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Not all children with type 2 diabetes have obesity
Obesity is not a universal phenotype in children with type 2 diabetes (T2D), a global systematic review and meta-analysis reported. In fact, the study found, as many as one in four children with T2D do not have obesity and some have normal reference-range body mass measurements. Further studies should consider other mechanisms beyond obesity in the genesis of pediatric diabetes, the authors of the international analysis concluded, writing for JAMA Network Open.
“We were aware that some children and adolescents with T2D did not have obesity, but we didn’t know the scale of obesity in T2D, or what variables may impact the occurrence of diabetes in this group,” endocrinologist M. Constantine Samaan, MD, MSc, associate professor of pediatrics at McMaster University in Hamilton, Ont., told this news organization. “So, the analysis did help us understand the body mass distribution of this group in more detail.”
The international investigators included in their meta-analysis 53 articles with 8,942 participants from multiple world regions and races/ethnicities. The overall prevalence of obesity in pediatric patients with T2D was 75.27% (95% confidence interval [CI], 70.47%-79.78%). The prevalence of obesity at time of diagnosis in 4,688 participants was 77.24% (95% CI, 70.55%-83.34%). Male participants had higher odds of obesity than females: odds ratio, 2.10 (95% CI, 1.33-3.31) – although girls are generally more likely to develop T2D. The highest prevalence of obesity occurred in Whites at 89.86% (95% CI, 71.50%-99.74%), while prevalence was lowest in Asian participants at 64.50% (95% CI, 53.28%-74.99%).
The authors noted that childhood obesity affects approximately 340 million children worldwide and is a major driver of pediatric T2D, an aggressive disease with a high treatment failure rate. Understanding the contribution of body mass to the evolution of insulin resistance, glucose intolerance, and T2D with its attendant comorbidities and complications, such as nonalcoholic fatty liver disease, remains crucial for developing personalized interventions.
Known risk factors for T2D include interactions between genetics and the environment, including lifestyle factors such as diet and low physical activity levels, Dr. Samaan noted. Certain ethnic groups have higher T2D risks, as do babies exposed in the womb to maternal obesity or diabetes, he said. “And there are likely many other factors that contribute to the risk of T2D, though these remain to be defined.”
Is “lean” T2D in children without obesity likely then to be hereditary, more severe, and harder to control with lifestyle modification? “That’s a great question, but the answer is we don’t know,” Dr. Samaan said.
Commenting on the study but not involved in it, Timothy J. Joos, MD, a pediatrician in Seattle affiliated with the Swedish Medical Center, said the findings raise the question of how many pediatric T2D patients are being missed because they don’t meet current screening criteria. “In nonobese T2D pediatric patients, genetics (and by proxy family history) obviously play a heavier role. In my practice, I often get parents asking me to screen their skinny teenager for diabetes because of diabetes in a family member. In the past I would begrudgingly comply with a smirk on my face. Now the smirk will be gone.”
Dr. Joos said it would be interesting to see what percentage of these T2D patients without obesity (body mass index < 95th percentile) would still meet the criteria for being overweight (BMI > 85th percentile) as this is the primary criterion for screening according to the American Diabetes Association guidelines.
Current guidelines generally look for elevated body mass measures as a main screening indication, Dr. Samaan’s group noted. But in their view, while factors such as ethnicity and in utero exposure to diabetes are already used in combination with BMI-based measures to justify screening, more sophisticated prediabetes and diabetes prediction models are needed to support a more comprehensive screening approach.
“Because being overweight is the initial criterion, children with multiple other criteria are not being screened,” Dr. Joos said. He agreed that more research is needed to sort out the other risk factors for pediatric T2D without obesity so these patients may be detected earlier.
New models may need to incorporate lifestyle factors, hormones, puberty, growth, and sex as well, the authors wrote. Markers of insulin resistance, insulin production capacity, and other markers are needed to refine the identification of those who should be screened.
Dr. Samaan’s group is planning to study the findings in more detail to clarify the effect of body mass on the comorbidities and complications of pediatric T2D.
In addition to the study limitation of significant interstudy heterogeneity, the authors acknowledged varying degrees of glycemic control and dyslipidemia among participants.
No specific funding was provided for this review and meta-analysis. The authors disclosed no conflicts of interest. Dr. Joos disclosed no competing interests with regard to his comments.
Obesity is not a universal phenotype in children with type 2 diabetes (T2D), a global systematic review and meta-analysis reported. In fact, the study found, as many as one in four children with T2D do not have obesity and some have normal reference-range body mass measurements. Further studies should consider other mechanisms beyond obesity in the genesis of pediatric diabetes, the authors of the international analysis concluded, writing for JAMA Network Open.
“We were aware that some children and adolescents with T2D did not have obesity, but we didn’t know the scale of obesity in T2D, or what variables may impact the occurrence of diabetes in this group,” endocrinologist M. Constantine Samaan, MD, MSc, associate professor of pediatrics at McMaster University in Hamilton, Ont., told this news organization. “So, the analysis did help us understand the body mass distribution of this group in more detail.”
The international investigators included in their meta-analysis 53 articles with 8,942 participants from multiple world regions and races/ethnicities. The overall prevalence of obesity in pediatric patients with T2D was 75.27% (95% confidence interval [CI], 70.47%-79.78%). The prevalence of obesity at time of diagnosis in 4,688 participants was 77.24% (95% CI, 70.55%-83.34%). Male participants had higher odds of obesity than females: odds ratio, 2.10 (95% CI, 1.33-3.31) – although girls are generally more likely to develop T2D. The highest prevalence of obesity occurred in Whites at 89.86% (95% CI, 71.50%-99.74%), while prevalence was lowest in Asian participants at 64.50% (95% CI, 53.28%-74.99%).
The authors noted that childhood obesity affects approximately 340 million children worldwide and is a major driver of pediatric T2D, an aggressive disease with a high treatment failure rate. Understanding the contribution of body mass to the evolution of insulin resistance, glucose intolerance, and T2D with its attendant comorbidities and complications, such as nonalcoholic fatty liver disease, remains crucial for developing personalized interventions.
Known risk factors for T2D include interactions between genetics and the environment, including lifestyle factors such as diet and low physical activity levels, Dr. Samaan noted. Certain ethnic groups have higher T2D risks, as do babies exposed in the womb to maternal obesity or diabetes, he said. “And there are likely many other factors that contribute to the risk of T2D, though these remain to be defined.”
Is “lean” T2D in children without obesity likely then to be hereditary, more severe, and harder to control with lifestyle modification? “That’s a great question, but the answer is we don’t know,” Dr. Samaan said.
Commenting on the study but not involved in it, Timothy J. Joos, MD, a pediatrician in Seattle affiliated with the Swedish Medical Center, said the findings raise the question of how many pediatric T2D patients are being missed because they don’t meet current screening criteria. “In nonobese T2D pediatric patients, genetics (and by proxy family history) obviously play a heavier role. In my practice, I often get parents asking me to screen their skinny teenager for diabetes because of diabetes in a family member. In the past I would begrudgingly comply with a smirk on my face. Now the smirk will be gone.”
Dr. Joos said it would be interesting to see what percentage of these T2D patients without obesity (body mass index < 95th percentile) would still meet the criteria for being overweight (BMI > 85th percentile) as this is the primary criterion for screening according to the American Diabetes Association guidelines.
Current guidelines generally look for elevated body mass measures as a main screening indication, Dr. Samaan’s group noted. But in their view, while factors such as ethnicity and in utero exposure to diabetes are already used in combination with BMI-based measures to justify screening, more sophisticated prediabetes and diabetes prediction models are needed to support a more comprehensive screening approach.
“Because being overweight is the initial criterion, children with multiple other criteria are not being screened,” Dr. Joos said. He agreed that more research is needed to sort out the other risk factors for pediatric T2D without obesity so these patients may be detected earlier.
New models may need to incorporate lifestyle factors, hormones, puberty, growth, and sex as well, the authors wrote. Markers of insulin resistance, insulin production capacity, and other markers are needed to refine the identification of those who should be screened.
Dr. Samaan’s group is planning to study the findings in more detail to clarify the effect of body mass on the comorbidities and complications of pediatric T2D.
In addition to the study limitation of significant interstudy heterogeneity, the authors acknowledged varying degrees of glycemic control and dyslipidemia among participants.
No specific funding was provided for this review and meta-analysis. The authors disclosed no conflicts of interest. Dr. Joos disclosed no competing interests with regard to his comments.
Obesity is not a universal phenotype in children with type 2 diabetes (T2D), a global systematic review and meta-analysis reported. In fact, the study found, as many as one in four children with T2D do not have obesity and some have normal reference-range body mass measurements. Further studies should consider other mechanisms beyond obesity in the genesis of pediatric diabetes, the authors of the international analysis concluded, writing for JAMA Network Open.
“We were aware that some children and adolescents with T2D did not have obesity, but we didn’t know the scale of obesity in T2D, or what variables may impact the occurrence of diabetes in this group,” endocrinologist M. Constantine Samaan, MD, MSc, associate professor of pediatrics at McMaster University in Hamilton, Ont., told this news organization. “So, the analysis did help us understand the body mass distribution of this group in more detail.”
The international investigators included in their meta-analysis 53 articles with 8,942 participants from multiple world regions and races/ethnicities. The overall prevalence of obesity in pediatric patients with T2D was 75.27% (95% confidence interval [CI], 70.47%-79.78%). The prevalence of obesity at time of diagnosis in 4,688 participants was 77.24% (95% CI, 70.55%-83.34%). Male participants had higher odds of obesity than females: odds ratio, 2.10 (95% CI, 1.33-3.31) – although girls are generally more likely to develop T2D. The highest prevalence of obesity occurred in Whites at 89.86% (95% CI, 71.50%-99.74%), while prevalence was lowest in Asian participants at 64.50% (95% CI, 53.28%-74.99%).
The authors noted that childhood obesity affects approximately 340 million children worldwide and is a major driver of pediatric T2D, an aggressive disease with a high treatment failure rate. Understanding the contribution of body mass to the evolution of insulin resistance, glucose intolerance, and T2D with its attendant comorbidities and complications, such as nonalcoholic fatty liver disease, remains crucial for developing personalized interventions.
Known risk factors for T2D include interactions between genetics and the environment, including lifestyle factors such as diet and low physical activity levels, Dr. Samaan noted. Certain ethnic groups have higher T2D risks, as do babies exposed in the womb to maternal obesity or diabetes, he said. “And there are likely many other factors that contribute to the risk of T2D, though these remain to be defined.”
Is “lean” T2D in children without obesity likely then to be hereditary, more severe, and harder to control with lifestyle modification? “That’s a great question, but the answer is we don’t know,” Dr. Samaan said.
Commenting on the study but not involved in it, Timothy J. Joos, MD, a pediatrician in Seattle affiliated with the Swedish Medical Center, said the findings raise the question of how many pediatric T2D patients are being missed because they don’t meet current screening criteria. “In nonobese T2D pediatric patients, genetics (and by proxy family history) obviously play a heavier role. In my practice, I often get parents asking me to screen their skinny teenager for diabetes because of diabetes in a family member. In the past I would begrudgingly comply with a smirk on my face. Now the smirk will be gone.”
Dr. Joos said it would be interesting to see what percentage of these T2D patients without obesity (body mass index < 95th percentile) would still meet the criteria for being overweight (BMI > 85th percentile) as this is the primary criterion for screening according to the American Diabetes Association guidelines.
Current guidelines generally look for elevated body mass measures as a main screening indication, Dr. Samaan’s group noted. But in their view, while factors such as ethnicity and in utero exposure to diabetes are already used in combination with BMI-based measures to justify screening, more sophisticated prediabetes and diabetes prediction models are needed to support a more comprehensive screening approach.
“Because being overweight is the initial criterion, children with multiple other criteria are not being screened,” Dr. Joos said. He agreed that more research is needed to sort out the other risk factors for pediatric T2D without obesity so these patients may be detected earlier.
New models may need to incorporate lifestyle factors, hormones, puberty, growth, and sex as well, the authors wrote. Markers of insulin resistance, insulin production capacity, and other markers are needed to refine the identification of those who should be screened.
Dr. Samaan’s group is planning to study the findings in more detail to clarify the effect of body mass on the comorbidities and complications of pediatric T2D.
In addition to the study limitation of significant interstudy heterogeneity, the authors acknowledged varying degrees of glycemic control and dyslipidemia among participants.
No specific funding was provided for this review and meta-analysis. The authors disclosed no conflicts of interest. Dr. Joos disclosed no competing interests with regard to his comments.
FROM JAMA NETWORK OPEN
Intermittent fasting can lead to type 2 diabetes remission
In a small randomized controlled trial of patients with type 2 diabetes in China, close to half of those who followed a novel intermittent fasting program for 3 months had diabetes remission (A1c less than 6.5% without taking antidiabetic drugs) that persisted for 1 year.
Importantly, “this study was performed under real-life conditions, and the intervention was delivered by trained nurses in primary care rather than by specialized staff at a research institute, making it a more practical and achievable way to manage” type 2 diabetes, the authors report.
Moreover, 65% of the patients in the intervention group who achieved diabetes remission had had diabetes for more than 6 years, which “suggests the possibility of remission for patients with longer duration” of diabetes, they note.
In addition, antidiabetic medication costs decreased by 77%, compared with baseline, in patients in the intermittent-fasting intervention group.
Although intermittent fasting has been studied for weight loss, it had not been investigated for effectiveness for diabetes remission.
These findings suggest that intermittent fasting “could be a paradigm shift in the management goals in diabetes care,” Xiao Yang and colleagues conclude in their study, published online in The Journal of Clinical Endocrinology & Metabolism.
“Type 2 diabetes is not necessarily a permanent, lifelong disease,” senior author Dongbo Liu, PhD, from the Hunan Agricultural University, Changsha, China, added in a press release from The Endocrine Society.
“Diabetes remission is possible if patients lose weight by changing their diet and exercise habits,” Dr. Liu said.
‘Excellent outcome’
Invited to comment, Amy E. Rothberg, MD, PhD, who was not involved with the research, agreed that the study indicates that intermittent fasting works for diabetes remission.
“We know that diabetes remission is possible with calorie restriction and subsequent weight loss, and intermittent fasting is just one of the many [dietary] approaches that may be suitable, appealing, and sustainable to some individuals, and usually results in calorie restriction and therefore weight loss,” she said.
The most studied types of intermittent fasting diets are alternate-day fasting, the 5:2 diet, and time-restricted consumption, Dr. Rothberg told this news organization.
This study presented a novel type of intermittent fasting, she noted. The intervention consisted of 6 cycles (3 months) of 5 fasting days followed by 10 ad libitum days, and then 3 months of follow-up (with no fasting days).
After 3 months of the intervention plus 3 months of follow-up, 47% of the 36 patients in the intervention group achieved diabetes remission (with a mean A1c of 5.66%), compared with only 2.8% of the 36 patients in the control group.
At 12 months, 44% of patients in the intervention group had sustained diabetes remission (with a mean A1c of 6.33%).
This was “an excellent outcome,” said Dr. Rothberg, professor of nutritional sciences, School of Public Health, University of Michigan, Ann Arbor, and a co-author of an international consensus statement that defined diabetes remission.
On average, patients in the intermittent fasting group lost 5.93 kg (13.0 lb) in 3 months, which was sustained over 12 months. “The large amount of weight reduction is key to continuing to achieve diabetes remission,” she noted.
This contrasted with an average weight loss of just 0.27 kg (0.6 lb) in the control group.
Participants who were prescribed fewer antidiabetic medications were more likely to achieve diabetes remission. The researchers acknowledge that the study was not blinded, and they did not record physical activity (although participants were encouraged to maintain their usual physical activity).
This was a small study, Dr. Rothberg acknowledged. The researchers did not specify which specific antidiabetic drugs patients were taking, and they did not determine waist or hip circumference or assess lipids.
The diet was culturally sensitive, appropriate, and feasible in this Chinese population and would not be generalizable to non-Asians.
Nevertheless, a similar approach could be used in any population if the diet is tailored to the individual, according to Dr. Rothberg. Importantly, patients would need to receive guidance from a dietician to make sure their diet comprises all the necessary micronutrients, vitamins, and minerals on fasting days, and they would need to maintain a relatively balanced diet and not gorge themselves on feast days.
“I think we should campaign widely about lifestyle approaches to achieve diabetes remission,” she urged.
72 patients with diabetes for an average of 6.6 years
“Despite a widespread public consensus that [type 2 diabetes] is irreversible and requires drug treatment escalation, there is some evidence of the possibility of remission,” Dr. Yang and colleagues write in their article.
They aimed to evaluate the effectiveness of intermittent fasting for diabetes remission and the durability of diabetes remission at 1 year.
Diabetes remission was defined having a stable A1c less than 6.5% for at least 3 months after discontinuing all antidiabetic medications, confirmed in at least annual A1c measurements (according to a 2021 consensus statement initiated by the American Diabetes Association).
Between 2019 and 2020, the researchers enrolled 72 participants aged 38-72 years who had had type 2 diabetes (duration 1 to 11 years) and a body mass index (BMI) of 19.1-30.4 kg/m2. Patients were randomized 1:1 to the intermittent fasting group or control group.
Baseline characteristics were similar in both groups. Patients were a mean age of 53 years and roughly 60% were men. They had a mean BMI of 24 kg/m2, a mean duration of diabetes of 6.6 years, and a mean A1c of 7.6%, and they were taking an average of 1.8 glucose-lowering medications.
On fasting days, patients in the intervention group received a Chinese Medical Nutrition Therapy kit that provided approximately 840 kcal/day (46% carbohydrates, 46% fat, 8% protein). The kit included a breakfast of a fruit and vegetable gruel, lunch of a solid beverage plus a nutritional rice composite, and dinner of a solid beverage and a meal replacement biscuit, which participants reconstituted by mixing with boiling water. They were allowed to consume noncaloric beverages.
On nonfasting days, patients chose foods ad libitum based on the 2017 Dietary Guidelines for Diabetes in China, which recommend approximately 50%-65% of total energy intake from carbohydrates, 15%-20% from protein, and 20%-30% from fat, and had greater than or equal to 5 g fiber per serving.
Patients in the control group chose foods ad libitum from the dietary guidelines during the entire study.
The study received funding from the National Natural Science Foundation of China. The authors have reported no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
In a small randomized controlled trial of patients with type 2 diabetes in China, close to half of those who followed a novel intermittent fasting program for 3 months had diabetes remission (A1c less than 6.5% without taking antidiabetic drugs) that persisted for 1 year.
Importantly, “this study was performed under real-life conditions, and the intervention was delivered by trained nurses in primary care rather than by specialized staff at a research institute, making it a more practical and achievable way to manage” type 2 diabetes, the authors report.
Moreover, 65% of the patients in the intervention group who achieved diabetes remission had had diabetes for more than 6 years, which “suggests the possibility of remission for patients with longer duration” of diabetes, they note.
In addition, antidiabetic medication costs decreased by 77%, compared with baseline, in patients in the intermittent-fasting intervention group.
Although intermittent fasting has been studied for weight loss, it had not been investigated for effectiveness for diabetes remission.
These findings suggest that intermittent fasting “could be a paradigm shift in the management goals in diabetes care,” Xiao Yang and colleagues conclude in their study, published online in The Journal of Clinical Endocrinology & Metabolism.
“Type 2 diabetes is not necessarily a permanent, lifelong disease,” senior author Dongbo Liu, PhD, from the Hunan Agricultural University, Changsha, China, added in a press release from The Endocrine Society.
“Diabetes remission is possible if patients lose weight by changing their diet and exercise habits,” Dr. Liu said.
‘Excellent outcome’
Invited to comment, Amy E. Rothberg, MD, PhD, who was not involved with the research, agreed that the study indicates that intermittent fasting works for diabetes remission.
“We know that diabetes remission is possible with calorie restriction and subsequent weight loss, and intermittent fasting is just one of the many [dietary] approaches that may be suitable, appealing, and sustainable to some individuals, and usually results in calorie restriction and therefore weight loss,” she said.
The most studied types of intermittent fasting diets are alternate-day fasting, the 5:2 diet, and time-restricted consumption, Dr. Rothberg told this news organization.
This study presented a novel type of intermittent fasting, she noted. The intervention consisted of 6 cycles (3 months) of 5 fasting days followed by 10 ad libitum days, and then 3 months of follow-up (with no fasting days).
After 3 months of the intervention plus 3 months of follow-up, 47% of the 36 patients in the intervention group achieved diabetes remission (with a mean A1c of 5.66%), compared with only 2.8% of the 36 patients in the control group.
At 12 months, 44% of patients in the intervention group had sustained diabetes remission (with a mean A1c of 6.33%).
This was “an excellent outcome,” said Dr. Rothberg, professor of nutritional sciences, School of Public Health, University of Michigan, Ann Arbor, and a co-author of an international consensus statement that defined diabetes remission.
On average, patients in the intermittent fasting group lost 5.93 kg (13.0 lb) in 3 months, which was sustained over 12 months. “The large amount of weight reduction is key to continuing to achieve diabetes remission,” she noted.
This contrasted with an average weight loss of just 0.27 kg (0.6 lb) in the control group.
Participants who were prescribed fewer antidiabetic medications were more likely to achieve diabetes remission. The researchers acknowledge that the study was not blinded, and they did not record physical activity (although participants were encouraged to maintain their usual physical activity).
This was a small study, Dr. Rothberg acknowledged. The researchers did not specify which specific antidiabetic drugs patients were taking, and they did not determine waist or hip circumference or assess lipids.
The diet was culturally sensitive, appropriate, and feasible in this Chinese population and would not be generalizable to non-Asians.
Nevertheless, a similar approach could be used in any population if the diet is tailored to the individual, according to Dr. Rothberg. Importantly, patients would need to receive guidance from a dietician to make sure their diet comprises all the necessary micronutrients, vitamins, and minerals on fasting days, and they would need to maintain a relatively balanced diet and not gorge themselves on feast days.
“I think we should campaign widely about lifestyle approaches to achieve diabetes remission,” she urged.
72 patients with diabetes for an average of 6.6 years
“Despite a widespread public consensus that [type 2 diabetes] is irreversible and requires drug treatment escalation, there is some evidence of the possibility of remission,” Dr. Yang and colleagues write in their article.
They aimed to evaluate the effectiveness of intermittent fasting for diabetes remission and the durability of diabetes remission at 1 year.
Diabetes remission was defined having a stable A1c less than 6.5% for at least 3 months after discontinuing all antidiabetic medications, confirmed in at least annual A1c measurements (according to a 2021 consensus statement initiated by the American Diabetes Association).
Between 2019 and 2020, the researchers enrolled 72 participants aged 38-72 years who had had type 2 diabetes (duration 1 to 11 years) and a body mass index (BMI) of 19.1-30.4 kg/m2. Patients were randomized 1:1 to the intermittent fasting group or control group.
Baseline characteristics were similar in both groups. Patients were a mean age of 53 years and roughly 60% were men. They had a mean BMI of 24 kg/m2, a mean duration of diabetes of 6.6 years, and a mean A1c of 7.6%, and they were taking an average of 1.8 glucose-lowering medications.
On fasting days, patients in the intervention group received a Chinese Medical Nutrition Therapy kit that provided approximately 840 kcal/day (46% carbohydrates, 46% fat, 8% protein). The kit included a breakfast of a fruit and vegetable gruel, lunch of a solid beverage plus a nutritional rice composite, and dinner of a solid beverage and a meal replacement biscuit, which participants reconstituted by mixing with boiling water. They were allowed to consume noncaloric beverages.
On nonfasting days, patients chose foods ad libitum based on the 2017 Dietary Guidelines for Diabetes in China, which recommend approximately 50%-65% of total energy intake from carbohydrates, 15%-20% from protein, and 20%-30% from fat, and had greater than or equal to 5 g fiber per serving.
Patients in the control group chose foods ad libitum from the dietary guidelines during the entire study.
The study received funding from the National Natural Science Foundation of China. The authors have reported no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
In a small randomized controlled trial of patients with type 2 diabetes in China, close to half of those who followed a novel intermittent fasting program for 3 months had diabetes remission (A1c less than 6.5% without taking antidiabetic drugs) that persisted for 1 year.
Importantly, “this study was performed under real-life conditions, and the intervention was delivered by trained nurses in primary care rather than by specialized staff at a research institute, making it a more practical and achievable way to manage” type 2 diabetes, the authors report.
Moreover, 65% of the patients in the intervention group who achieved diabetes remission had had diabetes for more than 6 years, which “suggests the possibility of remission for patients with longer duration” of diabetes, they note.
In addition, antidiabetic medication costs decreased by 77%, compared with baseline, in patients in the intermittent-fasting intervention group.
Although intermittent fasting has been studied for weight loss, it had not been investigated for effectiveness for diabetes remission.
These findings suggest that intermittent fasting “could be a paradigm shift in the management goals in diabetes care,” Xiao Yang and colleagues conclude in their study, published online in The Journal of Clinical Endocrinology & Metabolism.
“Type 2 diabetes is not necessarily a permanent, lifelong disease,” senior author Dongbo Liu, PhD, from the Hunan Agricultural University, Changsha, China, added in a press release from The Endocrine Society.
“Diabetes remission is possible if patients lose weight by changing their diet and exercise habits,” Dr. Liu said.
‘Excellent outcome’
Invited to comment, Amy E. Rothberg, MD, PhD, who was not involved with the research, agreed that the study indicates that intermittent fasting works for diabetes remission.
“We know that diabetes remission is possible with calorie restriction and subsequent weight loss, and intermittent fasting is just one of the many [dietary] approaches that may be suitable, appealing, and sustainable to some individuals, and usually results in calorie restriction and therefore weight loss,” she said.
The most studied types of intermittent fasting diets are alternate-day fasting, the 5:2 diet, and time-restricted consumption, Dr. Rothberg told this news organization.
This study presented a novel type of intermittent fasting, she noted. The intervention consisted of 6 cycles (3 months) of 5 fasting days followed by 10 ad libitum days, and then 3 months of follow-up (with no fasting days).
After 3 months of the intervention plus 3 months of follow-up, 47% of the 36 patients in the intervention group achieved diabetes remission (with a mean A1c of 5.66%), compared with only 2.8% of the 36 patients in the control group.
At 12 months, 44% of patients in the intervention group had sustained diabetes remission (with a mean A1c of 6.33%).
This was “an excellent outcome,” said Dr. Rothberg, professor of nutritional sciences, School of Public Health, University of Michigan, Ann Arbor, and a co-author of an international consensus statement that defined diabetes remission.
On average, patients in the intermittent fasting group lost 5.93 kg (13.0 lb) in 3 months, which was sustained over 12 months. “The large amount of weight reduction is key to continuing to achieve diabetes remission,” she noted.
This contrasted with an average weight loss of just 0.27 kg (0.6 lb) in the control group.
Participants who were prescribed fewer antidiabetic medications were more likely to achieve diabetes remission. The researchers acknowledge that the study was not blinded, and they did not record physical activity (although participants were encouraged to maintain their usual physical activity).
This was a small study, Dr. Rothberg acknowledged. The researchers did not specify which specific antidiabetic drugs patients were taking, and they did not determine waist or hip circumference or assess lipids.
The diet was culturally sensitive, appropriate, and feasible in this Chinese population and would not be generalizable to non-Asians.
Nevertheless, a similar approach could be used in any population if the diet is tailored to the individual, according to Dr. Rothberg. Importantly, patients would need to receive guidance from a dietician to make sure their diet comprises all the necessary micronutrients, vitamins, and minerals on fasting days, and they would need to maintain a relatively balanced diet and not gorge themselves on feast days.
“I think we should campaign widely about lifestyle approaches to achieve diabetes remission,” she urged.
72 patients with diabetes for an average of 6.6 years
“Despite a widespread public consensus that [type 2 diabetes] is irreversible and requires drug treatment escalation, there is some evidence of the possibility of remission,” Dr. Yang and colleagues write in their article.
They aimed to evaluate the effectiveness of intermittent fasting for diabetes remission and the durability of diabetes remission at 1 year.
Diabetes remission was defined having a stable A1c less than 6.5% for at least 3 months after discontinuing all antidiabetic medications, confirmed in at least annual A1c measurements (according to a 2021 consensus statement initiated by the American Diabetes Association).
Between 2019 and 2020, the researchers enrolled 72 participants aged 38-72 years who had had type 2 diabetes (duration 1 to 11 years) and a body mass index (BMI) of 19.1-30.4 kg/m2. Patients were randomized 1:1 to the intermittent fasting group or control group.
Baseline characteristics were similar in both groups. Patients were a mean age of 53 years and roughly 60% were men. They had a mean BMI of 24 kg/m2, a mean duration of diabetes of 6.6 years, and a mean A1c of 7.6%, and they were taking an average of 1.8 glucose-lowering medications.
On fasting days, patients in the intervention group received a Chinese Medical Nutrition Therapy kit that provided approximately 840 kcal/day (46% carbohydrates, 46% fat, 8% protein). The kit included a breakfast of a fruit and vegetable gruel, lunch of a solid beverage plus a nutritional rice composite, and dinner of a solid beverage and a meal replacement biscuit, which participants reconstituted by mixing with boiling water. They were allowed to consume noncaloric beverages.
On nonfasting days, patients chose foods ad libitum based on the 2017 Dietary Guidelines for Diabetes in China, which recommend approximately 50%-65% of total energy intake from carbohydrates, 15%-20% from protein, and 20%-30% from fat, and had greater than or equal to 5 g fiber per serving.
Patients in the control group chose foods ad libitum from the dietary guidelines during the entire study.
The study received funding from the National Natural Science Foundation of China. The authors have reported no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
DELIVER subanalysis ‘seals deal’ for dapagliflozin in HF
A prespecified analysis of a large global trial of patients with symptomatic heart failure with mildly reduced and preserved ejection fraction “seals the deal” on the efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors to manage and improve their symptoms.
The prespecified analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trial included 5,795 patients with mildly reduced and preserved ejection fraction who completed the Kansas City Cardiomyopathy Questionnaire (KCCQ) after taking the SGLT2 inhibitor dapagliflozin or placebo. The results were published online in the Journal of the American College of Cardiology.
“We’ve known from studies prior to DELIVER that SGLT2 inhibitors have been shown to improve health status, patient symptoms and quality of life among those that are living with heart failure and mildly reduced [HFmrEF] and preserved [HFpEF] ejection fraction,” lead author Mikhail N. Kosiborod, MD, vice president for research at Saint Luke’s Health System, and codirector of the St. Luke’s Michael and Marly Haverty Cardiometabolic Center of Excellence at St. Luke’s Mid America Heart Institute, Kansas City, Mo., said in an interview. “But the picture was incomplete for a number of different reasons, partly because the previous studies were either relatively modest in size, geographically limited, or suggested potential attenuation of these benefits in patients with completely normal ejection fraction.”
Specifically, the study authors noted the EMPEROR-Preserved trial of the SGLT2 inhibitor empagliflozin showed improvement in health status vs. placebo across the range of EF except in those with normal EF of 65% or greater. The PRESERVED-HF trial of dapagliflozin demonstrated a more robust response than EMPEROR-Preserved or DELIVER, but PRESERVED-HF patients were recruited only in the United States and had more debilitating HF symptoms at baseline.
“Because of the results of the DELIVER trial and because of how large, extensive, and inclusive the trial was, it really seals the deal on the value of SGLT2 inhibitors in patients with heart failure,” said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri–Kansas City.
The DELIVER analysis found that the effects of dapagliflozin on reducing cardiovascular death and worsening HF were greatest in patients who had the most debilitating symptoms at baseline, measured as KCCQ total symptom score (TSS) as 63 or less, the lowest of three tertiles used in the analysis. At baseline, these patients had the highest rates of CV death or worsening HF than those in the other two tertiles: KCCQ-TSS of 63-84, and greater than 84.
Compared with placebo, treated patients in the lowest KCCQ-TSS quartile had a 30% reduction in risk for the primary composite outcome, which consisted of time to first CV death or HF event (hazard ratio, 0.70; 95% confidence interval, 0.58-0.84; P < .001). In the second tertile, the relative risk reduction was 19% (HR, 0.81; 95% CI, 0.65-1.01; P < .006), and the highest quartile showed no significant difference between treatment and placebo (HR, 1.07; 95% CI, 0.83-1.37; P < .62).
“The most important take home message is that the SGLT2 inhibitor dapagliflozin significantly improved patient symptoms as measured by the Kansas City Cardiomyopathy Questionnaire symptom score,” Dr. Kosiborod said. “It improved those symptoms within 1 month and those benefits were sustained out to 8 months.”
DELIVER patients also showed improvement in all other key KCCQ domains across the board, he added. “In addition, dapagliflozin also improved the proportion of patients who had small, moderate, and large improvements in a responder analysis. So really, by every measure that we had, dapagliflozin had a significant beneficial effect.”
The DELIVER results taken collectively with the EMPEROR-Preserved and PRESERVED-HF trials cinch the deal for SGLT2 inhibitors, Dr. Kosiborod said. “They deliver on the triple goal of care in patients with heart failure. They reduce the risk of cardiovascular death and worsening heart failure and they improve patient symptoms, function and quality of life – and they accomplish that across the entire continuum of heart failure regardless of ejection fraction, regardless of whether patients are hospitalized or in an ambulatory setting, regardless of age or background therapies or other comorbidities.”
He added: “It’s a pretty historic development because we haven’t had that before.”
AstraZeneca funded the DELIVER trial. Dr. Kosiborod disclosed financial relationships with Alnylam, Amgen, Applied Therapeutics, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Janssen, Lexicon, Merck (Diabetes and Cardiovascular), Novo Nordisk, Sanofi, Pharmacosmos and Vifor Pharma.
A prespecified analysis of a large global trial of patients with symptomatic heart failure with mildly reduced and preserved ejection fraction “seals the deal” on the efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors to manage and improve their symptoms.
The prespecified analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trial included 5,795 patients with mildly reduced and preserved ejection fraction who completed the Kansas City Cardiomyopathy Questionnaire (KCCQ) after taking the SGLT2 inhibitor dapagliflozin or placebo. The results were published online in the Journal of the American College of Cardiology.
“We’ve known from studies prior to DELIVER that SGLT2 inhibitors have been shown to improve health status, patient symptoms and quality of life among those that are living with heart failure and mildly reduced [HFmrEF] and preserved [HFpEF] ejection fraction,” lead author Mikhail N. Kosiborod, MD, vice president for research at Saint Luke’s Health System, and codirector of the St. Luke’s Michael and Marly Haverty Cardiometabolic Center of Excellence at St. Luke’s Mid America Heart Institute, Kansas City, Mo., said in an interview. “But the picture was incomplete for a number of different reasons, partly because the previous studies were either relatively modest in size, geographically limited, or suggested potential attenuation of these benefits in patients with completely normal ejection fraction.”
Specifically, the study authors noted the EMPEROR-Preserved trial of the SGLT2 inhibitor empagliflozin showed improvement in health status vs. placebo across the range of EF except in those with normal EF of 65% or greater. The PRESERVED-HF trial of dapagliflozin demonstrated a more robust response than EMPEROR-Preserved or DELIVER, but PRESERVED-HF patients were recruited only in the United States and had more debilitating HF symptoms at baseline.
“Because of the results of the DELIVER trial and because of how large, extensive, and inclusive the trial was, it really seals the deal on the value of SGLT2 inhibitors in patients with heart failure,” said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri–Kansas City.
The DELIVER analysis found that the effects of dapagliflozin on reducing cardiovascular death and worsening HF were greatest in patients who had the most debilitating symptoms at baseline, measured as KCCQ total symptom score (TSS) as 63 or less, the lowest of three tertiles used in the analysis. At baseline, these patients had the highest rates of CV death or worsening HF than those in the other two tertiles: KCCQ-TSS of 63-84, and greater than 84.
Compared with placebo, treated patients in the lowest KCCQ-TSS quartile had a 30% reduction in risk for the primary composite outcome, which consisted of time to first CV death or HF event (hazard ratio, 0.70; 95% confidence interval, 0.58-0.84; P < .001). In the second tertile, the relative risk reduction was 19% (HR, 0.81; 95% CI, 0.65-1.01; P < .006), and the highest quartile showed no significant difference between treatment and placebo (HR, 1.07; 95% CI, 0.83-1.37; P < .62).
“The most important take home message is that the SGLT2 inhibitor dapagliflozin significantly improved patient symptoms as measured by the Kansas City Cardiomyopathy Questionnaire symptom score,” Dr. Kosiborod said. “It improved those symptoms within 1 month and those benefits were sustained out to 8 months.”
DELIVER patients also showed improvement in all other key KCCQ domains across the board, he added. “In addition, dapagliflozin also improved the proportion of patients who had small, moderate, and large improvements in a responder analysis. So really, by every measure that we had, dapagliflozin had a significant beneficial effect.”
The DELIVER results taken collectively with the EMPEROR-Preserved and PRESERVED-HF trials cinch the deal for SGLT2 inhibitors, Dr. Kosiborod said. “They deliver on the triple goal of care in patients with heart failure. They reduce the risk of cardiovascular death and worsening heart failure and they improve patient symptoms, function and quality of life – and they accomplish that across the entire continuum of heart failure regardless of ejection fraction, regardless of whether patients are hospitalized or in an ambulatory setting, regardless of age or background therapies or other comorbidities.”
He added: “It’s a pretty historic development because we haven’t had that before.”
AstraZeneca funded the DELIVER trial. Dr. Kosiborod disclosed financial relationships with Alnylam, Amgen, Applied Therapeutics, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Janssen, Lexicon, Merck (Diabetes and Cardiovascular), Novo Nordisk, Sanofi, Pharmacosmos and Vifor Pharma.
A prespecified analysis of a large global trial of patients with symptomatic heart failure with mildly reduced and preserved ejection fraction “seals the deal” on the efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors to manage and improve their symptoms.
The prespecified analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trial included 5,795 patients with mildly reduced and preserved ejection fraction who completed the Kansas City Cardiomyopathy Questionnaire (KCCQ) after taking the SGLT2 inhibitor dapagliflozin or placebo. The results were published online in the Journal of the American College of Cardiology.
“We’ve known from studies prior to DELIVER that SGLT2 inhibitors have been shown to improve health status, patient symptoms and quality of life among those that are living with heart failure and mildly reduced [HFmrEF] and preserved [HFpEF] ejection fraction,” lead author Mikhail N. Kosiborod, MD, vice president for research at Saint Luke’s Health System, and codirector of the St. Luke’s Michael and Marly Haverty Cardiometabolic Center of Excellence at St. Luke’s Mid America Heart Institute, Kansas City, Mo., said in an interview. “But the picture was incomplete for a number of different reasons, partly because the previous studies were either relatively modest in size, geographically limited, or suggested potential attenuation of these benefits in patients with completely normal ejection fraction.”
Specifically, the study authors noted the EMPEROR-Preserved trial of the SGLT2 inhibitor empagliflozin showed improvement in health status vs. placebo across the range of EF except in those with normal EF of 65% or greater. The PRESERVED-HF trial of dapagliflozin demonstrated a more robust response than EMPEROR-Preserved or DELIVER, but PRESERVED-HF patients were recruited only in the United States and had more debilitating HF symptoms at baseline.
“Because of the results of the DELIVER trial and because of how large, extensive, and inclusive the trial was, it really seals the deal on the value of SGLT2 inhibitors in patients with heart failure,” said Dr. Kosiborod, who is also a professor of medicine at the University of Missouri–Kansas City.
The DELIVER analysis found that the effects of dapagliflozin on reducing cardiovascular death and worsening HF were greatest in patients who had the most debilitating symptoms at baseline, measured as KCCQ total symptom score (TSS) as 63 or less, the lowest of three tertiles used in the analysis. At baseline, these patients had the highest rates of CV death or worsening HF than those in the other two tertiles: KCCQ-TSS of 63-84, and greater than 84.
Compared with placebo, treated patients in the lowest KCCQ-TSS quartile had a 30% reduction in risk for the primary composite outcome, which consisted of time to first CV death or HF event (hazard ratio, 0.70; 95% confidence interval, 0.58-0.84; P < .001). In the second tertile, the relative risk reduction was 19% (HR, 0.81; 95% CI, 0.65-1.01; P < .006), and the highest quartile showed no significant difference between treatment and placebo (HR, 1.07; 95% CI, 0.83-1.37; P < .62).
“The most important take home message is that the SGLT2 inhibitor dapagliflozin significantly improved patient symptoms as measured by the Kansas City Cardiomyopathy Questionnaire symptom score,” Dr. Kosiborod said. “It improved those symptoms within 1 month and those benefits were sustained out to 8 months.”
DELIVER patients also showed improvement in all other key KCCQ domains across the board, he added. “In addition, dapagliflozin also improved the proportion of patients who had small, moderate, and large improvements in a responder analysis. So really, by every measure that we had, dapagliflozin had a significant beneficial effect.”
The DELIVER results taken collectively with the EMPEROR-Preserved and PRESERVED-HF trials cinch the deal for SGLT2 inhibitors, Dr. Kosiborod said. “They deliver on the triple goal of care in patients with heart failure. They reduce the risk of cardiovascular death and worsening heart failure and they improve patient symptoms, function and quality of life – and they accomplish that across the entire continuum of heart failure regardless of ejection fraction, regardless of whether patients are hospitalized or in an ambulatory setting, regardless of age or background therapies or other comorbidities.”
He added: “It’s a pretty historic development because we haven’t had that before.”
AstraZeneca funded the DELIVER trial. Dr. Kosiborod disclosed financial relationships with Alnylam, Amgen, Applied Therapeutics, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Janssen, Lexicon, Merck (Diabetes and Cardiovascular), Novo Nordisk, Sanofi, Pharmacosmos and Vifor Pharma.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
ADA issues 2023 ‘Standards of Care’ for diabetes: Focus on tight BP, lipids
New more aggressive targets for blood pressure and lipids are among the changes to the annual American Diabetes Association (ADA) Standards of Care in Diabetes – 2023.
The document, long considered the gold standard for care of the more than 100 million Americans living with diabetes and prediabetes, was published as a supplement in Diabetes Care. The guidelines are also accessible to doctors via an app; last year’s standards were accessed more than 4 million times.
The standards now advise a blood pressure target for people with diabetes of less than 130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol targets of below 70 mg/dL or no greater than 55 mg/dL, depending on the individual’s cardiovascular risk.
“In this year’s version of the ADA Standards of Care – the longstanding guidelines for diabetes management globally – you’ll see information that really speaks to how we can more aggressively treat diabetes and reduce complications in a variety of different ways,” ADA Chief Scientific and Medical Officer Robert A. Gabbay, MD, PhD, said in an interview.
Other changes for 2023 include a new emphasis on weight loss as a goal of therapy for type 2 diabetes; guidance for screening and assessing peripheral arterial disease in an effort to prevent amputations; use of finerenone in people with diabetes and chronic kidney disease; use of approved point-of-care A1c tests; and guidance on screening for food insecurity, along with an elevated role for community health workers.
“The management of type 2 diabetes is not just about glucose,” Dr. Gabbay emphasized, noting that the ADA Standards have increasingly focused on cardiorenal risk as well as weight management. “We need to think about all those things, not just one. We have better tools now that have been helpful in being able to move forward with this.”
New targets in cardiovascular disease and risk management
As it has been for the past 6 years, the section on cardiovascular disease and risk management is also endorsed by the American College of Cardiology.
The new definition of hypertension in people with diabetes is ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic blood pressure, repeated on two measurements at different times. Among individuals with established cardiovascular disease, hypertension can be diagnosed with one measurement of ≥ 180/110 mm Hg.
The goal of treatment is now less than 130/80 mm Hg if it can be reached safely.
In 2012, easing of the systolic target to 140 mm Hg by the ADA caused some controversy.
But, as Dr. Gabbay explained: “The evidence wasn’t there 10 years ago. We stuck to the evidence at that time, although there was a belief that lower was better. Over the past decade, a number of studies have made it quite clear that there is benefit to a lower target. That’s why we staked out the ground on this.”
The new Standards of Care also has new lipid targets. For people with diabetes aged 40-75 years at increased cardiovascular risk, including those with one or more atherosclerotic risk factors, high-intensity statin therapy is recommended to reduce LDL cholesterol by 50% or more from baseline and to a target of less than 70 mg/dL, in contrast to the previous target of 100 mg/dL.
To achieve that goal, the document advises to consider adding ezetimibe or a PCSK9 inhibitor to maximally tolerated statin therapy.
For people with diabetes aged 40-75 who have established cardiovascular disease, treatment with high-intensity statin therapy is recommended with the target of a 50% or greater reduction from baseline and an LDL cholesterol level of 55 mg/dL or lower, in contrast to the previous 70 mg/dL.
“That is a lower goal than previously recommended, and based on strong evidence in the literature,” Dr. Gabbay noted.
Here, a stronger recommendation is made for ezetimibe or a PCSK9 inhibitor added to maximal statins.
And for people with diabetes older than 75 years, those already on statins should continue taking them. For those who aren’t, it may be reasonable to initiate moderate-intensity statin therapy after discussion of the benefits and risks.
Another new recommendation based on recent trial data is use of a sodium–glucose cotransporter 2 (SGLT2) inhibitor in people with diabetes and heart failure with preserved, as well as reduced, ejection fraction.
Kidney disease guidance updated: SGLT2 inhibitors, finerenone
Another recommendation calls for the addition of finerenone for people with type 2 diabetes who have chronic kidney disease (CKD) with albuminuria and have been treated with the maximum tolerated doses of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to improve cardiovascular outcomes as well as reduce the risk of CKD progression.
The threshold for initiating an SGLT2 inhibitor for kidney protection has changed to an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m2 and urinary albumin ≥ 200 mg/g creatinine (previously ≥ 25 mL/min/1.73 m2 and ≥ 300 mg/g, respectively). An SGLT2 inhibitor may also be beneficial in people with a urinary albumin of normal to ≥ 200 mg/g creatinine, but supporting data have not yet been published.
Referral to a nephrologist is advised for individuals with increasing urinary albumin levels or continued decreasing eGFR or eGFR < 30 mL/min/1.73 m2.
Weight loss, point-of-care testing, food insecurity assessment
Other changes for 2023 include fresh emphasis on supporting weight loss of up to 15% with the new twincretin tirzepatide (Mounjaro) – approved in the United States in May for type 2 diabetes – added as a glucose-lowering drug with weight loss potential.
A novel section was added with guidance for peripheral arterial disease screening.
And a new recommendation advises use of point-of-care A1c testing for diabetes screening and diagnosis using only tests approved by the Food and Drug Administration.
Also introduced for 2023 is guidance to use community health workers to support the management of diabetes and cardiovascular risk factors, particularly in underserved areas and health systems.
“Community health workers can be a link to help people navigate and engage with the health system for better outcomes,” said Dr. Gabbay.
He added that these professionals are among those who can also assist with screening for food insecurity, another new recommendation. “We talk about screening for food insecurity and tools to use. That shouldn’t be something only dietitians do.”
Dr. Gabbay said he’d like to see more clinicians partner with community health workers. “We’d like to see more of that ... They should be considered part of the health care team,” he said.
Dr. Gabbay has reported serving on advisory boards for Lark, Health Reveal, Sweetch, StartUp Health, Vida Health, and Onduo.
A version of this article first appeared on Medscape.com.
New more aggressive targets for blood pressure and lipids are among the changes to the annual American Diabetes Association (ADA) Standards of Care in Diabetes – 2023.
The document, long considered the gold standard for care of the more than 100 million Americans living with diabetes and prediabetes, was published as a supplement in Diabetes Care. The guidelines are also accessible to doctors via an app; last year’s standards were accessed more than 4 million times.
The standards now advise a blood pressure target for people with diabetes of less than 130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol targets of below 70 mg/dL or no greater than 55 mg/dL, depending on the individual’s cardiovascular risk.
“In this year’s version of the ADA Standards of Care – the longstanding guidelines for diabetes management globally – you’ll see information that really speaks to how we can more aggressively treat diabetes and reduce complications in a variety of different ways,” ADA Chief Scientific and Medical Officer Robert A. Gabbay, MD, PhD, said in an interview.
Other changes for 2023 include a new emphasis on weight loss as a goal of therapy for type 2 diabetes; guidance for screening and assessing peripheral arterial disease in an effort to prevent amputations; use of finerenone in people with diabetes and chronic kidney disease; use of approved point-of-care A1c tests; and guidance on screening for food insecurity, along with an elevated role for community health workers.
“The management of type 2 diabetes is not just about glucose,” Dr. Gabbay emphasized, noting that the ADA Standards have increasingly focused on cardiorenal risk as well as weight management. “We need to think about all those things, not just one. We have better tools now that have been helpful in being able to move forward with this.”
New targets in cardiovascular disease and risk management
As it has been for the past 6 years, the section on cardiovascular disease and risk management is also endorsed by the American College of Cardiology.
The new definition of hypertension in people with diabetes is ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic blood pressure, repeated on two measurements at different times. Among individuals with established cardiovascular disease, hypertension can be diagnosed with one measurement of ≥ 180/110 mm Hg.
The goal of treatment is now less than 130/80 mm Hg if it can be reached safely.
In 2012, easing of the systolic target to 140 mm Hg by the ADA caused some controversy.
But, as Dr. Gabbay explained: “The evidence wasn’t there 10 years ago. We stuck to the evidence at that time, although there was a belief that lower was better. Over the past decade, a number of studies have made it quite clear that there is benefit to a lower target. That’s why we staked out the ground on this.”
The new Standards of Care also has new lipid targets. For people with diabetes aged 40-75 years at increased cardiovascular risk, including those with one or more atherosclerotic risk factors, high-intensity statin therapy is recommended to reduce LDL cholesterol by 50% or more from baseline and to a target of less than 70 mg/dL, in contrast to the previous target of 100 mg/dL.
To achieve that goal, the document advises to consider adding ezetimibe or a PCSK9 inhibitor to maximally tolerated statin therapy.
For people with diabetes aged 40-75 who have established cardiovascular disease, treatment with high-intensity statin therapy is recommended with the target of a 50% or greater reduction from baseline and an LDL cholesterol level of 55 mg/dL or lower, in contrast to the previous 70 mg/dL.
“That is a lower goal than previously recommended, and based on strong evidence in the literature,” Dr. Gabbay noted.
Here, a stronger recommendation is made for ezetimibe or a PCSK9 inhibitor added to maximal statins.
And for people with diabetes older than 75 years, those already on statins should continue taking them. For those who aren’t, it may be reasonable to initiate moderate-intensity statin therapy after discussion of the benefits and risks.
Another new recommendation based on recent trial data is use of a sodium–glucose cotransporter 2 (SGLT2) inhibitor in people with diabetes and heart failure with preserved, as well as reduced, ejection fraction.
Kidney disease guidance updated: SGLT2 inhibitors, finerenone
Another recommendation calls for the addition of finerenone for people with type 2 diabetes who have chronic kidney disease (CKD) with albuminuria and have been treated with the maximum tolerated doses of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to improve cardiovascular outcomes as well as reduce the risk of CKD progression.
The threshold for initiating an SGLT2 inhibitor for kidney protection has changed to an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m2 and urinary albumin ≥ 200 mg/g creatinine (previously ≥ 25 mL/min/1.73 m2 and ≥ 300 mg/g, respectively). An SGLT2 inhibitor may also be beneficial in people with a urinary albumin of normal to ≥ 200 mg/g creatinine, but supporting data have not yet been published.
Referral to a nephrologist is advised for individuals with increasing urinary albumin levels or continued decreasing eGFR or eGFR < 30 mL/min/1.73 m2.
Weight loss, point-of-care testing, food insecurity assessment
Other changes for 2023 include fresh emphasis on supporting weight loss of up to 15% with the new twincretin tirzepatide (Mounjaro) – approved in the United States in May for type 2 diabetes – added as a glucose-lowering drug with weight loss potential.
A novel section was added with guidance for peripheral arterial disease screening.
And a new recommendation advises use of point-of-care A1c testing for diabetes screening and diagnosis using only tests approved by the Food and Drug Administration.
Also introduced for 2023 is guidance to use community health workers to support the management of diabetes and cardiovascular risk factors, particularly in underserved areas and health systems.
“Community health workers can be a link to help people navigate and engage with the health system for better outcomes,” said Dr. Gabbay.
He added that these professionals are among those who can also assist with screening for food insecurity, another new recommendation. “We talk about screening for food insecurity and tools to use. That shouldn’t be something only dietitians do.”
Dr. Gabbay said he’d like to see more clinicians partner with community health workers. “We’d like to see more of that ... They should be considered part of the health care team,” he said.
Dr. Gabbay has reported serving on advisory boards for Lark, Health Reveal, Sweetch, StartUp Health, Vida Health, and Onduo.
A version of this article first appeared on Medscape.com.
New more aggressive targets for blood pressure and lipids are among the changes to the annual American Diabetes Association (ADA) Standards of Care in Diabetes – 2023.
The document, long considered the gold standard for care of the more than 100 million Americans living with diabetes and prediabetes, was published as a supplement in Diabetes Care. The guidelines are also accessible to doctors via an app; last year’s standards were accessed more than 4 million times.
The standards now advise a blood pressure target for people with diabetes of less than 130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol targets of below 70 mg/dL or no greater than 55 mg/dL, depending on the individual’s cardiovascular risk.
“In this year’s version of the ADA Standards of Care – the longstanding guidelines for diabetes management globally – you’ll see information that really speaks to how we can more aggressively treat diabetes and reduce complications in a variety of different ways,” ADA Chief Scientific and Medical Officer Robert A. Gabbay, MD, PhD, said in an interview.
Other changes for 2023 include a new emphasis on weight loss as a goal of therapy for type 2 diabetes; guidance for screening and assessing peripheral arterial disease in an effort to prevent amputations; use of finerenone in people with diabetes and chronic kidney disease; use of approved point-of-care A1c tests; and guidance on screening for food insecurity, along with an elevated role for community health workers.
“The management of type 2 diabetes is not just about glucose,” Dr. Gabbay emphasized, noting that the ADA Standards have increasingly focused on cardiorenal risk as well as weight management. “We need to think about all those things, not just one. We have better tools now that have been helpful in being able to move forward with this.”
New targets in cardiovascular disease and risk management
As it has been for the past 6 years, the section on cardiovascular disease and risk management is also endorsed by the American College of Cardiology.
The new definition of hypertension in people with diabetes is ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic blood pressure, repeated on two measurements at different times. Among individuals with established cardiovascular disease, hypertension can be diagnosed with one measurement of ≥ 180/110 mm Hg.
The goal of treatment is now less than 130/80 mm Hg if it can be reached safely.
In 2012, easing of the systolic target to 140 mm Hg by the ADA caused some controversy.
But, as Dr. Gabbay explained: “The evidence wasn’t there 10 years ago. We stuck to the evidence at that time, although there was a belief that lower was better. Over the past decade, a number of studies have made it quite clear that there is benefit to a lower target. That’s why we staked out the ground on this.”
The new Standards of Care also has new lipid targets. For people with diabetes aged 40-75 years at increased cardiovascular risk, including those with one or more atherosclerotic risk factors, high-intensity statin therapy is recommended to reduce LDL cholesterol by 50% or more from baseline and to a target of less than 70 mg/dL, in contrast to the previous target of 100 mg/dL.
To achieve that goal, the document advises to consider adding ezetimibe or a PCSK9 inhibitor to maximally tolerated statin therapy.
For people with diabetes aged 40-75 who have established cardiovascular disease, treatment with high-intensity statin therapy is recommended with the target of a 50% or greater reduction from baseline and an LDL cholesterol level of 55 mg/dL or lower, in contrast to the previous 70 mg/dL.
“That is a lower goal than previously recommended, and based on strong evidence in the literature,” Dr. Gabbay noted.
Here, a stronger recommendation is made for ezetimibe or a PCSK9 inhibitor added to maximal statins.
And for people with diabetes older than 75 years, those already on statins should continue taking them. For those who aren’t, it may be reasonable to initiate moderate-intensity statin therapy after discussion of the benefits and risks.
Another new recommendation based on recent trial data is use of a sodium–glucose cotransporter 2 (SGLT2) inhibitor in people with diabetes and heart failure with preserved, as well as reduced, ejection fraction.
Kidney disease guidance updated: SGLT2 inhibitors, finerenone
Another recommendation calls for the addition of finerenone for people with type 2 diabetes who have chronic kidney disease (CKD) with albuminuria and have been treated with the maximum tolerated doses of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to improve cardiovascular outcomes as well as reduce the risk of CKD progression.
The threshold for initiating an SGLT2 inhibitor for kidney protection has changed to an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m2 and urinary albumin ≥ 200 mg/g creatinine (previously ≥ 25 mL/min/1.73 m2 and ≥ 300 mg/g, respectively). An SGLT2 inhibitor may also be beneficial in people with a urinary albumin of normal to ≥ 200 mg/g creatinine, but supporting data have not yet been published.
Referral to a nephrologist is advised for individuals with increasing urinary albumin levels or continued decreasing eGFR or eGFR < 30 mL/min/1.73 m2.
Weight loss, point-of-care testing, food insecurity assessment
Other changes for 2023 include fresh emphasis on supporting weight loss of up to 15% with the new twincretin tirzepatide (Mounjaro) – approved in the United States in May for type 2 diabetes – added as a glucose-lowering drug with weight loss potential.
A novel section was added with guidance for peripheral arterial disease screening.
And a new recommendation advises use of point-of-care A1c testing for diabetes screening and diagnosis using only tests approved by the Food and Drug Administration.
Also introduced for 2023 is guidance to use community health workers to support the management of diabetes and cardiovascular risk factors, particularly in underserved areas and health systems.
“Community health workers can be a link to help people navigate and engage with the health system for better outcomes,” said Dr. Gabbay.
He added that these professionals are among those who can also assist with screening for food insecurity, another new recommendation. “We talk about screening for food insecurity and tools to use. That shouldn’t be something only dietitians do.”
Dr. Gabbay said he’d like to see more clinicians partner with community health workers. “We’d like to see more of that ... They should be considered part of the health care team,” he said.
Dr. Gabbay has reported serving on advisory boards for Lark, Health Reveal, Sweetch, StartUp Health, Vida Health, and Onduo.
A version of this article first appeared on Medscape.com.
Low-carb, high-fat, calorie-unrestricted diet improves type 2 diabetes
This was true regardless of an individual’s calorie intake, in the randomized controlled trial published in the Annals of Internal Medicine.
Patients with T2D who ate a low-carb, high-fat diet (LCHF) lost more weight and saw greater improvements in both glycemic control and insulin resistance than those who ate a high-carb, low-fat diet (HCLF), reported lead author Camilla Dalby Hansen, MD, of University of Southern Denmark, Odense, and colleagues, suggesting that this is an effective, nonpharmaceutical treatment option for T2D.
The trial enrolled 185 patients with T2D, for whom low-calorie diets are often recommended to induce weight loss and improve glycemic control.
The trouble with this common recommendation, the investigators wrote, is that it induces hunger, so few patients stick to it.
“Therefore, calorie-unrestricted diets may be a better alternative to achieve long-term maintenance,” Dr. Hansen and colleagues wrote, noting that this approach “is not widely investigated.”
Study methods and results
In the new study, participants were randomized in a 2:1 ratio to follow the LCHF or HCLF diet for 6 months, with no restriction on calorie intake. Patients were evaluated at baseline, 3 months, 6 months, and 9 months (3 months after discontinuation). Parameters included glycemic control, serum lipid levels, and metabolic markers. The final analysis included 165 patients.
While patients in both groups lost weight, those in the LCHF group lost, on average, about 8 pounds more than the HCLF group, a significant difference. While the LCHF diet was associated with greater improvements in glycemic control (HbA1c) than the HCLF diet, it also led to slightly greater increases in LDL levels. In both groups, HDL levels increased, and triglycerides decreased, without significant differences between groups.
The above changes were not sustained 3 months after finishing the diet.
“I believe we have sufficient data to include LCHF as one of the diet options for people with type 2 diabetes,” Dr. Hansen said in a written comment, considering all available data.
Although the diet did lead to significant clinical benefits, she predicted that some patients would still struggle with adherence in the real world.
“The LCHF diet can be difficult for some people to follow,” Dr. Hansen said. “It is a bit more expensive, and it can be difficult to comply to in social gatherings, simply because our society is not suited for this type of diet.”
The magic of unrestricted calories
Jay H. Shubrook, DO, diabetologist and professor at Touro University of California, Vallejo, offered a similar view.
“When you start to fiddle with the diet, it affects not only the person, but all the people they eat with, because eating is a communal experience,” Dr. Shubrook said, in an interview.
Still, he said the present study is “a big deal,” because T2D is a “noncommunicable pandemic,” and “anything we could do that disrupts this process is very important.”
While some may struggle to follow the LCHF diet, Dr. Shubrook predicted better long-term adherence than the low-calorie diet usually recommended.
“What’s magic about this study is because it wasn’t calorie restricted, I think it made it a little bit more flexible for people to continue,” Dr. Shubrook said.
He added that he thinks patients will need a fair amount of coaching and education about food choices in order to lose weight on a diet without calorie restrictions.
Not the first study of its kind
In a written comment, Jeff Volek, PhD, RD, professor at the Ohio State University, Columbus, called the present study “another important piece of work, demonstrating yet again, that a low-carbohydrate eating pattern is superior to a high-carbohydrate approach in people with insulin resistance.”
Yet Dr. Volek, who has conducted numerous studies on low-carbohydrate diets, also said there is “little here that is new or surprising.”
He went on to admonish Dr. Hansen and colleagues for failing to recognize those who have already broken ground in this area.
“Unfortunately, these authors do not give credit to the many researchers who have published extensively on low-carbohydrate diets in the past, and instead make claims about being the first to study a calorie unrestricted low-carb diet in individuals with T2D, which is clearly not the case,” Dr. Volek said. “There is a large body of literature showing similar findings with better control over diet, larger cohorts, longer follow-up, and more comprehensive biomarker assessment.”
He noted that data supporting low-carb diets for T2D have been sufficient since at least 2019, when the American Diabetes Association updated their guidance on the subject.
Citing a paper published in Diabetes Care, he said, “Low-carbohydrate eating patterns, especially very-low-carbohydrate eating patterns, have been shown to reduce A1C and the need for antihyperglycemic medications.”
The study was funded by Novo Nordisk Foundation, Danish Diabetes Academy, Odense University Hospital, and others. The investigators disclosed additional relationships with Eli Lilly, Amgen, UCB, and others. Dr. Shubrook disclosed relationships with Abbot, AstraZeneca, Bayer, and others.
This was true regardless of an individual’s calorie intake, in the randomized controlled trial published in the Annals of Internal Medicine.
Patients with T2D who ate a low-carb, high-fat diet (LCHF) lost more weight and saw greater improvements in both glycemic control and insulin resistance than those who ate a high-carb, low-fat diet (HCLF), reported lead author Camilla Dalby Hansen, MD, of University of Southern Denmark, Odense, and colleagues, suggesting that this is an effective, nonpharmaceutical treatment option for T2D.
The trial enrolled 185 patients with T2D, for whom low-calorie diets are often recommended to induce weight loss and improve glycemic control.
The trouble with this common recommendation, the investigators wrote, is that it induces hunger, so few patients stick to it.
“Therefore, calorie-unrestricted diets may be a better alternative to achieve long-term maintenance,” Dr. Hansen and colleagues wrote, noting that this approach “is not widely investigated.”
Study methods and results
In the new study, participants were randomized in a 2:1 ratio to follow the LCHF or HCLF diet for 6 months, with no restriction on calorie intake. Patients were evaluated at baseline, 3 months, 6 months, and 9 months (3 months after discontinuation). Parameters included glycemic control, serum lipid levels, and metabolic markers. The final analysis included 165 patients.
While patients in both groups lost weight, those in the LCHF group lost, on average, about 8 pounds more than the HCLF group, a significant difference. While the LCHF diet was associated with greater improvements in glycemic control (HbA1c) than the HCLF diet, it also led to slightly greater increases in LDL levels. In both groups, HDL levels increased, and triglycerides decreased, without significant differences between groups.
The above changes were not sustained 3 months after finishing the diet.
“I believe we have sufficient data to include LCHF as one of the diet options for people with type 2 diabetes,” Dr. Hansen said in a written comment, considering all available data.
Although the diet did lead to significant clinical benefits, she predicted that some patients would still struggle with adherence in the real world.
“The LCHF diet can be difficult for some people to follow,” Dr. Hansen said. “It is a bit more expensive, and it can be difficult to comply to in social gatherings, simply because our society is not suited for this type of diet.”
The magic of unrestricted calories
Jay H. Shubrook, DO, diabetologist and professor at Touro University of California, Vallejo, offered a similar view.
“When you start to fiddle with the diet, it affects not only the person, but all the people they eat with, because eating is a communal experience,” Dr. Shubrook said, in an interview.
Still, he said the present study is “a big deal,” because T2D is a “noncommunicable pandemic,” and “anything we could do that disrupts this process is very important.”
While some may struggle to follow the LCHF diet, Dr. Shubrook predicted better long-term adherence than the low-calorie diet usually recommended.
“What’s magic about this study is because it wasn’t calorie restricted, I think it made it a little bit more flexible for people to continue,” Dr. Shubrook said.
He added that he thinks patients will need a fair amount of coaching and education about food choices in order to lose weight on a diet without calorie restrictions.
Not the first study of its kind
In a written comment, Jeff Volek, PhD, RD, professor at the Ohio State University, Columbus, called the present study “another important piece of work, demonstrating yet again, that a low-carbohydrate eating pattern is superior to a high-carbohydrate approach in people with insulin resistance.”
Yet Dr. Volek, who has conducted numerous studies on low-carbohydrate diets, also said there is “little here that is new or surprising.”
He went on to admonish Dr. Hansen and colleagues for failing to recognize those who have already broken ground in this area.
“Unfortunately, these authors do not give credit to the many researchers who have published extensively on low-carbohydrate diets in the past, and instead make claims about being the first to study a calorie unrestricted low-carb diet in individuals with T2D, which is clearly not the case,” Dr. Volek said. “There is a large body of literature showing similar findings with better control over diet, larger cohorts, longer follow-up, and more comprehensive biomarker assessment.”
He noted that data supporting low-carb diets for T2D have been sufficient since at least 2019, when the American Diabetes Association updated their guidance on the subject.
Citing a paper published in Diabetes Care, he said, “Low-carbohydrate eating patterns, especially very-low-carbohydrate eating patterns, have been shown to reduce A1C and the need for antihyperglycemic medications.”
The study was funded by Novo Nordisk Foundation, Danish Diabetes Academy, Odense University Hospital, and others. The investigators disclosed additional relationships with Eli Lilly, Amgen, UCB, and others. Dr. Shubrook disclosed relationships with Abbot, AstraZeneca, Bayer, and others.
This was true regardless of an individual’s calorie intake, in the randomized controlled trial published in the Annals of Internal Medicine.
Patients with T2D who ate a low-carb, high-fat diet (LCHF) lost more weight and saw greater improvements in both glycemic control and insulin resistance than those who ate a high-carb, low-fat diet (HCLF), reported lead author Camilla Dalby Hansen, MD, of University of Southern Denmark, Odense, and colleagues, suggesting that this is an effective, nonpharmaceutical treatment option for T2D.
The trial enrolled 185 patients with T2D, for whom low-calorie diets are often recommended to induce weight loss and improve glycemic control.
The trouble with this common recommendation, the investigators wrote, is that it induces hunger, so few patients stick to it.
“Therefore, calorie-unrestricted diets may be a better alternative to achieve long-term maintenance,” Dr. Hansen and colleagues wrote, noting that this approach “is not widely investigated.”
Study methods and results
In the new study, participants were randomized in a 2:1 ratio to follow the LCHF or HCLF diet for 6 months, with no restriction on calorie intake. Patients were evaluated at baseline, 3 months, 6 months, and 9 months (3 months after discontinuation). Parameters included glycemic control, serum lipid levels, and metabolic markers. The final analysis included 165 patients.
While patients in both groups lost weight, those in the LCHF group lost, on average, about 8 pounds more than the HCLF group, a significant difference. While the LCHF diet was associated with greater improvements in glycemic control (HbA1c) than the HCLF diet, it also led to slightly greater increases in LDL levels. In both groups, HDL levels increased, and triglycerides decreased, without significant differences between groups.
The above changes were not sustained 3 months after finishing the diet.
“I believe we have sufficient data to include LCHF as one of the diet options for people with type 2 diabetes,” Dr. Hansen said in a written comment, considering all available data.
Although the diet did lead to significant clinical benefits, she predicted that some patients would still struggle with adherence in the real world.
“The LCHF diet can be difficult for some people to follow,” Dr. Hansen said. “It is a bit more expensive, and it can be difficult to comply to in social gatherings, simply because our society is not suited for this type of diet.”
The magic of unrestricted calories
Jay H. Shubrook, DO, diabetologist and professor at Touro University of California, Vallejo, offered a similar view.
“When you start to fiddle with the diet, it affects not only the person, but all the people they eat with, because eating is a communal experience,” Dr. Shubrook said, in an interview.
Still, he said the present study is “a big deal,” because T2D is a “noncommunicable pandemic,” and “anything we could do that disrupts this process is very important.”
While some may struggle to follow the LCHF diet, Dr. Shubrook predicted better long-term adherence than the low-calorie diet usually recommended.
“What’s magic about this study is because it wasn’t calorie restricted, I think it made it a little bit more flexible for people to continue,” Dr. Shubrook said.
He added that he thinks patients will need a fair amount of coaching and education about food choices in order to lose weight on a diet without calorie restrictions.
Not the first study of its kind
In a written comment, Jeff Volek, PhD, RD, professor at the Ohio State University, Columbus, called the present study “another important piece of work, demonstrating yet again, that a low-carbohydrate eating pattern is superior to a high-carbohydrate approach in people with insulin resistance.”
Yet Dr. Volek, who has conducted numerous studies on low-carbohydrate diets, also said there is “little here that is new or surprising.”
He went on to admonish Dr. Hansen and colleagues for failing to recognize those who have already broken ground in this area.
“Unfortunately, these authors do not give credit to the many researchers who have published extensively on low-carbohydrate diets in the past, and instead make claims about being the first to study a calorie unrestricted low-carb diet in individuals with T2D, which is clearly not the case,” Dr. Volek said. “There is a large body of literature showing similar findings with better control over diet, larger cohorts, longer follow-up, and more comprehensive biomarker assessment.”
He noted that data supporting low-carb diets for T2D have been sufficient since at least 2019, when the American Diabetes Association updated their guidance on the subject.
Citing a paper published in Diabetes Care, he said, “Low-carbohydrate eating patterns, especially very-low-carbohydrate eating patterns, have been shown to reduce A1C and the need for antihyperglycemic medications.”
The study was funded by Novo Nordisk Foundation, Danish Diabetes Academy, Odense University Hospital, and others. The investigators disclosed additional relationships with Eli Lilly, Amgen, UCB, and others. Dr. Shubrook disclosed relationships with Abbot, AstraZeneca, Bayer, and others.
FROM ANNALS OF INTERNAL MEDICINE
Cognitive behavioral therapy app lowers A1c in type 2 diabetes
CHICAGO – A smartphone app that delivers nutritional cognitive behavioral therapy (CBT) to people with type 2 diabetes produced an average 0.29 percentage point drop in hemoglobin A1c during 180 days of use compared with controls, and an average 0.37 percentage point reduction in A1c compared with baseline values in a randomized, pivotal trial with 669 adults.
Use of the app for 180 days also significantly linked with a reduced need for additional medications, reduced weight and blood pressure, and improved patient-reported outcomes, and it led to fewer adverse effects than seen in control subjects, Marc P. Bonaca, MD, reported at the American Heart Association scientific sessions.
The findings also showed a clear dose-response relationship: The more CBT lessons a person completed with the app, the greater the A1c reduction.
The results suggest that the app, called BT-001, “potentially provides a scalable treatment option for patients with type 2 diabetes,” concluded Dr. Bonaca.
On the basis of the results from this trial, also called BT-001, the company developing the app, Better Therapeutics, announced in September 2022 that it had filed a classification request with the Food and Drug Administration that would allow marketing authorization for the BT-001 app. Better Therapeutics envisions that once authorized by the FDA, the app would be available to people with type 2 diabetes by prescriptions written by health care providers and that the cost for the app would be covered by health insurance, explained a company spokesperson.
A ‘modest positive impact’
“CBT is an empirically supported psychotherapy for a variety of emotional disorders, and it has been adapted to target specific emotional distress in the context of chronic illness,” said Amit Shapira, PhD, a clinical psychologist at the Joslin Diabetes Center in Boston who has not been involved in the BT-001 studies. A CBT protocol designed for diabetes, CBT for Adherence and Depression, “has been shown to have a positive impact on depression symptoms and glycemic control in adults with type 2 diabetes,” Dr. Shapira said in an interview.
Based on published results, the BT-001 app “seems to have a modest positive impact on glycemic control, especially among people who completed more than 10 [lesson] modules.” The evidence appears to suggest that the app “might be a good supplement to working with a behavioral health counselor.”
The BT-001 trial enrolled 669 adults with type 2 diabetes for an average of 11 years and an A1c of 7%-10.9% with an average level of 8.2%. Participants had to be on a stable medication regimen for at least 3 months but not using insulin, and their treatment regimens could undergo adjustment during the trial. At baseline, each subject was on an average of 2.1 antidiabetes medications, including 90% on metformin and 42% on a sulfonylurea. The researchers also highlighted that the enrolled cohort of people with type 2 diabetes had a demographic profile that was “generally representative” of U.S. adults with type 2 diabetes.
The researchers told the 326 people who were randomized to the active intervention group to use the app but subjects were free to determine their frequency of use. The app introduced a new lesson module weekly that took 10-20 minutes to complete, and each weekly lesson came with associated exercises aimed at practicing skills related to behavioral beliefs.
The study’s primary efficacy endpoint was the average change from baseline in A1c compared with the 343 control participants after 90 days of app use, and 610 of the 669 enrolled participants (91%) had paired baseline and 90-day measurements. At 90 days, people in the app group had an average 0.28 percentage point decrease in their A1c compared with an average 0.11 percentage point increase among the controls, a between-group difference of 0.39 percentage points. Both the reduction from baseline with app use and the reduction relative to the controls were significant. These results appeared in an article published online in in Diabetes Care.
At the scientific sessions, Dr. Bonaca presented additional outcome data after 180 days of app use. He reported an average 0.37 percentage point reduction from baseline in A1c among app users and a 0.08 percentage point decrease from baseline among the controls, for a net 0.29 percentage point incremental decline with the app, a significant difference. At 180 days, 50% of the people in the app group had an A1c decline from baseline of at least 0.4 percentage points compared with 34% of the controls, a significant difference.
A dose-response relationship
Notably, app use showed a clear dose-response pattern. During 180 days of app availability, people who used the app fewer than 10 times had an average reduction from baseline in their A1c of less than 0.1 percentage points. Among those who used the app 10-20 times (a subgroup with roughly one-third of the people randomized to app use) average A1c reduction increased to about 0.4 percentage points, and among those who used the app more than 20 times, also one-third of the intervention group, the average A1c reduction from baseline was about 0.6 percentage points.
“It would be interesting to learn more about the adults who engaged with the app” and had a higher use rate “to provide more targeted care” with the app to people who match the profiles of those who were more likely to use the app during the trial, said Dr. Shapira.
Dr. Bonaca, a cardiologist and vascular medicine specialist and executive director of CPC Clinical Research and CPC Community Health, an academic research organization created by and affiliated with the University of Colorado Anschutz Medical Campus in Aurora, Colo., reported several other 180-day outcomes in the BT-001 trial:
- A 33% relative decrease in the percentage of subjects who needed during the study an additional antidiabetes medication or increased dosages of their baseline medications, which occurred at a rate of 21% among the controls and 14% among those who used the app.
- An average weight loss from baseline of 5.5 pounds using the app compared with an average 1.9 pound decrease among controls, a significant difference.
- A decline in average systolic blood pressure of 4.7 mm Hg with app use compared with a 1.8 mm Hg average decline among the controls, a significant difference.
- Significant incremental average improvements in a self-reported Short Form-12 physical component score with the app compared with controls, and increased average improvement in the PHQ9 self-reported measure of depression in app users compared with controls.
- Significantly fewer treatment-emergent adverse effects, and significantly fewer serious treatment-emergent adverse effects among the app users compared with the controls.
‘Ready for clinical use’
Based on these findings, “in my view the app is ready for [routine] clinical use,” declared Judith Hsia, MD, a cardiologist and professor of medicine at the University of Colorado in Aurora, and with Dr. Bonaca a co-lead investigator for the study.
The BT-001 app can serve as “an addition to the toolkit of diabetes treatments,” Dr. Hsia said in an interview. One key advantage of the app is that, once approved, it could be available to many more people with type 2 diabetes than would be able to receive CBT directly from a therapist. Another potential plus for the CBT app is that “the effects should be durable in contrast to medications,” which must be taken on an ongoing basis to maintain effectiveness. In addition, the safety profile “is favorable compared with drug therapies, which should appeal to health care providers,” said Dr. Hsia, chief science officer for CPC Clinical Research.
However, Dr. Shapira cited the issue that therapeutic apps “raise privacy and licensing liability concerns.”
The BT-001 trial was sponsored by Better Therapeutics, the company developing the app. CPC Clinical Research receives research and consulting funding from numerous companies. Dr. Bonaca has been a consultant to Audentes, and is a stockholder of Medtronic and Pfizer. Dr. Shapira had no disclosures. Dr. Hsia is a stockholder of AstraZeneca.
CHICAGO – A smartphone app that delivers nutritional cognitive behavioral therapy (CBT) to people with type 2 diabetes produced an average 0.29 percentage point drop in hemoglobin A1c during 180 days of use compared with controls, and an average 0.37 percentage point reduction in A1c compared with baseline values in a randomized, pivotal trial with 669 adults.
Use of the app for 180 days also significantly linked with a reduced need for additional medications, reduced weight and blood pressure, and improved patient-reported outcomes, and it led to fewer adverse effects than seen in control subjects, Marc P. Bonaca, MD, reported at the American Heart Association scientific sessions.
The findings also showed a clear dose-response relationship: The more CBT lessons a person completed with the app, the greater the A1c reduction.
The results suggest that the app, called BT-001, “potentially provides a scalable treatment option for patients with type 2 diabetes,” concluded Dr. Bonaca.
On the basis of the results from this trial, also called BT-001, the company developing the app, Better Therapeutics, announced in September 2022 that it had filed a classification request with the Food and Drug Administration that would allow marketing authorization for the BT-001 app. Better Therapeutics envisions that once authorized by the FDA, the app would be available to people with type 2 diabetes by prescriptions written by health care providers and that the cost for the app would be covered by health insurance, explained a company spokesperson.
A ‘modest positive impact’
“CBT is an empirically supported psychotherapy for a variety of emotional disorders, and it has been adapted to target specific emotional distress in the context of chronic illness,” said Amit Shapira, PhD, a clinical psychologist at the Joslin Diabetes Center in Boston who has not been involved in the BT-001 studies. A CBT protocol designed for diabetes, CBT for Adherence and Depression, “has been shown to have a positive impact on depression symptoms and glycemic control in adults with type 2 diabetes,” Dr. Shapira said in an interview.
Based on published results, the BT-001 app “seems to have a modest positive impact on glycemic control, especially among people who completed more than 10 [lesson] modules.” The evidence appears to suggest that the app “might be a good supplement to working with a behavioral health counselor.”
The BT-001 trial enrolled 669 adults with type 2 diabetes for an average of 11 years and an A1c of 7%-10.9% with an average level of 8.2%. Participants had to be on a stable medication regimen for at least 3 months but not using insulin, and their treatment regimens could undergo adjustment during the trial. At baseline, each subject was on an average of 2.1 antidiabetes medications, including 90% on metformin and 42% on a sulfonylurea. The researchers also highlighted that the enrolled cohort of people with type 2 diabetes had a demographic profile that was “generally representative” of U.S. adults with type 2 diabetes.
The researchers told the 326 people who were randomized to the active intervention group to use the app but subjects were free to determine their frequency of use. The app introduced a new lesson module weekly that took 10-20 minutes to complete, and each weekly lesson came with associated exercises aimed at practicing skills related to behavioral beliefs.
The study’s primary efficacy endpoint was the average change from baseline in A1c compared with the 343 control participants after 90 days of app use, and 610 of the 669 enrolled participants (91%) had paired baseline and 90-day measurements. At 90 days, people in the app group had an average 0.28 percentage point decrease in their A1c compared with an average 0.11 percentage point increase among the controls, a between-group difference of 0.39 percentage points. Both the reduction from baseline with app use and the reduction relative to the controls were significant. These results appeared in an article published online in in Diabetes Care.
At the scientific sessions, Dr. Bonaca presented additional outcome data after 180 days of app use. He reported an average 0.37 percentage point reduction from baseline in A1c among app users and a 0.08 percentage point decrease from baseline among the controls, for a net 0.29 percentage point incremental decline with the app, a significant difference. At 180 days, 50% of the people in the app group had an A1c decline from baseline of at least 0.4 percentage points compared with 34% of the controls, a significant difference.
A dose-response relationship
Notably, app use showed a clear dose-response pattern. During 180 days of app availability, people who used the app fewer than 10 times had an average reduction from baseline in their A1c of less than 0.1 percentage points. Among those who used the app 10-20 times (a subgroup with roughly one-third of the people randomized to app use) average A1c reduction increased to about 0.4 percentage points, and among those who used the app more than 20 times, also one-third of the intervention group, the average A1c reduction from baseline was about 0.6 percentage points.
“It would be interesting to learn more about the adults who engaged with the app” and had a higher use rate “to provide more targeted care” with the app to people who match the profiles of those who were more likely to use the app during the trial, said Dr. Shapira.
Dr. Bonaca, a cardiologist and vascular medicine specialist and executive director of CPC Clinical Research and CPC Community Health, an academic research organization created by and affiliated with the University of Colorado Anschutz Medical Campus in Aurora, Colo., reported several other 180-day outcomes in the BT-001 trial:
- A 33% relative decrease in the percentage of subjects who needed during the study an additional antidiabetes medication or increased dosages of their baseline medications, which occurred at a rate of 21% among the controls and 14% among those who used the app.
- An average weight loss from baseline of 5.5 pounds using the app compared with an average 1.9 pound decrease among controls, a significant difference.
- A decline in average systolic blood pressure of 4.7 mm Hg with app use compared with a 1.8 mm Hg average decline among the controls, a significant difference.
- Significant incremental average improvements in a self-reported Short Form-12 physical component score with the app compared with controls, and increased average improvement in the PHQ9 self-reported measure of depression in app users compared with controls.
- Significantly fewer treatment-emergent adverse effects, and significantly fewer serious treatment-emergent adverse effects among the app users compared with the controls.
‘Ready for clinical use’
Based on these findings, “in my view the app is ready for [routine] clinical use,” declared Judith Hsia, MD, a cardiologist and professor of medicine at the University of Colorado in Aurora, and with Dr. Bonaca a co-lead investigator for the study.
The BT-001 app can serve as “an addition to the toolkit of diabetes treatments,” Dr. Hsia said in an interview. One key advantage of the app is that, once approved, it could be available to many more people with type 2 diabetes than would be able to receive CBT directly from a therapist. Another potential plus for the CBT app is that “the effects should be durable in contrast to medications,” which must be taken on an ongoing basis to maintain effectiveness. In addition, the safety profile “is favorable compared with drug therapies, which should appeal to health care providers,” said Dr. Hsia, chief science officer for CPC Clinical Research.
However, Dr. Shapira cited the issue that therapeutic apps “raise privacy and licensing liability concerns.”
The BT-001 trial was sponsored by Better Therapeutics, the company developing the app. CPC Clinical Research receives research and consulting funding from numerous companies. Dr. Bonaca has been a consultant to Audentes, and is a stockholder of Medtronic and Pfizer. Dr. Shapira had no disclosures. Dr. Hsia is a stockholder of AstraZeneca.
CHICAGO – A smartphone app that delivers nutritional cognitive behavioral therapy (CBT) to people with type 2 diabetes produced an average 0.29 percentage point drop in hemoglobin A1c during 180 days of use compared with controls, and an average 0.37 percentage point reduction in A1c compared with baseline values in a randomized, pivotal trial with 669 adults.
Use of the app for 180 days also significantly linked with a reduced need for additional medications, reduced weight and blood pressure, and improved patient-reported outcomes, and it led to fewer adverse effects than seen in control subjects, Marc P. Bonaca, MD, reported at the American Heart Association scientific sessions.
The findings also showed a clear dose-response relationship: The more CBT lessons a person completed with the app, the greater the A1c reduction.
The results suggest that the app, called BT-001, “potentially provides a scalable treatment option for patients with type 2 diabetes,” concluded Dr. Bonaca.
On the basis of the results from this trial, also called BT-001, the company developing the app, Better Therapeutics, announced in September 2022 that it had filed a classification request with the Food and Drug Administration that would allow marketing authorization for the BT-001 app. Better Therapeutics envisions that once authorized by the FDA, the app would be available to people with type 2 diabetes by prescriptions written by health care providers and that the cost for the app would be covered by health insurance, explained a company spokesperson.
A ‘modest positive impact’
“CBT is an empirically supported psychotherapy for a variety of emotional disorders, and it has been adapted to target specific emotional distress in the context of chronic illness,” said Amit Shapira, PhD, a clinical psychologist at the Joslin Diabetes Center in Boston who has not been involved in the BT-001 studies. A CBT protocol designed for diabetes, CBT for Adherence and Depression, “has been shown to have a positive impact on depression symptoms and glycemic control in adults with type 2 diabetes,” Dr. Shapira said in an interview.
Based on published results, the BT-001 app “seems to have a modest positive impact on glycemic control, especially among people who completed more than 10 [lesson] modules.” The evidence appears to suggest that the app “might be a good supplement to working with a behavioral health counselor.”
The BT-001 trial enrolled 669 adults with type 2 diabetes for an average of 11 years and an A1c of 7%-10.9% with an average level of 8.2%. Participants had to be on a stable medication regimen for at least 3 months but not using insulin, and their treatment regimens could undergo adjustment during the trial. At baseline, each subject was on an average of 2.1 antidiabetes medications, including 90% on metformin and 42% on a sulfonylurea. The researchers also highlighted that the enrolled cohort of people with type 2 diabetes had a demographic profile that was “generally representative” of U.S. adults with type 2 diabetes.
The researchers told the 326 people who were randomized to the active intervention group to use the app but subjects were free to determine their frequency of use. The app introduced a new lesson module weekly that took 10-20 minutes to complete, and each weekly lesson came with associated exercises aimed at practicing skills related to behavioral beliefs.
The study’s primary efficacy endpoint was the average change from baseline in A1c compared with the 343 control participants after 90 days of app use, and 610 of the 669 enrolled participants (91%) had paired baseline and 90-day measurements. At 90 days, people in the app group had an average 0.28 percentage point decrease in their A1c compared with an average 0.11 percentage point increase among the controls, a between-group difference of 0.39 percentage points. Both the reduction from baseline with app use and the reduction relative to the controls were significant. These results appeared in an article published online in in Diabetes Care.
At the scientific sessions, Dr. Bonaca presented additional outcome data after 180 days of app use. He reported an average 0.37 percentage point reduction from baseline in A1c among app users and a 0.08 percentage point decrease from baseline among the controls, for a net 0.29 percentage point incremental decline with the app, a significant difference. At 180 days, 50% of the people in the app group had an A1c decline from baseline of at least 0.4 percentage points compared with 34% of the controls, a significant difference.
A dose-response relationship
Notably, app use showed a clear dose-response pattern. During 180 days of app availability, people who used the app fewer than 10 times had an average reduction from baseline in their A1c of less than 0.1 percentage points. Among those who used the app 10-20 times (a subgroup with roughly one-third of the people randomized to app use) average A1c reduction increased to about 0.4 percentage points, and among those who used the app more than 20 times, also one-third of the intervention group, the average A1c reduction from baseline was about 0.6 percentage points.
“It would be interesting to learn more about the adults who engaged with the app” and had a higher use rate “to provide more targeted care” with the app to people who match the profiles of those who were more likely to use the app during the trial, said Dr. Shapira.
Dr. Bonaca, a cardiologist and vascular medicine specialist and executive director of CPC Clinical Research and CPC Community Health, an academic research organization created by and affiliated with the University of Colorado Anschutz Medical Campus in Aurora, Colo., reported several other 180-day outcomes in the BT-001 trial:
- A 33% relative decrease in the percentage of subjects who needed during the study an additional antidiabetes medication or increased dosages of their baseline medications, which occurred at a rate of 21% among the controls and 14% among those who used the app.
- An average weight loss from baseline of 5.5 pounds using the app compared with an average 1.9 pound decrease among controls, a significant difference.
- A decline in average systolic blood pressure of 4.7 mm Hg with app use compared with a 1.8 mm Hg average decline among the controls, a significant difference.
- Significant incremental average improvements in a self-reported Short Form-12 physical component score with the app compared with controls, and increased average improvement in the PHQ9 self-reported measure of depression in app users compared with controls.
- Significantly fewer treatment-emergent adverse effects, and significantly fewer serious treatment-emergent adverse effects among the app users compared with the controls.
‘Ready for clinical use’
Based on these findings, “in my view the app is ready for [routine] clinical use,” declared Judith Hsia, MD, a cardiologist and professor of medicine at the University of Colorado in Aurora, and with Dr. Bonaca a co-lead investigator for the study.
The BT-001 app can serve as “an addition to the toolkit of diabetes treatments,” Dr. Hsia said in an interview. One key advantage of the app is that, once approved, it could be available to many more people with type 2 diabetes than would be able to receive CBT directly from a therapist. Another potential plus for the CBT app is that “the effects should be durable in contrast to medications,” which must be taken on an ongoing basis to maintain effectiveness. In addition, the safety profile “is favorable compared with drug therapies, which should appeal to health care providers,” said Dr. Hsia, chief science officer for CPC Clinical Research.
However, Dr. Shapira cited the issue that therapeutic apps “raise privacy and licensing liability concerns.”
The BT-001 trial was sponsored by Better Therapeutics, the company developing the app. CPC Clinical Research receives research and consulting funding from numerous companies. Dr. Bonaca has been a consultant to Audentes, and is a stockholder of Medtronic and Pfizer. Dr. Shapira had no disclosures. Dr. Hsia is a stockholder of AstraZeneca.
AT AHA 2022
Given the choice, T2D patients find their own best meds
Allowing people with type 2 diabetes to try agents from three different classes of antidiabetes drugs showed they usually find a clear preference, often the drug that gives them the best glycemic control and least bothersome adverse effects, according to secondary findings from a randomized study of patients in the United Kingdom.
“This is the first study in which the same patient has tried three different types of glucose-lowering drug, enabling them to directly compare them and then choose which one is best for them,” Andrew Hattersley, BMBCh, DM, the study’s principal investigator, said in a written statement. “We’ve shown that going with the patients’ choice results in better glucose control and fewer side effects than any other approach. When it’s not clear which drug is best to use, then patients should try before they choose. Surprisingly, that approach has never been tried before.”
These secondary results from the TriMaster study were recently published in Nature Medicine and presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in September, as reported by this news organization.
TriMaster enrolled adults aged 30-80 years with a clinical diagnosis of type 2 diabetes for at least 12 months. Their glycemia was inadequately controlled despite treatment with metformin alone or two classes of oral glucose-lowering therapy that did not include an agent from any of the three classes tested in the study: dipeptidyl peptidase–4 (DPP-4) inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and thiazolidinediones. The people taking two different drug classes at entry were most often taking metformin and a sulfonylurea.
Do BMI and renal function affect treatment response?
TriMaster tested two hypotheses. Firstly, would people with a body mass index of more than 30 kg/m2 have greater glucose lowering with the thiazolidinedione pioglitazone (Actos) than with the DPP-4 inhibitor sitagliptin (Januvia), compared to people with a lower BMI?
Secondly, would people with an estimated glomerular filtration rate (eGFR) of 60-90 mL/min/1.73 m2 have greater glucose lowering with sitagliptin than with the SGLT2 inhibitor canagliflozin (Invokana), compared with people with higher levels of renal function? The metric for both hypotheses was change in A1c levels from baseline.
The study included 525 adults with type 2 diabetes in a double-blind, three-way crossover trial that assigned each participant a random order of serial 16-week trials of treatment with sitagliptin 100 mg once daily, canagliflozin 100 mg once daily, and pioglitazone 30 mg once daily, with each agent added to the preexisting background regimen.
Analysis showed that for second- or third-line therapy in people with type 2 diabetes “simple predefined stratification using BMI and renal function can determine the choice of the drug most likely to be effective for glucose lowering,” the researchers concluded.
Among those with a BMI of more than 30 kg/m2, patients achieved a lower A1c on pioglitazone, compared with sitagliptin, while those with a lower BMI had their best A1c response on sitagliptin. Patients with impaired renal function (eGFR 60-90 mL/min/1.73 m2) had better A1c lowering with sitagliptin, while those with a higher eGFR had better A1c lowering with canagliflozin.
These results appeared in a second article published in Nature Medicine, and the researchers also presented these findings at the EASD 2021 annual meeting, as reported by this news organization at the time.
Patients identified the agent they liked best
Dr. Hattersley and associates used the TriMaster study to also address the secondary question of which of the three tested agents patients preferred, focusing on the 457 patients who provided information on their treatment preference.
The results showed that patient preference varied: Twenty-four percent liked pioglitazone best, 33% preferred sitagliptin, and 37% said canagliflozin was their favorite, with 6% having no preference. These numbers barely budged when participants learned how well each agent worked for them in terms of reducing their A1c and lowering their BMI.
The findings also showed good correlation between patient preferences and their A1c and adverse-effect responses. The agents that patients identified as their favorites were also the drugs that lowered their A1c the most 53% of the time before they got any feedback on which one gave them their best glycemic control. Once they had this feedback, 70% preferred the most effective agent, with the results likely reflecting that patients feel better when they have improved glucose levels as well as the education patients received that lower A1c levels are better.
Patients also tended to understandably favor the agents that caused the fewest and mildest adverse effects: Sixty-eight percent of the patients who identified a favorite drug picked the one that gave them the best adverse-effect profile.
In an interview at the EASD 2022 annual meeting, Dr. Hattersley promoted the study’s design as a best-practice approach to deciding which drug to next give a person with type 2 diabetes who needs additional glycemic control.
“Whenever you’re not sure how to balance adverse effects and positive effects the best person to decide is the one who experiences the effects,” he said. “Patients had overwhelming positivity about being able to choose their drug. Do it when you’re not certain which drug to prescribe,” suggested Dr. Hattersley, a professor and diabetologist at the University of Exeter, England. “We can’t know which drug a patient might prefer.”
But he stressed cautioning patients to return for treatment adjustment sooner than 4 months if they can’t tolerate a new drug they’re trying.
TriMaster received no commercial funding. Dr. Hattersley has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Allowing people with type 2 diabetes to try agents from three different classes of antidiabetes drugs showed they usually find a clear preference, often the drug that gives them the best glycemic control and least bothersome adverse effects, according to secondary findings from a randomized study of patients in the United Kingdom.
“This is the first study in which the same patient has tried three different types of glucose-lowering drug, enabling them to directly compare them and then choose which one is best for them,” Andrew Hattersley, BMBCh, DM, the study’s principal investigator, said in a written statement. “We’ve shown that going with the patients’ choice results in better glucose control and fewer side effects than any other approach. When it’s not clear which drug is best to use, then patients should try before they choose. Surprisingly, that approach has never been tried before.”
These secondary results from the TriMaster study were recently published in Nature Medicine and presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in September, as reported by this news organization.
TriMaster enrolled adults aged 30-80 years with a clinical diagnosis of type 2 diabetes for at least 12 months. Their glycemia was inadequately controlled despite treatment with metformin alone or two classes of oral glucose-lowering therapy that did not include an agent from any of the three classes tested in the study: dipeptidyl peptidase–4 (DPP-4) inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and thiazolidinediones. The people taking two different drug classes at entry were most often taking metformin and a sulfonylurea.
Do BMI and renal function affect treatment response?
TriMaster tested two hypotheses. Firstly, would people with a body mass index of more than 30 kg/m2 have greater glucose lowering with the thiazolidinedione pioglitazone (Actos) than with the DPP-4 inhibitor sitagliptin (Januvia), compared to people with a lower BMI?
Secondly, would people with an estimated glomerular filtration rate (eGFR) of 60-90 mL/min/1.73 m2 have greater glucose lowering with sitagliptin than with the SGLT2 inhibitor canagliflozin (Invokana), compared with people with higher levels of renal function? The metric for both hypotheses was change in A1c levels from baseline.
The study included 525 adults with type 2 diabetes in a double-blind, three-way crossover trial that assigned each participant a random order of serial 16-week trials of treatment with sitagliptin 100 mg once daily, canagliflozin 100 mg once daily, and pioglitazone 30 mg once daily, with each agent added to the preexisting background regimen.
Analysis showed that for second- or third-line therapy in people with type 2 diabetes “simple predefined stratification using BMI and renal function can determine the choice of the drug most likely to be effective for glucose lowering,” the researchers concluded.
Among those with a BMI of more than 30 kg/m2, patients achieved a lower A1c on pioglitazone, compared with sitagliptin, while those with a lower BMI had their best A1c response on sitagliptin. Patients with impaired renal function (eGFR 60-90 mL/min/1.73 m2) had better A1c lowering with sitagliptin, while those with a higher eGFR had better A1c lowering with canagliflozin.
These results appeared in a second article published in Nature Medicine, and the researchers also presented these findings at the EASD 2021 annual meeting, as reported by this news organization at the time.
Patients identified the agent they liked best
Dr. Hattersley and associates used the TriMaster study to also address the secondary question of which of the three tested agents patients preferred, focusing on the 457 patients who provided information on their treatment preference.
The results showed that patient preference varied: Twenty-four percent liked pioglitazone best, 33% preferred sitagliptin, and 37% said canagliflozin was their favorite, with 6% having no preference. These numbers barely budged when participants learned how well each agent worked for them in terms of reducing their A1c and lowering their BMI.
The findings also showed good correlation between patient preferences and their A1c and adverse-effect responses. The agents that patients identified as their favorites were also the drugs that lowered their A1c the most 53% of the time before they got any feedback on which one gave them their best glycemic control. Once they had this feedback, 70% preferred the most effective agent, with the results likely reflecting that patients feel better when they have improved glucose levels as well as the education patients received that lower A1c levels are better.
Patients also tended to understandably favor the agents that caused the fewest and mildest adverse effects: Sixty-eight percent of the patients who identified a favorite drug picked the one that gave them the best adverse-effect profile.
In an interview at the EASD 2022 annual meeting, Dr. Hattersley promoted the study’s design as a best-practice approach to deciding which drug to next give a person with type 2 diabetes who needs additional glycemic control.
“Whenever you’re not sure how to balance adverse effects and positive effects the best person to decide is the one who experiences the effects,” he said. “Patients had overwhelming positivity about being able to choose their drug. Do it when you’re not certain which drug to prescribe,” suggested Dr. Hattersley, a professor and diabetologist at the University of Exeter, England. “We can’t know which drug a patient might prefer.”
But he stressed cautioning patients to return for treatment adjustment sooner than 4 months if they can’t tolerate a new drug they’re trying.
TriMaster received no commercial funding. Dr. Hattersley has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Allowing people with type 2 diabetes to try agents from three different classes of antidiabetes drugs showed they usually find a clear preference, often the drug that gives them the best glycemic control and least bothersome adverse effects, according to secondary findings from a randomized study of patients in the United Kingdom.
“This is the first study in which the same patient has tried three different types of glucose-lowering drug, enabling them to directly compare them and then choose which one is best for them,” Andrew Hattersley, BMBCh, DM, the study’s principal investigator, said in a written statement. “We’ve shown that going with the patients’ choice results in better glucose control and fewer side effects than any other approach. When it’s not clear which drug is best to use, then patients should try before they choose. Surprisingly, that approach has never been tried before.”
These secondary results from the TriMaster study were recently published in Nature Medicine and presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in September, as reported by this news organization.
TriMaster enrolled adults aged 30-80 years with a clinical diagnosis of type 2 diabetes for at least 12 months. Their glycemia was inadequately controlled despite treatment with metformin alone or two classes of oral glucose-lowering therapy that did not include an agent from any of the three classes tested in the study: dipeptidyl peptidase–4 (DPP-4) inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and thiazolidinediones. The people taking two different drug classes at entry were most often taking metformin and a sulfonylurea.
Do BMI and renal function affect treatment response?
TriMaster tested two hypotheses. Firstly, would people with a body mass index of more than 30 kg/m2 have greater glucose lowering with the thiazolidinedione pioglitazone (Actos) than with the DPP-4 inhibitor sitagliptin (Januvia), compared to people with a lower BMI?
Secondly, would people with an estimated glomerular filtration rate (eGFR) of 60-90 mL/min/1.73 m2 have greater glucose lowering with sitagliptin than with the SGLT2 inhibitor canagliflozin (Invokana), compared with people with higher levels of renal function? The metric for both hypotheses was change in A1c levels from baseline.
The study included 525 adults with type 2 diabetes in a double-blind, three-way crossover trial that assigned each participant a random order of serial 16-week trials of treatment with sitagliptin 100 mg once daily, canagliflozin 100 mg once daily, and pioglitazone 30 mg once daily, with each agent added to the preexisting background regimen.
Analysis showed that for second- or third-line therapy in people with type 2 diabetes “simple predefined stratification using BMI and renal function can determine the choice of the drug most likely to be effective for glucose lowering,” the researchers concluded.
Among those with a BMI of more than 30 kg/m2, patients achieved a lower A1c on pioglitazone, compared with sitagliptin, while those with a lower BMI had their best A1c response on sitagliptin. Patients with impaired renal function (eGFR 60-90 mL/min/1.73 m2) had better A1c lowering with sitagliptin, while those with a higher eGFR had better A1c lowering with canagliflozin.
These results appeared in a second article published in Nature Medicine, and the researchers also presented these findings at the EASD 2021 annual meeting, as reported by this news organization at the time.
Patients identified the agent they liked best
Dr. Hattersley and associates used the TriMaster study to also address the secondary question of which of the three tested agents patients preferred, focusing on the 457 patients who provided information on their treatment preference.
The results showed that patient preference varied: Twenty-four percent liked pioglitazone best, 33% preferred sitagliptin, and 37% said canagliflozin was their favorite, with 6% having no preference. These numbers barely budged when participants learned how well each agent worked for them in terms of reducing their A1c and lowering their BMI.
The findings also showed good correlation between patient preferences and their A1c and adverse-effect responses. The agents that patients identified as their favorites were also the drugs that lowered their A1c the most 53% of the time before they got any feedback on which one gave them their best glycemic control. Once they had this feedback, 70% preferred the most effective agent, with the results likely reflecting that patients feel better when they have improved glucose levels as well as the education patients received that lower A1c levels are better.
Patients also tended to understandably favor the agents that caused the fewest and mildest adverse effects: Sixty-eight percent of the patients who identified a favorite drug picked the one that gave them the best adverse-effect profile.
In an interview at the EASD 2022 annual meeting, Dr. Hattersley promoted the study’s design as a best-practice approach to deciding which drug to next give a person with type 2 diabetes who needs additional glycemic control.
“Whenever you’re not sure how to balance adverse effects and positive effects the best person to decide is the one who experiences the effects,” he said. “Patients had overwhelming positivity about being able to choose their drug. Do it when you’re not certain which drug to prescribe,” suggested Dr. Hattersley, a professor and diabetologist at the University of Exeter, England. “We can’t know which drug a patient might prefer.”
But he stressed cautioning patients to return for treatment adjustment sooner than 4 months if they can’t tolerate a new drug they’re trying.
TriMaster received no commercial funding. Dr. Hattersley has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FDA okays Dexcom G7 continuous glucose monitoring system
The U.S. Food and Drug Administration has cleared the Dexcom G7 continuous glucose monitoring (CGM) system for people with all types of diabetes aged 2 years and older and for use during pregnancy.
The G7 has several improvements over the current G6 model, including a 60% smaller size, a 30-minute warm-up period (compared with 2 hours), an all-in-one sensor and transmitter (as opposed to the two separate devices), a mean absolute relative difference (compared with a standard, an assessment of accuracy) of 8.2% (compared with 12.8%), a 12-hour grace period (in contrast to the G6’s hard shutoff), and a redesigned mobile app.
It is indicated for wear on the back of the upper arm for people aged 2 years and older or the upper buttocks for ages 2-17 years old.
As an “integrated” CGM, the G7 has the capacity to work as part of automated insulin delivery systems, but that will require further FDA action. “Dexcom is working closely with its insulin pump partners to integrate Dexcom G7 into current and future automated insulin delivery systems as quickly as possible,” the company said in a statement.
Like the G6, it requires no fingersticks, scanning, or calibration. It provides real-time glucose readings every 5 minutes to a compatible device, including Apple Watch and other digital health apps, and allows for remote monitoring of data by as many as 10 followers.
Dexcom expects to initiate a U.S. launch of Dexcom G7 in early 2023. To facilitate immediate access to G7 for as many users as possible, the company will have accessible cash pay options in place as the company transitions coverage with availability for G7, the statement says.
The Dexcom G7 was granted a CE Mark (Conformité Européenne) in March 2022, which means it is approved for use in people with diabetes aged 2 years and older, including pregnant women, in Europe.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has cleared the Dexcom G7 continuous glucose monitoring (CGM) system for people with all types of diabetes aged 2 years and older and for use during pregnancy.
The G7 has several improvements over the current G6 model, including a 60% smaller size, a 30-minute warm-up period (compared with 2 hours), an all-in-one sensor and transmitter (as opposed to the two separate devices), a mean absolute relative difference (compared with a standard, an assessment of accuracy) of 8.2% (compared with 12.8%), a 12-hour grace period (in contrast to the G6’s hard shutoff), and a redesigned mobile app.
It is indicated for wear on the back of the upper arm for people aged 2 years and older or the upper buttocks for ages 2-17 years old.
As an “integrated” CGM, the G7 has the capacity to work as part of automated insulin delivery systems, but that will require further FDA action. “Dexcom is working closely with its insulin pump partners to integrate Dexcom G7 into current and future automated insulin delivery systems as quickly as possible,” the company said in a statement.
Like the G6, it requires no fingersticks, scanning, or calibration. It provides real-time glucose readings every 5 minutes to a compatible device, including Apple Watch and other digital health apps, and allows for remote monitoring of data by as many as 10 followers.
Dexcom expects to initiate a U.S. launch of Dexcom G7 in early 2023. To facilitate immediate access to G7 for as many users as possible, the company will have accessible cash pay options in place as the company transitions coverage with availability for G7, the statement says.
The Dexcom G7 was granted a CE Mark (Conformité Européenne) in March 2022, which means it is approved for use in people with diabetes aged 2 years and older, including pregnant women, in Europe.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has cleared the Dexcom G7 continuous glucose monitoring (CGM) system for people with all types of diabetes aged 2 years and older and for use during pregnancy.
The G7 has several improvements over the current G6 model, including a 60% smaller size, a 30-minute warm-up period (compared with 2 hours), an all-in-one sensor and transmitter (as opposed to the two separate devices), a mean absolute relative difference (compared with a standard, an assessment of accuracy) of 8.2% (compared with 12.8%), a 12-hour grace period (in contrast to the G6’s hard shutoff), and a redesigned mobile app.
It is indicated for wear on the back of the upper arm for people aged 2 years and older or the upper buttocks for ages 2-17 years old.
As an “integrated” CGM, the G7 has the capacity to work as part of automated insulin delivery systems, but that will require further FDA action. “Dexcom is working closely with its insulin pump partners to integrate Dexcom G7 into current and future automated insulin delivery systems as quickly as possible,” the company said in a statement.
Like the G6, it requires no fingersticks, scanning, or calibration. It provides real-time glucose readings every 5 minutes to a compatible device, including Apple Watch and other digital health apps, and allows for remote monitoring of data by as many as 10 followers.
Dexcom expects to initiate a U.S. launch of Dexcom G7 in early 2023. To facilitate immediate access to G7 for as many users as possible, the company will have accessible cash pay options in place as the company transitions coverage with availability for G7, the statement says.
The Dexcom G7 was granted a CE Mark (Conformité Européenne) in March 2022, which means it is approved for use in people with diabetes aged 2 years and older, including pregnant women, in Europe.
A version of this article first appeared on Medscape.com.
Cold water immersion can have benefits
according to researchers from the Arctic University of Norway and the University Hospital of North Norway.
What to know
- Immersion in cold water has a major impact on the body. It elevates the heart rate and has positive effects on brown adipose tissue, a type of “good” body fat that is activated by cold and may protect against and cardiovascular disease.
- Exposure to cold water or cold air also appears to increase the production of the protein adiponectin by adipose tissue. Adiponectin plays a key role in protecting against , diabetes, and other diseases.
- Repeated cold-water immersions by inexperienced as well as experienced swimmers during the winter months significantly increased sensitivity and decreased insulin concentrations.
- Numerous health and well-being claims from regular exposure to the cold, such as weight loss, better mental health, and increased libido, may be explained by other factors, including an active lifestyle, trained stress handling, and social interactions, as well as a positive mindset.
- Those seeking to voluntarily practice cold-water immersion need to be educated about possible health risks associated with taking a dip in icy water, which include the consequences of hypothermia, and of heart and lung problems, which are often related to the shock from the cold.
This is a summary of the article, “Health effects of voluntary exposure to cold water – a continuing subject of debate,” published by the International Journal of Circumpolar Health.
A version of this article first appeared on Medscape.com.
according to researchers from the Arctic University of Norway and the University Hospital of North Norway.
What to know
- Immersion in cold water has a major impact on the body. It elevates the heart rate and has positive effects on brown adipose tissue, a type of “good” body fat that is activated by cold and may protect against and cardiovascular disease.
- Exposure to cold water or cold air also appears to increase the production of the protein adiponectin by adipose tissue. Adiponectin plays a key role in protecting against , diabetes, and other diseases.
- Repeated cold-water immersions by inexperienced as well as experienced swimmers during the winter months significantly increased sensitivity and decreased insulin concentrations.
- Numerous health and well-being claims from regular exposure to the cold, such as weight loss, better mental health, and increased libido, may be explained by other factors, including an active lifestyle, trained stress handling, and social interactions, as well as a positive mindset.
- Those seeking to voluntarily practice cold-water immersion need to be educated about possible health risks associated with taking a dip in icy water, which include the consequences of hypothermia, and of heart and lung problems, which are often related to the shock from the cold.
This is a summary of the article, “Health effects of voluntary exposure to cold water – a continuing subject of debate,” published by the International Journal of Circumpolar Health.
A version of this article first appeared on Medscape.com.
according to researchers from the Arctic University of Norway and the University Hospital of North Norway.
What to know
- Immersion in cold water has a major impact on the body. It elevates the heart rate and has positive effects on brown adipose tissue, a type of “good” body fat that is activated by cold and may protect against and cardiovascular disease.
- Exposure to cold water or cold air also appears to increase the production of the protein adiponectin by adipose tissue. Adiponectin plays a key role in protecting against , diabetes, and other diseases.
- Repeated cold-water immersions by inexperienced as well as experienced swimmers during the winter months significantly increased sensitivity and decreased insulin concentrations.
- Numerous health and well-being claims from regular exposure to the cold, such as weight loss, better mental health, and increased libido, may be explained by other factors, including an active lifestyle, trained stress handling, and social interactions, as well as a positive mindset.
- Those seeking to voluntarily practice cold-water immersion need to be educated about possible health risks associated with taking a dip in icy water, which include the consequences of hypothermia, and of heart and lung problems, which are often related to the shock from the cold.
This is a summary of the article, “Health effects of voluntary exposure to cold water – a continuing subject of debate,” published by the International Journal of Circumpolar Health.
A version of this article first appeared on Medscape.com.
FROM THE INTERNATIONAL JOURNAL OF CIRCUMPOLAR HEALTH
Guideline stresses new strategies for hypoglycemia management
The Endocrine Society has issued an updated clinical practice guideline on the prevention and management of hypoglycemia in patients with diabetes who are at high risk, addressing the wide variety of treatment advances, such as insulin pumps and continuous glucose monitoring (CGM) systems, that have appeared since the publication of the society’s last guideline on hypoglycemia, in 2009.
“CGM and insulin pumps have been much more commonly used in the last decade among people with diabetes, including children, and there are new forms of glucagon available,” said Anthony L. McCall, MD, PhD, chair of the panel that wrote the guideline.
“We had to update our guideline to match these developments in the diabetes field,” noted Dr. McCall, University of Virginia, Charlottesville, in a press statement.
The new guideline, developed by a multidisciplinary panel of clinical experts and published in the Journal of Clinical Endocrinology and Metabolism, addresses 10 key clinical questions regarding current issues relevant to hypoglycemia prevention and treatment in adult or pediatric patients with either type 1 or type 2 diabetes in the outpatient or inpatient setting.
Key guideline recommendations
The recommendations are based on factors including critical outcomes, implementation feasibility, and patient preferences.
Key guideline recommendations that are considered “strong,” based on evidence, include:
- The use of CGM rather than self-monitoring of blood glucose by fingerstick for patients with type 1 diabetes receiving multiple daily injections. The panel underscored that “comprehensive patient education on how to use and troubleshoot CGM devices and interpret these data is critically important for maximum benefit and successful outcomes.”
The use of a structured program for patient education versus unstructured advice for adult and pediatric outpatients with type 1 diabetes or type 2 diabetes receiving insulin therapy.
- Structured education on how to avoid repeated hypoglycemia is critical, and this education should be performed by experienced diabetes clinicians,” the panel asserts. “Moreover, insurance coverage for education should be available for all insulin-using patients.”
- The use of glucagon preparations that do not have to be reconstituted, as opposed to those that do (that is, available as a powder and diluent) in the treatment of outpatients with severe hypoglycemia.
Guideline recommendations that received conditional recommendations include:
- Use of real-time CGM and algorithm-driven insulin pumps in people with type 1 diabetes.
- Use of CGM for outpatients with type 2 diabetes at high risk for hypoglycemia.
- Use of long-acting and rapid-acting insulin analogs for patients at high risk for hypoglycemia.
Noting that there is “moderate-certainty” evidence for severe hypoglycemia reduction as an outcome in those using long-acting analog insulins versus human neutral protamine Hagedorn (NPH) insulin, the panel cautions that “most studies of long-acting analog insulins do not assess for significant adverse effects, including cardiovascular outcomes, and that many studies were designed to demonstrate noninferiority of analog insulin, compared with human NPH insulin.”
- Initiation of and continuation of CGM for select inpatient populations at high risk for hypoglycemia.
Hypoglycemia: One of top three preventable adverse drug reactions
The updated guidelines are especially important considering the common incidence of hypoglycemia, which the U.S. Department of Health and Human Services has determined to be one of the top 3 preventable adverse drug reactions, the panel says.
They note that between January 2007 and December 2011, emergency department visits for therapy-associated hypoglycemia among Medicare beneficiaries resulted in more than $600 million in spending.
Meanwhile, many people with type 1 or 2 diabetes may not experience or recognize the symptoms of hypoglycemia, which, in severe cases, can lead to unconsciousness or seizures, in addition to affecting quality of life, social life, work productivity, and ability to drive safely.
The key to accurate diagnosis of those patients is assessment of the three levels of hypoglycemia, described in a 2018 consensus statement:
- Level 1: Glucose less than 70 mg/dL (3.9 mmol/L) and greater than or equal to 54 mg/dL (3.0 mmol/L). This level of hypoglycemia should alert patients that they may need to ingest carbohydrate to prevent progressive hypoglycemia.
- Level 2: Glucose less than 54 mg/dL (3.0 mmol/L). This level of hypoglycemia is associated with increased risk for cognitive dysfunction and mortality.
- Level 3: A severe event characterized by altered mental and/or physical status requiring assistance. This level of hypoglycemia is life-threatening and requires emergent treatment, typically with glucagon.
Ultimately, “new technology and medications will help reduce hypoglycemia, and [clinicians] can better treat patients now with new, easier glucagons,” Dr. McCall told this news organization.
“People with diabetes, their caregivers, and diabetes specialists will all benefit from our guideline with a better understanding of best practices and interventions,” the panel notes.
Disparities still exist in access to insulin pumps
Separately, new research shows that while use of insulin pumps to manage type 1 diabetes has grown over 20 years, there has been no improvement in racial, ethnic, and socioeconomic disparities in their use in the United States. The findings are reported in Diabetes Technology & Therapeutics.
Using data from the SEARCH for Diabetes Youth Study across four time periods between 2001 and 2019, the researchers show that by the end of the period studied, insulin pump use was 67% among non-Hispanic White people, 41% among Hispanic people, 29% among Black people, and 46% among other racial and ethnic groups.
In addition, 70% of people with bachelor’s degrees or higher used the pumps, compared with 56% among those with some college, 40% among holders of high school degrees, and 18% among those with no high school education. By income level, 74% of those with household incomes of $75,000 or more, 66% with $50,000-$74,999, 51% with $25,000-$49,999, and 41% with less than $25,000 used the pumps.
“Diabetes technology has numerous benefits for patients with type 1 diabetes, but the problem is that there is a huge divide in who actually has access to these technologies,” said study lead Estelle Everett, MD, assistant professor of medicine in the division of endocrinology, diabetes & metabolism at the University of California, Los Angeles.
A version of this article first appeared on Medscape.com.
The Endocrine Society has issued an updated clinical practice guideline on the prevention and management of hypoglycemia in patients with diabetes who are at high risk, addressing the wide variety of treatment advances, such as insulin pumps and continuous glucose monitoring (CGM) systems, that have appeared since the publication of the society’s last guideline on hypoglycemia, in 2009.
“CGM and insulin pumps have been much more commonly used in the last decade among people with diabetes, including children, and there are new forms of glucagon available,” said Anthony L. McCall, MD, PhD, chair of the panel that wrote the guideline.
“We had to update our guideline to match these developments in the diabetes field,” noted Dr. McCall, University of Virginia, Charlottesville, in a press statement.
The new guideline, developed by a multidisciplinary panel of clinical experts and published in the Journal of Clinical Endocrinology and Metabolism, addresses 10 key clinical questions regarding current issues relevant to hypoglycemia prevention and treatment in adult or pediatric patients with either type 1 or type 2 diabetes in the outpatient or inpatient setting.
Key guideline recommendations
The recommendations are based on factors including critical outcomes, implementation feasibility, and patient preferences.
Key guideline recommendations that are considered “strong,” based on evidence, include:
- The use of CGM rather than self-monitoring of blood glucose by fingerstick for patients with type 1 diabetes receiving multiple daily injections. The panel underscored that “comprehensive patient education on how to use and troubleshoot CGM devices and interpret these data is critically important for maximum benefit and successful outcomes.”
The use of a structured program for patient education versus unstructured advice for adult and pediatric outpatients with type 1 diabetes or type 2 diabetes receiving insulin therapy.
- Structured education on how to avoid repeated hypoglycemia is critical, and this education should be performed by experienced diabetes clinicians,” the panel asserts. “Moreover, insurance coverage for education should be available for all insulin-using patients.”
- The use of glucagon preparations that do not have to be reconstituted, as opposed to those that do (that is, available as a powder and diluent) in the treatment of outpatients with severe hypoglycemia.
Guideline recommendations that received conditional recommendations include:
- Use of real-time CGM and algorithm-driven insulin pumps in people with type 1 diabetes.
- Use of CGM for outpatients with type 2 diabetes at high risk for hypoglycemia.
- Use of long-acting and rapid-acting insulin analogs for patients at high risk for hypoglycemia.
Noting that there is “moderate-certainty” evidence for severe hypoglycemia reduction as an outcome in those using long-acting analog insulins versus human neutral protamine Hagedorn (NPH) insulin, the panel cautions that “most studies of long-acting analog insulins do not assess for significant adverse effects, including cardiovascular outcomes, and that many studies were designed to demonstrate noninferiority of analog insulin, compared with human NPH insulin.”
- Initiation of and continuation of CGM for select inpatient populations at high risk for hypoglycemia.
Hypoglycemia: One of top three preventable adverse drug reactions
The updated guidelines are especially important considering the common incidence of hypoglycemia, which the U.S. Department of Health and Human Services has determined to be one of the top 3 preventable adverse drug reactions, the panel says.
They note that between January 2007 and December 2011, emergency department visits for therapy-associated hypoglycemia among Medicare beneficiaries resulted in more than $600 million in spending.
Meanwhile, many people with type 1 or 2 diabetes may not experience or recognize the symptoms of hypoglycemia, which, in severe cases, can lead to unconsciousness or seizures, in addition to affecting quality of life, social life, work productivity, and ability to drive safely.
The key to accurate diagnosis of those patients is assessment of the three levels of hypoglycemia, described in a 2018 consensus statement:
- Level 1: Glucose less than 70 mg/dL (3.9 mmol/L) and greater than or equal to 54 mg/dL (3.0 mmol/L). This level of hypoglycemia should alert patients that they may need to ingest carbohydrate to prevent progressive hypoglycemia.
- Level 2: Glucose less than 54 mg/dL (3.0 mmol/L). This level of hypoglycemia is associated with increased risk for cognitive dysfunction and mortality.
- Level 3: A severe event characterized by altered mental and/or physical status requiring assistance. This level of hypoglycemia is life-threatening and requires emergent treatment, typically with glucagon.
Ultimately, “new technology and medications will help reduce hypoglycemia, and [clinicians] can better treat patients now with new, easier glucagons,” Dr. McCall told this news organization.
“People with diabetes, their caregivers, and diabetes specialists will all benefit from our guideline with a better understanding of best practices and interventions,” the panel notes.
Disparities still exist in access to insulin pumps
Separately, new research shows that while use of insulin pumps to manage type 1 diabetes has grown over 20 years, there has been no improvement in racial, ethnic, and socioeconomic disparities in their use in the United States. The findings are reported in Diabetes Technology & Therapeutics.
Using data from the SEARCH for Diabetes Youth Study across four time periods between 2001 and 2019, the researchers show that by the end of the period studied, insulin pump use was 67% among non-Hispanic White people, 41% among Hispanic people, 29% among Black people, and 46% among other racial and ethnic groups.
In addition, 70% of people with bachelor’s degrees or higher used the pumps, compared with 56% among those with some college, 40% among holders of high school degrees, and 18% among those with no high school education. By income level, 74% of those with household incomes of $75,000 or more, 66% with $50,000-$74,999, 51% with $25,000-$49,999, and 41% with less than $25,000 used the pumps.
“Diabetes technology has numerous benefits for patients with type 1 diabetes, but the problem is that there is a huge divide in who actually has access to these technologies,” said study lead Estelle Everett, MD, assistant professor of medicine in the division of endocrinology, diabetes & metabolism at the University of California, Los Angeles.
A version of this article first appeared on Medscape.com.
The Endocrine Society has issued an updated clinical practice guideline on the prevention and management of hypoglycemia in patients with diabetes who are at high risk, addressing the wide variety of treatment advances, such as insulin pumps and continuous glucose monitoring (CGM) systems, that have appeared since the publication of the society’s last guideline on hypoglycemia, in 2009.
“CGM and insulin pumps have been much more commonly used in the last decade among people with diabetes, including children, and there are new forms of glucagon available,” said Anthony L. McCall, MD, PhD, chair of the panel that wrote the guideline.
“We had to update our guideline to match these developments in the diabetes field,” noted Dr. McCall, University of Virginia, Charlottesville, in a press statement.
The new guideline, developed by a multidisciplinary panel of clinical experts and published in the Journal of Clinical Endocrinology and Metabolism, addresses 10 key clinical questions regarding current issues relevant to hypoglycemia prevention and treatment in adult or pediatric patients with either type 1 or type 2 diabetes in the outpatient or inpatient setting.
Key guideline recommendations
The recommendations are based on factors including critical outcomes, implementation feasibility, and patient preferences.
Key guideline recommendations that are considered “strong,” based on evidence, include:
- The use of CGM rather than self-monitoring of blood glucose by fingerstick for patients with type 1 diabetes receiving multiple daily injections. The panel underscored that “comprehensive patient education on how to use and troubleshoot CGM devices and interpret these data is critically important for maximum benefit and successful outcomes.”
The use of a structured program for patient education versus unstructured advice for adult and pediatric outpatients with type 1 diabetes or type 2 diabetes receiving insulin therapy.
- Structured education on how to avoid repeated hypoglycemia is critical, and this education should be performed by experienced diabetes clinicians,” the panel asserts. “Moreover, insurance coverage for education should be available for all insulin-using patients.”
- The use of glucagon preparations that do not have to be reconstituted, as opposed to those that do (that is, available as a powder and diluent) in the treatment of outpatients with severe hypoglycemia.
Guideline recommendations that received conditional recommendations include:
- Use of real-time CGM and algorithm-driven insulin pumps in people with type 1 diabetes.
- Use of CGM for outpatients with type 2 diabetes at high risk for hypoglycemia.
- Use of long-acting and rapid-acting insulin analogs for patients at high risk for hypoglycemia.
Noting that there is “moderate-certainty” evidence for severe hypoglycemia reduction as an outcome in those using long-acting analog insulins versus human neutral protamine Hagedorn (NPH) insulin, the panel cautions that “most studies of long-acting analog insulins do not assess for significant adverse effects, including cardiovascular outcomes, and that many studies were designed to demonstrate noninferiority of analog insulin, compared with human NPH insulin.”
- Initiation of and continuation of CGM for select inpatient populations at high risk for hypoglycemia.
Hypoglycemia: One of top three preventable adverse drug reactions
The updated guidelines are especially important considering the common incidence of hypoglycemia, which the U.S. Department of Health and Human Services has determined to be one of the top 3 preventable adverse drug reactions, the panel says.
They note that between January 2007 and December 2011, emergency department visits for therapy-associated hypoglycemia among Medicare beneficiaries resulted in more than $600 million in spending.
Meanwhile, many people with type 1 or 2 diabetes may not experience or recognize the symptoms of hypoglycemia, which, in severe cases, can lead to unconsciousness or seizures, in addition to affecting quality of life, social life, work productivity, and ability to drive safely.
The key to accurate diagnosis of those patients is assessment of the three levels of hypoglycemia, described in a 2018 consensus statement:
- Level 1: Glucose less than 70 mg/dL (3.9 mmol/L) and greater than or equal to 54 mg/dL (3.0 mmol/L). This level of hypoglycemia should alert patients that they may need to ingest carbohydrate to prevent progressive hypoglycemia.
- Level 2: Glucose less than 54 mg/dL (3.0 mmol/L). This level of hypoglycemia is associated with increased risk for cognitive dysfunction and mortality.
- Level 3: A severe event characterized by altered mental and/or physical status requiring assistance. This level of hypoglycemia is life-threatening and requires emergent treatment, typically with glucagon.
Ultimately, “new technology and medications will help reduce hypoglycemia, and [clinicians] can better treat patients now with new, easier glucagons,” Dr. McCall told this news organization.
“People with diabetes, their caregivers, and diabetes specialists will all benefit from our guideline with a better understanding of best practices and interventions,” the panel notes.
Disparities still exist in access to insulin pumps
Separately, new research shows that while use of insulin pumps to manage type 1 diabetes has grown over 20 years, there has been no improvement in racial, ethnic, and socioeconomic disparities in their use in the United States. The findings are reported in Diabetes Technology & Therapeutics.
Using data from the SEARCH for Diabetes Youth Study across four time periods between 2001 and 2019, the researchers show that by the end of the period studied, insulin pump use was 67% among non-Hispanic White people, 41% among Hispanic people, 29% among Black people, and 46% among other racial and ethnic groups.
In addition, 70% of people with bachelor’s degrees or higher used the pumps, compared with 56% among those with some college, 40% among holders of high school degrees, and 18% among those with no high school education. By income level, 74% of those with household incomes of $75,000 or more, 66% with $50,000-$74,999, 51% with $25,000-$49,999, and 41% with less than $25,000 used the pumps.
“Diabetes technology has numerous benefits for patients with type 1 diabetes, but the problem is that there is a huge divide in who actually has access to these technologies,” said study lead Estelle Everett, MD, assistant professor of medicine in the division of endocrinology, diabetes & metabolism at the University of California, Los Angeles.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM