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Another lot of extended-release metformin is recalled in the U.S.
Nostrum Laboratories has voluntarily recalled another lot of metformin HCl extended-release tablets 750-mg dosage, expanding their initial announcement in November 2020. According to the new notice, issued by the Food and Drug Administration earlier this week, the recalled tablets are off-white and oblong with a debossed ID “NM7.”
The lot number, NDC, and expiration dates can be found on the FDA website.
Nostrum noted that the tablets were distributed across the United States to wholesalers; these distributors are being notified of the recall and the company is arranging for the drug to be returned.
Metformin is the most prescribed medication worldwide for the treatment of type 2 diabetes.
Nostrum said that anyone in possession of any of the affected lots should consult their physician or pharmacist to obtain a replacement treatment option because it can be dangerous for patients with type 2 diabetes to stop taking metformin.
This new announcement expands further the number of metformin HCl extended-release tablets recalled in the United States because they contain potentially high levels of nitrosamines, also known as N-nitrosodimethylamine (NDMA), which are possible carcinogens.
The risks of nitrosamines are not clear. The FDA said they may increase the risk of cancer in people who are exposed to high levels over a long period of time, “but we do not anticipate that shorter-term exposure at levels above the acceptable intake limit would lead to an increase in the risk of cancer.”
As well as the November recall of 2 lots of metformin by Nostrum, 76 more lots of metformin extended-release tablets were flagged in October 2020 from various manufacturers for possible contamination with NDMA, on top of an earlier recall for the same problem in May 2020.
More than 175 different drug combinations, all extended release with either 500 mg or 750 mg of metformin, have now been recalled since late May 2020, and a list of those recalled to November 2020 is available here.
A version of this article first appeared on Medscape.com.
Nostrum Laboratories has voluntarily recalled another lot of metformin HCl extended-release tablets 750-mg dosage, expanding their initial announcement in November 2020. According to the new notice, issued by the Food and Drug Administration earlier this week, the recalled tablets are off-white and oblong with a debossed ID “NM7.”
The lot number, NDC, and expiration dates can be found on the FDA website.
Nostrum noted that the tablets were distributed across the United States to wholesalers; these distributors are being notified of the recall and the company is arranging for the drug to be returned.
Metformin is the most prescribed medication worldwide for the treatment of type 2 diabetes.
Nostrum said that anyone in possession of any of the affected lots should consult their physician or pharmacist to obtain a replacement treatment option because it can be dangerous for patients with type 2 diabetes to stop taking metformin.
This new announcement expands further the number of metformin HCl extended-release tablets recalled in the United States because they contain potentially high levels of nitrosamines, also known as N-nitrosodimethylamine (NDMA), which are possible carcinogens.
The risks of nitrosamines are not clear. The FDA said they may increase the risk of cancer in people who are exposed to high levels over a long period of time, “but we do not anticipate that shorter-term exposure at levels above the acceptable intake limit would lead to an increase in the risk of cancer.”
As well as the November recall of 2 lots of metformin by Nostrum, 76 more lots of metformin extended-release tablets were flagged in October 2020 from various manufacturers for possible contamination with NDMA, on top of an earlier recall for the same problem in May 2020.
More than 175 different drug combinations, all extended release with either 500 mg or 750 mg of metformin, have now been recalled since late May 2020, and a list of those recalled to November 2020 is available here.
A version of this article first appeared on Medscape.com.
Nostrum Laboratories has voluntarily recalled another lot of metformin HCl extended-release tablets 750-mg dosage, expanding their initial announcement in November 2020. According to the new notice, issued by the Food and Drug Administration earlier this week, the recalled tablets are off-white and oblong with a debossed ID “NM7.”
The lot number, NDC, and expiration dates can be found on the FDA website.
Nostrum noted that the tablets were distributed across the United States to wholesalers; these distributors are being notified of the recall and the company is arranging for the drug to be returned.
Metformin is the most prescribed medication worldwide for the treatment of type 2 diabetes.
Nostrum said that anyone in possession of any of the affected lots should consult their physician or pharmacist to obtain a replacement treatment option because it can be dangerous for patients with type 2 diabetes to stop taking metformin.
This new announcement expands further the number of metformin HCl extended-release tablets recalled in the United States because they contain potentially high levels of nitrosamines, also known as N-nitrosodimethylamine (NDMA), which are possible carcinogens.
The risks of nitrosamines are not clear. The FDA said they may increase the risk of cancer in people who are exposed to high levels over a long period of time, “but we do not anticipate that shorter-term exposure at levels above the acceptable intake limit would lead to an increase in the risk of cancer.”
As well as the November recall of 2 lots of metformin by Nostrum, 76 more lots of metformin extended-release tablets were flagged in October 2020 from various manufacturers for possible contamination with NDMA, on top of an earlier recall for the same problem in May 2020.
More than 175 different drug combinations, all extended release with either 500 mg or 750 mg of metformin, have now been recalled since late May 2020, and a list of those recalled to November 2020 is available here.
A version of this article first appeared on Medscape.com.
Large study links brown fat with lower rates of cardiometabolic disease
People who have brown fat detected on imaging seem to be at reduced risk of cardiac and metabolic conditions, ranging from type 2 diabetes to hypertension and coronary artery disease, with a notably strong effect in people with obesity, according to a new study of more than 52,000 individuals who had PET/CT scans as part of cancer evaluation.
Although this has been studied for decades in newborns and animals, only in the past decade have scientists appreciated that some adults have brown fat, typically around the neck and shoulders.
The new study, by far the largest of its kind in humans, appears to confirm the health benefits of brown fat suggested by previous studies, Tobias Becher, MD, and colleagues from The Rockefeller University, New York, wrote in their article published online Jan. 4 in Nature Medicine.
“Our study indicates an important contribution of brown adipose tissue to cardiometabolic health and suggests ... [it] has therapeutic potential in humans,” they stated.
But Caroline M. Apovian, MD, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, is more cautious in her interpretation of the findings.
“It’s nice to see that what we believe about this is correct, and it’s great to see that with obesity and more brown fat there is reduced diabetes and hypertension, but it’s only an association,” she said in an interview.
“This is a good study, but I don’t think we have an understanding of exactly why some people have more brown fat than others, how white fat becomes brown fat, the role of therapeutics, or if it’s important to try to create more brown fat.
“We don’t know if it’s a matter of exercise or something like living in a colder environment, so we need to find out whether or not brown fat is, for instance, a genetic issue, and if it is, if there is a way to increase it in humans,” she added.
And the fact that the study included patients with or being screened for cancer is one of the most important limitations of the study, Dr. Apovian noted.
Brown fat detected in 10% of participants
Contrary to white fat, which stores energy, brown fat is thermogenic, activated by cold conditions, and instead burns energy. And although animal studies have shown a link between brown fat and improvements in glucose and lipid homeostasis, the effects of brown fat in humans are not well understood.
Dr. Becher and colleagues explained that large-scale studies of brown fat have been practically impossible because the tissue only shows up on medical imaging and it would be unethical to expose people to radiation just to study brown fat.
But they realized that, across the street from their lab, many thousands of people visit Memorial Sloan Kettering Cancer Center each year to undergo PET/CT scans for cancer evaluation.
Because radiologists routinely take note when brown adipose tissue is detected to prevent its misinterpretation as a tumor, the information was readily available with the scan data.
“We realized this could be a valuable resource to get us started with looking at brown fat at a population scale,” Dr. Becher said in a press statement from The Rockefeller University.
So they reviewed 134,529 PET/CT scans from 52,487 individuals attending Memorial Sloan Kettering between June 2009 and March 2018 for indications ranging from cancer diagnosis to treatment or surveillance.
Participants were classified by the presence or absence of brown adipose tissue and researchers were able to use electronic health records to comprehensively examine associations between brown fat and rates of disease.
Overall, brown adipose tissue was identified in 5,070 (9.7%) of patients, with higher rates of brown fat among women than men (13.8% vs. 4.9%; P < .0001) and reduced rates with advancing age (P < .0001), as has been observed in previous studies.
The researchers noted, however, that this rate of around 10% of people having brown fat is likely an underestimate because the patients had been instructed to avoid cold exposure, exercise, and caffeine – all of which are thought to increase brown adipose tissue – prior to having their scans.
Does brown fat mitigate some harms of obesity?
Among those with brown fat, the rate of type 2 diabetes was 4.6% compared with 9.5% in those with no detected brown fat (P < .0001), and in a multivariate analysis, the odds ratio (OR) for type 2 diabetes in the presence of brown fat was 0.44.
The occurrence of coronary artery disease was significantly lower in those with brown fat (OR, 0.68; P = .0002), as was cerebrovascular disease (OR, 0.77; P = .0317), heart failure (OR, 0.62; P = .0043), and hypertension (OR, 0.85; P = .0014).
Brown fat also was associated with notable improvements in glucose, triglycerides, and HDL-C levels (all P < .0001), while no differences were seen in measures of LDL-Cs or total cholesterol.
Leukocyte and platelet counts were significantly decreased in individuals with brown fat (both P < .0001).
The findings “suggest potential roles for brown adipose beyond regulation of lipid and glucose metabolism,” the authors wrote.
Most notably, the effects were more pronounced in people with obesity. For example, the prevalence of type 2 diabetes in those with obesity and brown fat was less than half the rate in those with obesity without brown fat (7.5% vs. 20.3%; P < .0001).
This could indicate that brown adipose tissue “might play a role in mitigating the deleterious effects of obesity,” the researchers stated.
“Future research should aim to improve our understanding of brown adipose tissue regulation in humans and to develop mechanisms to safely modulate [its activity],” they concluded.
The study received funding from the American Diabetes Association, the Sinsheimer Foundation, and the National Center for Advancing Translational Sciences of the U.S. Department of Health & Human Services. The authors and Dr. Apovian have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
People who have brown fat detected on imaging seem to be at reduced risk of cardiac and metabolic conditions, ranging from type 2 diabetes to hypertension and coronary artery disease, with a notably strong effect in people with obesity, according to a new study of more than 52,000 individuals who had PET/CT scans as part of cancer evaluation.
Although this has been studied for decades in newborns and animals, only in the past decade have scientists appreciated that some adults have brown fat, typically around the neck and shoulders.
The new study, by far the largest of its kind in humans, appears to confirm the health benefits of brown fat suggested by previous studies, Tobias Becher, MD, and colleagues from The Rockefeller University, New York, wrote in their article published online Jan. 4 in Nature Medicine.
“Our study indicates an important contribution of brown adipose tissue to cardiometabolic health and suggests ... [it] has therapeutic potential in humans,” they stated.
But Caroline M. Apovian, MD, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, is more cautious in her interpretation of the findings.
“It’s nice to see that what we believe about this is correct, and it’s great to see that with obesity and more brown fat there is reduced diabetes and hypertension, but it’s only an association,” she said in an interview.
“This is a good study, but I don’t think we have an understanding of exactly why some people have more brown fat than others, how white fat becomes brown fat, the role of therapeutics, or if it’s important to try to create more brown fat.
“We don’t know if it’s a matter of exercise or something like living in a colder environment, so we need to find out whether or not brown fat is, for instance, a genetic issue, and if it is, if there is a way to increase it in humans,” she added.
And the fact that the study included patients with or being screened for cancer is one of the most important limitations of the study, Dr. Apovian noted.
Brown fat detected in 10% of participants
Contrary to white fat, which stores energy, brown fat is thermogenic, activated by cold conditions, and instead burns energy. And although animal studies have shown a link between brown fat and improvements in glucose and lipid homeostasis, the effects of brown fat in humans are not well understood.
Dr. Becher and colleagues explained that large-scale studies of brown fat have been practically impossible because the tissue only shows up on medical imaging and it would be unethical to expose people to radiation just to study brown fat.
But they realized that, across the street from their lab, many thousands of people visit Memorial Sloan Kettering Cancer Center each year to undergo PET/CT scans for cancer evaluation.
Because radiologists routinely take note when brown adipose tissue is detected to prevent its misinterpretation as a tumor, the information was readily available with the scan data.
“We realized this could be a valuable resource to get us started with looking at brown fat at a population scale,” Dr. Becher said in a press statement from The Rockefeller University.
So they reviewed 134,529 PET/CT scans from 52,487 individuals attending Memorial Sloan Kettering between June 2009 and March 2018 for indications ranging from cancer diagnosis to treatment or surveillance.
Participants were classified by the presence or absence of brown adipose tissue and researchers were able to use electronic health records to comprehensively examine associations between brown fat and rates of disease.
Overall, brown adipose tissue was identified in 5,070 (9.7%) of patients, with higher rates of brown fat among women than men (13.8% vs. 4.9%; P < .0001) and reduced rates with advancing age (P < .0001), as has been observed in previous studies.
The researchers noted, however, that this rate of around 10% of people having brown fat is likely an underestimate because the patients had been instructed to avoid cold exposure, exercise, and caffeine – all of which are thought to increase brown adipose tissue – prior to having their scans.
Does brown fat mitigate some harms of obesity?
Among those with brown fat, the rate of type 2 diabetes was 4.6% compared with 9.5% in those with no detected brown fat (P < .0001), and in a multivariate analysis, the odds ratio (OR) for type 2 diabetes in the presence of brown fat was 0.44.
The occurrence of coronary artery disease was significantly lower in those with brown fat (OR, 0.68; P = .0002), as was cerebrovascular disease (OR, 0.77; P = .0317), heart failure (OR, 0.62; P = .0043), and hypertension (OR, 0.85; P = .0014).
Brown fat also was associated with notable improvements in glucose, triglycerides, and HDL-C levels (all P < .0001), while no differences were seen in measures of LDL-Cs or total cholesterol.
Leukocyte and platelet counts were significantly decreased in individuals with brown fat (both P < .0001).
The findings “suggest potential roles for brown adipose beyond regulation of lipid and glucose metabolism,” the authors wrote.
Most notably, the effects were more pronounced in people with obesity. For example, the prevalence of type 2 diabetes in those with obesity and brown fat was less than half the rate in those with obesity without brown fat (7.5% vs. 20.3%; P < .0001).
This could indicate that brown adipose tissue “might play a role in mitigating the deleterious effects of obesity,” the researchers stated.
“Future research should aim to improve our understanding of brown adipose tissue regulation in humans and to develop mechanisms to safely modulate [its activity],” they concluded.
The study received funding from the American Diabetes Association, the Sinsheimer Foundation, and the National Center for Advancing Translational Sciences of the U.S. Department of Health & Human Services. The authors and Dr. Apovian have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
People who have brown fat detected on imaging seem to be at reduced risk of cardiac and metabolic conditions, ranging from type 2 diabetes to hypertension and coronary artery disease, with a notably strong effect in people with obesity, according to a new study of more than 52,000 individuals who had PET/CT scans as part of cancer evaluation.
Although this has been studied for decades in newborns and animals, only in the past decade have scientists appreciated that some adults have brown fat, typically around the neck and shoulders.
The new study, by far the largest of its kind in humans, appears to confirm the health benefits of brown fat suggested by previous studies, Tobias Becher, MD, and colleagues from The Rockefeller University, New York, wrote in their article published online Jan. 4 in Nature Medicine.
“Our study indicates an important contribution of brown adipose tissue to cardiometabolic health and suggests ... [it] has therapeutic potential in humans,” they stated.
But Caroline M. Apovian, MD, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, is more cautious in her interpretation of the findings.
“It’s nice to see that what we believe about this is correct, and it’s great to see that with obesity and more brown fat there is reduced diabetes and hypertension, but it’s only an association,” she said in an interview.
“This is a good study, but I don’t think we have an understanding of exactly why some people have more brown fat than others, how white fat becomes brown fat, the role of therapeutics, or if it’s important to try to create more brown fat.
“We don’t know if it’s a matter of exercise or something like living in a colder environment, so we need to find out whether or not brown fat is, for instance, a genetic issue, and if it is, if there is a way to increase it in humans,” she added.
And the fact that the study included patients with or being screened for cancer is one of the most important limitations of the study, Dr. Apovian noted.
Brown fat detected in 10% of participants
Contrary to white fat, which stores energy, brown fat is thermogenic, activated by cold conditions, and instead burns energy. And although animal studies have shown a link between brown fat and improvements in glucose and lipid homeostasis, the effects of brown fat in humans are not well understood.
Dr. Becher and colleagues explained that large-scale studies of brown fat have been practically impossible because the tissue only shows up on medical imaging and it would be unethical to expose people to radiation just to study brown fat.
But they realized that, across the street from their lab, many thousands of people visit Memorial Sloan Kettering Cancer Center each year to undergo PET/CT scans for cancer evaluation.
Because radiologists routinely take note when brown adipose tissue is detected to prevent its misinterpretation as a tumor, the information was readily available with the scan data.
“We realized this could be a valuable resource to get us started with looking at brown fat at a population scale,” Dr. Becher said in a press statement from The Rockefeller University.
So they reviewed 134,529 PET/CT scans from 52,487 individuals attending Memorial Sloan Kettering between June 2009 and March 2018 for indications ranging from cancer diagnosis to treatment or surveillance.
Participants were classified by the presence or absence of brown adipose tissue and researchers were able to use electronic health records to comprehensively examine associations between brown fat and rates of disease.
Overall, brown adipose tissue was identified in 5,070 (9.7%) of patients, with higher rates of brown fat among women than men (13.8% vs. 4.9%; P < .0001) and reduced rates with advancing age (P < .0001), as has been observed in previous studies.
The researchers noted, however, that this rate of around 10% of people having brown fat is likely an underestimate because the patients had been instructed to avoid cold exposure, exercise, and caffeine – all of which are thought to increase brown adipose tissue – prior to having their scans.
Does brown fat mitigate some harms of obesity?
Among those with brown fat, the rate of type 2 diabetes was 4.6% compared with 9.5% in those with no detected brown fat (P < .0001), and in a multivariate analysis, the odds ratio (OR) for type 2 diabetes in the presence of brown fat was 0.44.
The occurrence of coronary artery disease was significantly lower in those with brown fat (OR, 0.68; P = .0002), as was cerebrovascular disease (OR, 0.77; P = .0317), heart failure (OR, 0.62; P = .0043), and hypertension (OR, 0.85; P = .0014).
Brown fat also was associated with notable improvements in glucose, triglycerides, and HDL-C levels (all P < .0001), while no differences were seen in measures of LDL-Cs or total cholesterol.
Leukocyte and platelet counts were significantly decreased in individuals with brown fat (both P < .0001).
The findings “suggest potential roles for brown adipose beyond regulation of lipid and glucose metabolism,” the authors wrote.
Most notably, the effects were more pronounced in people with obesity. For example, the prevalence of type 2 diabetes in those with obesity and brown fat was less than half the rate in those with obesity without brown fat (7.5% vs. 20.3%; P < .0001).
This could indicate that brown adipose tissue “might play a role in mitigating the deleterious effects of obesity,” the researchers stated.
“Future research should aim to improve our understanding of brown adipose tissue regulation in humans and to develop mechanisms to safely modulate [its activity],” they concluded.
The study received funding from the American Diabetes Association, the Sinsheimer Foundation, and the National Center for Advancing Translational Sciences of the U.S. Department of Health & Human Services. The authors and Dr. Apovian have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Ultraprocessed food again linked to increased CVD, death
Yet another study has linked the consumption of ultraprocessed, or “junk,” foods to bad health outcomes.
In a longitudinal analysis of more than 22,000 men and women from southern Italy, those who consumed the most ultraprocessed food (UPF) had the highest risk for cardiovascular disease (CVD) and all-cause mortality, likely mediated through a diet high in sugar, researchers said.
High consumption of UPF in this Mediterranean cohort was associated with a 58% increased risk for CVD mortality and 52% higher risk of dying from ischemic heart disease (IHD) and cerebrovascular causes, independently of known risk factors for CVD, even among individuals who otherwise adhered to the Mediterranean diet.
The findings “should serve as an incentive for limiting consumption of UPF and encouraging natural or minimally processed foods, as several national nutritional policies recommend,” Marialaura Bonaccio, PhD, department of epidemiology and prevention, IRCCS Neuromed, Pozzilli, Italy, and colleagues wrote. The results were published online Dec. 18 in the American Journal of Clinical Nutrition.
Earlier this year, as reported by this news organization, researchers found mounting evidence that the obesity epidemic and the increase in incidence of related chronic conditions corresponded with an increase in the intake of UPF.
A study that was conducted in a European cohort found that adults whose diet included more UPF and beverages, such as ice cream, soda, and hamburgers, were more likely to develop CVD or die sooner than others who had a more wholesome diet.
As reported previously by this news organization, among adults in France who had a 10% higher intake of UPF and beverages, the rate of CVD, coronary heart disease, and cerebrovascular disease was 11% to 13% higher over a period of about 5 years.
Similarly, university graduates in Spain who consumed more than four servings of UPF and beverages a day were 62% more likely to die of any cause over about a decade than those who consumed less than two servings per day.
Where’s the food?
There is very little actual food in UPF. “The NOVA classification provides 4 main classes of food and beverages, the last of which is represented by the ultraprocessed food group. This comprises products (e.g., snacks, drinks, and ready meals, ‘created mostly or entirely from substances extracted from foods or derived from food constituents with little, if any intact food, which often contain flavors, colors, and other additives that imitate or intensify the sensory qualities of foods or culinary preparations made from foods,’ ” Dr. Bonaccio and colleagues wrote.
Such foods are very convenient, tasty, inexpensive, and have a long shelf life. They are highly competitive with foods that are naturally ready to consume and freshly prepared dishes and meals, the authors add.
The researchers conducted a longitudinal analysis on 22,475 men and women (mean age, 55 years; range, 43-67 years) who were recruited from the Moli-sani Study, a population-based cohort of men and women aged 35 years and older in the Molise region of southern Italy, between 2005 and 2010. Participants were followed for 8.2 years.
Food intake was assessed with the Food Frequency Questionnaire; UPF was defined using the NOVA classification according to degree of processing.
UPF intakes were categorized as quartiles of the ratio of UPF to total food consumed.
Overall, study participants reported a median of 10% (interquartile range, 6.6%-14.6%) of dietary intake as UPF and a total of 181.5 g/d of UPF intake.
The foods that contributed most to total UPF consumed were processed meat, which accounted for 19.8% of UPF intake; pizza (16.8%); and cakes and pies (13.4%).
High consumers of UPF, defined as those for whom UPF constituted more than 14.6% of their total diet, were more likely to be women, to be younger, and to have a higher educational level. They also reported fewer risk factors and fewer baseline chronic diseases and health conditions than persons who consumed UPF less frequently.
In addition, high consumption of UPF was associated with lower adherence to the Mediterranean diet; higher intake of fat, sugar, dietary cholesterol, and sodium; and lower intake of fiber.
During a median follow-up of 8.2 years, 1,216 all-cause deaths occurred. Of these, 439 were attributed to CVD, 255 to IHD/cerebrovascular disease, 477 to cancer, and 300 to other causes.
The more UPF, the higher the risk for CVD, death
The researchers found a direct linear dose-response relation between a 5% increase in the proportion of UPF in the diet and risk for all-cause and CVD mortality.
Individuals who reported the highest intake of UPF (fourth quartile, 14.6% of total food) as opposed to the lowest (first quartile, UPF <6.6%) experienced increased risks for CVD mortality (hazard ratio, 1.58; 95% CI, 1.23-2.03), death from IHD/cerebrovascular disease (HR, 1.52, 95% CI, 1.10-2.09), and all-cause mortality (HR, 1.26; 95% CI, 1.09-1.46).
High sugar content accounted for 36.3% of the relation of UPF with IHD/cerebrovascular mortality. Other nutritional factors, such as saturated fats, were unlikely to play a role, the researchers wrote.
Biomarkers of renal function accounted for 20.1% of the association of UPF with all-cause mortality and 12.0% for that of UPF with CVD mortality.
Subgroup analyses indicated that the magnitude of the association between UPF and all-cause mortality risk was greater among high-risk individuals, such as those with a history of CVD or diabetes. UPF was also likely to be more strongly associated with CVD mortality among those high-risk groups.
The interesting finding that the association between UPF and CVD mortality was greater among individuals with good adherence to the Mediterranean diet, which is known to have health benefits, could be explained by the fact that people who may benefit from a Mediterranean diet are more susceptible to losing health advantages when they also include “detrimental dietary behavior,” whereas those who consume a poor-quality diet are less likely to be harmed by an additional unhealthy behavior such as eating UPF regularly, wrote Dr. Bonaccio and colleagues.
“This is an interesting study confirming that consumption of highly processed foods such as pizza, processed meats, and soda are associated with greater risks of cardiovascular disease,” Walter Willett, MD, professor of epidemiology and nutrition, Harvard School of Public Health, Boston, said in an interview.
“These higher risks appear to be mediated in part by high intakes of saturated fat and sugar, but lower intakes of health-promoting aspects of diet also likely contribute to the findings,” Dr. Willett said.
“Some processing of food can be useful for preservation and control of infectious agents, but in general, a diet emphasizing minimally processed fruits and vegetables, whole grains, nuts, legumes, and plant sources of fat will be best for long-term well-being,” he said.
The study was supported in part by the Italian Ministry of Health and the HYPERCAN Study Italian Association for Cancer Research. Dr. Bonaccio and Dr. Willett reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Yet another study has linked the consumption of ultraprocessed, or “junk,” foods to bad health outcomes.
In a longitudinal analysis of more than 22,000 men and women from southern Italy, those who consumed the most ultraprocessed food (UPF) had the highest risk for cardiovascular disease (CVD) and all-cause mortality, likely mediated through a diet high in sugar, researchers said.
High consumption of UPF in this Mediterranean cohort was associated with a 58% increased risk for CVD mortality and 52% higher risk of dying from ischemic heart disease (IHD) and cerebrovascular causes, independently of known risk factors for CVD, even among individuals who otherwise adhered to the Mediterranean diet.
The findings “should serve as an incentive for limiting consumption of UPF and encouraging natural or minimally processed foods, as several national nutritional policies recommend,” Marialaura Bonaccio, PhD, department of epidemiology and prevention, IRCCS Neuromed, Pozzilli, Italy, and colleagues wrote. The results were published online Dec. 18 in the American Journal of Clinical Nutrition.
Earlier this year, as reported by this news organization, researchers found mounting evidence that the obesity epidemic and the increase in incidence of related chronic conditions corresponded with an increase in the intake of UPF.
A study that was conducted in a European cohort found that adults whose diet included more UPF and beverages, such as ice cream, soda, and hamburgers, were more likely to develop CVD or die sooner than others who had a more wholesome diet.
As reported previously by this news organization, among adults in France who had a 10% higher intake of UPF and beverages, the rate of CVD, coronary heart disease, and cerebrovascular disease was 11% to 13% higher over a period of about 5 years.
Similarly, university graduates in Spain who consumed more than four servings of UPF and beverages a day were 62% more likely to die of any cause over about a decade than those who consumed less than two servings per day.
Where’s the food?
There is very little actual food in UPF. “The NOVA classification provides 4 main classes of food and beverages, the last of which is represented by the ultraprocessed food group. This comprises products (e.g., snacks, drinks, and ready meals, ‘created mostly or entirely from substances extracted from foods or derived from food constituents with little, if any intact food, which often contain flavors, colors, and other additives that imitate or intensify the sensory qualities of foods or culinary preparations made from foods,’ ” Dr. Bonaccio and colleagues wrote.
Such foods are very convenient, tasty, inexpensive, and have a long shelf life. They are highly competitive with foods that are naturally ready to consume and freshly prepared dishes and meals, the authors add.
The researchers conducted a longitudinal analysis on 22,475 men and women (mean age, 55 years; range, 43-67 years) who were recruited from the Moli-sani Study, a population-based cohort of men and women aged 35 years and older in the Molise region of southern Italy, between 2005 and 2010. Participants were followed for 8.2 years.
Food intake was assessed with the Food Frequency Questionnaire; UPF was defined using the NOVA classification according to degree of processing.
UPF intakes were categorized as quartiles of the ratio of UPF to total food consumed.
Overall, study participants reported a median of 10% (interquartile range, 6.6%-14.6%) of dietary intake as UPF and a total of 181.5 g/d of UPF intake.
The foods that contributed most to total UPF consumed were processed meat, which accounted for 19.8% of UPF intake; pizza (16.8%); and cakes and pies (13.4%).
High consumers of UPF, defined as those for whom UPF constituted more than 14.6% of their total diet, were more likely to be women, to be younger, and to have a higher educational level. They also reported fewer risk factors and fewer baseline chronic diseases and health conditions than persons who consumed UPF less frequently.
In addition, high consumption of UPF was associated with lower adherence to the Mediterranean diet; higher intake of fat, sugar, dietary cholesterol, and sodium; and lower intake of fiber.
During a median follow-up of 8.2 years, 1,216 all-cause deaths occurred. Of these, 439 were attributed to CVD, 255 to IHD/cerebrovascular disease, 477 to cancer, and 300 to other causes.
The more UPF, the higher the risk for CVD, death
The researchers found a direct linear dose-response relation between a 5% increase in the proportion of UPF in the diet and risk for all-cause and CVD mortality.
Individuals who reported the highest intake of UPF (fourth quartile, 14.6% of total food) as opposed to the lowest (first quartile, UPF <6.6%) experienced increased risks for CVD mortality (hazard ratio, 1.58; 95% CI, 1.23-2.03), death from IHD/cerebrovascular disease (HR, 1.52, 95% CI, 1.10-2.09), and all-cause mortality (HR, 1.26; 95% CI, 1.09-1.46).
High sugar content accounted for 36.3% of the relation of UPF with IHD/cerebrovascular mortality. Other nutritional factors, such as saturated fats, were unlikely to play a role, the researchers wrote.
Biomarkers of renal function accounted for 20.1% of the association of UPF with all-cause mortality and 12.0% for that of UPF with CVD mortality.
Subgroup analyses indicated that the magnitude of the association between UPF and all-cause mortality risk was greater among high-risk individuals, such as those with a history of CVD or diabetes. UPF was also likely to be more strongly associated with CVD mortality among those high-risk groups.
The interesting finding that the association between UPF and CVD mortality was greater among individuals with good adherence to the Mediterranean diet, which is known to have health benefits, could be explained by the fact that people who may benefit from a Mediterranean diet are more susceptible to losing health advantages when they also include “detrimental dietary behavior,” whereas those who consume a poor-quality diet are less likely to be harmed by an additional unhealthy behavior such as eating UPF regularly, wrote Dr. Bonaccio and colleagues.
“This is an interesting study confirming that consumption of highly processed foods such as pizza, processed meats, and soda are associated with greater risks of cardiovascular disease,” Walter Willett, MD, professor of epidemiology and nutrition, Harvard School of Public Health, Boston, said in an interview.
“These higher risks appear to be mediated in part by high intakes of saturated fat and sugar, but lower intakes of health-promoting aspects of diet also likely contribute to the findings,” Dr. Willett said.
“Some processing of food can be useful for preservation and control of infectious agents, but in general, a diet emphasizing minimally processed fruits and vegetables, whole grains, nuts, legumes, and plant sources of fat will be best for long-term well-being,” he said.
The study was supported in part by the Italian Ministry of Health and the HYPERCAN Study Italian Association for Cancer Research. Dr. Bonaccio and Dr. Willett reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Yet another study has linked the consumption of ultraprocessed, or “junk,” foods to bad health outcomes.
In a longitudinal analysis of more than 22,000 men and women from southern Italy, those who consumed the most ultraprocessed food (UPF) had the highest risk for cardiovascular disease (CVD) and all-cause mortality, likely mediated through a diet high in sugar, researchers said.
High consumption of UPF in this Mediterranean cohort was associated with a 58% increased risk for CVD mortality and 52% higher risk of dying from ischemic heart disease (IHD) and cerebrovascular causes, independently of known risk factors for CVD, even among individuals who otherwise adhered to the Mediterranean diet.
The findings “should serve as an incentive for limiting consumption of UPF and encouraging natural or minimally processed foods, as several national nutritional policies recommend,” Marialaura Bonaccio, PhD, department of epidemiology and prevention, IRCCS Neuromed, Pozzilli, Italy, and colleagues wrote. The results were published online Dec. 18 in the American Journal of Clinical Nutrition.
Earlier this year, as reported by this news organization, researchers found mounting evidence that the obesity epidemic and the increase in incidence of related chronic conditions corresponded with an increase in the intake of UPF.
A study that was conducted in a European cohort found that adults whose diet included more UPF and beverages, such as ice cream, soda, and hamburgers, were more likely to develop CVD or die sooner than others who had a more wholesome diet.
As reported previously by this news organization, among adults in France who had a 10% higher intake of UPF and beverages, the rate of CVD, coronary heart disease, and cerebrovascular disease was 11% to 13% higher over a period of about 5 years.
Similarly, university graduates in Spain who consumed more than four servings of UPF and beverages a day were 62% more likely to die of any cause over about a decade than those who consumed less than two servings per day.
Where’s the food?
There is very little actual food in UPF. “The NOVA classification provides 4 main classes of food and beverages, the last of which is represented by the ultraprocessed food group. This comprises products (e.g., snacks, drinks, and ready meals, ‘created mostly or entirely from substances extracted from foods or derived from food constituents with little, if any intact food, which often contain flavors, colors, and other additives that imitate or intensify the sensory qualities of foods or culinary preparations made from foods,’ ” Dr. Bonaccio and colleagues wrote.
Such foods are very convenient, tasty, inexpensive, and have a long shelf life. They are highly competitive with foods that are naturally ready to consume and freshly prepared dishes and meals, the authors add.
The researchers conducted a longitudinal analysis on 22,475 men and women (mean age, 55 years; range, 43-67 years) who were recruited from the Moli-sani Study, a population-based cohort of men and women aged 35 years and older in the Molise region of southern Italy, between 2005 and 2010. Participants were followed for 8.2 years.
Food intake was assessed with the Food Frequency Questionnaire; UPF was defined using the NOVA classification according to degree of processing.
UPF intakes were categorized as quartiles of the ratio of UPF to total food consumed.
Overall, study participants reported a median of 10% (interquartile range, 6.6%-14.6%) of dietary intake as UPF and a total of 181.5 g/d of UPF intake.
The foods that contributed most to total UPF consumed were processed meat, which accounted for 19.8% of UPF intake; pizza (16.8%); and cakes and pies (13.4%).
High consumers of UPF, defined as those for whom UPF constituted more than 14.6% of their total diet, were more likely to be women, to be younger, and to have a higher educational level. They also reported fewer risk factors and fewer baseline chronic diseases and health conditions than persons who consumed UPF less frequently.
In addition, high consumption of UPF was associated with lower adherence to the Mediterranean diet; higher intake of fat, sugar, dietary cholesterol, and sodium; and lower intake of fiber.
During a median follow-up of 8.2 years, 1,216 all-cause deaths occurred. Of these, 439 were attributed to CVD, 255 to IHD/cerebrovascular disease, 477 to cancer, and 300 to other causes.
The more UPF, the higher the risk for CVD, death
The researchers found a direct linear dose-response relation between a 5% increase in the proportion of UPF in the diet and risk for all-cause and CVD mortality.
Individuals who reported the highest intake of UPF (fourth quartile, 14.6% of total food) as opposed to the lowest (first quartile, UPF <6.6%) experienced increased risks for CVD mortality (hazard ratio, 1.58; 95% CI, 1.23-2.03), death from IHD/cerebrovascular disease (HR, 1.52, 95% CI, 1.10-2.09), and all-cause mortality (HR, 1.26; 95% CI, 1.09-1.46).
High sugar content accounted for 36.3% of the relation of UPF with IHD/cerebrovascular mortality. Other nutritional factors, such as saturated fats, were unlikely to play a role, the researchers wrote.
Biomarkers of renal function accounted for 20.1% of the association of UPF with all-cause mortality and 12.0% for that of UPF with CVD mortality.
Subgroup analyses indicated that the magnitude of the association between UPF and all-cause mortality risk was greater among high-risk individuals, such as those with a history of CVD or diabetes. UPF was also likely to be more strongly associated with CVD mortality among those high-risk groups.
The interesting finding that the association between UPF and CVD mortality was greater among individuals with good adherence to the Mediterranean diet, which is known to have health benefits, could be explained by the fact that people who may benefit from a Mediterranean diet are more susceptible to losing health advantages when they also include “detrimental dietary behavior,” whereas those who consume a poor-quality diet are less likely to be harmed by an additional unhealthy behavior such as eating UPF regularly, wrote Dr. Bonaccio and colleagues.
“This is an interesting study confirming that consumption of highly processed foods such as pizza, processed meats, and soda are associated with greater risks of cardiovascular disease,” Walter Willett, MD, professor of epidemiology and nutrition, Harvard School of Public Health, Boston, said in an interview.
“These higher risks appear to be mediated in part by high intakes of saturated fat and sugar, but lower intakes of health-promoting aspects of diet also likely contribute to the findings,” Dr. Willett said.
“Some processing of food can be useful for preservation and control of infectious agents, but in general, a diet emphasizing minimally processed fruits and vegetables, whole grains, nuts, legumes, and plant sources of fat will be best for long-term well-being,” he said.
The study was supported in part by the Italian Ministry of Health and the HYPERCAN Study Italian Association for Cancer Research. Dr. Bonaccio and Dr. Willett reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
‘Hidden’ danger of type 2 diabetes diagnosis at early age
Those who are found to have type 2 diabetes at a younger age face “hidden” dangers. The issue is becoming more and more important, “since new diagnoses in this younger age group continue to rise,” said the authors of a new study, led by Natalie Nanayakkara, MD.
They believe clinical approaches should be based on age at diagnosis. The results of their new meta-analysis, published online in Diabetologia, reveal the extent of the problem.
Believed to be the first systematic review of its kind, the study showed that the younger the age at diagnosis of type 2 diabetes, the greater the risks of dying and of having either microvascular or macrovascular complications each subsequent year (adjusted for current age).
“This difference in risk between younger and older people in terms of absolute versus lifetime risks of type 2 diabetes complications should perhaps be recognized in diabetes management guidelines,” wrote Dr. Nanayakkara, an endocrinologist at Monash University, Melbourne, and colleagues.
Those diagnosed at younger ages are more likely to develop complications that cause greater disability and lead to loss of productivity compared with people diagnosed at an older age, they stressed.
Hence, they suggested “a greater emphasis on preventive measures for younger people with type 2 diabetes,” with “early intensive multifactorial risk factor intervention ... sustained long term to minimize risks over time.”
Large dataset: Use age at diagnosis to risk stratify patients
Rates of type 2 diabetes have increased in all age groups and virtually all countries over the past 3 decades. Particularly worrying is a trend toward increased rates among adults aged 20-44 years. The increases are associated with higher rates of overweight and obesity, poor diet, and decreasing levels of physical activity, numerous studies have shown.
But few studies have examined the association between age at diagnosis and subsequent complications from type 2 diabetes, the authors noted.
Their review included 26 observational studies involving more than one million individuals from 30 countries in the Asia Pacific, Europe, and North America. The investigators found that each 1-year increase in age at diabetes diagnosis was significantly associated with a 4%, 3%, and 5% decreased risk for all-cause mortality, macrovascular disease, and microvascular disease, respectively, adjusted for current age (all P < .001).
Similar decreases in risk per 1-year increase in age at diabetes diagnosis were seen for coronary heart disease (2%), cerebrovascular disease (2%), peripheral vascular disease (3%), retinopathy (8%), nephropathy (6%), and neuropathy (5%); all associations were significant (P < .001).
Dr. Nanayakkara and colleagues noted that current treatment guidelines are limited in that they’re related to the management of patients with suboptimal blood glucose control, and there is no way to predict which people require intensified treatment.
Therefore, they said, “refined stratification using age at diagnosis may provide a method of identifying, at diagnosis, those at greatest risk of complications who would most benefit from targeted, individualized treatment regimens.”
Awareness of this “hidden” danger to younger adults with type 2 diabetes is becoming more and more important, because such cases continue to rise, they reiterated.
They also advised that “public health measures to delay and/or prevent the onset of type 2 diabetes until older age may yield benefits by reducing the duration of diabetes and the burden of complications.”
Dr. Nanayakkara disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Those who are found to have type 2 diabetes at a younger age face “hidden” dangers. The issue is becoming more and more important, “since new diagnoses in this younger age group continue to rise,” said the authors of a new study, led by Natalie Nanayakkara, MD.
They believe clinical approaches should be based on age at diagnosis. The results of their new meta-analysis, published online in Diabetologia, reveal the extent of the problem.
Believed to be the first systematic review of its kind, the study showed that the younger the age at diagnosis of type 2 diabetes, the greater the risks of dying and of having either microvascular or macrovascular complications each subsequent year (adjusted for current age).
“This difference in risk between younger and older people in terms of absolute versus lifetime risks of type 2 diabetes complications should perhaps be recognized in diabetes management guidelines,” wrote Dr. Nanayakkara, an endocrinologist at Monash University, Melbourne, and colleagues.
Those diagnosed at younger ages are more likely to develop complications that cause greater disability and lead to loss of productivity compared with people diagnosed at an older age, they stressed.
Hence, they suggested “a greater emphasis on preventive measures for younger people with type 2 diabetes,” with “early intensive multifactorial risk factor intervention ... sustained long term to minimize risks over time.”
Large dataset: Use age at diagnosis to risk stratify patients
Rates of type 2 diabetes have increased in all age groups and virtually all countries over the past 3 decades. Particularly worrying is a trend toward increased rates among adults aged 20-44 years. The increases are associated with higher rates of overweight and obesity, poor diet, and decreasing levels of physical activity, numerous studies have shown.
But few studies have examined the association between age at diagnosis and subsequent complications from type 2 diabetes, the authors noted.
Their review included 26 observational studies involving more than one million individuals from 30 countries in the Asia Pacific, Europe, and North America. The investigators found that each 1-year increase in age at diabetes diagnosis was significantly associated with a 4%, 3%, and 5% decreased risk for all-cause mortality, macrovascular disease, and microvascular disease, respectively, adjusted for current age (all P < .001).
Similar decreases in risk per 1-year increase in age at diabetes diagnosis were seen for coronary heart disease (2%), cerebrovascular disease (2%), peripheral vascular disease (3%), retinopathy (8%), nephropathy (6%), and neuropathy (5%); all associations were significant (P < .001).
Dr. Nanayakkara and colleagues noted that current treatment guidelines are limited in that they’re related to the management of patients with suboptimal blood glucose control, and there is no way to predict which people require intensified treatment.
Therefore, they said, “refined stratification using age at diagnosis may provide a method of identifying, at diagnosis, those at greatest risk of complications who would most benefit from targeted, individualized treatment regimens.”
Awareness of this “hidden” danger to younger adults with type 2 diabetes is becoming more and more important, because such cases continue to rise, they reiterated.
They also advised that “public health measures to delay and/or prevent the onset of type 2 diabetes until older age may yield benefits by reducing the duration of diabetes and the burden of complications.”
Dr. Nanayakkara disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Those who are found to have type 2 diabetes at a younger age face “hidden” dangers. The issue is becoming more and more important, “since new diagnoses in this younger age group continue to rise,” said the authors of a new study, led by Natalie Nanayakkara, MD.
They believe clinical approaches should be based on age at diagnosis. The results of their new meta-analysis, published online in Diabetologia, reveal the extent of the problem.
Believed to be the first systematic review of its kind, the study showed that the younger the age at diagnosis of type 2 diabetes, the greater the risks of dying and of having either microvascular or macrovascular complications each subsequent year (adjusted for current age).
“This difference in risk between younger and older people in terms of absolute versus lifetime risks of type 2 diabetes complications should perhaps be recognized in diabetes management guidelines,” wrote Dr. Nanayakkara, an endocrinologist at Monash University, Melbourne, and colleagues.
Those diagnosed at younger ages are more likely to develop complications that cause greater disability and lead to loss of productivity compared with people diagnosed at an older age, they stressed.
Hence, they suggested “a greater emphasis on preventive measures for younger people with type 2 diabetes,” with “early intensive multifactorial risk factor intervention ... sustained long term to minimize risks over time.”
Large dataset: Use age at diagnosis to risk stratify patients
Rates of type 2 diabetes have increased in all age groups and virtually all countries over the past 3 decades. Particularly worrying is a trend toward increased rates among adults aged 20-44 years. The increases are associated with higher rates of overweight and obesity, poor diet, and decreasing levels of physical activity, numerous studies have shown.
But few studies have examined the association between age at diagnosis and subsequent complications from type 2 diabetes, the authors noted.
Their review included 26 observational studies involving more than one million individuals from 30 countries in the Asia Pacific, Europe, and North America. The investigators found that each 1-year increase in age at diabetes diagnosis was significantly associated with a 4%, 3%, and 5% decreased risk for all-cause mortality, macrovascular disease, and microvascular disease, respectively, adjusted for current age (all P < .001).
Similar decreases in risk per 1-year increase in age at diabetes diagnosis were seen for coronary heart disease (2%), cerebrovascular disease (2%), peripheral vascular disease (3%), retinopathy (8%), nephropathy (6%), and neuropathy (5%); all associations were significant (P < .001).
Dr. Nanayakkara and colleagues noted that current treatment guidelines are limited in that they’re related to the management of patients with suboptimal blood glucose control, and there is no way to predict which people require intensified treatment.
Therefore, they said, “refined stratification using age at diagnosis may provide a method of identifying, at diagnosis, those at greatest risk of complications who would most benefit from targeted, individualized treatment regimens.”
Awareness of this “hidden” danger to younger adults with type 2 diabetes is becoming more and more important, because such cases continue to rise, they reiterated.
They also advised that “public health measures to delay and/or prevent the onset of type 2 diabetes until older age may yield benefits by reducing the duration of diabetes and the burden of complications.”
Dr. Nanayakkara disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FDA okays first generic injected glucagon for hypoglycemia
The FDA determined that Amphastar’s Glucagon for Injection Emergency Kit, 1 mg, a synthetic peptide product, is bioequivalent and therapeutically equivalent to Eli Lilly’s recombinant DNA Glucagon Emergency Kit for Low Blood Sugar.
Both require a multistep mixing process that means they are complicated to use.
In 2019, FDA approved two branded, easier-to-use formulations of glucagon – one nasally administered (Baqsimi, Eli Lilly & Co) and the other a prefilled pen or syringe (Gvoke HypoPen and Gvoke PFS, respectively, Xeris Pharmaceuticals).
The new generic will have the advantage of lower cost, Amphastar spokesman Dan Dischner said in an interview.
“Our generic glucagon will be priced as a generic product so that patients will benefit from a lower price. As we are just at the beginning of the commercialization of the product, we are unable to discuss our specific product price,” he wrote.
As with the branded Lilly injectable glucagon, the new generic is also indicated as a diagnostic aid in gastrointestinal radiologic imaging, as glucagon slows gastric motility.
According to an FDA statement, glucagon is a “complex product” that has been difficult to manufacture generically despite the lifting of patent protection. This approval was the result of the FDA’s efforts to encourage the development and submission of applications for such drugs.
Amphastar specializes in “developing, manufacturing, marketing, and selling technically-challenging generic and proprietary injectable, inhalation, and intranasal products,” the company website says.
Mr. Dischner said, “Glucagon is a complex product that requires R&D and manufacturing capabilities to develop a highly purified synthetic peptide product bioequivalent and therapeutically equivalent to the recombinant DNA origin Glucagon. Given that this product has been through various review cycles, its complexity, and the technological capabilities required to manufacture, it is no surprise that there hasn’t been a generic of glucagon until now.”
Side effects of injected glucagon include nausea, vomiting, transient increase in heart rate, and redness/swelling of the injection site.
Mr. Dischner added, “We are confident that our generic to Lilly’s time-tested glucagon will provide a favorable option, at a reasonable price, to patients who rely on this product.”
A version of this article first appeared on Medscape.com.
The FDA determined that Amphastar’s Glucagon for Injection Emergency Kit, 1 mg, a synthetic peptide product, is bioequivalent and therapeutically equivalent to Eli Lilly’s recombinant DNA Glucagon Emergency Kit for Low Blood Sugar.
Both require a multistep mixing process that means they are complicated to use.
In 2019, FDA approved two branded, easier-to-use formulations of glucagon – one nasally administered (Baqsimi, Eli Lilly & Co) and the other a prefilled pen or syringe (Gvoke HypoPen and Gvoke PFS, respectively, Xeris Pharmaceuticals).
The new generic will have the advantage of lower cost, Amphastar spokesman Dan Dischner said in an interview.
“Our generic glucagon will be priced as a generic product so that patients will benefit from a lower price. As we are just at the beginning of the commercialization of the product, we are unable to discuss our specific product price,” he wrote.
As with the branded Lilly injectable glucagon, the new generic is also indicated as a diagnostic aid in gastrointestinal radiologic imaging, as glucagon slows gastric motility.
According to an FDA statement, glucagon is a “complex product” that has been difficult to manufacture generically despite the lifting of patent protection. This approval was the result of the FDA’s efforts to encourage the development and submission of applications for such drugs.
Amphastar specializes in “developing, manufacturing, marketing, and selling technically-challenging generic and proprietary injectable, inhalation, and intranasal products,” the company website says.
Mr. Dischner said, “Glucagon is a complex product that requires R&D and manufacturing capabilities to develop a highly purified synthetic peptide product bioequivalent and therapeutically equivalent to the recombinant DNA origin Glucagon. Given that this product has been through various review cycles, its complexity, and the technological capabilities required to manufacture, it is no surprise that there hasn’t been a generic of glucagon until now.”
Side effects of injected glucagon include nausea, vomiting, transient increase in heart rate, and redness/swelling of the injection site.
Mr. Dischner added, “We are confident that our generic to Lilly’s time-tested glucagon will provide a favorable option, at a reasonable price, to patients who rely on this product.”
A version of this article first appeared on Medscape.com.
The FDA determined that Amphastar’s Glucagon for Injection Emergency Kit, 1 mg, a synthetic peptide product, is bioequivalent and therapeutically equivalent to Eli Lilly’s recombinant DNA Glucagon Emergency Kit for Low Blood Sugar.
Both require a multistep mixing process that means they are complicated to use.
In 2019, FDA approved two branded, easier-to-use formulations of glucagon – one nasally administered (Baqsimi, Eli Lilly & Co) and the other a prefilled pen or syringe (Gvoke HypoPen and Gvoke PFS, respectively, Xeris Pharmaceuticals).
The new generic will have the advantage of lower cost, Amphastar spokesman Dan Dischner said in an interview.
“Our generic glucagon will be priced as a generic product so that patients will benefit from a lower price. As we are just at the beginning of the commercialization of the product, we are unable to discuss our specific product price,” he wrote.
As with the branded Lilly injectable glucagon, the new generic is also indicated as a diagnostic aid in gastrointestinal radiologic imaging, as glucagon slows gastric motility.
According to an FDA statement, glucagon is a “complex product” that has been difficult to manufacture generically despite the lifting of patent protection. This approval was the result of the FDA’s efforts to encourage the development and submission of applications for such drugs.
Amphastar specializes in “developing, manufacturing, marketing, and selling technically-challenging generic and proprietary injectable, inhalation, and intranasal products,” the company website says.
Mr. Dischner said, “Glucagon is a complex product that requires R&D and manufacturing capabilities to develop a highly purified synthetic peptide product bioequivalent and therapeutically equivalent to the recombinant DNA origin Glucagon. Given that this product has been through various review cycles, its complexity, and the technological capabilities required to manufacture, it is no surprise that there hasn’t been a generic of glucagon until now.”
Side effects of injected glucagon include nausea, vomiting, transient increase in heart rate, and redness/swelling of the injection site.
Mr. Dischner added, “We are confident that our generic to Lilly’s time-tested glucagon will provide a favorable option, at a reasonable price, to patients who rely on this product.”
A version of this article first appeared on Medscape.com.
FDA clears device to remove dead pancreatic tissue
The Food and Drug Administration has approved the EndoRotor System (Interscope, Inc.) for removal of necrotic tissue in patients with walled-off pancreatic necrosis (WOPN).
“This device has shown its potential to provide a minimally invasive way to remove harmful necrotic pancreatic tissue in patients with walled-off pancreatic necrosis,” Charles Viviano, MD, PhD, acting director, Reproductive, Gastro-Renal, Urological, General Hospital Device and Human Factors Office, FDA Center for Devices and Radiological Health, said in a statement.
“Currently, in order to remove dead tissue from a patient’s necrotic pancreatic cavity, health care providers need to perform an invasive surgery or use other endoscopic tools not specifically indicated to treat this condition. With [this] marketing authorization, patients with walled-off pancreatic necrosis now have a new treatment option,” said Dr. Viviano.
WOPN is a potentially deadly condition that occurs in about 15% of patients with severe pancreatitis. Often, the dead tissue must be removed.
The EndoRotor System is made up of a power console, foot control, specimen trap, and single-use catheter.
The device is used to perform endoscopic necrosectomy. In this procedure, a stent is used to create a portal between the stomach and the necrotic cavity in the pancreas to accommodate a standard endoscope through which the EndoRotor cuts and removes necrotized tissue.
The FDA approved the EndoRotor System on the basis of a clinical trial involving 30 patients with WOPN who underwent a total of 63 direct endoscopic necrosectomies with the EndoRotor System (average, 2.1 procedures per patient).
The effectiveness of the EndoRotor System was determined by how well it cleared pancreatic necrotic tissue measured during CT with contrast before and after the procedure, endoscopy, or MRI 14 to 28 days after the last procedure.
Results showed an average 85% reduction in the amount of necrotic tissue, with half of the patients having 98.5% clearance of necrotic tissue, the FDA said.
Three patients suffered procedure-related serious adverse events (10% complication rate). Two patients experienced gastrointestinal bleeding. One patient had a pneumoperitoneum and later died after suffering from sepsis and multiorgan system failure caused by massive collections of infected pancreatic necrotic tissue.
Other serious adverse events, which were thought to be due to the patient’s underlying condition and not related to the device or procedure, included hematemesis, deep vein thrombosis, and pancreatitis.
The EndoRotor System should not be used for patients with known or suspected pancreatic cancer, and the device will carry a boxed warning stating this.
The FDA said it knows of one patient who died from pancreatic cancer 3 months after having necrotic pancreatic tissue removed with the EndoRotor System.
“This patient did not have a diagnosis of pancreatic cancer prior to treatment, although the patient’s outcome is believed to be unrelated to the device or procedure,” the FDA said.
The EndoRotor System should be used only after patients have undergone other procedures to drain the WOPN.
It is also not appropriate for patients with walled-off necrosis who have a documented pseudoaneurysm greater than 1 cm within the cavity or with intervening gastric varices or unavoidable blood vessels within the access tract.
The EndoRotor System was approved under the de novo premarket review pathway for new low- to moderate-risk devices.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved the EndoRotor System (Interscope, Inc.) for removal of necrotic tissue in patients with walled-off pancreatic necrosis (WOPN).
“This device has shown its potential to provide a minimally invasive way to remove harmful necrotic pancreatic tissue in patients with walled-off pancreatic necrosis,” Charles Viviano, MD, PhD, acting director, Reproductive, Gastro-Renal, Urological, General Hospital Device and Human Factors Office, FDA Center for Devices and Radiological Health, said in a statement.
“Currently, in order to remove dead tissue from a patient’s necrotic pancreatic cavity, health care providers need to perform an invasive surgery or use other endoscopic tools not specifically indicated to treat this condition. With [this] marketing authorization, patients with walled-off pancreatic necrosis now have a new treatment option,” said Dr. Viviano.
WOPN is a potentially deadly condition that occurs in about 15% of patients with severe pancreatitis. Often, the dead tissue must be removed.
The EndoRotor System is made up of a power console, foot control, specimen trap, and single-use catheter.
The device is used to perform endoscopic necrosectomy. In this procedure, a stent is used to create a portal between the stomach and the necrotic cavity in the pancreas to accommodate a standard endoscope through which the EndoRotor cuts and removes necrotized tissue.
The FDA approved the EndoRotor System on the basis of a clinical trial involving 30 patients with WOPN who underwent a total of 63 direct endoscopic necrosectomies with the EndoRotor System (average, 2.1 procedures per patient).
The effectiveness of the EndoRotor System was determined by how well it cleared pancreatic necrotic tissue measured during CT with contrast before and after the procedure, endoscopy, or MRI 14 to 28 days after the last procedure.
Results showed an average 85% reduction in the amount of necrotic tissue, with half of the patients having 98.5% clearance of necrotic tissue, the FDA said.
Three patients suffered procedure-related serious adverse events (10% complication rate). Two patients experienced gastrointestinal bleeding. One patient had a pneumoperitoneum and later died after suffering from sepsis and multiorgan system failure caused by massive collections of infected pancreatic necrotic tissue.
Other serious adverse events, which were thought to be due to the patient’s underlying condition and not related to the device or procedure, included hematemesis, deep vein thrombosis, and pancreatitis.
The EndoRotor System should not be used for patients with known or suspected pancreatic cancer, and the device will carry a boxed warning stating this.
The FDA said it knows of one patient who died from pancreatic cancer 3 months after having necrotic pancreatic tissue removed with the EndoRotor System.
“This patient did not have a diagnosis of pancreatic cancer prior to treatment, although the patient’s outcome is believed to be unrelated to the device or procedure,” the FDA said.
The EndoRotor System should be used only after patients have undergone other procedures to drain the WOPN.
It is also not appropriate for patients with walled-off necrosis who have a documented pseudoaneurysm greater than 1 cm within the cavity or with intervening gastric varices or unavoidable blood vessels within the access tract.
The EndoRotor System was approved under the de novo premarket review pathway for new low- to moderate-risk devices.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved the EndoRotor System (Interscope, Inc.) for removal of necrotic tissue in patients with walled-off pancreatic necrosis (WOPN).
“This device has shown its potential to provide a minimally invasive way to remove harmful necrotic pancreatic tissue in patients with walled-off pancreatic necrosis,” Charles Viviano, MD, PhD, acting director, Reproductive, Gastro-Renal, Urological, General Hospital Device and Human Factors Office, FDA Center for Devices and Radiological Health, said in a statement.
“Currently, in order to remove dead tissue from a patient’s necrotic pancreatic cavity, health care providers need to perform an invasive surgery or use other endoscopic tools not specifically indicated to treat this condition. With [this] marketing authorization, patients with walled-off pancreatic necrosis now have a new treatment option,” said Dr. Viviano.
WOPN is a potentially deadly condition that occurs in about 15% of patients with severe pancreatitis. Often, the dead tissue must be removed.
The EndoRotor System is made up of a power console, foot control, specimen trap, and single-use catheter.
The device is used to perform endoscopic necrosectomy. In this procedure, a stent is used to create a portal between the stomach and the necrotic cavity in the pancreas to accommodate a standard endoscope through which the EndoRotor cuts and removes necrotized tissue.
The FDA approved the EndoRotor System on the basis of a clinical trial involving 30 patients with WOPN who underwent a total of 63 direct endoscopic necrosectomies with the EndoRotor System (average, 2.1 procedures per patient).
The effectiveness of the EndoRotor System was determined by how well it cleared pancreatic necrotic tissue measured during CT with contrast before and after the procedure, endoscopy, or MRI 14 to 28 days after the last procedure.
Results showed an average 85% reduction in the amount of necrotic tissue, with half of the patients having 98.5% clearance of necrotic tissue, the FDA said.
Three patients suffered procedure-related serious adverse events (10% complication rate). Two patients experienced gastrointestinal bleeding. One patient had a pneumoperitoneum and later died after suffering from sepsis and multiorgan system failure caused by massive collections of infected pancreatic necrotic tissue.
Other serious adverse events, which were thought to be due to the patient’s underlying condition and not related to the device or procedure, included hematemesis, deep vein thrombosis, and pancreatitis.
The EndoRotor System should not be used for patients with known or suspected pancreatic cancer, and the device will carry a boxed warning stating this.
The FDA said it knows of one patient who died from pancreatic cancer 3 months after having necrotic pancreatic tissue removed with the EndoRotor System.
“This patient did not have a diagnosis of pancreatic cancer prior to treatment, although the patient’s outcome is believed to be unrelated to the device or procedure,” the FDA said.
The EndoRotor System should be used only after patients have undergone other procedures to drain the WOPN.
It is also not appropriate for patients with walled-off necrosis who have a documented pseudoaneurysm greater than 1 cm within the cavity or with intervening gastric varices or unavoidable blood vessels within the access tract.
The EndoRotor System was approved under the de novo premarket review pathway for new low- to moderate-risk devices.
A version of this article first appeared on Medscape.com.
PTSD, depression combo tied to high risk for early death in women
Middle-aged women with PTSD and comorbid depression have a nearly fourfold increased risk for early death from a variety of causes in comparison with their peers who do not have those conditions, new research shows.
“Women with more severe symptoms of depression and PTSD were more at risk, compared with those with fewer symptoms or women with symptoms of only PTSD or only depression,” lead investigator Andrea Roberts, PhD, Harvard School of Public Health, Boston, said in an interview.
Health care providers “should be aware that mental health is a critical component of overall health and is tightly entwined with physical health. Identifying and treating mental health issues should be a foundational part of general health practice,” said Dr. Roberts.
The study was published online Dec. 4 in JAMA Network Open.
Mental health fundamental to survival
The researchers studied more than 51,000 mostly White women from the Nurses Health Study II who were followed for 9 years (2008-2017). At baseline in 2008, the women were aged between 43 and 64 years (mean age, 53.3 years).
Women with high levels of PTSD (six or seven symptoms) and probable depression were nearly four times more likely to die during follow-up than their peers who did not have these conditions (hazard ratio, 3.8; 95% confidence interval, 2.65-5.45; P < .001).
With adjustment for health factors such as smoking and body mass index, women with a high level of PTSD and depression remained at increased risk for early death (HR, 3.11; 95% CI, 2.16-4.47; P < .001).
The risk for early death was also elevated among women with moderate PTSD (four or five symptoms) and depression (HR, 2.03; 95% CI, 1.35-3.03; P < .001) and women with subclinical PTSD and depression (HR, 2.85; 95% CI, 1.99-4.07; P < .001) compared with those who did not have PTSD or depression.
Among women with PTSD symptoms and depression, the incidence of death from nearly all major causes was increased, including death from cardiovascular disease, respiratory disease, type 2 diabetes, unintentional injury, suicide, and other causes.
“These findings provide further evidence that mental health is fundamental to physical health – and to our very survival. We ignore our emotional well-being at our peril,” senior author Karestan Koenen, PhD, said in a news release.
New knowledge
Commenting on the findings, Jennifer Sumner, PhD, said that it’s “critical to appreciate the physical health consequences of psychopathology in individuals who have experienced trauma. This study adds to a growing literature demonstrating that the impact extends far beyond emotional health.
“Furthermore, these results highlight the potential value of promoting healthy lifestyle changes in order to reduce the elevated mortality risk in trauma-exposed individuals with co-occurring PTSD and depression,” said Dr. Sumner, who is with the department of psychology, University of California, Los Angeles.
She noted that this study builds on other work that links PTSD to mortality in men.
“Most work on posttraumatic psychopathology and physical health has actually been conducted in predominantly male samples of veterans, so said Dr. Sumner.
“It’s also important to note that PTSD and depression are more prevalent in women than in men, so demonstrating these associations in women is particularly relevant,” she added.
Funding for the study was provided by the National Institutes of Heath. The authors disclosed no relevant financial relationships. Dr. Sumner has collaborated with the study investigators on prior studies.
A version of this article originally appeared on Medscape.com.
Middle-aged women with PTSD and comorbid depression have a nearly fourfold increased risk for early death from a variety of causes in comparison with their peers who do not have those conditions, new research shows.
“Women with more severe symptoms of depression and PTSD were more at risk, compared with those with fewer symptoms or women with symptoms of only PTSD or only depression,” lead investigator Andrea Roberts, PhD, Harvard School of Public Health, Boston, said in an interview.
Health care providers “should be aware that mental health is a critical component of overall health and is tightly entwined with physical health. Identifying and treating mental health issues should be a foundational part of general health practice,” said Dr. Roberts.
The study was published online Dec. 4 in JAMA Network Open.
Mental health fundamental to survival
The researchers studied more than 51,000 mostly White women from the Nurses Health Study II who were followed for 9 years (2008-2017). At baseline in 2008, the women were aged between 43 and 64 years (mean age, 53.3 years).
Women with high levels of PTSD (six or seven symptoms) and probable depression were nearly four times more likely to die during follow-up than their peers who did not have these conditions (hazard ratio, 3.8; 95% confidence interval, 2.65-5.45; P < .001).
With adjustment for health factors such as smoking and body mass index, women with a high level of PTSD and depression remained at increased risk for early death (HR, 3.11; 95% CI, 2.16-4.47; P < .001).
The risk for early death was also elevated among women with moderate PTSD (four or five symptoms) and depression (HR, 2.03; 95% CI, 1.35-3.03; P < .001) and women with subclinical PTSD and depression (HR, 2.85; 95% CI, 1.99-4.07; P < .001) compared with those who did not have PTSD or depression.
Among women with PTSD symptoms and depression, the incidence of death from nearly all major causes was increased, including death from cardiovascular disease, respiratory disease, type 2 diabetes, unintentional injury, suicide, and other causes.
“These findings provide further evidence that mental health is fundamental to physical health – and to our very survival. We ignore our emotional well-being at our peril,” senior author Karestan Koenen, PhD, said in a news release.
New knowledge
Commenting on the findings, Jennifer Sumner, PhD, said that it’s “critical to appreciate the physical health consequences of psychopathology in individuals who have experienced trauma. This study adds to a growing literature demonstrating that the impact extends far beyond emotional health.
“Furthermore, these results highlight the potential value of promoting healthy lifestyle changes in order to reduce the elevated mortality risk in trauma-exposed individuals with co-occurring PTSD and depression,” said Dr. Sumner, who is with the department of psychology, University of California, Los Angeles.
She noted that this study builds on other work that links PTSD to mortality in men.
“Most work on posttraumatic psychopathology and physical health has actually been conducted in predominantly male samples of veterans, so said Dr. Sumner.
“It’s also important to note that PTSD and depression are more prevalent in women than in men, so demonstrating these associations in women is particularly relevant,” she added.
Funding for the study was provided by the National Institutes of Heath. The authors disclosed no relevant financial relationships. Dr. Sumner has collaborated with the study investigators on prior studies.
A version of this article originally appeared on Medscape.com.
Middle-aged women with PTSD and comorbid depression have a nearly fourfold increased risk for early death from a variety of causes in comparison with their peers who do not have those conditions, new research shows.
“Women with more severe symptoms of depression and PTSD were more at risk, compared with those with fewer symptoms or women with symptoms of only PTSD or only depression,” lead investigator Andrea Roberts, PhD, Harvard School of Public Health, Boston, said in an interview.
Health care providers “should be aware that mental health is a critical component of overall health and is tightly entwined with physical health. Identifying and treating mental health issues should be a foundational part of general health practice,” said Dr. Roberts.
The study was published online Dec. 4 in JAMA Network Open.
Mental health fundamental to survival
The researchers studied more than 51,000 mostly White women from the Nurses Health Study II who were followed for 9 years (2008-2017). At baseline in 2008, the women were aged between 43 and 64 years (mean age, 53.3 years).
Women with high levels of PTSD (six or seven symptoms) and probable depression were nearly four times more likely to die during follow-up than their peers who did not have these conditions (hazard ratio, 3.8; 95% confidence interval, 2.65-5.45; P < .001).
With adjustment for health factors such as smoking and body mass index, women with a high level of PTSD and depression remained at increased risk for early death (HR, 3.11; 95% CI, 2.16-4.47; P < .001).
The risk for early death was also elevated among women with moderate PTSD (four or five symptoms) and depression (HR, 2.03; 95% CI, 1.35-3.03; P < .001) and women with subclinical PTSD and depression (HR, 2.85; 95% CI, 1.99-4.07; P < .001) compared with those who did not have PTSD or depression.
Among women with PTSD symptoms and depression, the incidence of death from nearly all major causes was increased, including death from cardiovascular disease, respiratory disease, type 2 diabetes, unintentional injury, suicide, and other causes.
“These findings provide further evidence that mental health is fundamental to physical health – and to our very survival. We ignore our emotional well-being at our peril,” senior author Karestan Koenen, PhD, said in a news release.
New knowledge
Commenting on the findings, Jennifer Sumner, PhD, said that it’s “critical to appreciate the physical health consequences of psychopathology in individuals who have experienced trauma. This study adds to a growing literature demonstrating that the impact extends far beyond emotional health.
“Furthermore, these results highlight the potential value of promoting healthy lifestyle changes in order to reduce the elevated mortality risk in trauma-exposed individuals with co-occurring PTSD and depression,” said Dr. Sumner, who is with the department of psychology, University of California, Los Angeles.
She noted that this study builds on other work that links PTSD to mortality in men.
“Most work on posttraumatic psychopathology and physical health has actually been conducted in predominantly male samples of veterans, so said Dr. Sumner.
“It’s also important to note that PTSD and depression are more prevalent in women than in men, so demonstrating these associations in women is particularly relevant,” she added.
Funding for the study was provided by the National Institutes of Heath. The authors disclosed no relevant financial relationships. Dr. Sumner has collaborated with the study investigators on prior studies.
A version of this article originally appeared on Medscape.com.
ADA 2021 standards address financial hardship in diabetes
For 2021, the American Diabetes Association offers new guidance on assessing patients’ financial and social barriers to care, especially given the COVID-19 pandemic, individualizing treatment of patients with type 2 diabetes, and use of diabetes technology.
As it does every year, the annual update incorporates new clinical information that has become available since the last guideline, with occasional revisions during the year as needed. “Standards of Medical Care in Diabetes – 2021,” was published online as a supplement to Diabetes Care.
The new standards advise that patients be assessed for food and housing insecurity, social support, and “cost-related medication nonadherence,” and those found to have difficulty referred to appropriate community resources.
“Clinicians need to be sensitive to the fact that patients may have very good reasons for not taking their medication, [as in] if they can’t afford it,” ADA chief science & medical officer Robert A. Gabbay, MD, PhD, said in an interview.
Dr. Gabbay noted that “a heightened awareness” of social determinants of health is weaved throughout the 2021 standards because of the pandemic, with information on the topic derived from a July 2020 joint consensus statement in Diabetes Care, endorsed by a number of other societies, as well as a November publication also in Diabetes Care.
“We made several recommendations that speak to social determinants of health, placing an emphasis on engaging in conversations around this subject and screening for related issues such as food insecurity that weren’t there previously,” he said.
“Screening tools are suggested. It helped us to have an in-depth scientific review of the literature to know the prevalence of this in people with diabetes. ... Having the science to put it in was a key step,” Dr. Gabbay noted.
Consider kidney, heart disease in type 2 treatment individualization
Recent data from trials such as CREDENCE and DAPA-HF, among others, have been added to inform the choice of pharmacologic treatment in patients with type 2 diabetes with comorbid diabetic kidney disease and chronic heart failure.
“ADA has been advocating individualization of treatment based on comorbidities for a while, but we’ve taken more steps in that direction. Beyond lifestyle for all individuals with type 2 diabetes, clinicians want to think early on about which comorbidities patients have and then think about the appropriate treatment based on that,” Dr. Gabbay said.
And for the third year in a row, the section on cardiovascular disease and risk management has been endorsed by the American College of Cardiology.
“All the things in that section are very much aligned with ACC and that’s been a great partnership,” Dr. Gabbay said.
Now, ADA is in discussions with other professional societies representing relevant specialties to create further such unified messages.
“What we all want to avoid is having multiple different guidelines. We want to speak with one voice and find common ground as much as possible. … It makes it much easier for clinicians to know what to do. That’s the goal of all this,” he noted.
Diabetes technology: The rise of CGM during pandemic and beyond
New information about continuous glucose monitoring (CGM) has been added to the diabetes technology section. Use of CGM is now recommended for anyone with diabetes who takes multiple daily injections or uses an insulin pump, regardless of age or diabetes type. The document provides expanded advice on use of time in range data for glycemic monitoring, particularly during the COVID-19 pandemic when remote monitoring is preferable.
Insurers are increasingly covering CGM for patients on insulin, but it’s far from universal. While the ultimate goal is to ensure access to CGM for everyone with diabetes, those treated with multiple daily insulin doses are the priority for now.
“Our hope is that as there’s greater evidence there will be more movement towards coverage. There are still so many people for whom it’s quite clear they would benefit because they’re on insulin but don’t have access to it. That’s an important area that ADA is advocating for, and it’s reflected in the standards of care,” Dr. Gabbay said.
In another technology-related revision, the term “blinded” CGM has been replaced with “professional CGM,” because clinic-based use of the devices can be “blinded” to the patient or monitored in real-time by both the patient and clinician. Also, a new recommendation has been added to address skin reactions associated with diabetes technology use.
Information about use of CGM in hospital settings during the COVID-19 pandemic has also been added in the technology section.
The COVID-19 pandemic comes up again in the section on vaccines.
“We mention that people with diabetes should be considered high priority [for COVID-19 vaccines], and that’s something that ADA is strongly advocating for because 40% of COVID-19 deaths have been in people with diabetes,” Dr. Gabbay said.
Dr. Gabbay reported being on the advisory boards of Onduo, Health Reveal, Vida Health, Lark, and Form Health.
A version of this article originally appeared on Medscape.com.
For 2021, the American Diabetes Association offers new guidance on assessing patients’ financial and social barriers to care, especially given the COVID-19 pandemic, individualizing treatment of patients with type 2 diabetes, and use of diabetes technology.
As it does every year, the annual update incorporates new clinical information that has become available since the last guideline, with occasional revisions during the year as needed. “Standards of Medical Care in Diabetes – 2021,” was published online as a supplement to Diabetes Care.
The new standards advise that patients be assessed for food and housing insecurity, social support, and “cost-related medication nonadherence,” and those found to have difficulty referred to appropriate community resources.
“Clinicians need to be sensitive to the fact that patients may have very good reasons for not taking their medication, [as in] if they can’t afford it,” ADA chief science & medical officer Robert A. Gabbay, MD, PhD, said in an interview.
Dr. Gabbay noted that “a heightened awareness” of social determinants of health is weaved throughout the 2021 standards because of the pandemic, with information on the topic derived from a July 2020 joint consensus statement in Diabetes Care, endorsed by a number of other societies, as well as a November publication also in Diabetes Care.
“We made several recommendations that speak to social determinants of health, placing an emphasis on engaging in conversations around this subject and screening for related issues such as food insecurity that weren’t there previously,” he said.
“Screening tools are suggested. It helped us to have an in-depth scientific review of the literature to know the prevalence of this in people with diabetes. ... Having the science to put it in was a key step,” Dr. Gabbay noted.
Consider kidney, heart disease in type 2 treatment individualization
Recent data from trials such as CREDENCE and DAPA-HF, among others, have been added to inform the choice of pharmacologic treatment in patients with type 2 diabetes with comorbid diabetic kidney disease and chronic heart failure.
“ADA has been advocating individualization of treatment based on comorbidities for a while, but we’ve taken more steps in that direction. Beyond lifestyle for all individuals with type 2 diabetes, clinicians want to think early on about which comorbidities patients have and then think about the appropriate treatment based on that,” Dr. Gabbay said.
And for the third year in a row, the section on cardiovascular disease and risk management has been endorsed by the American College of Cardiology.
“All the things in that section are very much aligned with ACC and that’s been a great partnership,” Dr. Gabbay said.
Now, ADA is in discussions with other professional societies representing relevant specialties to create further such unified messages.
“What we all want to avoid is having multiple different guidelines. We want to speak with one voice and find common ground as much as possible. … It makes it much easier for clinicians to know what to do. That’s the goal of all this,” he noted.
Diabetes technology: The rise of CGM during pandemic and beyond
New information about continuous glucose monitoring (CGM) has been added to the diabetes technology section. Use of CGM is now recommended for anyone with diabetes who takes multiple daily injections or uses an insulin pump, regardless of age or diabetes type. The document provides expanded advice on use of time in range data for glycemic monitoring, particularly during the COVID-19 pandemic when remote monitoring is preferable.
Insurers are increasingly covering CGM for patients on insulin, but it’s far from universal. While the ultimate goal is to ensure access to CGM for everyone with diabetes, those treated with multiple daily insulin doses are the priority for now.
“Our hope is that as there’s greater evidence there will be more movement towards coverage. There are still so many people for whom it’s quite clear they would benefit because they’re on insulin but don’t have access to it. That’s an important area that ADA is advocating for, and it’s reflected in the standards of care,” Dr. Gabbay said.
In another technology-related revision, the term “blinded” CGM has been replaced with “professional CGM,” because clinic-based use of the devices can be “blinded” to the patient or monitored in real-time by both the patient and clinician. Also, a new recommendation has been added to address skin reactions associated with diabetes technology use.
Information about use of CGM in hospital settings during the COVID-19 pandemic has also been added in the technology section.
The COVID-19 pandemic comes up again in the section on vaccines.
“We mention that people with diabetes should be considered high priority [for COVID-19 vaccines], and that’s something that ADA is strongly advocating for because 40% of COVID-19 deaths have been in people with diabetes,” Dr. Gabbay said.
Dr. Gabbay reported being on the advisory boards of Onduo, Health Reveal, Vida Health, Lark, and Form Health.
A version of this article originally appeared on Medscape.com.
For 2021, the American Diabetes Association offers new guidance on assessing patients’ financial and social barriers to care, especially given the COVID-19 pandemic, individualizing treatment of patients with type 2 diabetes, and use of diabetes technology.
As it does every year, the annual update incorporates new clinical information that has become available since the last guideline, with occasional revisions during the year as needed. “Standards of Medical Care in Diabetes – 2021,” was published online as a supplement to Diabetes Care.
The new standards advise that patients be assessed for food and housing insecurity, social support, and “cost-related medication nonadherence,” and those found to have difficulty referred to appropriate community resources.
“Clinicians need to be sensitive to the fact that patients may have very good reasons for not taking their medication, [as in] if they can’t afford it,” ADA chief science & medical officer Robert A. Gabbay, MD, PhD, said in an interview.
Dr. Gabbay noted that “a heightened awareness” of social determinants of health is weaved throughout the 2021 standards because of the pandemic, with information on the topic derived from a July 2020 joint consensus statement in Diabetes Care, endorsed by a number of other societies, as well as a November publication also in Diabetes Care.
“We made several recommendations that speak to social determinants of health, placing an emphasis on engaging in conversations around this subject and screening for related issues such as food insecurity that weren’t there previously,” he said.
“Screening tools are suggested. It helped us to have an in-depth scientific review of the literature to know the prevalence of this in people with diabetes. ... Having the science to put it in was a key step,” Dr. Gabbay noted.
Consider kidney, heart disease in type 2 treatment individualization
Recent data from trials such as CREDENCE and DAPA-HF, among others, have been added to inform the choice of pharmacologic treatment in patients with type 2 diabetes with comorbid diabetic kidney disease and chronic heart failure.
“ADA has been advocating individualization of treatment based on comorbidities for a while, but we’ve taken more steps in that direction. Beyond lifestyle for all individuals with type 2 diabetes, clinicians want to think early on about which comorbidities patients have and then think about the appropriate treatment based on that,” Dr. Gabbay said.
And for the third year in a row, the section on cardiovascular disease and risk management has been endorsed by the American College of Cardiology.
“All the things in that section are very much aligned with ACC and that’s been a great partnership,” Dr. Gabbay said.
Now, ADA is in discussions with other professional societies representing relevant specialties to create further such unified messages.
“What we all want to avoid is having multiple different guidelines. We want to speak with one voice and find common ground as much as possible. … It makes it much easier for clinicians to know what to do. That’s the goal of all this,” he noted.
Diabetes technology: The rise of CGM during pandemic and beyond
New information about continuous glucose monitoring (CGM) has been added to the diabetes technology section. Use of CGM is now recommended for anyone with diabetes who takes multiple daily injections or uses an insulin pump, regardless of age or diabetes type. The document provides expanded advice on use of time in range data for glycemic monitoring, particularly during the COVID-19 pandemic when remote monitoring is preferable.
Insurers are increasingly covering CGM for patients on insulin, but it’s far from universal. While the ultimate goal is to ensure access to CGM for everyone with diabetes, those treated with multiple daily insulin doses are the priority for now.
“Our hope is that as there’s greater evidence there will be more movement towards coverage. There are still so many people for whom it’s quite clear they would benefit because they’re on insulin but don’t have access to it. That’s an important area that ADA is advocating for, and it’s reflected in the standards of care,” Dr. Gabbay said.
In another technology-related revision, the term “blinded” CGM has been replaced with “professional CGM,” because clinic-based use of the devices can be “blinded” to the patient or monitored in real-time by both the patient and clinician. Also, a new recommendation has been added to address skin reactions associated with diabetes technology use.
Information about use of CGM in hospital settings during the COVID-19 pandemic has also been added in the technology section.
The COVID-19 pandemic comes up again in the section on vaccines.
“We mention that people with diabetes should be considered high priority [for COVID-19 vaccines], and that’s something that ADA is strongly advocating for because 40% of COVID-19 deaths have been in people with diabetes,” Dr. Gabbay said.
Dr. Gabbay reported being on the advisory boards of Onduo, Health Reveal, Vida Health, Lark, and Form Health.
A version of this article originally appeared on Medscape.com.
Sac/val heart failure benefit extends to diabetes patients
The beneficial effects of sacubitril/valsartan on reverse cardiac remodeling in patients with heart failure and reduced ejection fraction have been well established, but those benefits haven’t been as clearly demonstrated to carry over to HFrEF patients who also have type 2 diabetes mellitus (T2DM).
Now, a post-hoc analysis of a pivotal clinical trial reports that those benefits do extend to patients with HFrEF and T2DM.
“It’s really not about a Sophie’s choice of whether you give this or that drug in these patients,” said corresponding author Javed Butler, MD, MPH, MBA. “We really ought to be giving all of these drugs – the angiotensin receptor neprilysin inhibitors (ARNIs) and sodium-glucose transporter 2 (SGLT-2) inhibitors – to our patients for the best outcomes.”
The post-hoc analysis, published in JACC: Heart Failure, evaluated 361 patients with T2DM who were enrolled in the PROVE-HF trial of sac/val therapy for HF, published in JAMA.
PROVE-HF evaluated biomarkers, myocardial remodeling, and outcomes through a year of treatment with sac/val. The primary endpoint was the level of changes in natriuretic peptide (NT-proBNP) concentrations, left-ventricle ejection fraction (LVEF) and overall Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 scores through 12 months of treatment.
The post hoc study reported that baseline NT-proBNP concentrations were higher in the DM patients (854 pg/mL vs. 706 pg/mL), but at 12 months those levels were 513 and 441 pg/mL, respectively.
LVEF changed similarly from baseline to 12 months in both groups: from 28.3% to 37% in the DM patients and from 28.1% to 38.34% in non-DM patients. Overall KCCQ-23 scores improved similarly in both groups, but longitudinal analyses found modestly higher gains in the T2DM group, 9.3 vs. 8.6 points (P = .07).
“The real reason I wanted to do this study is that I’m a huge fan of all the SGLT-2 inhibitors, and I’m very involved in those trials, and there is right now so much momentum behind SGLT-2 inhibitors that I don’t want people to forget that ARNI is still the base therapy for HF,” said Dr. Butler, chair of cardiovascular research and the department of medicine at the University of Mississippi in Jackson.
He noted that the size of the diabetes cohort in PROVE-HF “is a nonissue” for evaluating power of the post hoc analysis because it tracked key measures in the study population continuously at eight intervals over the 12 months.
The analysis further demonstrates the synergistic effects of ARNI and SGLT-2 inhibitors in patients with T2DM and HF that were also reported in the PARADIGM-HF study, Dr. Butler said.
“We have sort of moved on, saying that SGLT-2 inhibitors have a benefit on the heart, but the reverse is also true: ARNIs are still heart failure drugs, and we don’t think of them as diabetes drugs, but the PARADIGM-HF data showed that there was a substantial reduction in hemoglobin A1c in those who had diabetes,” he said.
The researchers noted that an absence of a control group may contribute to an overestimation of reverse cardiac remodeling in the T2DM patients, and that the PROVE-HF study wasn’t prospectively powered to delineate differences in how sac/val therapy affected patients with or without diabetes. “Future investigations seeking to evaluate differences by T2DM status after sacubitril/valsartan initiation may use our findings to plan prospective sample sizes,” the researchers wrote.
Dr. Butler disclosed financial relationships with Abbott, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, CVRx, Eli Lilly, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Sequana, StealthPeptide and Vifor. Lead author Muhammad Shahzeb Khan, MD, MSc, a professor at the University of Mississippi, has no relevant financial relationships to disclose.
SOURCE: Kahn MS et al. JACC: HF. 2020 Dec 9. doi: 10.1016/j.jchf.2020.09.014.
The beneficial effects of sacubitril/valsartan on reverse cardiac remodeling in patients with heart failure and reduced ejection fraction have been well established, but those benefits haven’t been as clearly demonstrated to carry over to HFrEF patients who also have type 2 diabetes mellitus (T2DM).
Now, a post-hoc analysis of a pivotal clinical trial reports that those benefits do extend to patients with HFrEF and T2DM.
“It’s really not about a Sophie’s choice of whether you give this or that drug in these patients,” said corresponding author Javed Butler, MD, MPH, MBA. “We really ought to be giving all of these drugs – the angiotensin receptor neprilysin inhibitors (ARNIs) and sodium-glucose transporter 2 (SGLT-2) inhibitors – to our patients for the best outcomes.”
The post-hoc analysis, published in JACC: Heart Failure, evaluated 361 patients with T2DM who were enrolled in the PROVE-HF trial of sac/val therapy for HF, published in JAMA.
PROVE-HF evaluated biomarkers, myocardial remodeling, and outcomes through a year of treatment with sac/val. The primary endpoint was the level of changes in natriuretic peptide (NT-proBNP) concentrations, left-ventricle ejection fraction (LVEF) and overall Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 scores through 12 months of treatment.
The post hoc study reported that baseline NT-proBNP concentrations were higher in the DM patients (854 pg/mL vs. 706 pg/mL), but at 12 months those levels were 513 and 441 pg/mL, respectively.
LVEF changed similarly from baseline to 12 months in both groups: from 28.3% to 37% in the DM patients and from 28.1% to 38.34% in non-DM patients. Overall KCCQ-23 scores improved similarly in both groups, but longitudinal analyses found modestly higher gains in the T2DM group, 9.3 vs. 8.6 points (P = .07).
“The real reason I wanted to do this study is that I’m a huge fan of all the SGLT-2 inhibitors, and I’m very involved in those trials, and there is right now so much momentum behind SGLT-2 inhibitors that I don’t want people to forget that ARNI is still the base therapy for HF,” said Dr. Butler, chair of cardiovascular research and the department of medicine at the University of Mississippi in Jackson.
He noted that the size of the diabetes cohort in PROVE-HF “is a nonissue” for evaluating power of the post hoc analysis because it tracked key measures in the study population continuously at eight intervals over the 12 months.
The analysis further demonstrates the synergistic effects of ARNI and SGLT-2 inhibitors in patients with T2DM and HF that were also reported in the PARADIGM-HF study, Dr. Butler said.
“We have sort of moved on, saying that SGLT-2 inhibitors have a benefit on the heart, but the reverse is also true: ARNIs are still heart failure drugs, and we don’t think of them as diabetes drugs, but the PARADIGM-HF data showed that there was a substantial reduction in hemoglobin A1c in those who had diabetes,” he said.
The researchers noted that an absence of a control group may contribute to an overestimation of reverse cardiac remodeling in the T2DM patients, and that the PROVE-HF study wasn’t prospectively powered to delineate differences in how sac/val therapy affected patients with or without diabetes. “Future investigations seeking to evaluate differences by T2DM status after sacubitril/valsartan initiation may use our findings to plan prospective sample sizes,” the researchers wrote.
Dr. Butler disclosed financial relationships with Abbott, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, CVRx, Eli Lilly, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Sequana, StealthPeptide and Vifor. Lead author Muhammad Shahzeb Khan, MD, MSc, a professor at the University of Mississippi, has no relevant financial relationships to disclose.
SOURCE: Kahn MS et al. JACC: HF. 2020 Dec 9. doi: 10.1016/j.jchf.2020.09.014.
The beneficial effects of sacubitril/valsartan on reverse cardiac remodeling in patients with heart failure and reduced ejection fraction have been well established, but those benefits haven’t been as clearly demonstrated to carry over to HFrEF patients who also have type 2 diabetes mellitus (T2DM).
Now, a post-hoc analysis of a pivotal clinical trial reports that those benefits do extend to patients with HFrEF and T2DM.
“It’s really not about a Sophie’s choice of whether you give this or that drug in these patients,” said corresponding author Javed Butler, MD, MPH, MBA. “We really ought to be giving all of these drugs – the angiotensin receptor neprilysin inhibitors (ARNIs) and sodium-glucose transporter 2 (SGLT-2) inhibitors – to our patients for the best outcomes.”
The post-hoc analysis, published in JACC: Heart Failure, evaluated 361 patients with T2DM who were enrolled in the PROVE-HF trial of sac/val therapy for HF, published in JAMA.
PROVE-HF evaluated biomarkers, myocardial remodeling, and outcomes through a year of treatment with sac/val. The primary endpoint was the level of changes in natriuretic peptide (NT-proBNP) concentrations, left-ventricle ejection fraction (LVEF) and overall Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 scores through 12 months of treatment.
The post hoc study reported that baseline NT-proBNP concentrations were higher in the DM patients (854 pg/mL vs. 706 pg/mL), but at 12 months those levels were 513 and 441 pg/mL, respectively.
LVEF changed similarly from baseline to 12 months in both groups: from 28.3% to 37% in the DM patients and from 28.1% to 38.34% in non-DM patients. Overall KCCQ-23 scores improved similarly in both groups, but longitudinal analyses found modestly higher gains in the T2DM group, 9.3 vs. 8.6 points (P = .07).
“The real reason I wanted to do this study is that I’m a huge fan of all the SGLT-2 inhibitors, and I’m very involved in those trials, and there is right now so much momentum behind SGLT-2 inhibitors that I don’t want people to forget that ARNI is still the base therapy for HF,” said Dr. Butler, chair of cardiovascular research and the department of medicine at the University of Mississippi in Jackson.
He noted that the size of the diabetes cohort in PROVE-HF “is a nonissue” for evaluating power of the post hoc analysis because it tracked key measures in the study population continuously at eight intervals over the 12 months.
The analysis further demonstrates the synergistic effects of ARNI and SGLT-2 inhibitors in patients with T2DM and HF that were also reported in the PARADIGM-HF study, Dr. Butler said.
“We have sort of moved on, saying that SGLT-2 inhibitors have a benefit on the heart, but the reverse is also true: ARNIs are still heart failure drugs, and we don’t think of them as diabetes drugs, but the PARADIGM-HF data showed that there was a substantial reduction in hemoglobin A1c in those who had diabetes,” he said.
The researchers noted that an absence of a control group may contribute to an overestimation of reverse cardiac remodeling in the T2DM patients, and that the PROVE-HF study wasn’t prospectively powered to delineate differences in how sac/val therapy affected patients with or without diabetes. “Future investigations seeking to evaluate differences by T2DM status after sacubitril/valsartan initiation may use our findings to plan prospective sample sizes,” the researchers wrote.
Dr. Butler disclosed financial relationships with Abbott, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, CVRx, Eli Lilly, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Sequana, StealthPeptide and Vifor. Lead author Muhammad Shahzeb Khan, MD, MSc, a professor at the University of Mississippi, has no relevant financial relationships to disclose.
SOURCE: Kahn MS et al. JACC: HF. 2020 Dec 9. doi: 10.1016/j.jchf.2020.09.014.
FROM JACC: HEART FAILURE
Twincretin ‘impressive’: Topline data from phase 3 trial in diabetes
Tirzepatide, a novel subcutaneously injected drug that acts via two related but separate pathways of glucose control, produced strikingly positive effects in top-line results from the phase 3, placebo-controlled study SURPASS-1 in 478 adults with type 2 diabetes, according to a Dec. 9 press release from the manufacturer, Lilly.
The tirzepatide molecule exerts agonist effects at both the glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 (GLP-1) receptor, and has been called a “twincretin” for its activity encompassing two different incretins. Phase 2 trial results caused excitement, with one physician calling the data “unbelievable” when reported in 2018.
SURPASS-1 enrolled patients who were very early in the course of their disease, had on average relatively mild elevation in glucose levels, and few metabolic comorbidities. They took one of three doses of the agent (5, 10, or 15 mg) as monotherapy or placebo for 40 weeks.
Julio Rosenstock, MD, said in the Lilly statement: “The study took a bold approach in assessing A1c targets. Not only did nearly 90% of all participants taking tirzepatide meet the standard A1c goal of less than 7%, more than half taking the highest dose also achieved an A1c less than 5.7%, the level seen in people without diabetes.”
Dr. Rosenstock is principal investigator of SURPASS-1 and director of the Dallas Diabetes Research Center in Texas.
The discontinuation rate in the high-dose group was 21.5% compared with less than 10% in the two lower-dose cohorts. Lilly said most of the dropouts “were due to the pandemic and family or work reasons.” The dropout rate in the placebo group was 14.8%.
These data were not included in the efficacy analysis, however, which “muddied” the analysis somewhat, one pharma analyst told BioPharma Dive.
Commenting on the new trial data, Ildiko Lingvay, MD, said in an interview: “I am very impressed with these results,” which are “unprecedented for any glucose-lowering medication that has ever been tested.”
Dr. Lingvay, of the department of internal medicine/endocrinology, and medical director, office of clinical trials management at UT Southwestern Medical Center, Dallas, was not involved in the study.
She added that the weight loss seen with tirzepatide “is equally impressive with greater than 10% of body weight loss above placebo achieved within 40 weeks of treatment and without any directed weight loss efforts.”
If the agent is eventually approved, “I am enthusiastic about the prospect of having another very powerful tool to address both diabetes and obesity,” she added.
The full results of SURPASS-1 will be presented at the American Diabetes Association 81st Scientific Sessions and published in a peer-reviewed journal in 2021.
SURPASS-1 is one of eight phase 3 studies of the drug, including five registration studies and one large 12,500-patient cardiovascular outcomes trial.
Tirzepatide patients lost up to 20 lb, side effect profile ‘reassuring’
In the study, patients had been recently diagnosed with type 2 diabetes (average duration, 4.8 years) and 54% were treatment-naive. Average baseline hemoglobin A1c was 7.9% and mean weight was 85.9 kg (189 pounds).
Patients started on a subcutaneous injectable dose of tirzepatide of 2.5 mg per week, which was titrated up to the final dose – 5, 10, or 15 mg – in 2.5-mg increments given as monotherapy for 40 weeks and compared with placebo.
Treatment with tirzepatide resulted in average reductions in A1c from baseline that ranged from 1.87% to 2.07%, depending on the dose, and were all significant compared with an increase of 0.4% with placebo.
The percentage of patients whose A1c fell to normal levels (less than 5.7%) ranged from 30.5% to 51.7%, compared with 0.9% among controls, and again, was significant for all doses.
Patients treated with tirzepatide also lost weight. Average weight reductions after 40 weeks were significant and ranged from 7.0 to 9.5 kg (15-21 pounds) compared with an average loss of 0.7 kg (1.5 pounds) among patients who received placebo.
The most common adverse events were gastrointestinal-related and mild to moderate in severity, and usually occurred during dose escalation.
Dr. Lingvay said the safety data reported are “reassuring, with side effects in the anticipated range and comparable with other medications in the GLP-1 agonist class.”
And no hypoglycemic (level 2, < 54 mg/dL) events were reported, “which is impressive considering the overall glucose level achieved,” she noted.
“I am eagerly awaiting the results of the other studies within the SURPASS program and hope those will confirm these initial findings and provide additional safety and efficacy information in a wider range of patients with type 2 diabetes,” she concluded.
Dr. Lingvay has reported receiving research funding, advisory/consulting fees, and/or other support from Novo Nordisk, Eli Lilly, Sanofi, AstraZeneca, Boehringer Ingelheim, Janssen, Intercept, Intarcia, Target Pharma, Merck, Pfizer, Novartis, GI Dynamics, Mylan, MannKind, Valeritas, Bayer, and Zealand Pharma.
A version of this article originally appeared on Medscape.com.
Tirzepatide, a novel subcutaneously injected drug that acts via two related but separate pathways of glucose control, produced strikingly positive effects in top-line results from the phase 3, placebo-controlled study SURPASS-1 in 478 adults with type 2 diabetes, according to a Dec. 9 press release from the manufacturer, Lilly.
The tirzepatide molecule exerts agonist effects at both the glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 (GLP-1) receptor, and has been called a “twincretin” for its activity encompassing two different incretins. Phase 2 trial results caused excitement, with one physician calling the data “unbelievable” when reported in 2018.
SURPASS-1 enrolled patients who were very early in the course of their disease, had on average relatively mild elevation in glucose levels, and few metabolic comorbidities. They took one of three doses of the agent (5, 10, or 15 mg) as monotherapy or placebo for 40 weeks.
Julio Rosenstock, MD, said in the Lilly statement: “The study took a bold approach in assessing A1c targets. Not only did nearly 90% of all participants taking tirzepatide meet the standard A1c goal of less than 7%, more than half taking the highest dose also achieved an A1c less than 5.7%, the level seen in people without diabetes.”
Dr. Rosenstock is principal investigator of SURPASS-1 and director of the Dallas Diabetes Research Center in Texas.
The discontinuation rate in the high-dose group was 21.5% compared with less than 10% in the two lower-dose cohorts. Lilly said most of the dropouts “were due to the pandemic and family or work reasons.” The dropout rate in the placebo group was 14.8%.
These data were not included in the efficacy analysis, however, which “muddied” the analysis somewhat, one pharma analyst told BioPharma Dive.
Commenting on the new trial data, Ildiko Lingvay, MD, said in an interview: “I am very impressed with these results,” which are “unprecedented for any glucose-lowering medication that has ever been tested.”
Dr. Lingvay, of the department of internal medicine/endocrinology, and medical director, office of clinical trials management at UT Southwestern Medical Center, Dallas, was not involved in the study.
She added that the weight loss seen with tirzepatide “is equally impressive with greater than 10% of body weight loss above placebo achieved within 40 weeks of treatment and without any directed weight loss efforts.”
If the agent is eventually approved, “I am enthusiastic about the prospect of having another very powerful tool to address both diabetes and obesity,” she added.
The full results of SURPASS-1 will be presented at the American Diabetes Association 81st Scientific Sessions and published in a peer-reviewed journal in 2021.
SURPASS-1 is one of eight phase 3 studies of the drug, including five registration studies and one large 12,500-patient cardiovascular outcomes trial.
Tirzepatide patients lost up to 20 lb, side effect profile ‘reassuring’
In the study, patients had been recently diagnosed with type 2 diabetes (average duration, 4.8 years) and 54% were treatment-naive. Average baseline hemoglobin A1c was 7.9% and mean weight was 85.9 kg (189 pounds).
Patients started on a subcutaneous injectable dose of tirzepatide of 2.5 mg per week, which was titrated up to the final dose – 5, 10, or 15 mg – in 2.5-mg increments given as monotherapy for 40 weeks and compared with placebo.
Treatment with tirzepatide resulted in average reductions in A1c from baseline that ranged from 1.87% to 2.07%, depending on the dose, and were all significant compared with an increase of 0.4% with placebo.
The percentage of patients whose A1c fell to normal levels (less than 5.7%) ranged from 30.5% to 51.7%, compared with 0.9% among controls, and again, was significant for all doses.
Patients treated with tirzepatide also lost weight. Average weight reductions after 40 weeks were significant and ranged from 7.0 to 9.5 kg (15-21 pounds) compared with an average loss of 0.7 kg (1.5 pounds) among patients who received placebo.
The most common adverse events were gastrointestinal-related and mild to moderate in severity, and usually occurred during dose escalation.
Dr. Lingvay said the safety data reported are “reassuring, with side effects in the anticipated range and comparable with other medications in the GLP-1 agonist class.”
And no hypoglycemic (level 2, < 54 mg/dL) events were reported, “which is impressive considering the overall glucose level achieved,” she noted.
“I am eagerly awaiting the results of the other studies within the SURPASS program and hope those will confirm these initial findings and provide additional safety and efficacy information in a wider range of patients with type 2 diabetes,” she concluded.
Dr. Lingvay has reported receiving research funding, advisory/consulting fees, and/or other support from Novo Nordisk, Eli Lilly, Sanofi, AstraZeneca, Boehringer Ingelheim, Janssen, Intercept, Intarcia, Target Pharma, Merck, Pfizer, Novartis, GI Dynamics, Mylan, MannKind, Valeritas, Bayer, and Zealand Pharma.
A version of this article originally appeared on Medscape.com.
Tirzepatide, a novel subcutaneously injected drug that acts via two related but separate pathways of glucose control, produced strikingly positive effects in top-line results from the phase 3, placebo-controlled study SURPASS-1 in 478 adults with type 2 diabetes, according to a Dec. 9 press release from the manufacturer, Lilly.
The tirzepatide molecule exerts agonist effects at both the glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 (GLP-1) receptor, and has been called a “twincretin” for its activity encompassing two different incretins. Phase 2 trial results caused excitement, with one physician calling the data “unbelievable” when reported in 2018.
SURPASS-1 enrolled patients who were very early in the course of their disease, had on average relatively mild elevation in glucose levels, and few metabolic comorbidities. They took one of three doses of the agent (5, 10, or 15 mg) as monotherapy or placebo for 40 weeks.
Julio Rosenstock, MD, said in the Lilly statement: “The study took a bold approach in assessing A1c targets. Not only did nearly 90% of all participants taking tirzepatide meet the standard A1c goal of less than 7%, more than half taking the highest dose also achieved an A1c less than 5.7%, the level seen in people without diabetes.”
Dr. Rosenstock is principal investigator of SURPASS-1 and director of the Dallas Diabetes Research Center in Texas.
The discontinuation rate in the high-dose group was 21.5% compared with less than 10% in the two lower-dose cohorts. Lilly said most of the dropouts “were due to the pandemic and family or work reasons.” The dropout rate in the placebo group was 14.8%.
These data were not included in the efficacy analysis, however, which “muddied” the analysis somewhat, one pharma analyst told BioPharma Dive.
Commenting on the new trial data, Ildiko Lingvay, MD, said in an interview: “I am very impressed with these results,” which are “unprecedented for any glucose-lowering medication that has ever been tested.”
Dr. Lingvay, of the department of internal medicine/endocrinology, and medical director, office of clinical trials management at UT Southwestern Medical Center, Dallas, was not involved in the study.
She added that the weight loss seen with tirzepatide “is equally impressive with greater than 10% of body weight loss above placebo achieved within 40 weeks of treatment and without any directed weight loss efforts.”
If the agent is eventually approved, “I am enthusiastic about the prospect of having another very powerful tool to address both diabetes and obesity,” she added.
The full results of SURPASS-1 will be presented at the American Diabetes Association 81st Scientific Sessions and published in a peer-reviewed journal in 2021.
SURPASS-1 is one of eight phase 3 studies of the drug, including five registration studies and one large 12,500-patient cardiovascular outcomes trial.
Tirzepatide patients lost up to 20 lb, side effect profile ‘reassuring’
In the study, patients had been recently diagnosed with type 2 diabetes (average duration, 4.8 years) and 54% were treatment-naive. Average baseline hemoglobin A1c was 7.9% and mean weight was 85.9 kg (189 pounds).
Patients started on a subcutaneous injectable dose of tirzepatide of 2.5 mg per week, which was titrated up to the final dose – 5, 10, or 15 mg – in 2.5-mg increments given as monotherapy for 40 weeks and compared with placebo.
Treatment with tirzepatide resulted in average reductions in A1c from baseline that ranged from 1.87% to 2.07%, depending on the dose, and were all significant compared with an increase of 0.4% with placebo.
The percentage of patients whose A1c fell to normal levels (less than 5.7%) ranged from 30.5% to 51.7%, compared with 0.9% among controls, and again, was significant for all doses.
Patients treated with tirzepatide also lost weight. Average weight reductions after 40 weeks were significant and ranged from 7.0 to 9.5 kg (15-21 pounds) compared with an average loss of 0.7 kg (1.5 pounds) among patients who received placebo.
The most common adverse events were gastrointestinal-related and mild to moderate in severity, and usually occurred during dose escalation.
Dr. Lingvay said the safety data reported are “reassuring, with side effects in the anticipated range and comparable with other medications in the GLP-1 agonist class.”
And no hypoglycemic (level 2, < 54 mg/dL) events were reported, “which is impressive considering the overall glucose level achieved,” she noted.
“I am eagerly awaiting the results of the other studies within the SURPASS program and hope those will confirm these initial findings and provide additional safety and efficacy information in a wider range of patients with type 2 diabetes,” she concluded.
Dr. Lingvay has reported receiving research funding, advisory/consulting fees, and/or other support from Novo Nordisk, Eli Lilly, Sanofi, AstraZeneca, Boehringer Ingelheim, Janssen, Intercept, Intarcia, Target Pharma, Merck, Pfizer, Novartis, GI Dynamics, Mylan, MannKind, Valeritas, Bayer, and Zealand Pharma.
A version of this article originally appeared on Medscape.com.