study as a correspondence “does not allow for a lot of the detail that I would have expected as an academic,” and consequently some questions remain.
The most important is whether the music itself is required to trigger the insulin release, as opposed simply to sounds in general.
Is Music or Sound the “Trigger?”
Music is “frequency, it’s the amplitude of the waveform, and it’s the duration for which those waveforms are present,” he noted, but the same profile can be achieved by cutting up and editing the melody so it becomes a jumble of sounds.
For Dr. Hardikar, the “best control” for the study would be to have no music as well as the edited song, with “bits of pieces” played randomly so “it sounds like it’s the same frequency and amplitude.”
Then it would be clear whether the effect is owing to the “noise, or we have to appreciate the melody.”
The other outstanding question is whether the results “can directly translate to larger animals,” such as humans, Dr. Hardikar said.
The authors point out that when translated into mechanical vibrations in the middle ear, the acoustic waves of music activate mechanosensitive ion channels, a form of trigger that is seen across the animal kingdom.
They go on to highlight that while gene switches have been developed for use in next-generation cell-based therapies for a range of conditions, small-molecular trigger compounds face a number of challenges and may cause adverse effects.
With “traceless triggers” such as light, ultrasound, magnetic fields, radio waves, electricity, and heat also facing issues, there is a “need for new switching modalities.”
The researchers therefore developed a music-inducible cellular control (MUSIC) system, which leverages the known intracellular calcium surge in response to music, via calcium-permeable mechanosensitive channels, to drive the release of biopharmaceuticals from vesicles.
They then generated MUSIC-controlled insulin-releasing cell lines, finding that, using a customized box containing off-the-shelf loudspeakers, they could induce channel activation and insulin release with 60 dB at 50 Hz, which is “within the safe range for the human ear.”
Further experiments revealed that insulin release was greatest at 50-100 Hz, and higher than that seen with potassium chloride, the “gold-standard” depolarization control for calcium channels.
The researchers then showed that with optimal stimulation at 50 Hz and 60 dB, channel activation and subsequent insulin release required at least 3 seconds of continuous music, “which might protect the cellular device from inadvertent activation during everyday activities.”
Next, they examined the impact of different musical genres on insulin release, finding that low-bass heavy popular music and movie soundtracks induced maximum release, while the responses were more diverse to classical and guitar-based music.
Specifically, “We Will Rock You,” by the British rock band Queen, induced the release of 70% of available insulin within 5 minutes and 100% within 15 minutes. This, the team notes, is “similar to the dynamics of glucose-triggered insulin release by human pancreatic islets.”
Exposing the cells to a second music session at different intervals revealed that full insulin refill was achieved within 4 hours, which “would be appropriate to attenuate glycemic excursions associated with typical dietary habits.”
Finally, the researchers tested the system in vivo, constructing a box with two off-the-shelf loudspeakers that focuses acoustic waves, via deflectors, onto the abdomens of mice with type 1 diabetes.
Exposing the mice, which had been implanted with microencapsulated MUSIC cells in the peritoneum, to low-bass acoustic waves at 60 dB (50 m/s2) for 15 minutes allowed them to achieve near wild-type levels of insulin in the blood and restored normoglycemia.
Moreover, “Queen’s song ‘We Will Rock You’ generated sufficient insulin to rapidly attenuate postprandial glycemic excursions during glucose tolerance tests,” the team says.
In contrast, animals without implants, or those that had implants but did not have music immersion, remained severely hyperglycemic, they add.
They also note that the effect was seen only when the sound waves “directly impinge on the skin just above the implantation site” for at least 15 minutes, with no increase in insulin release observed with commercially available headphones or ear plugs, such as Apple AirPods, or with loud environmental noises.
Consequently, “therapeutic MUSIC sessions would still be compatible with listening to other types of music or listening to all types of music via headphones,” the researchers write, and are “compatible with standard drug administration schemes.”
The study was supported by a European Research Council advanced grant and in part by the Swiss National Science Foundation NCCR Molecular Systems Engineering. One author acknowledges the support of the Chinese Scholarship Council.
No relevant financial relationships were declared.
A version of this article appeared on Medscape.com.
, reveals a series of experiments.
The research was published in The Lancet Diabetes & Endocrinology.
After developing a cell line in which music-sensitive calcium channels triggered the release of insulin-containing vesicles, the researchers conducted a series of studies identifying the optimal frequency, pitch, and volume of sounds for triggering release.
After settling on low-bass heavy popular music, they tested their system on mice with type 1 diabetes that had the insulin-releasing cells implanted in their abdomen. Applying the music directly at 60 dB led to near wild-type levels of insulin in the blood within 15 minutes.
“With only 4 hours required for a full refill, [the system] can provide several therapeutic doses a day,” says Martin Fussenegger, PhD, professor of biotechnology and bioengineering, Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland, and colleagues.
“This would match the typical needs of people with type 2 diabetes consuming three meals a day, and for whom administration of prandial insulin is an established treatment option, as they do not have capability for early postprandial insulin secretion from preformed insulin.”
As the system requires nothing more than portable battery-powered commercially available loudspeakers, the multiple daily dosing of biopharmaceuticals becomes “straightforward in the absence of medical infrastructure or staff, simply by having the patient listen to the prescribed music.”
It therefore “could be an interesting option for cell-based therapies, especially where the need for frequent dosing raises compliance issues.”
It is a “very exciting piece of work, no doubt,” said Anandwardhan A. Hardikar, PhD, group leader, Diabetes and Islet Biology Group, Translational Health Research Institute, Western Sydney University, Penrith NSW, Australia.
He pointed out that the concept of using music to drive gene expression “is something we’ve known for the last 20 years,” but bringing the different strands of research together to generate cells that can be implanted into mice is “an amazing idea.”
Dr. Hardikar, who was not involved in the study, said, however, the publication of the study as a correspondence “does not allow for a lot of the detail that I would have expected as an academic,” and consequently some questions remain.
The most important is whether the music itself is required to trigger the insulin release, as opposed simply to sounds in general.
Is Music or Sound the “Trigger?”
Music is “frequency, it’s the amplitude of the waveform, and it’s the duration for which those waveforms are present,” he noted, but the same profile can be achieved by cutting up and editing the melody so it becomes a jumble of sounds.
For Dr. Hardikar, the “best control” for the study would be to have no music as well as the edited song, with “bits of pieces” played randomly so “it sounds like it’s the same frequency and amplitude.”
Then it would be clear whether the effect is owing to the “noise, or we have to appreciate the melody.”
The other outstanding question is whether the results “can directly translate to larger animals,” such as humans, Dr. Hardikar said.
The authors point out that when translated into mechanical vibrations in the middle ear, the acoustic waves of music activate mechanosensitive ion channels, a form of trigger that is seen across the animal kingdom.
They go on to highlight that while gene switches have been developed for use in next-generation cell-based therapies for a range of conditions, small-molecular trigger compounds face a number of challenges and may cause adverse effects.
With “traceless triggers” such as light, ultrasound, magnetic fields, radio waves, electricity, and heat also facing issues, there is a “need for new switching modalities.”
The researchers therefore developed a music-inducible cellular control (MUSIC) system, which leverages the known intracellular calcium surge in response to music, via calcium-permeable mechanosensitive channels, to drive the release of biopharmaceuticals from vesicles.
They then generated MUSIC-controlled insulin-releasing cell lines, finding that, using a customized box containing off-the-shelf loudspeakers, they could induce channel activation and insulin release with 60 dB at 50 Hz, which is “within the safe range for the human ear.”
Further experiments revealed that insulin release was greatest at 50-100 Hz, and higher than that seen with potassium chloride, the “gold-standard” depolarization control for calcium channels.
The researchers then showed that with optimal stimulation at 50 Hz and 60 dB, channel activation and subsequent insulin release required at least 3 seconds of continuous music, “which might protect the cellular device from inadvertent activation during everyday activities.”
Next, they examined the impact of different musical genres on insulin release, finding that low-bass heavy popular music and movie soundtracks induced maximum release, while the responses were more diverse to classical and guitar-based music.
Specifically, “We Will Rock You,” by the British rock band Queen, induced the release of 70% of available insulin within 5 minutes and 100% within 15 minutes. This, the team notes, is “similar to the dynamics of glucose-triggered insulin release by human pancreatic islets.”
Exposing the cells to a second music session at different intervals revealed that full insulin refill was achieved within 4 hours, which “would be appropriate to attenuate glycemic excursions associated with typical dietary habits.”
Finally, the researchers tested the system in vivo, constructing a box with two off-the-shelf loudspeakers that focuses acoustic waves, via deflectors, onto the abdomens of mice with type 1 diabetes.
Exposing the mice, which had been implanted with microencapsulated MUSIC cells in the peritoneum, to low-bass acoustic waves at 60 dB (50 m/s2) for 15 minutes allowed them to achieve near wild-type levels of insulin in the blood and restored normoglycemia.
Moreover, “Queen’s song ‘We Will Rock You’ generated sufficient insulin to rapidly attenuate postprandial glycemic excursions during glucose tolerance tests,” the team says.
In contrast, animals without implants, or those that had implants but did not have music immersion, remained severely hyperglycemic, they add.
They also note that the effect was seen only when the sound waves “directly impinge on the skin just above the implantation site” for at least 15 minutes, with no increase in insulin release observed with commercially available headphones or ear plugs, such as Apple AirPods, or with loud environmental noises.
Consequently, “therapeutic MUSIC sessions would still be compatible with listening to other types of music or listening to all types of music via headphones,” the researchers write, and are “compatible with standard drug administration schemes.”
The study was supported by a European Research Council advanced grant and in part by the Swiss National Science Foundation NCCR Molecular Systems Engineering. One author acknowledges the support of the Chinese Scholarship Council.
No relevant financial relationships were declared.
A version of this article appeared on Medscape.com.
, reveals a series of experiments.
The research was published in The Lancet Diabetes & Endocrinology.
After developing a cell line in which music-sensitive calcium channels triggered the release of insulin-containing vesicles, the researchers conducted a series of studies identifying the optimal frequency, pitch, and volume of sounds for triggering release.
After settling on low-bass heavy popular music, they tested their system on mice with type 1 diabetes that had the insulin-releasing cells implanted in their abdomen. Applying the music directly at 60 dB led to near wild-type levels of insulin in the blood within 15 minutes.
“With only 4 hours required for a full refill, [the system] can provide several therapeutic doses a day,” says Martin Fussenegger, PhD, professor of biotechnology and bioengineering, Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland, and colleagues.
“This would match the typical needs of people with type 2 diabetes consuming three meals a day, and for whom administration of prandial insulin is an established treatment option, as they do not have capability for early postprandial insulin secretion from preformed insulin.”
As the system requires nothing more than portable battery-powered commercially available loudspeakers, the multiple daily dosing of biopharmaceuticals becomes “straightforward in the absence of medical infrastructure or staff, simply by having the patient listen to the prescribed music.”
It therefore “could be an interesting option for cell-based therapies, especially where the need for frequent dosing raises compliance issues.”
It is a “very exciting piece of work, no doubt,” said Anandwardhan A. Hardikar, PhD, group leader, Diabetes and Islet Biology Group, Translational Health Research Institute, Western Sydney University, Penrith NSW, Australia.
He pointed out that the concept of using music to drive gene expression “is something we’ve known for the last 20 years,” but bringing the different strands of research together to generate cells that can be implanted into mice is “an amazing idea.”
Dr. Hardikar, who was not involved in the study, said, however, the publication of the study as a correspondence “does not allow for a lot of the detail that I would have expected as an academic,” and consequently some questions remain.
The most important is whether the music itself is required to trigger the insulin release, as opposed simply to sounds in general.
Is Music or Sound the “Trigger?”
Music is “frequency, it’s the amplitude of the waveform, and it’s the duration for which those waveforms are present,” he noted, but the same profile can be achieved by cutting up and editing the melody so it becomes a jumble of sounds.
For Dr. Hardikar, the “best control” for the study would be to have no music as well as the edited song, with “bits of pieces” played randomly so “it sounds like it’s the same frequency and amplitude.”
Then it would be clear whether the effect is owing to the “noise, or we have to appreciate the melody.”
The other outstanding question is whether the results “can directly translate to larger animals,” such as humans, Dr. Hardikar said.
The authors point out that when translated into mechanical vibrations in the middle ear, the acoustic waves of music activate mechanosensitive ion channels, a form of trigger that is seen across the animal kingdom.
They go on to highlight that while gene switches have been developed for use in next-generation cell-based therapies for a range of conditions, small-molecular trigger compounds face a number of challenges and may cause adverse effects.
With “traceless triggers” such as light, ultrasound, magnetic fields, radio waves, electricity, and heat also facing issues, there is a “need for new switching modalities.”
The researchers therefore developed a music-inducible cellular control (MUSIC) system, which leverages the known intracellular calcium surge in response to music, via calcium-permeable mechanosensitive channels, to drive the release of biopharmaceuticals from vesicles.
They then generated MUSIC-controlled insulin-releasing cell lines, finding that, using a customized box containing off-the-shelf loudspeakers, they could induce channel activation and insulin release with 60 dB at 50 Hz, which is “within the safe range for the human ear.”
Further experiments revealed that insulin release was greatest at 50-100 Hz, and higher than that seen with potassium chloride, the “gold-standard” depolarization control for calcium channels.
The researchers then showed that with optimal stimulation at 50 Hz and 60 dB, channel activation and subsequent insulin release required at least 3 seconds of continuous music, “which might protect the cellular device from inadvertent activation during everyday activities.”
Next, they examined the impact of different musical genres on insulin release, finding that low-bass heavy popular music and movie soundtracks induced maximum release, while the responses were more diverse to classical and guitar-based music.
Specifically, “We Will Rock You,” by the British rock band Queen, induced the release of 70% of available insulin within 5 minutes and 100% within 15 minutes. This, the team notes, is “similar to the dynamics of glucose-triggered insulin release by human pancreatic islets.”
Exposing the cells to a second music session at different intervals revealed that full insulin refill was achieved within 4 hours, which “would be appropriate to attenuate glycemic excursions associated with typical dietary habits.”
Finally, the researchers tested the system in vivo, constructing a box with two off-the-shelf loudspeakers that focuses acoustic waves, via deflectors, onto the abdomens of mice with type 1 diabetes.
Exposing the mice, which had been implanted with microencapsulated MUSIC cells in the peritoneum, to low-bass acoustic waves at 60 dB (50 m/s2) for 15 minutes allowed them to achieve near wild-type levels of insulin in the blood and restored normoglycemia.
Moreover, “Queen’s song ‘We Will Rock You’ generated sufficient insulin to rapidly attenuate postprandial glycemic excursions during glucose tolerance tests,” the team says.
In contrast, animals without implants, or those that had implants but did not have music immersion, remained severely hyperglycemic, they add.
They also note that the effect was seen only when the sound waves “directly impinge on the skin just above the implantation site” for at least 15 minutes, with no increase in insulin release observed with commercially available headphones or ear plugs, such as Apple AirPods, or with loud environmental noises.
Consequently, “therapeutic MUSIC sessions would still be compatible with listening to other types of music or listening to all types of music via headphones,” the researchers write, and are “compatible with standard drug administration schemes.”
The study was supported by a European Research Council advanced grant and in part by the Swiss National Science Foundation NCCR Molecular Systems Engineering. One author acknowledges the support of the Chinese Scholarship Council.
No relevant financial relationships were declared.
A version of this article appeared on Medscape.com.
FROM THE LANCET DIABETES & ENDOCRINOLOGY
Erectile Dysfunction Rx: Give It a Shot
This transcript has been edited for clarity.
I’m Dr Rachel Rubin. I am a urologist with fellowship training in sexual medicine. Today I’m going to explain why I may recommend that your patients put a needle directly into their penises for help with erectile dysfunction (ED).
I know that sounds crazy, but in a recent video when I talked about erection hardness, I acknowledged that it may not be easy to talk with patients about their penises, but it’s important.
ED can be a marker for cardiovascular disease, with 50% of our 50-year-old patients having ED. As physicians, we must do a better job of talking to our patients about ED and letting them know that it’s a marker for overall health.
How do we treat ED? Primary care doctors can do a great deal for patients with ED, and there are other things that urologists can do when you run out of options in your own toolbox.
What’s important for a healthy erection? You need three things: healthy muscle, healthy nerves, and healthy arteries. If anything goes wrong with muscles, nerves, or arteries, this is what leads to ED. Think through the algorithm of your patient’s medical history: Do they have diabetes, which can affect their nerves? Do they have high blood pressure, which can affect their arteries? Do they have problems with testosterone, which can affect the smooth muscles of the penis? Understanding your patient’s history can be really helpful when you figure out what is the best treatment strategy for your patient.
For the penis to work, those smooth muscles have to relax; therefore, your brain has to be relaxed, along with your pelvic floor muscles. The smooth muscle of the penis has to be relaxed so it can fill with blood, increase in girth and size, and hold that erection in place.
To treat ED, we have a biopsychosocial toolbox. Biology refers to the muscles, arteries, and nerves. The psychosocial component is stress: If your brain is stressed, you have a lot of adrenaline around that can tighten those smooth muscles and cause you to lose an erection.
So, what are these treatments? I’ll start with lifestyle. A healthy heart means a healthy penis, so, all of the things you already recommend for lifestyle changes can really help with ED. Sleep is important. Does your patient need a sleep study? Do they have sleep apnea? Are they exercising? Recent data show that exercise may be just as effective, if not more effective, than Viagra. How about a good diet? The Mediterranean diet seems to be the most helpful. So, encourage your patients to make dietary, exercise, sleep, and other lifestyle changes if they want to improve erectile function.
What about sex education? Most physicians didn’t get great education about sex in medical school, but it’s very important to our patients who likewise have had inadequate sex education. Ask questions, talk to them, explain what is normal.
I can’t stress enough how important mental health is to a great sex life. Everyone would benefit from sex therapy and becoming better at sex. We need to get better at communicating and educating patients and their partners to maximize their quality of life. If you need to refer to a specialist, we recommend going to psychologytoday.com or aasect.org to find a local sex therapist. Call them and use them in your referral networks.
In the “bio” component of the biopsychosocial approach, we can do a lot to treat ED with medications and hormones. Testosterone has been shown to help with low libido and erectile function. Checking the patient’s testosterone level can be very helpful. Pills — we are familiar with Viagra, Cialis, Levitra, and Stendra. The oral PDE-5 inhibitors have been around since the late 1990s and they work quite well for many people with ED. Viagra and Cialis are generic now and patients can get them fairly inexpensively with discount coupons from GoodRx or Cost Plus Drugs. They may not even have to worry about insurance coverage.
Pills relax the smooth muscle of the penis so that it fills with blood and becomes erect, but they don’t work for everybody. If pills stop working, we often talk about synergistic treatments — combining pills and devices. Devices for ED should be discussed more often, and clinicians should consider prescribing them. We commonly discuss eyeglasses and wheelchairs, but we don’t talk about the sexual health devices that could help patients have more success and fun in the bedroom.
What are the various types of devices for ED? One common device is a vacuum pump, which can be very effective. This is how they work: The penis is lubricated and placed into the pump. A button on the pump creates suction that brings blood into the penis. The patient then applies a constriction band around the base of the penis to hold that erection in place.
“Sex tech” has really expanded to help patients with ED with devices that vibrate and hold the erection in place. Vibrating devices allow for a better orgasm. We even have devices that monitor erectile fitness (like a Fitbit for the penis), gathering data to help patients understand the firmness of their erections.
Devices are helpful adjuncts, but they don’t always do enough to achieve an erect penis that’s hard enough for penetration. In those cases, we can recommend injections that increase smooth muscle relaxation of the penis. I know it sounds crazy. If the muscles, arteries, and nerves of the penis aren’t functioning well, additional smooth muscle relaxation can be achieved by injecting alprostadil (prostaglandin E1) directly into the penis. It’s a tiny needle. It doesn’t hurt. These injections can be quite helpful for our patients, and we often recommend them.
But what happens when your patient doesn’t even respond to injections or any of the synergistic treatments? They’ve tried everything. Urologists may suggest a surgical option, the penile implant. Penile implants contain a pump inside the scrotum that fills with fluid, allowing a rigid erection. Penile implants are wonderful for patients who can no longer get erections. Talking to a urologist about the pros and the cons and the risks and benefits of surgically placed implants is very important.
Finally, ED is a marker for cardiovascular disease. These patients may need a cardiology workup. They need to improve their general health. We have to ask our patients about their goals and what they care about, and find a toolbox that makes sense for each patient and couple to maximize their sexual health and quality of life. Don’t give up. If you have questions, let us know.
Rachel S. Rubin, MD, is Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC; Private practice, Rachel Rubin MD PLLC, North Bethesda, Maryland. She disclosed ties with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
I’m Dr Rachel Rubin. I am a urologist with fellowship training in sexual medicine. Today I’m going to explain why I may recommend that your patients put a needle directly into their penises for help with erectile dysfunction (ED).
I know that sounds crazy, but in a recent video when I talked about erection hardness, I acknowledged that it may not be easy to talk with patients about their penises, but it’s important.
ED can be a marker for cardiovascular disease, with 50% of our 50-year-old patients having ED. As physicians, we must do a better job of talking to our patients about ED and letting them know that it’s a marker for overall health.
How do we treat ED? Primary care doctors can do a great deal for patients with ED, and there are other things that urologists can do when you run out of options in your own toolbox.
What’s important for a healthy erection? You need three things: healthy muscle, healthy nerves, and healthy arteries. If anything goes wrong with muscles, nerves, or arteries, this is what leads to ED. Think through the algorithm of your patient’s medical history: Do they have diabetes, which can affect their nerves? Do they have high blood pressure, which can affect their arteries? Do they have problems with testosterone, which can affect the smooth muscles of the penis? Understanding your patient’s history can be really helpful when you figure out what is the best treatment strategy for your patient.
For the penis to work, those smooth muscles have to relax; therefore, your brain has to be relaxed, along with your pelvic floor muscles. The smooth muscle of the penis has to be relaxed so it can fill with blood, increase in girth and size, and hold that erection in place.
To treat ED, we have a biopsychosocial toolbox. Biology refers to the muscles, arteries, and nerves. The psychosocial component is stress: If your brain is stressed, you have a lot of adrenaline around that can tighten those smooth muscles and cause you to lose an erection.
So, what are these treatments? I’ll start with lifestyle. A healthy heart means a healthy penis, so, all of the things you already recommend for lifestyle changes can really help with ED. Sleep is important. Does your patient need a sleep study? Do they have sleep apnea? Are they exercising? Recent data show that exercise may be just as effective, if not more effective, than Viagra. How about a good diet? The Mediterranean diet seems to be the most helpful. So, encourage your patients to make dietary, exercise, sleep, and other lifestyle changes if they want to improve erectile function.
What about sex education? Most physicians didn’t get great education about sex in medical school, but it’s very important to our patients who likewise have had inadequate sex education. Ask questions, talk to them, explain what is normal.
I can’t stress enough how important mental health is to a great sex life. Everyone would benefit from sex therapy and becoming better at sex. We need to get better at communicating and educating patients and their partners to maximize their quality of life. If you need to refer to a specialist, we recommend going to psychologytoday.com or aasect.org to find a local sex therapist. Call them and use them in your referral networks.
In the “bio” component of the biopsychosocial approach, we can do a lot to treat ED with medications and hormones. Testosterone has been shown to help with low libido and erectile function. Checking the patient’s testosterone level can be very helpful. Pills — we are familiar with Viagra, Cialis, Levitra, and Stendra. The oral PDE-5 inhibitors have been around since the late 1990s and they work quite well for many people with ED. Viagra and Cialis are generic now and patients can get them fairly inexpensively with discount coupons from GoodRx or Cost Plus Drugs. They may not even have to worry about insurance coverage.
Pills relax the smooth muscle of the penis so that it fills with blood and becomes erect, but they don’t work for everybody. If pills stop working, we often talk about synergistic treatments — combining pills and devices. Devices for ED should be discussed more often, and clinicians should consider prescribing them. We commonly discuss eyeglasses and wheelchairs, but we don’t talk about the sexual health devices that could help patients have more success and fun in the bedroom.
What are the various types of devices for ED? One common device is a vacuum pump, which can be very effective. This is how they work: The penis is lubricated and placed into the pump. A button on the pump creates suction that brings blood into the penis. The patient then applies a constriction band around the base of the penis to hold that erection in place.
“Sex tech” has really expanded to help patients with ED with devices that vibrate and hold the erection in place. Vibrating devices allow for a better orgasm. We even have devices that monitor erectile fitness (like a Fitbit for the penis), gathering data to help patients understand the firmness of their erections.
Devices are helpful adjuncts, but they don’t always do enough to achieve an erect penis that’s hard enough for penetration. In those cases, we can recommend injections that increase smooth muscle relaxation of the penis. I know it sounds crazy. If the muscles, arteries, and nerves of the penis aren’t functioning well, additional smooth muscle relaxation can be achieved by injecting alprostadil (prostaglandin E1) directly into the penis. It’s a tiny needle. It doesn’t hurt. These injections can be quite helpful for our patients, and we often recommend them.
But what happens when your patient doesn’t even respond to injections or any of the synergistic treatments? They’ve tried everything. Urologists may suggest a surgical option, the penile implant. Penile implants contain a pump inside the scrotum that fills with fluid, allowing a rigid erection. Penile implants are wonderful for patients who can no longer get erections. Talking to a urologist about the pros and the cons and the risks and benefits of surgically placed implants is very important.
Finally, ED is a marker for cardiovascular disease. These patients may need a cardiology workup. They need to improve their general health. We have to ask our patients about their goals and what they care about, and find a toolbox that makes sense for each patient and couple to maximize their sexual health and quality of life. Don’t give up. If you have questions, let us know.
Rachel S. Rubin, MD, is Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC; Private practice, Rachel Rubin MD PLLC, North Bethesda, Maryland. She disclosed ties with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
I’m Dr Rachel Rubin. I am a urologist with fellowship training in sexual medicine. Today I’m going to explain why I may recommend that your patients put a needle directly into their penises for help with erectile dysfunction (ED).
I know that sounds crazy, but in a recent video when I talked about erection hardness, I acknowledged that it may not be easy to talk with patients about their penises, but it’s important.
ED can be a marker for cardiovascular disease, with 50% of our 50-year-old patients having ED. As physicians, we must do a better job of talking to our patients about ED and letting them know that it’s a marker for overall health.
How do we treat ED? Primary care doctors can do a great deal for patients with ED, and there are other things that urologists can do when you run out of options in your own toolbox.
What’s important for a healthy erection? You need three things: healthy muscle, healthy nerves, and healthy arteries. If anything goes wrong with muscles, nerves, or arteries, this is what leads to ED. Think through the algorithm of your patient’s medical history: Do they have diabetes, which can affect their nerves? Do they have high blood pressure, which can affect their arteries? Do they have problems with testosterone, which can affect the smooth muscles of the penis? Understanding your patient’s history can be really helpful when you figure out what is the best treatment strategy for your patient.
For the penis to work, those smooth muscles have to relax; therefore, your brain has to be relaxed, along with your pelvic floor muscles. The smooth muscle of the penis has to be relaxed so it can fill with blood, increase in girth and size, and hold that erection in place.
To treat ED, we have a biopsychosocial toolbox. Biology refers to the muscles, arteries, and nerves. The psychosocial component is stress: If your brain is stressed, you have a lot of adrenaline around that can tighten those smooth muscles and cause you to lose an erection.
So, what are these treatments? I’ll start with lifestyle. A healthy heart means a healthy penis, so, all of the things you already recommend for lifestyle changes can really help with ED. Sleep is important. Does your patient need a sleep study? Do they have sleep apnea? Are they exercising? Recent data show that exercise may be just as effective, if not more effective, than Viagra. How about a good diet? The Mediterranean diet seems to be the most helpful. So, encourage your patients to make dietary, exercise, sleep, and other lifestyle changes if they want to improve erectile function.
What about sex education? Most physicians didn’t get great education about sex in medical school, but it’s very important to our patients who likewise have had inadequate sex education. Ask questions, talk to them, explain what is normal.
I can’t stress enough how important mental health is to a great sex life. Everyone would benefit from sex therapy and becoming better at sex. We need to get better at communicating and educating patients and their partners to maximize their quality of life. If you need to refer to a specialist, we recommend going to psychologytoday.com or aasect.org to find a local sex therapist. Call them and use them in your referral networks.
In the “bio” component of the biopsychosocial approach, we can do a lot to treat ED with medications and hormones. Testosterone has been shown to help with low libido and erectile function. Checking the patient’s testosterone level can be very helpful. Pills — we are familiar with Viagra, Cialis, Levitra, and Stendra. The oral PDE-5 inhibitors have been around since the late 1990s and they work quite well for many people with ED. Viagra and Cialis are generic now and patients can get them fairly inexpensively with discount coupons from GoodRx or Cost Plus Drugs. They may not even have to worry about insurance coverage.
Pills relax the smooth muscle of the penis so that it fills with blood and becomes erect, but they don’t work for everybody. If pills stop working, we often talk about synergistic treatments — combining pills and devices. Devices for ED should be discussed more often, and clinicians should consider prescribing them. We commonly discuss eyeglasses and wheelchairs, but we don’t talk about the sexual health devices that could help patients have more success and fun in the bedroom.
What are the various types of devices for ED? One common device is a vacuum pump, which can be very effective. This is how they work: The penis is lubricated and placed into the pump. A button on the pump creates suction that brings blood into the penis. The patient then applies a constriction band around the base of the penis to hold that erection in place.
“Sex tech” has really expanded to help patients with ED with devices that vibrate and hold the erection in place. Vibrating devices allow for a better orgasm. We even have devices that monitor erectile fitness (like a Fitbit for the penis), gathering data to help patients understand the firmness of their erections.
Devices are helpful adjuncts, but they don’t always do enough to achieve an erect penis that’s hard enough for penetration. In those cases, we can recommend injections that increase smooth muscle relaxation of the penis. I know it sounds crazy. If the muscles, arteries, and nerves of the penis aren’t functioning well, additional smooth muscle relaxation can be achieved by injecting alprostadil (prostaglandin E1) directly into the penis. It’s a tiny needle. It doesn’t hurt. These injections can be quite helpful for our patients, and we often recommend them.
But what happens when your patient doesn’t even respond to injections or any of the synergistic treatments? They’ve tried everything. Urologists may suggest a surgical option, the penile implant. Penile implants contain a pump inside the scrotum that fills with fluid, allowing a rigid erection. Penile implants are wonderful for patients who can no longer get erections. Talking to a urologist about the pros and the cons and the risks and benefits of surgically placed implants is very important.
Finally, ED is a marker for cardiovascular disease. These patients may need a cardiology workup. They need to improve their general health. We have to ask our patients about their goals and what they care about, and find a toolbox that makes sense for each patient and couple to maximize their sexual health and quality of life. Don’t give up. If you have questions, let us know.
Rachel S. Rubin, MD, is Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC; Private practice, Rachel Rubin MD PLLC, North Bethesda, Maryland. She disclosed ties with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.
A version of this article appeared on Medscape.com.
Report: CKD Severity Linked to Thinning of Retina, Choroid Layers
Changes in tissue thickness in the back of the eye can correlate with worsening or improvement of renal problems and could help predict who will have worsening of kidney function, a new analysis report finds.
The research, published in the journal Nature Communications, is the first to show an association between chronic kidney disease (CKD) and the thickness of the retinal and choroidal layers in the back of the eye as measured by optical coherence tomography (OCT), a noninvasive imaging technology commonly used to evaluate eye diseases such as age-related macular degeneration (AMD), diabetic eye disease, and retinal detachments.
“These are common scans that people get at the opticians and now in many hospitals,” said Neeraj Dhaun, MD, PhD, a professor of nephrology at the University of Edinburgh, Scotland. (Opticians in the United Kingdom are the equivalent of optometrists in North America.)
CKD Severity Equals Thinner Retinas
“We scanned the back of eye of healthy people as well as patients with various types and degrees of kidney disease, and we found that two layers in the back of eye, the retina and the choroid, were thinner in patients with kidney disease compared to people who are healthy, and that the extent of this thinning predicts whether kidney function would decline going forward over a period of 2 or 3 years,” Dr. Dhaun, the corresponding author of the new paper, said.
The publication is a report of four different studies. The first study measured OCT metrics in 112 patients with CKD, 92 patients with a functional kidney transplant, and 86 control volunteers. The researchers found the retina was 5% thinner in patients with CKD than in healthy controls. They also found that patients with CKD had reduced macular volume: 8.44 ± .44 mm3 vs 8.73 ± .36 mm3 (P < .001). The choroid was also found to be thinner at each of three macular locations measured in patients with CKD vs control volunteers. At baseline, CKD and transplant patients had significantly lower estimated glomerular filtration rate (eGFR) at 55 ± 27 and 55 ± 24 mL/min/1.73 m2 compared with control volunteers at 97 ± 14 mL/min/1.73 m2.
The second study reported on OCT measurements and kidney histologic injury in 50 patients who had a kidney biopsy within 30 days of their OCT. It found that choroidal thinning at all three macular locations was independently associated with more extensive kidney scarring.
The third study focused on 25 patients with kidney failure who had a kidney transplant. Their eGFR improved from 8 ± 3 to 58 ± 21 mL/min/1.73 m2 in the first week after the transplant. The choroid in these patients thickened about 5% at 1 week and by about 10% at 1 month posttransplant. OCT of 22 kidney donors showed thickening of the choroid a week after nephrectomy before a tendency to thinning over the next year.
The fourth study found that for patients with stable CKD, every 1 mm3 decrease in macular volume correlated to an increased odds of a decline in eGFR by more than 10% at 1 year (2.48; 95% CI, 1.26-5.08; P = .01) and by more than 20% at 2 years (3.75; 95% CI, 1.26-5.08; P = .004).
Exploring the Kidney-Eye Connection
The potential explanation for the correlation between retinal and choroidal thickness and kidney function is unclear, Dr. Dhaun said.
“We don’t know the exact mechanisms, and these are difficult to define from studies in patients, which is why we are doing more work in animal models of kidney disease to see if we can establish the pathways that lead to the changes in the eye,” he said.
“However,” Dr. Dhaun added, “what we do know is that kidney disease affects the whole body. For example, kidney disease can lead to high blood pressure and heart disease, as well as diseases in the brain, and it is these effects of kidney disease on the body as whole that we are probably picking up in the back of the eye.”
OCT has the potential to make the monitoring of patients with CKD and kidney transplant more convenient than it is now, Dr. Dhaun said. “These scanners are available in the community, and what would be ideal at some point in the future is to be able to do a patient’s kidney health check in the community potentially incorporating OCT scanning alongside blood-pressure monitoring and other healthcare measures,” he said.
“The findings provide an exciting example of how noninvasive retinal imaging using OCT can provide quantitative biomarkers of systemic disease,” Amir Kashani, MD, PhD, the Boone Pickens Professor of Ophthalmology and Biomedical Engineering at the Wilmer Eye Institute of Johns Hopkins University in Baltimore, told this news organization. “It is striking that their findings demonstrate some potential of reversible changes in choroidal perfusion after kidney transplantation.”
The finding that choroidal thickness changes in CKD are at least partly reversible with kidney transplantation is a revelation, Dr. Kashani said, and may point to a greater role for ophthalmologists in managing systemic disease.
“Ophthalmologists can and should use their unique experience and understanding of the eye to help monitor and manage systemic conditions in collaboration with our medicine colleagues,” he said. “There are many systemic diseases that can impact the eye and ophthalmologist are uniquely positioned to help interpret those findings.”
Dr. Kashani noted that a particular strength of the report was the comparison of choroidal measurements in patients who had kidney transplantation and those that had a nephrectomy. “The consistent direction of changes in these two groups suggests the study findings are real and meaningful,” he said.
The study was independently supported. Dr. Dhaun and co-authors report no relevant financial relationships. Dr. Kashani disclosed a financial relationship with Carl Zeiss Meditec.
A version of this article first appeared on Medscape.com.
Changes in tissue thickness in the back of the eye can correlate with worsening or improvement of renal problems and could help predict who will have worsening of kidney function, a new analysis report finds.
The research, published in the journal Nature Communications, is the first to show an association between chronic kidney disease (CKD) and the thickness of the retinal and choroidal layers in the back of the eye as measured by optical coherence tomography (OCT), a noninvasive imaging technology commonly used to evaluate eye diseases such as age-related macular degeneration (AMD), diabetic eye disease, and retinal detachments.
“These are common scans that people get at the opticians and now in many hospitals,” said Neeraj Dhaun, MD, PhD, a professor of nephrology at the University of Edinburgh, Scotland. (Opticians in the United Kingdom are the equivalent of optometrists in North America.)
CKD Severity Equals Thinner Retinas
“We scanned the back of eye of healthy people as well as patients with various types and degrees of kidney disease, and we found that two layers in the back of eye, the retina and the choroid, were thinner in patients with kidney disease compared to people who are healthy, and that the extent of this thinning predicts whether kidney function would decline going forward over a period of 2 or 3 years,” Dr. Dhaun, the corresponding author of the new paper, said.
The publication is a report of four different studies. The first study measured OCT metrics in 112 patients with CKD, 92 patients with a functional kidney transplant, and 86 control volunteers. The researchers found the retina was 5% thinner in patients with CKD than in healthy controls. They also found that patients with CKD had reduced macular volume: 8.44 ± .44 mm3 vs 8.73 ± .36 mm3 (P < .001). The choroid was also found to be thinner at each of three macular locations measured in patients with CKD vs control volunteers. At baseline, CKD and transplant patients had significantly lower estimated glomerular filtration rate (eGFR) at 55 ± 27 and 55 ± 24 mL/min/1.73 m2 compared with control volunteers at 97 ± 14 mL/min/1.73 m2.
The second study reported on OCT measurements and kidney histologic injury in 50 patients who had a kidney biopsy within 30 days of their OCT. It found that choroidal thinning at all three macular locations was independently associated with more extensive kidney scarring.
The third study focused on 25 patients with kidney failure who had a kidney transplant. Their eGFR improved from 8 ± 3 to 58 ± 21 mL/min/1.73 m2 in the first week after the transplant. The choroid in these patients thickened about 5% at 1 week and by about 10% at 1 month posttransplant. OCT of 22 kidney donors showed thickening of the choroid a week after nephrectomy before a tendency to thinning over the next year.
The fourth study found that for patients with stable CKD, every 1 mm3 decrease in macular volume correlated to an increased odds of a decline in eGFR by more than 10% at 1 year (2.48; 95% CI, 1.26-5.08; P = .01) and by more than 20% at 2 years (3.75; 95% CI, 1.26-5.08; P = .004).
Exploring the Kidney-Eye Connection
The potential explanation for the correlation between retinal and choroidal thickness and kidney function is unclear, Dr. Dhaun said.
“We don’t know the exact mechanisms, and these are difficult to define from studies in patients, which is why we are doing more work in animal models of kidney disease to see if we can establish the pathways that lead to the changes in the eye,” he said.
“However,” Dr. Dhaun added, “what we do know is that kidney disease affects the whole body. For example, kidney disease can lead to high blood pressure and heart disease, as well as diseases in the brain, and it is these effects of kidney disease on the body as whole that we are probably picking up in the back of the eye.”
OCT has the potential to make the monitoring of patients with CKD and kidney transplant more convenient than it is now, Dr. Dhaun said. “These scanners are available in the community, and what would be ideal at some point in the future is to be able to do a patient’s kidney health check in the community potentially incorporating OCT scanning alongside blood-pressure monitoring and other healthcare measures,” he said.
“The findings provide an exciting example of how noninvasive retinal imaging using OCT can provide quantitative biomarkers of systemic disease,” Amir Kashani, MD, PhD, the Boone Pickens Professor of Ophthalmology and Biomedical Engineering at the Wilmer Eye Institute of Johns Hopkins University in Baltimore, told this news organization. “It is striking that their findings demonstrate some potential of reversible changes in choroidal perfusion after kidney transplantation.”
The finding that choroidal thickness changes in CKD are at least partly reversible with kidney transplantation is a revelation, Dr. Kashani said, and may point to a greater role for ophthalmologists in managing systemic disease.
“Ophthalmologists can and should use their unique experience and understanding of the eye to help monitor and manage systemic conditions in collaboration with our medicine colleagues,” he said. “There are many systemic diseases that can impact the eye and ophthalmologist are uniquely positioned to help interpret those findings.”
Dr. Kashani noted that a particular strength of the report was the comparison of choroidal measurements in patients who had kidney transplantation and those that had a nephrectomy. “The consistent direction of changes in these two groups suggests the study findings are real and meaningful,” he said.
The study was independently supported. Dr. Dhaun and co-authors report no relevant financial relationships. Dr. Kashani disclosed a financial relationship with Carl Zeiss Meditec.
A version of this article first appeared on Medscape.com.
Changes in tissue thickness in the back of the eye can correlate with worsening or improvement of renal problems and could help predict who will have worsening of kidney function, a new analysis report finds.
The research, published in the journal Nature Communications, is the first to show an association between chronic kidney disease (CKD) and the thickness of the retinal and choroidal layers in the back of the eye as measured by optical coherence tomography (OCT), a noninvasive imaging technology commonly used to evaluate eye diseases such as age-related macular degeneration (AMD), diabetic eye disease, and retinal detachments.
“These are common scans that people get at the opticians and now in many hospitals,” said Neeraj Dhaun, MD, PhD, a professor of nephrology at the University of Edinburgh, Scotland. (Opticians in the United Kingdom are the equivalent of optometrists in North America.)
CKD Severity Equals Thinner Retinas
“We scanned the back of eye of healthy people as well as patients with various types and degrees of kidney disease, and we found that two layers in the back of eye, the retina and the choroid, were thinner in patients with kidney disease compared to people who are healthy, and that the extent of this thinning predicts whether kidney function would decline going forward over a period of 2 or 3 years,” Dr. Dhaun, the corresponding author of the new paper, said.
The publication is a report of four different studies. The first study measured OCT metrics in 112 patients with CKD, 92 patients with a functional kidney transplant, and 86 control volunteers. The researchers found the retina was 5% thinner in patients with CKD than in healthy controls. They also found that patients with CKD had reduced macular volume: 8.44 ± .44 mm3 vs 8.73 ± .36 mm3 (P < .001). The choroid was also found to be thinner at each of three macular locations measured in patients with CKD vs control volunteers. At baseline, CKD and transplant patients had significantly lower estimated glomerular filtration rate (eGFR) at 55 ± 27 and 55 ± 24 mL/min/1.73 m2 compared with control volunteers at 97 ± 14 mL/min/1.73 m2.
The second study reported on OCT measurements and kidney histologic injury in 50 patients who had a kidney biopsy within 30 days of their OCT. It found that choroidal thinning at all three macular locations was independently associated with more extensive kidney scarring.
The third study focused on 25 patients with kidney failure who had a kidney transplant. Their eGFR improved from 8 ± 3 to 58 ± 21 mL/min/1.73 m2 in the first week after the transplant. The choroid in these patients thickened about 5% at 1 week and by about 10% at 1 month posttransplant. OCT of 22 kidney donors showed thickening of the choroid a week after nephrectomy before a tendency to thinning over the next year.
The fourth study found that for patients with stable CKD, every 1 mm3 decrease in macular volume correlated to an increased odds of a decline in eGFR by more than 10% at 1 year (2.48; 95% CI, 1.26-5.08; P = .01) and by more than 20% at 2 years (3.75; 95% CI, 1.26-5.08; P = .004).
Exploring the Kidney-Eye Connection
The potential explanation for the correlation between retinal and choroidal thickness and kidney function is unclear, Dr. Dhaun said.
“We don’t know the exact mechanisms, and these are difficult to define from studies in patients, which is why we are doing more work in animal models of kidney disease to see if we can establish the pathways that lead to the changes in the eye,” he said.
“However,” Dr. Dhaun added, “what we do know is that kidney disease affects the whole body. For example, kidney disease can lead to high blood pressure and heart disease, as well as diseases in the brain, and it is these effects of kidney disease on the body as whole that we are probably picking up in the back of the eye.”
OCT has the potential to make the monitoring of patients with CKD and kidney transplant more convenient than it is now, Dr. Dhaun said. “These scanners are available in the community, and what would be ideal at some point in the future is to be able to do a patient’s kidney health check in the community potentially incorporating OCT scanning alongside blood-pressure monitoring and other healthcare measures,” he said.
“The findings provide an exciting example of how noninvasive retinal imaging using OCT can provide quantitative biomarkers of systemic disease,” Amir Kashani, MD, PhD, the Boone Pickens Professor of Ophthalmology and Biomedical Engineering at the Wilmer Eye Institute of Johns Hopkins University in Baltimore, told this news organization. “It is striking that their findings demonstrate some potential of reversible changes in choroidal perfusion after kidney transplantation.”
The finding that choroidal thickness changes in CKD are at least partly reversible with kidney transplantation is a revelation, Dr. Kashani said, and may point to a greater role for ophthalmologists in managing systemic disease.
“Ophthalmologists can and should use their unique experience and understanding of the eye to help monitor and manage systemic conditions in collaboration with our medicine colleagues,” he said. “There are many systemic diseases that can impact the eye and ophthalmologist are uniquely positioned to help interpret those findings.”
Dr. Kashani noted that a particular strength of the report was the comparison of choroidal measurements in patients who had kidney transplantation and those that had a nephrectomy. “The consistent direction of changes in these two groups suggests the study findings are real and meaningful,” he said.
The study was independently supported. Dr. Dhaun and co-authors report no relevant financial relationships. Dr. Kashani disclosed a financial relationship with Carl Zeiss Meditec.
A version of this article first appeared on Medscape.com.
FROM NATURE COMMUNICATIONS
What if a single GLP-1 shot could last for months?
As revolutionary as glucagon-like peptide 1 (GLP-1) drugs are, they still last for only so long in the body. Patients with diabetes typically must be injected once or twice a day (liraglutide) or once a week (semaglutide). This could hinder proper diabetes management, as adherence tends to go down the more frequent the dose.
But what if a single GLP-1 injection could last for 4 months?
“melts away like a sugar cube dissolving in water, molecule by molecule,” said Eric Appel, PhD, the project’s principal investigator and an associate professor of materials science and engineering at Stanford (Calif.) University.
So far, the team has tested the new drug delivery system in rats, and they say human clinical trials could start within 2 years.
Mathematical modeling indicated that one shot of liraglutide could maintain exposure in humans for 120 days, or about 4 months, according to their study in Cell Reports Medicine.
“Patient adherence is of critical importance to diabetes care,” said Alex Abramson, PhD, assistant professor in the chemical and biomolecular engineering department at Georgia Tech, who was not involved in the study. “It’s very exciting to have a potential new system that can last 4 months on a single injection.”
Long-Acting Injectables Have Come a Long Way
The first long-acting injectable — Lupron Depot, a monthly treatment for advanced prostate cancer — was approved in 1989. Since then, long-acting injectable depots have revolutionized the treatment and management of conditions ranging from osteoarthritis knee pain to schizophrenia to opioid use disorder. In 2021, the US Food and Drug Administration approved Apretude — an injectable treatment for HIV pre-exposure prevention that needs to be given every 2 months, compared with daily for the pill equivalent. Other new and innovative developments are underway: Researchers at the University of Connecticut are working on a transdermal microneedle patch — with many tiny vaccine-loaded needles — that could provide multiple doses of a vaccine over time, no boosters needed.
At Stanford, Appel’s lab has spent years developing gels for drug delivery. His team uses a class of hydrogel called polymer-nanoparticle (PNP), which features weakly bound polymers and nanoparticles that can dissipate slowly over time.
The goal is to address a longstanding challenge with long-acting formulations: Achieving steady release. Because the hydrogel is “self-healing” — able to repair damages and restore its shape — it’s less likely to burst and release its drug cargo too early.
“Our PNP hydrogels possess a number of really unique characteristics,” Dr. Appel said. They have “excellent” biocompatibility, based on animal studies, and could work with a wide range of drugs. In proof-of-concept mouse studies, Dr. Appel and his team have shown that these hydrogels could also be used to make vaccines last longer, ferry cancer immunotherapies directly to tumors, and deliver antibodies for the prevention of infectious diseases like SARS-CoV-2.
Though the recent study on GLP-1s focused on treating type 2 diabetes, the same formulation could also be used to treat obesity, said Dr. Appel.
The researchers tested the tech using two GLP-1 receptor agonists — semaglutide and liraglutide. In rats, one shot maintained therapeutic serum concentrations of semaglutide or liraglutide over 42 days. With semaglutide, a significant portion was released quickly, followed by controlled release. Liraglutide, on the other hand, was released gradually as the hydrogel dissolved. This suggests the liraglutide hydrogel may be better tolerated, as a sudden peak in drug serum concentration is associated with adverse effects.
The researchers used pharmacokinetic modeling to predict how liraglutide would behave in humans with a larger injection volume, finding that a single dose could maintain therapeutic levels for about 4 months.
“Moving forward, it will be important to determine whether a burst release from the formulation causes any side effects,” Dr. Abramson noted. “Furthermore, it will be important to minimize the injection volumes in humans.”
But first, more studies in larger animals are needed. Next, Dr. Appel and his team plan to test the technology in pigs, whose skin and endocrine systems are most like humans’. If those trials go well, Dr. Appel said, human clinical trials could start within 2 years.
A version of this article appeared on Medscape.com.
As revolutionary as glucagon-like peptide 1 (GLP-1) drugs are, they still last for only so long in the body. Patients with diabetes typically must be injected once or twice a day (liraglutide) or once a week (semaglutide). This could hinder proper diabetes management, as adherence tends to go down the more frequent the dose.
But what if a single GLP-1 injection could last for 4 months?
“melts away like a sugar cube dissolving in water, molecule by molecule,” said Eric Appel, PhD, the project’s principal investigator and an associate professor of materials science and engineering at Stanford (Calif.) University.
So far, the team has tested the new drug delivery system in rats, and they say human clinical trials could start within 2 years.
Mathematical modeling indicated that one shot of liraglutide could maintain exposure in humans for 120 days, or about 4 months, according to their study in Cell Reports Medicine.
“Patient adherence is of critical importance to diabetes care,” said Alex Abramson, PhD, assistant professor in the chemical and biomolecular engineering department at Georgia Tech, who was not involved in the study. “It’s very exciting to have a potential new system that can last 4 months on a single injection.”
Long-Acting Injectables Have Come a Long Way
The first long-acting injectable — Lupron Depot, a monthly treatment for advanced prostate cancer — was approved in 1989. Since then, long-acting injectable depots have revolutionized the treatment and management of conditions ranging from osteoarthritis knee pain to schizophrenia to opioid use disorder. In 2021, the US Food and Drug Administration approved Apretude — an injectable treatment for HIV pre-exposure prevention that needs to be given every 2 months, compared with daily for the pill equivalent. Other new and innovative developments are underway: Researchers at the University of Connecticut are working on a transdermal microneedle patch — with many tiny vaccine-loaded needles — that could provide multiple doses of a vaccine over time, no boosters needed.
At Stanford, Appel’s lab has spent years developing gels for drug delivery. His team uses a class of hydrogel called polymer-nanoparticle (PNP), which features weakly bound polymers and nanoparticles that can dissipate slowly over time.
The goal is to address a longstanding challenge with long-acting formulations: Achieving steady release. Because the hydrogel is “self-healing” — able to repair damages and restore its shape — it’s less likely to burst and release its drug cargo too early.
“Our PNP hydrogels possess a number of really unique characteristics,” Dr. Appel said. They have “excellent” biocompatibility, based on animal studies, and could work with a wide range of drugs. In proof-of-concept mouse studies, Dr. Appel and his team have shown that these hydrogels could also be used to make vaccines last longer, ferry cancer immunotherapies directly to tumors, and deliver antibodies for the prevention of infectious diseases like SARS-CoV-2.
Though the recent study on GLP-1s focused on treating type 2 diabetes, the same formulation could also be used to treat obesity, said Dr. Appel.
The researchers tested the tech using two GLP-1 receptor agonists — semaglutide and liraglutide. In rats, one shot maintained therapeutic serum concentrations of semaglutide or liraglutide over 42 days. With semaglutide, a significant portion was released quickly, followed by controlled release. Liraglutide, on the other hand, was released gradually as the hydrogel dissolved. This suggests the liraglutide hydrogel may be better tolerated, as a sudden peak in drug serum concentration is associated with adverse effects.
The researchers used pharmacokinetic modeling to predict how liraglutide would behave in humans with a larger injection volume, finding that a single dose could maintain therapeutic levels for about 4 months.
“Moving forward, it will be important to determine whether a burst release from the formulation causes any side effects,” Dr. Abramson noted. “Furthermore, it will be important to minimize the injection volumes in humans.”
But first, more studies in larger animals are needed. Next, Dr. Appel and his team plan to test the technology in pigs, whose skin and endocrine systems are most like humans’. If those trials go well, Dr. Appel said, human clinical trials could start within 2 years.
A version of this article appeared on Medscape.com.
As revolutionary as glucagon-like peptide 1 (GLP-1) drugs are, they still last for only so long in the body. Patients with diabetes typically must be injected once or twice a day (liraglutide) or once a week (semaglutide). This could hinder proper diabetes management, as adherence tends to go down the more frequent the dose.
But what if a single GLP-1 injection could last for 4 months?
“melts away like a sugar cube dissolving in water, molecule by molecule,” said Eric Appel, PhD, the project’s principal investigator and an associate professor of materials science and engineering at Stanford (Calif.) University.
So far, the team has tested the new drug delivery system in rats, and they say human clinical trials could start within 2 years.
Mathematical modeling indicated that one shot of liraglutide could maintain exposure in humans for 120 days, or about 4 months, according to their study in Cell Reports Medicine.
“Patient adherence is of critical importance to diabetes care,” said Alex Abramson, PhD, assistant professor in the chemical and biomolecular engineering department at Georgia Tech, who was not involved in the study. “It’s very exciting to have a potential new system that can last 4 months on a single injection.”
Long-Acting Injectables Have Come a Long Way
The first long-acting injectable — Lupron Depot, a monthly treatment for advanced prostate cancer — was approved in 1989. Since then, long-acting injectable depots have revolutionized the treatment and management of conditions ranging from osteoarthritis knee pain to schizophrenia to opioid use disorder. In 2021, the US Food and Drug Administration approved Apretude — an injectable treatment for HIV pre-exposure prevention that needs to be given every 2 months, compared with daily for the pill equivalent. Other new and innovative developments are underway: Researchers at the University of Connecticut are working on a transdermal microneedle patch — with many tiny vaccine-loaded needles — that could provide multiple doses of a vaccine over time, no boosters needed.
At Stanford, Appel’s lab has spent years developing gels for drug delivery. His team uses a class of hydrogel called polymer-nanoparticle (PNP), which features weakly bound polymers and nanoparticles that can dissipate slowly over time.
The goal is to address a longstanding challenge with long-acting formulations: Achieving steady release. Because the hydrogel is “self-healing” — able to repair damages and restore its shape — it’s less likely to burst and release its drug cargo too early.
“Our PNP hydrogels possess a number of really unique characteristics,” Dr. Appel said. They have “excellent” biocompatibility, based on animal studies, and could work with a wide range of drugs. In proof-of-concept mouse studies, Dr. Appel and his team have shown that these hydrogels could also be used to make vaccines last longer, ferry cancer immunotherapies directly to tumors, and deliver antibodies for the prevention of infectious diseases like SARS-CoV-2.
Though the recent study on GLP-1s focused on treating type 2 diabetes, the same formulation could also be used to treat obesity, said Dr. Appel.
The researchers tested the tech using two GLP-1 receptor agonists — semaglutide and liraglutide. In rats, one shot maintained therapeutic serum concentrations of semaglutide or liraglutide over 42 days. With semaglutide, a significant portion was released quickly, followed by controlled release. Liraglutide, on the other hand, was released gradually as the hydrogel dissolved. This suggests the liraglutide hydrogel may be better tolerated, as a sudden peak in drug serum concentration is associated with adverse effects.
The researchers used pharmacokinetic modeling to predict how liraglutide would behave in humans with a larger injection volume, finding that a single dose could maintain therapeutic levels for about 4 months.
“Moving forward, it will be important to determine whether a burst release from the formulation causes any side effects,” Dr. Abramson noted. “Furthermore, it will be important to minimize the injection volumes in humans.”
But first, more studies in larger animals are needed. Next, Dr. Appel and his team plan to test the technology in pigs, whose skin and endocrine systems are most like humans’. If those trials go well, Dr. Appel said, human clinical trials could start within 2 years.
A version of this article appeared on Medscape.com.
FROM CELL REPORTS MEDICINE
How to prescribe Zepbound
December marks the advent of the approval of tirzepatide (Zepbound) for on-label treatment of obesity. In November 2023, the US Food and Drug Administration (FDA) approved it for the treatment of obesity in adults.
In May 2022, the FDA approved Mounjaro, which is tirzepatide, for type 2 diabetes. Since then, many physicians, including myself, have prescribed it off-label for obesity. As an endocrinologist treating both obesity and diabetes, 
The Expertise
Because GLP-1 receptor agonists have been around since 2005, we’ve had over a decade of clinical experience with these medications. Table 2 provides more nuanced information on tirzepatide (as Zepbound, for obesity) based on our experiences with dulaglutide, liraglutide, semaglutide, and tirzepatide (as Mounjaro).
The Reality
In today’s increasingly complex healthcare system, the reality of providing high-quality obesity care is challenging. When discussing tirzepatide with patients, I use a 4 Cs schematic — comorbidities, cautions, costs, choices — to cover the most frequently asked questions.
Comorbidities
In trials, tirzepatide reduced A1c by about 2%. In one diabetes trial, tirzepatide reduced liver fat content significantly more than the comparator (insulin), and trials of tirzepatide in nonalcoholic steatohepatitis are ongoing. A prespecified meta-analysis of tirzepatide and cardiovascular disease estimated a 20% reduction in the risk for cardiovascular death, myocardial infarction, stroke, and hospitalized unstable angina. Tirzepatide as well as other GLP-1 agonists may be beneficial in alcohol use disorder. Prescribing tirzepatide to patients who have or are at risk of developing such comorbidities is an ideal way to target multiple metabolic diseases with one agent.
Cautions
The first principle of medicine is “do no harm.” Tirzepatide may be a poor option for individuals with a history of pancreatitis, gastroparesis, or severe gastroesophageal reflux disease. Because tirzepatide may interfere with the efficacy of estrogen-containing contraceptives during its uptitration phase, women should speak with their doctors about appropriate birth control options (eg, progestin-only, barrier methods). In clinical trials of tirzepatide, male participants were also advised to use reliable contraception. If patients are family-planning, tirzepatide should be discontinued 2 months (for women) and 4 months (for men) before conception, because its effects on fertility or pregnancy are currently unknown.
Costs
At a retail price of $1279 per month, Zepbound is only slightly more affordable than its main competitor, Wegovy (semaglutide 2.4 mg). Complex pharmacy negotiations may reduce this cost, but even with rebates, coupons, and commercial insurance, these costs still place tirzepatide out of reach for many patients. For patients who cannot access tirzepatide, clinicians should discuss more cost-feasible, evidence-based alternatives: for example, phentermine, phentermine-topiramate, naltrexone-bupropion, metformin, bupropion, or topiramate.
Choices
Patient preference drives much of today’s clinical decision-making. Some patients may be switching from semaglutide to tirzepatide, whether by choice or on the basis of physician recommendation. Although no head-to-head obesity trial exists, data from SURPASS-2 and SUSTAIN-FORTE can inform therapeutic equivalence:
- Semaglutide 1.0 mg to tirzepatide 2.5 mg will be a step-down; 5 mg will be a step-up
- Semaglutide 2.0 or 2.4 mg to tirzepatide 5 mg is probably equivalent
The decision to switch therapeutics may depend on weight loss goals, side effect tolerability, or insurance coverage. As with all medications, the use of tirzepatide should progress with shared decision-making, thorough discussions of risks vs benefits, and individualized regimens tailored to each patient’s needs.
The newly approved Zepbound is a valuable addition to our toolbox of obesity treatments. Patients and providers alike are excited for its potential as a highly effective antiobesity medication that can cause a degree of weight loss necessary to reverse comorbidities. The medical management of obesity with agents like tirzepatide holds great promise in addressing today’s obesity epidemic.
Dr. Tchang is Assistant Professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine; Physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York, NY. She disclosed ties to Gelesis and Novo Nordisk.
A version of this article appeared on Medscape.com.
December marks the advent of the approval of tirzepatide (Zepbound) for on-label treatment of obesity. In November 2023, the US Food and Drug Administration (FDA) approved it for the treatment of obesity in adults.
In May 2022, the FDA approved Mounjaro, which is tirzepatide, for type 2 diabetes. Since then, many physicians, including myself, have prescribed it off-label for obesity. As an endocrinologist treating both obesity and diabetes,
The Expertise
Because GLP-1 receptor agonists have been around since 2005, we’ve had over a decade of clinical experience with these medications. Table 2 provides more nuanced information on tirzepatide (as Zepbound, for obesity) based on our experiences with dulaglutide, liraglutide, semaglutide, and tirzepatide (as Mounjaro).
The Reality
In today’s increasingly complex healthcare system, the reality of providing high-quality obesity care is challenging. When discussing tirzepatide with patients, I use a 4 Cs schematic — comorbidities, cautions, costs, choices — to cover the most frequently asked questions.
Comorbidities
In trials, tirzepatide reduced A1c by about 2%. In one diabetes trial, tirzepatide reduced liver fat content significantly more than the comparator (insulin), and trials of tirzepatide in nonalcoholic steatohepatitis are ongoing. A prespecified meta-analysis of tirzepatide and cardiovascular disease estimated a 20% reduction in the risk for cardiovascular death, myocardial infarction, stroke, and hospitalized unstable angina. Tirzepatide as well as other GLP-1 agonists may be beneficial in alcohol use disorder. Prescribing tirzepatide to patients who have or are at risk of developing such comorbidities is an ideal way to target multiple metabolic diseases with one agent.
Cautions
The first principle of medicine is “do no harm.” Tirzepatide may be a poor option for individuals with a history of pancreatitis, gastroparesis, or severe gastroesophageal reflux disease. Because tirzepatide may interfere with the efficacy of estrogen-containing contraceptives during its uptitration phase, women should speak with their doctors about appropriate birth control options (eg, progestin-only, barrier methods). In clinical trials of tirzepatide, male participants were also advised to use reliable contraception. If patients are family-planning, tirzepatide should be discontinued 2 months (for women) and 4 months (for men) before conception, because its effects on fertility or pregnancy are currently unknown.
Costs
At a retail price of $1279 per month, Zepbound is only slightly more affordable than its main competitor, Wegovy (semaglutide 2.4 mg). Complex pharmacy negotiations may reduce this cost, but even with rebates, coupons, and commercial insurance, these costs still place tirzepatide out of reach for many patients. For patients who cannot access tirzepatide, clinicians should discuss more cost-feasible, evidence-based alternatives: for example, phentermine, phentermine-topiramate, naltrexone-bupropion, metformin, bupropion, or topiramate.
Choices
Patient preference drives much of today’s clinical decision-making. Some patients may be switching from semaglutide to tirzepatide, whether by choice or on the basis of physician recommendation. Although no head-to-head obesity trial exists, data from SURPASS-2 and SUSTAIN-FORTE can inform therapeutic equivalence:
- Semaglutide 1.0 mg to tirzepatide 2.5 mg will be a step-down; 5 mg will be a step-up
- Semaglutide 2.0 or 2.4 mg to tirzepatide 5 mg is probably equivalent
The decision to switch therapeutics may depend on weight loss goals, side effect tolerability, or insurance coverage. As with all medications, the use of tirzepatide should progress with shared decision-making, thorough discussions of risks vs benefits, and individualized regimens tailored to each patient’s needs.
The newly approved Zepbound is a valuable addition to our toolbox of obesity treatments. Patients and providers alike are excited for its potential as a highly effective antiobesity medication that can cause a degree of weight loss necessary to reverse comorbidities. The medical management of obesity with agents like tirzepatide holds great promise in addressing today’s obesity epidemic.
Dr. Tchang is Assistant Professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine; Physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York, NY. She disclosed ties to Gelesis and Novo Nordisk.
A version of this article appeared on Medscape.com.
December marks the advent of the approval of tirzepatide (Zepbound) for on-label treatment of obesity. In November 2023, the US Food and Drug Administration (FDA) approved it for the treatment of obesity in adults.
In May 2022, the FDA approved Mounjaro, which is tirzepatide, for type 2 diabetes. Since then, many physicians, including myself, have prescribed it off-label for obesity. As an endocrinologist treating both obesity and diabetes,
The Expertise
Because GLP-1 receptor agonists have been around since 2005, we’ve had over a decade of clinical experience with these medications. Table 2 provides more nuanced information on tirzepatide (as Zepbound, for obesity) based on our experiences with dulaglutide, liraglutide, semaglutide, and tirzepatide (as Mounjaro).
The Reality
In today’s increasingly complex healthcare system, the reality of providing high-quality obesity care is challenging. When discussing tirzepatide with patients, I use a 4 Cs schematic — comorbidities, cautions, costs, choices — to cover the most frequently asked questions.
Comorbidities
In trials, tirzepatide reduced A1c by about 2%. In one diabetes trial, tirzepatide reduced liver fat content significantly more than the comparator (insulin), and trials of tirzepatide in nonalcoholic steatohepatitis are ongoing. A prespecified meta-analysis of tirzepatide and cardiovascular disease estimated a 20% reduction in the risk for cardiovascular death, myocardial infarction, stroke, and hospitalized unstable angina. Tirzepatide as well as other GLP-1 agonists may be beneficial in alcohol use disorder. Prescribing tirzepatide to patients who have or are at risk of developing such comorbidities is an ideal way to target multiple metabolic diseases with one agent.
Cautions
The first principle of medicine is “do no harm.” Tirzepatide may be a poor option for individuals with a history of pancreatitis, gastroparesis, or severe gastroesophageal reflux disease. Because tirzepatide may interfere with the efficacy of estrogen-containing contraceptives during its uptitration phase, women should speak with their doctors about appropriate birth control options (eg, progestin-only, barrier methods). In clinical trials of tirzepatide, male participants were also advised to use reliable contraception. If patients are family-planning, tirzepatide should be discontinued 2 months (for women) and 4 months (for men) before conception, because its effects on fertility or pregnancy are currently unknown.
Costs
At a retail price of $1279 per month, Zepbound is only slightly more affordable than its main competitor, Wegovy (semaglutide 2.4 mg). Complex pharmacy negotiations may reduce this cost, but even with rebates, coupons, and commercial insurance, these costs still place tirzepatide out of reach for many patients. For patients who cannot access tirzepatide, clinicians should discuss more cost-feasible, evidence-based alternatives: for example, phentermine, phentermine-topiramate, naltrexone-bupropion, metformin, bupropion, or topiramate.
Choices
Patient preference drives much of today’s clinical decision-making. Some patients may be switching from semaglutide to tirzepatide, whether by choice or on the basis of physician recommendation. Although no head-to-head obesity trial exists, data from SURPASS-2 and SUSTAIN-FORTE can inform therapeutic equivalence:
- Semaglutide 1.0 mg to tirzepatide 2.5 mg will be a step-down; 5 mg will be a step-up
- Semaglutide 2.0 or 2.4 mg to tirzepatide 5 mg is probably equivalent
The decision to switch therapeutics may depend on weight loss goals, side effect tolerability, or insurance coverage. As with all medications, the use of tirzepatide should progress with shared decision-making, thorough discussions of risks vs benefits, and individualized regimens tailored to each patient’s needs.
The newly approved Zepbound is a valuable addition to our toolbox of obesity treatments. Patients and providers alike are excited for its potential as a highly effective antiobesity medication that can cause a degree of weight loss necessary to reverse comorbidities. The medical management of obesity with agents like tirzepatide holds great promise in addressing today’s obesity epidemic.
Dr. Tchang is Assistant Professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine; Physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York, NY. She disclosed ties to Gelesis and Novo Nordisk.
A version of this article appeared on Medscape.com.